EANS TRAINING COURSE - KRAKOW
24 FEBRUARY - 28 FEBRUARY 2013
EANS TRAINING COURSE
HEAD INJURY AND FUNCTIONAL KRAKOW, POLAND 24TH FEBRUARY - 28TH FEBRUARY 2013 Editors: Nejat Akalan, Ryszard Czepko, Susie Hide
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EANS TRAINING COURSE - KRAKOW
24 FEBRUARY - 28 FEBRUARY 2013
EANS MEMBERSHIP - Apply Online: www.eans.org
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Full Membership
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EANS Individual Membership Benefits include:
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EANS TRAINING COURSE - KRAKOW
24 FEBRUARY - 28 FEBRUARY 2013
PROGRAMME
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24 FEBRUARY - 28 FEBRUARY 2013
SOCIAL PROGRAMME AND ADDITIONAL EVENTS Saturday, February 23rd 12.00 – 21.00
Registration, Qubus Hotel
10.00 – 21.30
Midas Rex Drilling Courses, Room A
15.00 – 19.15
Part I Examination, Qubus Hotel, rooms B&C Candidates should register from 14.30 onwards
20.00
Welcome reception and buffet/drinks at Qubus Hotel
Sunday, February 24th 12.55
Training Committee Meeting: Room G
19.45
Assemble in lobby of Qubus Hotel for drinks and dinner at Drukarnia Jazz Club
Monday, February 25th 11.55
Training Committee Meeting: Room G
18.00
Assemble in lobby of Qubus hotel for bus transfer to Wieliczka Salt Mine
Tuesday, February 26th 11.00
Administrative Council Meeting: Room A
Afternoon
Free afternoon and Optional City tours for trainees
17:45
Faculty Only: Assemble in lobby of Qubus Hotel
18:30
Faculty Only: Organ Recital at St Anne’s Church followed by dinner at 3Rybki Restaurant
Wednesday, February 27th 09.00
Administrative Council Meeting: Room G
13.20
Training Committee Meeting: Room G
19.30
Assemble in hotel lobby for transfer to Stara Zajezdnia Krakow by DeSilva: drinks, dinner and entertainment
Thursday, February 28th 20.00 onwards
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Farewell Dinner, Qubus Hotel
EANS TRAINING COURSE - KRAKOW
24 FEBRUARY - 28 FEBRUARY 2013
CONTACT DETAILS FOR SOCIAL VENUES QUBUS HOTEL Krakow ul. Nadwislanska 6 30-527 Krakow +48 12 374 5 100 www.qubushotel.com
Tuesday, February 26th St.Anne’s Church ul. Sw. Anny 11, 31-008 Krakow www.kolegiata-anna.pl
Sunday, February 24th Drukarnia Jazz Club Nadwislanska 1 30-527 Krakow +48 12 656 65 60 www.drukarniaclub.pl
Tuesday, February 26th TRZY RYBKI Restaurant ul. Szczepanska 5 31-011 Krakow +48 12 384 08 06 www.likusrestauracje.pl
Monday, February 25th Wieliczka Salt Maine ul. Danilowicza 10 32-020 Wieliczka +48 12 278 73 02 www.kopalnia.pl
Wednesday, February 27th Stara Zajezdnia Krakow by DeSilva ul. Wawrzynca 12 31-060 Krakow +48 12 370 45 00 www.starazajezdniakrakow.pl
EMERGENCY CONTACT DETAILS Tereza Antoncikova: +420 (0) 602 254 411 Susie Hide: +44 (0) 7967 458028
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EANS TRAINING COURSE - KRAKOW
24 FEBRUARY - 28 FEBRUARY 2013
SUNDAY 24TH FEBRUARY 08:30 - 08:45
Introduction and Welcome
08.45 - 09.15 09.15 - 09.35 09.35 - 10.05 10.05 - 10.25 10.25 - 10.35
Pain Overview and Rationale for Surgery Microvascular Compression Syndromes Neuromodulation for Pain Surgical Management of Pain How I Do It: Neurovascular Decompression
10.35 - 11.15 11.15 - 12.50 12.50 - 14.00
Break Discussion Groups Lunch
14.00 - 14.20
15.40 - 15.50
Overview and Pre-surgical Selection of Epilepsy Patients Imaging in Epilepsy Anatomy of Temporal Structures Non-Resective Epilepsy Surgery How I Do It: Vagal Nerve Stimulation Procedure How I Do It: Hemispherotomy
15.50 - 16.20 16.20 - 18.45
Break Discussion Groups (three rotations)
14.20 - 14.40 14.40 - 15.10 15.10 - 15.30 15.30 - 15.40
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Czepko, Akalan and Hide Sindou Benes Tronnier Sindou Smolanka
See page 12
Van Roost Oguz Destrieux Van Roost d’Avella Akalan
See page 12
EANS TRAINING COURSE - KRAKOW
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MONDAY 25TH FEBRUARY 08.30 - 08.50 08.50 - 09.10 09.10 - 09.30 09.30 - 09.40 09.40 - 09.50
Temporal Lobe Epilepsy Surgery Extratemporal Epilepsy Surgery Outcome and Long Term Perspective in Epilepsy Surgery How I Do It: Temporal Lobectomy How I Do It: Amygdalohippocampectomy
09.50 - 10.20 10.20 - 11.55 11.55 - 12.55
Break Discussion Groups Lunch
12.55 - 13.15
14.55 - 15.05 15.05 - 15.15
DBS for mental disorders: new techniques and indications Classification and Pathophysiology of Movement Disorders Surgery for Parkinson’s Disease Neurosurgery for Dystonias and Non-Parkinson Movement Disorders Surgery for Spasticity Radiosurgery for Epilepsy and Movement Disorders How I Do It: DREZotomy How I Do It: DBS for Parkinson’s
15.15 - 15.45 15.45 - 17.20
Break Discussion Groups
13.15 - 13.35 13.35 - 13.55 13.55 - 14.15 14.15 - 14.35 14.35 - 14.55
Schramm Clusmann Sure Schramm Clusmann
See page 13
Barcia Dusek Israel Palmer Sindou Regis Sindou Tronnier
See page 13
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TUESDAY 26TH FEBRUARY 08.30 - 08.50 08.50 - 09.10 09.10 - 09.30 09.30 - 10.00
Psychosurgery Surgery for Neuropsychiatric Disorders Psychosurgery (Ethical Point) Codman sponsored lecture: Rescuing the injured brain
10.00 - 10.30
Break
10.30 - 11.00
Elekta sponsored lecture: Radiosurgical management of trigeminal neuralgia Present situation and perspectives of neurotraumatology in Nepal
11.00 - 12.00
Free Afternoon for Trainees (Optional city tours available)
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Fontaine Abosch Verlooy Hutchinson
Regis Mandera
EANS TRAINING COURSE - KRAKOW
24 FEBRUARY - 28 FEBRUARY 2013
WEDNESDAY 27TH FEBRUARY 08.15 - 08.35 08.35 - 08.55
09.35 - 09.55 09.55 - 10.05 10.05 - 10.15 10.15 - 10.25
Traumatic Brain Injury Pathophysiology of Brain Injury and Brain Protection Clinical Evaluation and Prognosis of TBI New Developments in Imagining Head Injured Patients Management of Polytraumatised Patient How I Do It: Decompressive Craniectomies How I Do It: Subdural Hematoma How I Do It: Epidural Hematoma
10.25 - 10.55 10.55 - 13.20 13.20 - 14.20
Break Discussion Groups (THREE ROTATIONS) Lunch
14.20 - 14.40 14.40 - 15.00 15.00 - 15.20 15.20 - 15.40 15.40 - 15.50 15.50 - 16.10 16.10 - 16.30
Traumatic Intracranial Hemorrhage Management / Monitoring in the ICU Management of Craniofacial Trauma and CSF Leaks Penetrating Brain Injuries How I Do It: Depressed Fractures Late Complications of Head Injury Research in Neurotraumatology
16.30 - 17.10 17.10 - 18.45
Break Discussion Groups
08.55 - 09.15 09.15 - 09.35
Buki Smrcka Buki Kurpad Hutchinson Hutchinson Roche Selviaridis
See page 14
Vukic Thome Roche Szabo Roche Selviaridis Marklund
See page 14
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THURSDAY 28TH FEBRUARY 08.30 - 08.50 08.50 - 09.10 09.10 - 09.30 09.30 - 09.50
Sports Related Concussions Traumatic Brain Injury During Childhood Non-Accidental Injury in Children Trauma in the Elderly
10.30 - 10.40
Trainee Lectures A comprehensive analysis of coagulation disorders in patients with severe isolated traumatic brain injury and correlation with CT scans Local fibrinolysis for the surgical treatment of traumatic intracranial hemorrhage Surgery for temporal lobe epilepsy in children: relevance of presurgical evaluation and analysis of outcome The warning sign hierarchy between quantitative subcortical motor mapping and continuous motor evoked potential monitoring during surgery of supratentorial brain tumors Subcortical Stimulation
10.50 - 11.20 11.20 - 12.55 12.55 - 14.00
Break Discussion Groups Lunch
14.00 - 15.30 14.00 - 14.20
Special Session - Research Group The importance of research to neurosurgical residents and qualified neurosurgeons Interactive group discussions focused on neurosurgical research
09.50 - 10.00
10.00 - 10.10 10.10 - 10.20
10.20 - 10.30
14.20 - 15.30
15.30 - 16.00 16.00 - 17.35 17.40
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Break Discussion Groups Course Evaluation
Marklund Grotenhuis Juhler Meling
Juratli
Kostyantyn Miserocchi
Seidel
Shiban
Grotenhuis
See page 15
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DISCUSSION GROUPS Sunday/Monday 1.
Technical Pitfalls in Epilepsy Surgery
2.
Lesions and Seizures: Lesionectomy or Epilepsy Surgery
3.
Epilepsy: Excise or Stimulate, Indications and Techniques
4.
Management of Epilepsy in Children
5.
Indications and Choice of Treatment For Trigeminal Neuralgia
6.
Neuromodulation for Pain Syndromes
7.
Cranial Nerve Compression Syndromes
8.
Movement Disorders: Stimulation or Lesioning
9.
Brainlab Hands-On Workshop
Clusmann/Schramm Sure/Akalan Van Roost/D’Avella Laakso/TBA Szaba/Sindou Tronnier/Peerdeman Smolanka/Verlooy Israel/Abosch
Wednesday/Thursday 10. Management of Severe Head Injury 11. Traumatic Dissection of Extracranial Vessels 12. Trauma to the Skull Base 13. Chronic Subdural Hematoma 14. Cranial defects/Craniectomy/Craniotomy in Children 15. Traumatic Intracerebral Hematoma Posterior Fossa 16. ICP (And Other) Monitoring: Indications and Timing 17. Subdural Collection/in Infants
Szabo/Kurpad/Buki Smolanka/Marklund Roche/Meling Selviaridis/Papanastassiou Grotenhuis/TBA Vukic/Lehecka Buki/Thome Juhler/Poeata
18. Cryolife Hands-On workshop
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DISCUSSION GROUP TIMETABLE AND ROOM ALLOCATIONS Sunday 24th February Group A B C D E F
Room Conference Room A Conference Room B Conference Room C Conference Room D Conference Room E Conference Room H (ground floor)
11.20 - 12.05 9 8 2 7 1 4
12.10 - 12.55 4 7 1 8 5 3
Group A
Room Conference Room H (ground floor) Conference Room A then Conference Room B Conference Room B Then Conference Room A Conference Room C Conference Room D Conference Room E
16.20 - 17.05
17.10 - 17.55
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8
9
6
4
9
1 3 6
2 7 5
Room Conference Room B Conference Room C Conference Room D Conference Room E Conference Room H (ground floor) Conference Room A
18.00 - 18.45 6 1 8 3
B C D E F Group A B C D E F
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Monday 25th February Group A B C D E F Group A B C D E F
Room Conference Room D Conference Room E Conference Room H (ground floor) Conference Room A Conference Room B Conference Room C
10.25 - 11.10 1 5 3
11.15 - 12.00 5 3 7
9 6 2
6 4 1
Room Conference Room C Conference Room D Conference Room E Conference Room H (ground floor) Conference Room A Conference Room B
16.00 - 16.45 3 2 5 4
16.50 - 17.35 2 4 6 5
9 8
8 7
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Wednesday 27th February Group A B C D E F
Room Conference Room A Conference Room B Conference Room C Conference Room D Conference Room E Conference Room H (ground floor)
10.55 - 11.40 18 17 11 16 10 13
Group A
Room Conference Room B (ground floor) Conference Room C Conference Room D Conference Room E Conference Room H Conference Room A
12.35 - 13.20 15
Room Conference Room H (ground floor) Conference Room A then Conference Room B Conference Room B Then Conference Room A Conference Room C Conference Room D Conference Room E
17.10 - 17.55 16
18.00 - 18.45 17
18
15
13
18
10 12 15
11 16 14
B C D E F Group A B C D E F
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11.45 - 12.30 13 16 10 17 14 12
10 17 12 11 18
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24 FEBRUARY - 28 FEBRUARY 2013
Thursday 28th February Group A B C D E F Group A B C D E F
Room Conference Room D Conference Room E Conference Room H (ground floor) Conference Room A Conference Room B Conference Room C
11.20 - 12.05 10 14 12
12.10 - 12.55 14 12 16
18 15 11
15 13 10
Room Conference Room C Conference Room D Conference Room E Conference Room H (ground floor) Conference Room A Conference Room B
15.45 - 16.30 12 11 14 13
16.35 - 17.20 11 13 15 14
18 17
17 16
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ABSTRACTS
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INDEX OF ABSTRACTS Sunday 24th February Microvascular Compression Syndromes
Benes
Page 23
Neuromodulation for Pain
Tronnier
Page 28
Surgical Management of Pain
Sindou
Page 42
Overview and Pre-surgical Selection of Epilepsy Patients
van Roost
Page 47
Imaging in Epilepsy
Oguz
Page 55
Anatomy of Temporal Structures
Destrieux
Page 59
Non-Resective Epilepsy Surgery
Van Roost
Page 70
Temporal Lobe Epilepsy Surgery
Schramm
Page 80
Extratemporal Epilepsy Surgery
Clusmann
Page 83
Outcome and Long Term Perspective in Epilepsy Surgery
Sure
Page 88
Classification and Pathophysiology of Movement Disorders
Dusek
Page 95
Surgery for Parkinson’s Disease
Israel
Page 98
Neurosurgery for Dystonias and Non-Parkinson Movement Disorders
Palmer
Page 102
Surgery for Spasticity
Sindou
Page 108
Radiosurgery for Epilepsy and Movement Disorders
Regis
Page 112
Monday 25th February
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Tuesday 26th February Psychosurgery
Fontaine
Page 127
Psychosurgery (Ethical Point)
Verlooy
Page 131
Elekta sponsored lecture: Radiosurgical management of trigeminal neuralgia
Regis
Page 133
Traumatic Brain Injury
Buki
Page 157
Pathophysiology of Brain Injury and Brain Protection
Smrcka
Page 161
New Developments in Imagining Head Injured Patients Kurpad
Page 168
Management of Polytraumatised Patient
Hutchinson
Page 174
Traumatic Intracranial Hemorrhage
Vukic
Page 178
Management / Monitoring in the ICU
Thome
Page 183
Management of Craniofacial Trauma and CSF Leaks
Roche
Page 187
Penetrating Brain Injuries
Szabo
Page 195
Late Complications of Head Injury
Selviaridis
Page 201
Research in Neurotraumatology
Marklund
Page 206
Sports Related Concussions
Marklund
Page 213
Traumatic Brain Injury During Childhood
Grotenhuis
Page 219
Non-Accidental Injury in Children
Juhler
Page 239
Wednesday 27th February
Thursday 28th February
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TRAINEE ABSTRACTS A comprehensive analysis of coagulation disorders in patients with severe isolated traumatic brain injury and correlation with CT scans
Juratli
Page 249
Local fibrinolysis for the surgical treatment of traumatic intracranial hemorrhage
Kostyantyn
Page 250
Surgery for temporal lobe epilepsy in children: relevance of presurgical evaluation and analysis of outcome
Miserocchi
Page 251
The warning sign hierarchy between quantitative subcortical motor mapping and continuous motor evoked potential monitoring during surgery of supratentorial brain tumors
Seidel
Page 253
Subcortical Stimulation
Shiban
Page 254
Emergency lumbar disc surgery: is it safe?
Al-Afif
Page 259
Effective management of lower divisional pain in trigeminal neuralgia using balloon traction
Teo
Page 260
Surgical treatment of va-pica complex pathology through far lateral approach: Size of craniotomy and surgical angle
Juan
Page 261
Combined transcranial-endonasal approach for an esthesioneuroblastoma with intradural invasion
Zoia
Page 262
ADDITIONAL TRAINEE ABSTRACTS
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CRANIAL NERVES COMPRESSION SYNDROMES V.Beneš, V. Masopust Department of Neurosurgery, Charles University, 1st Faculty of Medicine, Central Military Hospital, Prague, Czech Republic. Objective The objective of the article is to summarise the current state of knowledge on neurovascular conflict syndromes, to highlight some uncertainities we face, and to discuss some promising research avenues. Special emphasis is focused on the possible future diagnostic and therapeutic approaches. Definition of Syndromes Vascular compression of cranial nerves has been related to disorders such as trigeminal neuralgia, glossopharyngeal neuralgia, hemifacial spasm, disabling positional vertigo, geniculate neuralgia, spasmodic torticollis, cyclic oculomotor spasm with paresis, superior oblique myokymia, and arterial hypertension. Actually, all nerves except for VIth, XIIth and right Xth were blamed for this or other clinical neurovascular compression syndrome. See Tab.1. Recent Clinical and Research Developments The hypothesis that blood vessels compressing cranial nerves can cause clinical syndromes was first proposed by Dandy in 1934. First nerve decompression is credited to Gardner and Miklos, who reported first surgery in 1959. Recently the microvascular decompression is associated with Jeanetta and his group, who popularized the procedure not only for trigeminal neuralgia but for other syndromes as well. Several hypotheses regarding the development of cranial nerve compression syndromes have been published. Jannetta suggested that vascular compression develops when blood vessels elongate, leading to formation of vascular loops, thus causing an increased risk for vascular compression of one or more cranial nerves. He assumed that the mechanical effect of a pulsating blood vessel was the cause of the disease. He further hypothesized that the compression must be at the root entry zone of the cranial nerve to cause symptoms. Others (Leclercq, Ryu, and Moller) suggested that the compression can occur at any point along the cranial nerve, especially at the CNS segment, and not only at the root entry zone. In addition, there is considerable evidence that any vascular contact (artery or vein) can cause symptoms. Vascular contact with a cranial nerve is commonnly seen at autopsies; however, symptoms of vascular compression are rare. This discrepancy has been explained by the assumption that a second factor, such as previous minor injury, is necessary for creating symptoms such as hemifacial spasm, trigeminal neuralgia, and glossopharyngeal neuralgia. Damage of the central inhibitory mechanisms seems to play some role in the clinical symptoms development, too. Trigeminal neuralgia is more frequent in young patients with multiple sclerosis and 18% of patients harboring bilateral trigeminal neuralgia suffer from multiple sclerosis.
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Such data are absent in other neurovascular syndromes, however, these syndromes are too rare to allow gathering of enough specific pathophysiologic data. It has also been suggested that habitually small posterior fossa may be a predisposing factor for the development of neurovascular conflict. A group of patients with trigeminal neuralgia had statistically significant smaller posterior fossa than the control group of healthy subjects. Diagnosis of neurovascular syndrome is always clinical. Radiologically the neural compression can be proved by 3D MR programme (Nagaseki). With little patience any cranial nerve can be detected on MR, desired slices acquired and 3D reconstruction calculated. However, inability to show the compression should not be the contraindication of surgery. In certain part of patients the compression is found during surgery only (in our hands this is true for 5% of n.V. and 10% of n.VII). Surgery is thus based on clinical symptoms dominantly, the rarer the syndrome, the higher the caution to offer the surgery. Three basic approaches may be used. Upper one, situated at the junction of transverse and sigmoid sinuses (e.g.Fukushima), allows to attack nerves IV.-V. (A) Middle approach, regular small lateral suboccipital approach at the middle portion of sigmoid sinus, is suitable for nerves VII.-VIII. and would be appropriate for nerve VI – however no compression syndrome is described yet. (B) Modified (smaller) far lateral (e.g.Spetzler) approach is suitable for lower cranial nerves and ventral medulla. (C) See Fig.1. Surgery is easy and straightforward – all structures are at their respective anatomical locations, the CSF is clear, no retraction is needed (by patients positioning the gravity is used to move the cerebellar hemisphere). The compressing artery is moved away from the nerve and secured in the new position by either small piece of Dacron which is interposed between the artery and nerve or small Dacron sling is used to move the artery. The sling is then glued to the dura to hold the artery apart from the nerve. In extremely rare conditions the compression cannot by solved – either the artery pierces the nerve or the artery is fenestrated and the nerve passes through the fenestration. Sometimes the compression is caused by an extremely tortuous and/or sclerotic basilar artery, in such a case it may be difficult to separate the structures properly and permanently. Cave: The most frequent surgical failure is lack of proper nerve visualisation in its entire length. The entry zone must be seen even if the artery is found more laterally. The other artery may be compressing the nerve medially. Endoscope-assisted surgery solves this problem. Future Questions and Directions Few avenues should be cultivated within the clinical settings. Obviously the basic research on pathophysiological mechanisms of neurovascular compression syndromes is needed. The mechanisms of possible “second event” should be better defined. The role of veins in the compression syndromes should be either definitively proved or ruled out. Electrophysiology recently is able to show alterations of
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normal potentials, specific changes for vascular compression of cranial nerves (except n.V and n.VII) should be shown. Modern radiology recently is capable of showing vascular conflict of any given cranial nerve and surgical indications of rare compression syndromes should thus be based on radiologically proven contact of a vessel with the relevant cranial nerve. Probably the most important issue should be construction of multiinstitutional database of rare compression syndromes and our ability to use such a database empirically. Randomised trials are not feasible. Conclusion A neurosurgeon should be aware, that microvascular decompression is a procedure which is not restricted to trigeminal neuralgia and facial hemispasm. Actually, we have a procedure which could be used in many conditions and paradoxically we lack the pathophysiological understanding and diagnostic tools to use the procedure more frequently. Recommended Key Words and Authors Neurovascular compression syndrome, microvascular decompression, trigeminal neuralgia, facial hemispasm, disabling positional vertigo. Jeanetta PJ, Moeller AR, Moeller MB Recommended Literature 1.
Dandy WE. The treatment of trigeminal neuralgia by the cerebellar rout. Ann Surg 96:787-95, 1932.
2.
Dandy WE. Concerning the cause of trigeminal neural¬gia. Am 3 Surg 24:447-55, 1934.
3.
Fraioli B, Esposito V, Ferrante L, Trubiani L, Lunardi P : Microsurgical treatment of glossopharyngeal neuralgia : Case reports. Neurosurgery 25 : 630-632, 1989.
4.
Freckmann N, Hagenah R, Herrmann HD, Muller D : Treatment of neurogenic torticollis by microvascular lysis of the accessory roots : Indication, technique, and the first results. Acta Neurochir (Wien) 59 : 167-175, 1981.
1.
Janetta PJ: Neurovascular cross-compression in patients with hyperactive dysfunction symptoms of the eight cranial nerve. Surg Forum 26 : 467-469, 1975.
2.
Janetta PJ: Microsurgery of cranial cross-compression. Clin Neurosurg 26: 607-615, 1979.
3.
Janetta PJ: Neurovascular compression in cranial nerve and systemic disease. Ann Surg 192: 518-525, 1980.
4.
Janetta PJ, Møller MB, Møller AR: Disabling positional vertigo. N Engl J Med 310: 1700-1705, 1984.
5.
Kommerell G, Mehdorn E, Ketelsen UP, Vollrath-Junger CH: Oculomotor palsy with cyclic spasms: Electromyographic and electron microscopic 25
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evidence of chronic peripheral neuronal involvement. Neuro-ophthalmol 8: 9-21, 1988. 6.
Levy E, Clyde B, McLaughlin MR, Jannetta PJ: Micro-vascular decompression of the left lateral medulla ob¬longata for severe refractory neurogenic hypertension. Neurosurgery 43:1-6, 1998.
7.
Masopust V, Netuka D, Benes V: Constitutionally Small Posterior Fossa as a Predisposition for Neurovascular Conflict. J Neurosurgery 96: 190A, 2002.
8.
Møller MB: Controversy in Meniére´s disease: Results of microvascular decompression of the eighth nerve Am J Otol 9: 60-63, 1988.
9.
Møller AR: Cranial nerve dysfunction syndromes: Pathophysiology of microvascular compression, in Barrow DL (ed): Neurosurgical Topics Book 13: Surgery of Cranial Nerves of the Posterior Fossa. Park Ridge, AANS, 1993, pp 105-129.
10.
Møller AR: Vascular compression of cranial nerves: Part II-Pathophysiology. Neurol Res 21:432-443, 1999.
11.
Ouaknine GE, Robert F, Molina-Negro P, Hardy J: Geniculate neuralgia and audiovestibular disturbances due to compression of the intermediate and eighth nerves by the postero-inferior cerebellar artery. Surg Neurol 13:147150, 1980.
12.
Sunderland S: Microvascular relations and anomalies at the base of the brain. J Neurol Neurosurg Psychiatry 11: 243-257, 1948.
Table 1. : Microvascular compression syndromes Neurovascular conflict III.
Cyclic oculomotor spasm with paresis
IV.
Superior oblique myokymia
V.
Trigeminal neuralgia
VI.
???
VII.
Hemifacial spasm
VIII.
Disabling positional vertigo, (Meniére´s disease)
IX.
Glossopharyngeal neuralgia
X.
Arterial hypertension
XI.
Spasmodic torticollis
XII.
???
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Figure 1. : Basic approaches
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NEUROMODULATION FOR THE TREATMENT OF PAIN V.Tronnier Lübeck 1.
Introduction
2.
Stimulation for the treatment of chronic pain
2.1. Peripheral nerve stimulation 2.2. Subcutaneous peripheral field stimulation 2.3. Spinal Cord Stimulation 2.4. Motor Cortex Stimulation 2.5. Deep brain stimulation 2.6. TMS 3.
Intrathecal drug delivery for the treatment of chronic pain
4.
Recommended literature
1. Introduction Neuromodulation techniques to treat chronic pain have evolved enormously during the last 20 years. While in the early 70ies cordotomy was still the most frequent procedure to treat mainly pain due to malignant disease, the neurolesional procedures were rapidly replaced by neuroaugmentative or neuromodulational procedures. This was due to the improved neurophysiological knowledge of pain transduction and procession as well as the clinical experience of the temporary effect in patients with pain due to non-malignant causes and the findings that lesional procedures can cause pain themselves. Therefore neurotomies and rhizotomies are nowadays considered obsolete in non-malignant pain conditions. Only in cases with trigeminal neuralgia or facet syndrome lesional procedures are still accepted. The following chapters will give a short overview of the different neuromodulational procedures, the particular indications and the clinical evidence based on controlled studies or guidelines. 2. Stimulation for the Treatment of Chronic Pain 2.1 Peripheral Nerve stimulation (PNS) Stimulation of peripheral nerves preceded the development of spinal cord stimulation. Stimulation experiments by Pat Wall and William Sweet 1967 as well as Sweet and Wepsic 1974 lead to PNS to treat neuropathic pain after nerve lesions and later the failed back surgery syndrome, where different authors tried to stimulate the sciatic nerve directly. This latter however was disappointing. Soon it was clear that the stimulation has to be performed proximal to a nerve lesion and that it was easier to stimulate large nerves as the median or ulnar nerve instead of small peripheral nerves. Initial enthusiasm declined by the morbidity associated with the electrode design (cuff-electrode) and surgical technique (scarring, dislocation, 28
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motor stimulation). New electrode design with small leads allow a subepineural stimulation but the problem of transversing one or two joints before impulse generator placement still carries a high risk of electrode dislocation or breakage. Although there exist no randomized controlled series several cohort studies report even long-term success with stimulation for different pain syndromes. The following indications are considered worthwhile to be tried by PNS: t
CRPS II (Causalgia, this means, pain due to a nerve lesion which is distributed to the involved nerve)
t
Trigeminal neuropathy with stimulation in the foramen ovale or more peripherally at the involved branches (supraorbital, infraorbital or mental nerve)
t
Postherniotomy pain with stimulation of the , iliohypogastrical ilioinguinal or femorogenital nerve
t
Infrapatellar neuropathy
Stimulation of the infrapatellar nerve as well as femoral nerve
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Stimulation of the Foramen ovale with externalized lead
Stimulation of the iliohypogastric nerve for postherniotomy pain 2.2 Subcutaneous peripheral field stimulation This stimulation is carried by subcutaneous placement in the area of the projected field of one or more nerves. The mechanism of action is most likely a stimulation of small peripheral (subcutaneous) afferents of nerves responsible for the pain syndrome. It is nowadays widely used to treat low back pain although no controlled study is available. One to 4 electrodes are placed over the painful area in the back 30
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and usually wide fields are stimulated monopolarly or the stimulation is carried out between implanted electrodes. The main problem remains the electrode dislocation. Therefore the different companies work on special electrode designs (eg. with small hooks) to keep the electrodes better in place. A much better indication with good clinical evidence is the occipital nerve stimulation, better the peripheral field stimulation in the occipital area, (ONS). Although in early reports the occipital nerve was dissected and electrodes were placed adjacent in close contact to the nerve (PNS of the occipital nerve), it could be demonstrated that subcutaneous placement lead to similar results. Dependent on the nature of the pain and the side one or two electrodes are placed at the level of C1 or C2 from lateral or medial subcutaneously and horizontally to covered the area supplied by the occipital nerve.
uni-or lateral ONS The main indications for ONS (after more conservative treatments have failed) are: t
Chronic migraine
t
Chronic cluster headache
t
SUNCT (short unilateral neuralgiform headache with conjunctival injection and tearing)
t
Occipital neuralgia
There are conflicting results in the literature, whether occipital blocks are predictive. Controlled studies have demonstrated a clear reduction in pain intensity as well as frequency of attacks in the above mentioned syndromes and ONS is now preferable to hypothalamic stimulation in chronic cluster headache (even effective and less invasive!). For bilateral stimulation one midline incision is better than two lateral approaches (less patient discomfort).
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2.3. Spinal Cord Stimulation For spinal cord stimulation to treat different pain syndromes exist clear indications, questionable indications and clear contraindications Clear indications, proven by randomized studies, are: 1.
Neuropathic pain syndromes (neuropathic pain in its revised definition is: “pain arising as direct consequence of a lesion or disease affecting the somatosensory system”), neuropathic limb pain in FBSS and CRPS I (II)
2.
Vasculopathic Pain syndromes, eg. pain due to peripheral vascular disease or angina
Questionable indications (no controlled studies) are: 1.
Axial low back pain
2.
Pain due to incomplete spinal cord (with partially maintained sensory function)
3.
Pain caused by postherpetic neuralgia (dysesthetic pain)
Clear contraindications are: 1.
Complete spinal cord injury or other central pain syndromes
2.
Pain due to malignancies
3.
Pain without objective clinical or radiological findings
4.
Severe psychiatric or psychologic comorbidity, including addiction
5.
Missing patient compliance
Neuropathic pain syndromes: Well designed and controlled studies which support clinical effectiveness of SCS at least over several years exist for the indications t
radicular pain in FBSS (Kumar et al. 2008; Taylor et al. 2010) and
t
CRPS I (Kemler et al. 2008).
Other indications in whom at least a testing trial seems to be worthwhile, but no controlled studies exist are: t
Polyneuropathy (especially diabetic neuropathy) (Pluijms et al. 2012)
t
CRPS II
t
Peripheral plexopathy (eg. after irradiation)
t
Phantom or post-amputation pain
t
Postherpetic neuralgia with altered but sustained sensory function
Vasculopathic pain (pain due to critical limb ischemia or refractory angina) are good indications with well documented evidence. 32
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In patients with peripheral vascular disease, Fontaine IIb and III grades are the best candidates, but also patients with vasoconstrictive disease of the upper limbs (Raynaud´s disease and others) as well as patients with refractory angina are excellent candidates (Börjesson et al. 2011; Francaviglia et al. 1994, Simpson et al. 2009) Questionable indications are patients with spinal cord lesions and sustained sensory function (syringomyelia, incomplete spinal cord injury). At least a testing trial should be carried out, although in our opinion central stimulation as DBS or MCS offers a better solution. Another problem is the treatment of pure axial back pain. There is no clinical evidence from controlled studies that stimulation of a certain area in the spinal cord will suppress low back pain. On the other hand we have evidence from the PROCESS Study that after 24 months of spinal cord stimulation (although the low back was not especially targeted), the low back pain was not improved at all. Special lead designs and electrode combinations are currently tried out to handle this problem (de Vos et al. 2012; Rigoard et al. 2012). From the actual point of view, in patients with low back and leg pain, multipolar leads should be used and it should be tried to cover the back area as much as possible. We would not recommend placing spinal electrodes for pure back pain right now. It is clear from the above that patients with no sensory function are no candidates for spinal cord stimulation. In our experience this holds also true for patients with long standing postherpetic neuralgia with constant burning pain in anesthetic areas (in these, most likely an atrophy of the dorsal horn has occurred). With regard to the type of electrode we prefer to use a single octopolar lead for unilateral pain and usually to electrodes for bilateral pain, because very rarely with a single lead both sides are covered with equal intensity. For bilateral pain a single paddle electrode with two rows of contacts can be used. The advantage of percutaneous leads is the lesser invasiveness; the disadvantage the risk of dislocation, the possibility of stimulating other structures in the spinal canal with the circumferential poles causing stimulation induced discomfort and often the necessity of higher current intensity. Paddle leads usually need a surgical approach and should be used in our opinion in cases with former dislocation of percutaneous leads or for pain with a difficult geometry to mask. In cervical cases the use of paddles should be performed only in cases with a wide cervical spinal canal. 2.4. Motor cortex stimulation (MCS) Chronic motor cortex stimulation is a rapidly developing treatment modality indicated for the treatment of chronic neuropathic pain syndromes not amenable for pharmacologic or lesser invasive stimulation techniques. Although very impressive series with long-term successes are published up-to date not controlled randomized studies were performed. A large European multicenter trial (CONCEPT) was stopped by the sponsor due to slow recruitment. Motor cortex is recommended for the following pain syndromes and is usually preferred by the patients in comparison to 33
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DBS because it is less invasive: t
Central pain due to spinal cord, brainstem and cerebral lesions
t
Pain due to plexus avulsion
t
Pain due to peripheral nerve lesions (after failed SCS) eg. post amputation pain
t
Pain due to trigeminal neuropathy (dys- or anesthesia dolorosa)
Although MCS has not been compared to other treatment regimens in controlled studies, it allows an intraindividual blinded testing because the stimulation itself is not recognized by the patient. Therefore several studies recommend either a blinded testing trial or performed a cross-over stimulation protocol trying to improve the long-term results (Nuti et al. 2005, Rasche et al. 2006; Velasco et al. 2009). Nowadays the electrodes are implanted with the help of neuronavigation with integrated functional data (PET or f-MRI) and electrophysiology (Phase reversal of SSEP) in order to localize the homunculus of the motor cortex according to the involved pain area. Still unsolved are the discussions of a simple burrhole or a craniotomy is preferable; also whether the electrode(s) should be parallel to precentral gyrus or should cross the central sulcus. Most authors use 2 paddle electrodes to cover a larger stimulation area.
two parallel paddle leads parallel to the precentral gyrus Several authors recommend a subdural placement in order to bring the electrodes closer to the cortex (in cases of brain atrophy), prevent scarring (with loss of effect after years). But this approach needs a craniotomy and the risk of CSF fistula is increased. 34
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two paddle leads sutured together for subdural stimulation 2.5.
Deep brain stimulation
Deep brain stimulation for the treatment of chronic pain has been carried out since the 1950ies. Later on, based on the concept of the dichotomy of pain processing (D. Albe-Fessard, L. Kruger and others), stimulation of the neospinothalamic pain pathway was developed by Mazars targeting the ventrolateral thalamus (VPL or VPM according to Walker, VcPc according to Hassler), the other targets at that time, based on the experimental findings of “stimulation produced analgesia” was the Periaqueductal Grey (PAG). Later this target was shifted a little more cranially and ventrally with regard to the periventricular grey (PVG) because PAG stimulation often caused diplopia. While stimulation in the ventrolateral only revealed strong contralateral effects, PVG stimulation was believed to increase endorphins which were able to alleviate bilateral pain syndromes. Another stimulation target was the medial (interlaminar) thalamus which receives bilateral nociceptive brainstem projections. The nuclei stimulated here were the parafascicular (PF) and centre median (CM) nucleus. Because medially of this region is PVG situated, there is often an overlap of stimulation in these structures. Although large series were published, never a controlled study was performed, the selection criteria were unequivocal as well as the target coordinates. Therefore after a critical paper was published in “Pain” in 1991 (Duncan et al. 1991), this procedures was declared as investigational procedure by the FDA and lost its funding. Only a few centers afterwards continued to perform DBS for pain and this procedure found his renaissance after DBS was developed for movement disorders. Now other indications were (re) invented as
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hypothalamic DBS for the treatment of cluster headache. Modern series more critically evaluated their data and results, demonstrating for selected indications about 60% pain relief in about half of their patients (Boccard et al. 2012, Leone et al. 2010; Rasche et al. 2006). Today one need to decide whether DBS or ONS is the better choice of an individual patient with chronic cluster headache and whether DBS or MCS is used as central stimulation method. In our opinion MCS is superior to treat central post stroke pain in comparison to DBS, depending on the site of the lesion.
Post stroke pain after aneurysm clipping (arrowhead) with electrodes in VPL and 36
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PVG 2.5 Transcranial magnetic stimulation (TMS) Non-invasive stimulation is actually used to treat several neuropsychiatric diseases with different success. TMS is very helpful to treat pure-tone tinnitus and it seems to be beneficial in treating depression and chronic pain at least short-term. Therefore it is used by several authors as predictor for the success of motor cortex stimulation. However the transcranial stimulation have to mimic the latter invasive treatment. This is only possible with newer devices allowing a 10- or even 20Hz repetitive stimulation. It has been shown that with regular sessions several times a week a pain relieving effect for about one month could be obtained (Khedr et al. 2005). 3. Intrathecal Drug Delivery for the Treatment of Chronic Pain The reason for intrathecal drug delivery in a patient with chronic pain can be twofold: 1. to yield better pain relief and invrease the quality of life; 2. to reduce the side-effects by bringing the drug close to the intended target. Actually only morphine and ziconotide are FDA approved for the treatment of chronic pain, but in reality several other drugs alone or in combination are used, but one should be aware that the use of combinations or not-approved drugs makes a special informed consent necessary. Since several years a group of experts mainly from the US tries to create standards for intrathecal drug delivery and publishes the so called “Polyanalgesic Consensus” starting in 2000, them in 2003 and 2007 and most recently a PAC 2012 was published in the Volume 15 of the Journal “Neuromodulation”. Everybody interested in intrathecal drug delivery is recommended to read several important articles about the different aspects of intrathecal analgesia. Only a few key topics are addressed here. For the first time the authors recommend different drugs for nociceptive and neuropathic pain as first, second and third line treatments.
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The recommendations for initial dosing and maximal doses are given in the following:
Finally the following algorithm is suggested: 38
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Further details about neurotoxicity, preventing complications, recognizing granulomas are given in detail in the different articles of this dedicated volume of “Neuromodulation”. 4. Recommended Literature 4.1.Books Electrical Stimulation and the relief of pain (B.A. Simpson ed.) Pain Research and Clinical Management, vol. 15, Elsevier 2003 Surgical Management of Pain (Kim J. Burchiel ed.) Thieme, 2001 Neurostimulation for the treatment of chronic pain (Hayek S, Deer T, Levy R eds), W.B. Saunders 2012 Atlas of implantable therapies for pain management (Deer T, ed.) Springer 2011 4.2. Guidelines EUROPEAN GUIDELINES FOR NEUROSTIMULATION Cruccu G, Aziz TZ, Garcia-Larrea L, Hansson P, Jensen TS, Lefaucheur J-P, Simpson BA, Taylor RS (2007) 39
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EFNS guidelines on nerostimulation therapy for neuropathic pain. Eur J Neurol 14: 952–970. SPANISH GUIDELINES FOR NEUROSTIMULATION Cerdá-Olmedo G, Franco-Gay ML, Insausti J, López-Alarcón MD, López-Millán JM, Moliner-Velázquez S, Monsalve-Dolz V, Moreno LA; Pérez-Cajaraville J, M. Tió-Felip M, Uriarte E (2006) Eur J Pain 10, Issue S1, S158d–S159. BRITISH GUIDELINES FOR SPINAL CORD STIMULATION NICE technology appraisal guidance 159 Spinal cord stimulation for chronic pain of neuropathic or ischaemic origin. You can download the following documents from www.nice.org.uk/TA159 GERMAN GUIDELINES FOR SPINAL CORD STIMULATION Tronnier V, Baron R, Birklein F, Eckert S, Harke H, Horstkotte D, Hügler P, Hüppe M, Kniesel B, Maier C, Schütze G, Thoma R, Treede RD, Vadokas V; Arbeitsgruppe zur Erstellung der S3-Leitlinie. Epidural spinal cord stimulation for therapy of chronic pain. Summary of the S3 guidelines (2011).[Article in German]. Schmerz 25: 484-492. www.awmf.de POLYANALGESIC CONSENSUS CONFERENCE FOR INTRATHECAL DRUG DELIVERY Neuromodulation Volume 15(5) 2012 4.3.Selected articles Boccard SG, Pereira EA, Moir L, Aziz TZ, Green AL. Long-term Outcomes of Deep Brain Stimulation for Neuropathic Pain. Neurosurgery. 2012 Nov 10. [Epub ahead of print] Mats Börjesson, Paulin Andréll, and Clas Mannheimer. Spinal cord stimulation for long-term treatment of severe angina pectoris: what does the evidence say? Future Cardiology 2011; 7: 825-833 Fontaine D, Christophe Sol J, Raoul S, Fabre N, Geraud G, Magne C, Sakarovitch C, Lanteri-Minet M. Treatment of refractory chronic cluster headache by chronic occipital nerve stimulation. Cephalalgia. 2011; 31: 1101-1105. Francaviglia N, Silvestro C, Maiello M, Bragazzi R, Bernucci C. Spinal cord stimulation for the treatment of progressive systemic sclerosis and Raynaud’s syndrome. Br J Neurosurg 1994; 8: 567-571. Kemler MA, de Vet HC, Barendse GA, van den Wildenberg FA, van Kleef M. Effect of spinal cord stimulation for chronic complex regional pain syndrome Type I: fiveyear final follow-up of patients in a randomized controlled trial. J Neurosurg 2008; 108: 292-298. Khedr EM, Kotb H, Kamel NF, Ahmed MA, Sadek R, Rothwell JC. Longlasting antalgic effects of daily sessions of repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain.J Neurol Neurosurg Psychiatry 2005;76: 833-838. 40
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Kumar K, Taylor RS, Jacques L, Eldabe S, Meglio M, Molet J, Thomson S, O’Callaghan J, Eisenberg E, Milbouw G, Buchser E, Fortini G, Richardson J, North RB. The effects of spinal cord stimulation in neuropathic pain are sustained: a 24-month follow-up of the prospective randomized controlled multicenter trial of the effectiveness of spinal cord stimulation. Neurosurgery 2008; 63:762-770. Leone M, Franzini A, Cecchini AP, Broggi G, Bussone G. Hypothalamic deep brain stimulation in the treatment of chronic cluster headache. Ther Adv Neurol Disord. 2010; 3: 187-195. Nuti C, Peyron R, Garcia-Larrea L, Brunon J, Laurent B, Sindou M, Mertens P. Motor cortex stimulation for refractory neuropathic pain: four year outcome and predictors of efficacy. Pain. 2005; 118: 43-52. Pluijms WA, Slangen R, Bakkers M, Faber CG, Merkies IS, Kessels AG, Dirksen CD, Joosten EA, Reulen JP, van Dongen RT, Schaper NC, van Kleef M. Pain relief and quality-of-life improvement after spinal cord stimulation in painful diabetic polyneuropathy: a pilot study. Br J Anaesth 2012; 109: 623-629. Rasche D, Rinaldi PC, Young RF, Tronnier VM. Deep brain stimulation for the treatment of various chronic pain syndromes. Neurosurg Focus 2006; 21: E8. Rasche D, Ruppolt M, Stippich C, Unterberg A, Tronnier VM. Motor cortex stimulation for long-term relief of chronic neuropathic pain: a 10 year experience. Pain. 2006; 121: 43-52. Rigoard P, Delmotte A, D’Houtaud S, Misbert L, Diallo B, Roy-Moreau A, Durand S, Royoux S, Giot JP, Bataille B. Back pain: a real target for spinal cord stimulation? Neurosurgery 2012; 70: 574-584. Silberstein SD, Dodick DW, Saper J, Huh B, Slavin KV, Sharan A, Reed K, Narouze S, Mogilner A, Goldstein J, Trentman T, Vaisma J, Ordia J, Weber P, Deer T, Levy R, Diaz RL, Washburn SN, Mekhail N. Safety and efficacy of peripheral nerve stimulation of the occipital nerves for the management of chronic migraine: results from a randomized, multicenter, double-blinded, controlled study. Cephalalgia. 2012; 32: 1165-1179. Simpson EL, Duenas A, Holmes MW, Papaioannou D, Chilcott J. Spinal cord stimulation for chronic pain of neuropathic or ischaemic origin: systematic review and economic evaluation. Health Technol Assess. 2009; 13: 1-154 Taylor RS, Ryan J, O’Donnell R, Eldabe S, Kumar K, North RB. The cost-effectiveness of spinal cord stimulation in the treatment of failed back surgery syndrome. Clin J Pain. 2010; 26:463-469. Velasco F, Carrillo-Ruiz JD, Castro G, Argüelles C, Velasco AL, Kassian A, Guevara U. Motor cortex electrical stimulation applied to patients with complex regional pain syndrome. Pain 2009; 147: 91-98. de Vos CC, Dijkstra C, Lenders MW, Holsheimer J. Spinal cord stimulation with hybrid lead relieves pain in low back and legs.Neuromodulation 2012;15: 118-123.
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NEUROSURGICAL MANAGEMENT OF PAIN Marc Sindou, Department of Neurosurgery, Hopital Neurologique P. Wertheimer, University of Lyon 1 t
A number of patients referred for so-called « intractable neuropathic pain » actually harbour pain due to unrecognized and/or untreated compressive mechanisms, such as atypical tunnel syndromes, spondylotic radiculopathies/myelopathies, etc …. If such causal etiologies are retained, « anatomical surgery », i.e., decompression, should be considered first, and proposed before irreversible neural degeneration occurs.
t
Pain observed in cancer diseases may be from two different mechanisms : 1°) somatogenic, that is generated by the tumor itself through compression, inflammation, release of nociceptive substances from necrosis, …, 2°) neuropathic, due to destructive damages of nerves by the tumor mass, surgery, radiotherapy, … When nociceptive mechanisms are predominant and escape to medications or local/regional blocks, neurosurgery may be considered for long life – expectancy patients. Intrathecal infusion of morphine may be indicated when pain is regional at lower part of the body. Lesioning procedures (percutaneous or open) – namely dorsal rhizotomies, DREZotomies, spino-thalamic cordotomies/ tractotomies, cranial rhizotomies or nucleotomies – may be useful when pain is topographically – limited and well-circumscribed.
t
Complex Regional Pain Syndromes, whatever types I or II, when not reversed by sustained physical therapy are well-accessible to Transcutaneous Electrical NeuroStimulation (TENS), and if not working, to Spinal Cord Stimulation (SCS).
t
According to the definition of the International Association for the Study of Pain (IASP) Neuropathic Pain is that pain « arising as a direct consequence of a lesion or disease affecting the Somato-Sensory system, peripheral or central ».
Neurosurgical arsenal for treating neuropathic pain is diverse and includes : Transcutaneous Electrical NeuroStimulation, Implanted drug delivery systems and Neurolesioning methods. TENS can be effective provided the targeted peripheral nerve is close to the skin. SCS requires integrity of dorsal colum fibers. MCS can be indicated for Central Post-Stroke Pain. Lesioning-surgery is especially useful for pain after root avulsion or segmental pain after spinal cord lesions. Management has to be decided within the frame of a multidisciplinary team. Spinal Cord Stimulation Personal experience (350 patients), as well as literature data, show that Spinal Cord Stimulation (SCS) is long-term effective in Complex Regional Pain Syndromes and in a number of Neuropathic Pain Syndromes under precise conditions. Among the 42
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later entity most candidates are patients with pain after peripheral nerve injuries or patients affected with radiculopathies – especially those harbouring the so-called Failed Spine Surgery Syndrome. A few other candidates correspond to patients having spinal cord pathologies. Whatever the location / level of the causative lesion, to be effective SCS requires integrity of the Dorsal Column (DC) fibers, from the Dorsal Root Ganglion (DRG) to brainstem nuclei. Our SELECTION PROCESS is anatomically - based, and has the three following steps. 1)
When the causal lesion is peripheral to DRG, and therefore the dorsal roots and dorsal column functionally intact, SCS is generally long-term effective. The patient can be implanted without further testing.
2)
When the causal lesion is radicular and located centrally to the DRG or at the spinal cord level, SCS is not effective if the fibers from the DRG up to the brainstem are not functionally valid. If clinical examination and imaging investigations clearly evidence complete interruption of these fibers, the patient should not be implanted. If complete interruption cannot be established on the sole clinical and imaging basis, SomatoSensory Evoked Potentials (SSEPs) recording must be performed to assess Central Conduction Time (CCT). CCT is the value measured between the dorsal horn and the cortical potentials. If the CCT corresponding to the painful territory is significantly altered, SCS would not be effective.
3)
When the functional integrity of the DC fibers cannot be ascertained on clinical/imaging or SSEPs assessment, selection process should have recourse to a Percutaneous trial, before deciding implantation.
Whatever the technical modality chosen – percutaneous or open-surgical -, THE ELECTRODE should be placed at the level of the upper adjacent DC segment corresponding to the painful territory. Electrode should be located just in front of the DC and not too laterally to avoid diffusion to the neighbouring dorsal root(s). Motor Cortex Stimulation Stimulation of the motor cortex for pain was introduced by Tsubokawa in 1991 on the basis that hyperactivity in the thalamic relay neurons following spino-thalamic tractotomy in cats (a model of central neuropathic pain) was inhibited by Motor Cortex Stimulation (MCS). According to literature data and personal results (75 patients) MCS revealed useful (more than 50% pain relief) in patients having central post-stroke pain. FACTS AND HYPOTHESES ON MCS MECHANISMS. A common finding in chronic neuropathic pain is decrease of cerebral blood flow (CBF) in the thalamus contralateral to pain, suggesting that ongoing neuropathic pain (from peripheral or central origin) is linked to thalamic synaptic hypoactivity. CBF measurement by PET study with [150] H2O and fMRI shows that MCS performed at the contralateral hemisphere to pain increases rCBF in the
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corresponding (previously hypometabolic) thalamus. It additionally increases CBF in the orbito-frontal and the anterior cingular cortices, as well as in the insula and amygdala, which all are important brain structures implicated in pain, stress and mood processing (i.e., the pain matrix). An increase in CBF is also observed in upper brainstem, namely the periaqueductal grey, known to be rich in opioid receptors (OR). Activation persists and even intensifies after stimulation ended. For this reason the possible functional modifications of the opioid system under MCS were explored using [11 C] diprenorphine PET (MAARRAWI et al). Data suggest that MCS induces an endogenous opoid secretion in the intact part of the opioid system ; magnitude of enhancement is significantly correlated with pain relief. Implication of the opioid would explains the delayed as well as the lasting effects of MCS. Besides central supra-spinal metabolic effects, MCS is able to inhibit the lower limb RIII (nociceptive) withdrawal reflexes, which suggests an inhibitory action on pain modulation system at dorsal horn. CRITERIA FOR SELECTION OF PATIENTS. Neither pain characteristics, type or localization of the causal lesion, motor function status, sensory testing, SSEPs, nor the interval between pain and surgery, are predictive factors of efficacy or nonefficacy of MCS. Only the level of pain relief evaluated at one month following implantation is strong predictor of long-term relief (p95% reduction of seizure frequency, which was attained by 71% of patients with generalized epilepsy, 62% of patients with complex partial epilepsy, and 63% of patients with simple partial epilepsy [Spencer et al. 2002]. Besides in focal epilepsies that involve eloquent zones, MST is being applied for the treatment of Landau-Kleffner syndrome, which is an acquired aphasia associated with clinical seizures but especially with electrical status epilepticus in sleep (ESES). The corpus callosum plays the major role in the propagation of seizures, although not 70
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the only one. Other structures, such as the anterior and hippocampal commissures, the thalamus and the brainstem may also be involved in the generalization of seizures. Mostly a two-thirds to three-fourths anterior division of the corpus callosum is recommended, unless there is evidence of a predominantly posterior focus. Others advocate a complete callosotomy as the first-choice procedure in lower functioning children afflicted by atonic, myoclonic or absence seizures (Jalilian, Limbrick et al. 2010). The craniotomy crosses the superior sagittal sinus and the intradural approach is carried out between falx and non-dominant hemisphere down the interhemispheric fissure. Adhesions between the hemispheres are loosened and the callosal section is performed along the midline between the two pericallosal arteries, using e.g. ultrasonic aspiration [Roberts, Siegel 2001]. The patients, for whom callosotomy is considered/performed, usually have more than one type of seizures. The outcome varies dependent on the seizure type. In patients who experienced atonic seizures among their seizure types preoperatively, these were completely controlled by callosotomy in 51% of cases, reduced more than 80% in 14% of cases, and reduced between 50% and 80% in 7% of cases. The corresponding figures for major motor seizures were 34%, 16%, and 8% of cases, and those for absence seizures 46%, 22%, and 0% of cases, respectively [Roberts, Siegel 2001]. With respect to side-effects, anterior callosotomy is usually associated with a decreased spontaneity of speech and a decreased use of the nondominant limbs. Posterior callosotomy produces the well-recognized disconnection syndrome that results from a deficient access of the languagedominant hemisphere to somatosensory, auditory, and visual stimuli that are presented to the other hemisphere. It rarely leads to opposing actions of the right and left hands. Cognition is not impaired by callosotomy, but on the contrary often improves as a result of seizure control. The vagal nerve consists of about 80% afferent and 20% efferent fibers that connect the larynx and pharynx, the heart, aorta, lungs and gastrointestinal tract with the brain. Only the left vagal nerve, that carries a lesser number of cardiac fibers, is the recipient of VNS. VNS aims at activating the afferent vagal fibers and appears to act via the nucleus of the solitary tract, the locus coeruleus, the thalamus and the limbic structures, but the precise mechanism of action is yet to be elucidated. The usual stimulation parameters are: 30Hz, 500µs, up to 3,5mA, 30s on and 5min off. VNS achieves in 1/3 of patients a reduction of seizure frequency of at least 50% and in another 1/3 of patients a reduction of seizure frequency between 30% and 50%. VNS thus is comparable with new antiepileptic drugs in terms of efficacy, but, contrary to antiepileptic drugs, VNS tends to display an increasing efficacy with treatment duration up to 18 months after its start. The prospective multicenter double-blind randomized study “EO5” [Handforth et al. 1998] led to the FDA approval of VNS for patients with partial epilepsies. The open-label longitudinal multicenter “EO4” study [Labar et al. 1999] also included patients with generalized epilepsy, and these appeared to respond equally well as partial epilepsies. Generalized tonic seizures responded significantly better than generalized tonic-clonic seizures. A few case reports describe that refractory
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status epilepticus could be interrupted by VNS [De Herdt et al. 2009]. LennoxGastaut syndrome seems to be a beneficial VNS indication according to several reports. VNS with the above mentioned success rate has moreover been applied in patients with hypothalamic hamartomas, tuberous sclerosis, progressive myoclonic epilepsy, Landau-Kleffner syndrome, epileptic encephalopathies and syndromes with developmental disability and mental retardation. VNS shows less favorable results in infantile spasms, mitochondrial electron transport chain deficiencies, and previous but unsuccessful resective epilepsy surgery. The EO5 study reported a notable increase of the perceived well-being during VNS treatment. VNS device is labeled MRI compatible when used with a send-and-receive head coil [Nyenhuis et al. 1997]. Most frequent side effects were hoarseness in 19% of the patients and coughing in 5% of the patients at 2 years follow-up. A questionnaire showed that 95% of the patients show some kind of voice change but that 100% would have a VNS reimplanted knowing the vocal side effects they have. Bradycardia and ventricular asystole during intra-operative testing of the device (20Hz, 500µs, 1mA, ~17s) have been reported in a few patients. In some of them the implantation was aborted, in others it was completed with uneventful subsequent chronic stimulation. Obstructive lung disease and sleep apnoea are relative contraindications. The rate of sudden unexpected death in epilepsy (SUDEP) was found to be 4,1 per 1000 person-years in VNS patients versus 4,5 for patients with refractory epilepsy without VNS. In VNS-treated patients the SUDEP rates dropped from 5,5 for the first two years of treatment to 1,7 per 1000 person-years for the subsequent years [Annegers et al. 1998]. 3. Recent Clinical and Research Developments VNS can interrupt seizures (anti-seizure effect) and it can prevent seizures from recurring (anti-epileptic effect). So far, there is no proof, however, that VNS is also capable of reversing the development of the pathological process(es) that led to epilepsy (anti-epileptogenic effect). The mechanism of action of VNS is being explored using various animal models (motor cortex stimulation model, genetic absence epilepsy model, rapid kindling model, status epilepticus model, and kainate model). The involvement of norepinephrine in VNS has been suggested and recently verified in a limbic seizure model [Raedt et al. 2011]. In humans, the action of VNS is currently being explored by implantable devices that record the compound action potentials in the vagal nerve [El Tahry et al. 2010]. 4. Future Questions and Direction VNS generally is cyclic (30s on, 5min off), but can also be voluntarily induced by the patient who perceives the beginning of a seizure in order to arrest it. This additional stimulation period is obtained by manually moving a magnet over the pulse generator. The main manufacturer of VNS devices now developed a pulse generator that automates this “magnet function” by sensing heart rate changes (mainly tachycardia) that are correlated with the patient´s seizure activity; an according clinical trial is running.
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Besides VNS, that is widely established, other neuromodulation techniques are being explored on an experimental scale, more specifically deep brain stimulation (DBS), which has been targeted at a variety of brain structures, such as the thalamus, the caudate nucleus and the hippocampus [Vonck et al. 2013]. Recently, DBS of the anterior nucleus thalami obtained FDA approval after conclusion of a cooperative study [Fisher, Salanova et al. 2010]. Hemispherotomy – Functional Hemispherectomy 5. Objective Hemispherectomy is without doubt the most drastic procedure known in neurosurgery, whether it is carried out in the sense of a true resection (hemispherectomy) or in the sense of a disconnection (functional hemispherectomy = hemispherotomy). Its feasibility was originally demonstrated by Dandy and by L´Hermitte in cases in which an entire, seemingly single hemisphere was affected by a glioma. The first hemispherectomy for epilepsy was performed by McKenzie in 1938 and the first series was published by Krynauw in 1950. A specific complication was observed, called superficial cerebral hemosiderosis, which occurs about 10 years after surgery in ¼ of the patients and results from persistent leaking of blood into the resection cavity, producing recurrent seizures, sensori-neural deafness and hydrocephalus [Rasmussen 1973]. The anatomical hemispherectomy thus gave way to partial hemispherical resections with complete disconnection, that are coined “functional hemispherectomy”, “hemispheric disconnection”, “hemispheric deafferentation” or “hemispherotomy”. Various types of hemispherical disconnection have been described. The techniques evolved over time to less brain resection in favor of a greater ratio of disconnection. Functional hemispherectomy yields the same good to excellent seizure control as anatomical hemispherectomy, but it is associated with much less perioperative (massive blood loss, aseptic meningitis) and delayed postoperative (hemosiderosis, hydrocephalus) complications. 6. Modern Literature Review Hemispherectomy or hemispheric disconnection is indicated in patients with medically intractable, often catastrophic, epilepsy in which one, diffusely affected hemisphere drives the epilepsy, while the contralateral hemisphere is completely sound. The indication comprises hemispheric affections that are congenital or that arise at young age, such as hemispheric dysplasia or other migrational disorders, hemimegalencephaly, infantile hemiplegia seizure syndrome, Sturge-Weber syndrome, sequellae of trauma, hemorrhage, ischemia, or meningoencephalitis. A well-known acquired condition in children under the age of 10-15 years is Rasmussen´s encephalitis, in which one hemisphere is affected by a chronic inflammatory disease. Epilepsy in these disorders is accompanied by a deterioration of both motor and intellectual performances. In patients with pre-existing hemiplegia and/or hemianopia, hemispherectomy will cause no new deficit. By isolating the healthy hemisphere from seizure activity, hemispherectomy or hemispherotomy can, however, reverse the secondary impairments of cognition and behavior. In order to maximize the beneficial effects on development, surgery should be offered at the youngest possible age. 73
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After hemispherectomy or hemispherotomy, 50% to 80% of patients become seizure free, and a significant benefit (Engel class 1-2-3) is obtained in up to 90% of patients [Tuxhorn et al. 2008]. Devlin et al. stratified their results in 33 children: seizure freedom was attained in 82% of patients with acquired pathology, in 50% of patients with progressive pathology, and in 31% of patients with developmental pathology. While hemiparesis remained unchanged after surgery in the majority of patients, it deteriorated in 18% and it improved in 15%. Fine finger movements improved in only 6% of patients, visual fields in none. Behaviour, on the other hand, improved in more than half the patients (52%), remained unchanged in 33% and turned worse in 15% [Devlin et al. 2003]. In Rasmussen´s encephalitis, the dilemma is whether to perform surgery early and risk inflicting greater motor, visual and language impairments, from which there may be greater recovery at a young age, or to delay surgery and pursue other therapies until the disease produces similar motor and visual deficits to those which should be inflicted by surgery. However, during the delay there may be progressive impairment of language and intellect in addition to deterioration in motor and visual abilities, with reduced potential for recovery in the older patient [Devlin et al. 2003]. 7. Recent Clinical and Research Developments The turn from anatomical to functional hemispherectomy was taken 30 years ago by Rasmussen. His technique consists in a temporal lobectomy plus a large resection of the central region, combined with a disconnection of the frontal and parieto-occipital lobes. In the last 20 years different variations on functional hemispherectomy have been developed (Fig. 1). Schramm conceived the transsylvian transventricular deafferentation with temporal lobectomy, that was refined later on to a keyhole technique [Schramm et al. 2001]. Villemure described the – very similar – perisylvian window technique, Delalande et al. the dorsal transcortical subinsular central hemispherotomy, and Shimizu and Maehara a combination of the two former techniques. Whereas intraoperative blood loss in anatomical hemispherectomy regularly urged to stop the procedure and to continue it a week later, only 15% of patients require intraoperative blood replacement in the keyhole trans-sylvian hemispheric deafferentation. The keyhole trans-sylvian transventricular hemispheric deafferentation is especially suited for pathologies with enlarged ventricles, porencephalic cysts, and marked atrophy of the insula and basal ganglia. It starts with a small craniotomy and a trans-sylvian exposure of the insular cortex, which eventually will be resected. Through the circular sulcus of the insula, an amygdalo-hippocampectomy is first carried out and thereafter a continued access to the lateral ventricles, that reaches from the tip of the temporal horn to the tip of the frontal horn. Rostral to the anterior cerebral artery, the frontobasal cortex and white matter are disconnected. Through the lateral ventricle and along the anterior cerebral artery and, a mesial disconnection is performed immediately above the corpus callosum including the splenium. The procedure is concluded by a posteromedial disconnection along the falco-tentorial border to reach the mesio-temporal resection cavity.
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8. Future Questions and Directions Depending on the age of the patient, functional MR imaging (also: resting state fMRI), diffusion tensor imaging, repetitive transcranial magnetic stimulaton, and the Wada test are used for the assessment of the functional outcome. The predictive value of these tests has still to be established. 9. Conclusions MST and VNS are two very different procedures that offer solutions for patients with drug-resistant epilepsy in whom a resection of the epileptogenic zone is not possible. MST parcels out epileptic neocortex that serves eloquent function into its minimal functional units. VNS is a less invasive, extracranial neuromodulation technique that is broadly applicable in most partial and generalized epilepsies. Hemispherectomy and hemispheric disconnection are highly efficacious procedures in rare cases of catastrophic epilepsy in children, that is due to strictly unilateral hemispheric damage. Disconnection is, however, much safer than anatomical hemispherectomy, both in the peri-operative period and in the long term. Hemispheric disconnection reverses in more than half the patients the behavioral impairment that accompanies the epileptic disorder. 10. Key References, Recommended Reading Annegers JF, Coan SP, Hauser WA, Leestma J, Duffell W, Tarver B. Epilepsy, vagal nerve stimulation by the NCP system, mortality, and sudden, unexpected, unexplained death. Epilepsia 1998; 39:206-212. Ben-Menachem E. Vagus nerve stimulation for the treatment of epilepsy. Lancet Neurol 2002; 1:477-482. De Herdt V, Waterschoot L, Vonck K, Dermaut B, Verhelst H, Van Coster R, De Jaeger A, Van Roost D, Boon P. Vagus nerve stimulation for refractory status epilepticus. Eur J Paediatr Neurol 2009; 13:286-289. Delalande O, Pinard JM, Basdevant C, Gauthe C, Plouin P, Dulac O. Hemispherotomy: a new procedure for central disconnection. Epilepsia 1992; 33 (suppl 3):99-100 Devlin AM, Cross JH, Harkness W, Chong WK, Harding B, Vargha-Khadem F, Neville BGR. Clinical outcomes of hemispherectomy for epilepsy in childhood and adolescence. Brain 2003; 126:556-566. El Tahry R, Raedt R, De Herdt V, Wyckhuys T, Van Dycke A, Meurs A, Dewaele F, Van Roost D, Doguet P, Delbeke J, Vonck K, Boon P. A novel implantable vagus nerve stimulation system (ADNS-300): pilot trial at Ghent Universit Hospital. Epilepsy Research 2010; 92:231-239. Fauser S, Zentner J. Critical review of palliative surgical techniques for intractable epilepsy. Adv Techn Stand Neurosurg 2012; 39: 165-194. Fisher R, Salanova V et al. (SANTE Study Group). Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia 2010; 51: 899-908. 75
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Handforth A, DeGiorgio CM, Schachter SC, Uthman BM, Naritoku DK, Tecoma ES, Henry TR, Collins SD, Vaughn BV, Gilmartin RC, Labar DR, Morris GL 3rd, Salinsky MC, Osorio I, Ristanovic RK, Labiner DM, Jones JC, Murphy JV, Ney GC, Wheless JW. Vagus nerve stimulation therapy for partial-onset seizures: a randomized activecontrol trial. Neurology 1998; 51:48-55. Harkness W. Multiple subpial transections. In Lüders HO (ed.): Textbook of Epilepsy Surgery. London: Informa Healthcare, 2008, pp 1138-1148. Jalilian L, Limbrick DD, Steger-May K, Johnston J, Powers AK, Smyth MD. Complete versus anterior two-thirds corpus callosotomy in children: analysis of outcome. J Neurosurg Pediatr 2010; 6: 257-266. Krynauw RA. Infantile hemiplegia treated by removing one cerebral hemisphere. J Neurol Neurosurg Psychiatry 1950; 13:243-267. Labar D, Murphy J, Tecoma E. Vagus nerve stimulation for medication-resistant generalized epilepsy. EO4 VNS Study Group. Neurology 1999; 52:1510-1512. Morrell F, Whisler WW, Bleck TP. Multiple subpial transection: a new approach to the surgical treatment of focal epilepsy. J Neurosurg 1989; 70:231-239. Morrell F, Whisler WW. Multiple subpial transection. In Shorvon SD, Dreifuss F, Fish DR, Thomas D (eds.): The Treatment of Epilepsy. Oxford: Blackwell Science, 1996, pp 739-750. Nagel SJ, Elbabaa SK, Hadar EJ, Bingaman WE. Hemispherectomy techniques. In Lüders HO (ed.): Textbook of Epilepsy Surgery. London: Informa Healthcare, 2008, pp 1121-1130. Nyenhuis JA, Bourland JD, Foster KS, Graber GP, Terry RS, Adkins RA. Testing of MRI compatibility of the Cyberonics model 100 NCP and model 300 series lead. Epilepsia 1997; 38(S8):140. Raedt R, Clinckers R, Mollet L, Vonck K, El Tahry R, Wyckhuys T, De Herdt V, Carrette E, Wadman W, Michotte Y, Smolders I, Boon P, Meurs A. Increased hippocampal noradrenaline is a biomarker for efficacy of vagus nerve stimulation in a limbic seizure model. J Neurochem 2011; 117:461-469. Rasmussen T. Hemispherectomy for seizures revisited. Can J Neurol Sci 1983; 10:71-78. Rasmussen T. Postoperative superficial hemosiderosis of the brain, its diagnosis, treatment and prevention. Trans Am Neurol Assoc 1973; 98:133-137. Roberts DW, Siegel AM. Corpus callosotomy. In Lüders HO, Comair YG (eds.): Epilepsy Surgery. 2nd ed. Philadelphia: Lippincott Williams & Wilkins, 2001, pp 747-756. Schramm J. Hemispherectomy techniques. Neurosurg Clin N Am 2002; 37:113134. Schramm J, Kral T, Clusmann H. Transsylvian keyhole functional hemispherectomy. 76
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Neurosurgery 2001; 49:891-901. Shimizu H, Maehara T. Modification of peri-insular hemispherotomy and surgical results. Neurosurgery 2000; 47:367-372. Spencer SS, Schramm J, Wyler A, O´Connor M, Orbach D, Krauss G, Sperling M, Devinsky O, Elger C, Lesser R, Mulligan L, Westerveld M. Multiple subpial transection for intractable partial epilepsy: an international meta-analysis. Epilepsia 2002; 43:141-145. Tuxhorn I, Holthausen H, Kotagal P, Pannek H. Hemispherectomy: post-surgical seizure frequency. In Lüders HO (ed.): Textbook of Epilepsy Surgery. London: Informa Healthcare, 2008, pp 1149-1153. Villemure JG, Daniel RT. Functional hemispherectomy and periinsular hemispherotomy. In Baltuch GH, Villemure JG (eds.): Operative Techniques in Epilepsy Surgery. New York: Thieme Medical Publishers, 2009, pp 138-145. Vonck K, De Herdt V, Boon P. Vagal nerve stimulation – a 15-year survey of an established treatment modality in epilepsy surgery. Adv Techn Stand Neurosurg 2009; 34: 111-146. Vonck K, Sprengers M, Carrette E, Dauwe I, Miatton M, Meurs A, Goossens L, De Herdt V, Achten R, Thiery E, Raedt R, Van Roost D, Boon P. A decade of experience with deep brain stimulation for patients with refractory medial temporal lobe epilepsy. Int J Neural Syst 2013; 23 Epub 2012, Dec. 16.
Legend to figures
Figure 1 Multiple subpial transection. Schematic representation of the technique. Courtesy of Dept. of Epileptology, Bonn University Hospital. 77
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Figure 2 Vagal nerve stimulation. The three helices of the electrode are wrapped around the left vagal nerve in its lower cervical segment. The caudal helix (image top) serves as an anchor tether, the middle helix carries the positive contact, and the cranial helix (image bottom) carries the negative contact.
Figure 3 Vagal nerve stimulation. Connection of lead to pulse generator, intraoperative telemetric verification of system integrity and impedance using wand and handheld computer, placement of pulse generator into pectoral subcutaneous pocket. 78
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Figure 4 Functional hemispherectomy: various techniques. Schramm [20].
Illustration modified after
Figure 5 Axial MRI after keyhole transsylvian hemispheric deafferentation in an 8-monthold patient with unilateral West syndrome due to a right-hemispheric dysplasia and polymicrogyria.
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TEMPORAL LOBE EPILEPSY SURGERY Johannes Schramm, Hans Clusmann*, Marec von Lehe# Departments of Neurosurgery Bonn, Aachen*, Bochum#, Germany Purpose Temporal resections are the most frequent therapeutic epilepsy surgery procedure, comprising 1485 cases (57%) of 2590 epilepsy surgery procedures in Bonn. Details of presurgical evaluation, the influence of etiologies, resection types, and patient factors (e.g. duration of seizure disorder, presence of lesion) will be detailed. Results In surgery for temporal lobe epilepsy (TLE) modern diagnostic techniques include: video-EEG recording of seizures, interictal video-EEG recordings, specialized MRI examinations, and sometimes ictal SPECT and PET (4). These are established techniques whereas magnetoencephalography, dipole-source localization are not yet fully established. Invasive monitoring techniques with implanted depths electrodes, strip- and grid-electrodes are used frequently (up to 35% of cases in Bonn), usually if either MRI is non-lesional, or there is a discrepancy between ictal or interictal EEG recordings and MRI, or if there is a discrepancy between the seizure semiology and the imaging findings or seizure semiology and EEG recording. Presurgical neuropsychological testing of intelligence, attention, visual and verbal memory, and language, are done routinely and are very important to assess the impact of chronic epilepsy and of surgery. The traditional form of temporal lobe resection is anterior lobectomy. In the last 20 years, after the introduction of selective amygdalohippocampectomy for TLE the concept of limiting resections to the minimum necessary amount has become more popular. In TLE a differentiation has to be made between mesial and lateral (or neocortical) TLE. The latter is much rarer. Now a variety of resection types is used, differing somewhat from center to center. In our TLE surgery series 48% of patients had amygdalohippocampectomy (SAH), 24% had anterior temporal lobectomy (TLR), 23% had lesionectomy. In many centers the so-called Spencer type resection is popular, which consists of a temporal pole resection combined with a more posterior reaching mesial resection of hippocampus and parahippocampus. In an own series (2) of 321 TLE surgery patients 70.7% were seizure free (Engel class I) after a mean follow-up of 38 months. 11.2% were Engel class II, 7.5% were Engel class III and 10.6% were Engel class IV. Seizure outcome was mainly correlated with the diagnoses and clinical factors, it was not related to the different resection types. Five factors were predictive for a good seizure control in a logistic regression model: clear MRI abnormality, no status epilepticus, ganglioglioma or DNT on MRI, concordant lateralizing memory deficit and absence of dysplasia on MRI. Neuropsychological testing revealed improvements (41% for attentional performance, 28% for visual memory, 19% for verbal memory) deteriorations (attention 9 %, visual memory 30%, verbal memory 34%) and unchanged scores (attention 50%, visual memory 42%, verbal memory 46%). Overall neuropsychological scores for 80
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the total performance improved in 44% remained stable in 21% and deteriorated in 35%. In that series 8.5% surgical complications occurred, none with permanent sequelae. Neurological complications occurred in 5.2%, 2.4% resulting in transient morbidity, 2.7% permanent morbidity. Initial doubts that the smaller resection type amygdalohippocampectomy possibly leads to a lower rate of seizure freedom have been proven to be wrong. It is now clear, that seizure outcome is similar for SAH and TLR. A literature review (3) also found that with more limited resection types cognitive outcomes tended to be slightly better compared to standard anterior lobe resections. The question of how far back to go with the mesial resection of hippocampus and parahippocampus has been discussed by various authors and in a recent prospective randomized study on the extent of mesial resection it was found that maximal resection of mesial structures does not lead to best outcomes. It was concluded that adequate mesial resection extent leads to good outcomes(5,6,7). Indications for and results of epilepsy surgery in children and the pediatric population have to be considered separately (1,4). In the pediatric population the damage done to the developing brain by chronic drug resistant seizures is more extensive than in the adult brain. In the pediatric population the recovery of neuropsychological and other cognitive deficits is also better than in the adults. Conclusion Modern temporal lobe epilepsy surgery has changed considerably in the last 25 years due to large progress in imaging, presurgical diagnoses, and improvement of microsurgical techniques. Different surgical approaches result in equally good outcomes. Seizure outcome is dependant mostly on diagnoses and clinical factors, less so on the surgery type. However, neuropsychological results appear to be more beneficial with limited resections. 1.
Clusmann H, Kral T, Gleissner U,Sassen R, Urbach H, Blümcke I, Bogucki J, Schramm J: Analysis of different types of resection for pediatric patients with temporal lobe epilepsy. Neurosurgery 54: 847 – 859, 2004
2.
Clusmann H, Schramm J Kral T, Helmstaedter C,Ostertun B, Fimmers R, Haun D, Elger CE : Prognostic factors and outcome after different types of resection for temporal lobe epilepsy. J Neurosurg. 97: 1131 – 1141, 2002
3.
Schramm J: Temporal lobe epilepsy surgery and the quest for optimal extent of resection: A review. Epilepsia 49: 1296-1307, 2008
4.
Schramm J, Clusmann H: The Surgery of Epilepsy. Neurosurgery 62: 463481, 2008
5.
Helmstaedter C, Roeske S, Kaaden S, Elger CE, Schramm J: Hippocampal resection length and memory outcome in selective epilepsy surgery. J Neurol Neurosurg Psychiatry 82:1375 – 1381, 2011
6.
Schramm J, Lehmann TN, Zentner J, Mueller CA, Scorzin J, Fimmers R, Meencke HJ, Schulze-Bonhage A, Elger CE: Randomized controlled trial
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of 2.5 cm versus 3.5 cm mesial temporal resection – part 2: volumetric resection extent and subgroup analyses. Acta Neurochir 153: 221-228, 2011 7.
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Schramm J, Lehmann TN, Zentner J, Mueller CA, Scorzin J, Fimmers R, Meencke HJ, Schulze-Bonhage A, Elger CE: Randomized controlled trial of 2.5 cm versus 3.5 cm mesial temporal resection – part 1: intent-to-treat analysis. Acta Neurochir 153: 209-219, 2011
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SURGERY FOR EXTRATEMPORAL EPILEPSY Hans Clusmann, MD Department of Neurosurgery, Uniklinik RWTH Aachen University, Germany 1. Objective This abstract will deal with approaches and techniques applied to successfully treat various types of extratemporal epilepsies. It will not primarily focus on the details of presurgical diagnostics and evaluation. However, success of epilepsy surgery largely depends on thoughtful preoperative evaluation and transfer of relevant data to critical decision making, and resulting surgical strategy. 2. Modern Literature Review Important concepts for extratemporal epilepsy Former work resulted in a theory of different zones involved in the epilepsies (see for example Textbook of Epilepsy Surgery, edited by H.O. Lüders, 2008). In spite of some definition differences, these concepts turned out to be important, because they are the fundament of applying multiple diagnostic means to approach the “epileptogenic zone”.(Wieser 1998; Rosenow and Luders 2001; Palmini 2006) Six cortical zones that should be defined in the presurgical evaluation of candidates for epilepsy surgery are: the symptomatogenic zone (initial ictal clinical symptoms); the irritative zone (interictal EEG spikes); the ictal onset zone (initial EEG ictal seizure acticity); the epileptogenic lesion (MRI); the functional deficit zone (neurological or neuropsychological deficits), and the eloquent cortex (normal adjacent functional cortex). Different diagnostic techniques are used in the definition of these cortical zones, such as video-EEG monitoring and MRI. Presurgical diagnostics should result in an estimate of the “epileptogenic zone” (EZ), defined as a cortical area, which is inevitably necessary for the generation of clinical epileptic seizures. However, the EZ can only be proven by a circumscribed cortical resection or disconnection leading to seizure freedom. 3. Recent Clinical and Research Developments Transfer of presurgical results to surgery Following the abovementioned concepts, a more precise delineation of the presumed Epileptogenic Zone (EZ) enables smaller resections. The trend to smaller resection types should not lead to a decrease in seizure relief rates, but will probably improve functional outcomes. Tools aiding the neurosurgeon to precisely approach his target structure are increasingly contributing to epilepsy surgery. Neuronavigation carries the important role of being the direct link between imaging and surgery, which can be characterized as “enhanced reality”. This link can be extraordinarily close, if multimodal information is visualized in the surgical microscope. Not only target structures can be visualized but also information derived from electrophysiological recordings, functional MRI, or diffusion tensor imaging.(Krakow, Wieshmann et al. 1999) 3-D-visualization may further contribute to a valid three-dimensional 83
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orientation and resection planning. There are some hints towards an increasing role for intraoperative MRI in immediate resection control of epileptogenic lesions. However, applicability and superiority have not been proven yet.(Buchfelder, Fahlbusch et al. 2002) Strategies and tools for surgery in extratemporal epilepsies Several surgery types are used at present: lobectomy, lesionectomy (pure or with variable rim of cortex), and corticectomy. Complete removal of the epileptic zone can be compromised by the overlap with eloquent cortex, e.g. the primary motor cortex, cortex areas representing speech function, visual cortex etc. Established measures to reliably assess the eloquence of certain cortical areas are cortical mapping via chronically implanted electrodes, and intraoperative mapping during “awake craniotomy”.(Berger, Kincaid et al. 1989; Ojemann, Ojemann et al. 1989) The aim of these measures is to resect as much tissue as thought to be necessary to provide complete seizure relief, without causing inacceptable permanent neurological damage. The depth of resection should include the whole cortical surface, including the deep cortical folds. A resection of 2.5 – 3 cm in depth is usually sufficient. It is more difficult to define the horizontal extent of resection, and this decision may also depend on the pathology. A lesionectomy with rim is preferable whenever possible, although in many cases of focal cortical dysplasia (Type IIb)(Palmini and Luders 2002) nearly pure lesionectomies and leaving the deep “root” are thought to be sufficient (Urbach, Scheffler et al. 2002; Wellmer, Parpaley et al. 2010). A similar situation can be found with certain developmental tumors, e.g. gangliogliomas and dysembryoplastic neuroepithelial tumours (DNT), which can be treated with excellent seizure control rates in most patients. (DaumasDuport, Scheithauer et al. 1988; Campos, Clusmann et al. 2009; Englot, Berger et al. 2011) Also, certain types of low-grade gliomas (e.g. isomorphic subtype of lowgrade astrocytoma, pilocytic astrocotoma) can be operated with excellent success. (Schramm, Luyken et al. 2004) In all these lesions it is practically preferred to resect a small rim of adjacent cortex. However, it has to be noted, that there is no high class evidence for such or other strategies. In most cases the extent of resection depends on the experience of the surgeon, and he/she will be the one to carry the responsibility for the patient´s neurological integrity on one side, but also for resections considered to be incomplete and thus unsuccessful on the other side. Intraoperative (interictal) electrocorticography is mostly performed in extratemporal epilepsies after noninvasive evaluation to determine the border of extended lesionectomy in patients with neocortical lesions distant from eloquent areas. The disadvantages of this method are the poorly defined influence of anesthetics, the short recording time, and the lack of seizure recording. Basically, intraoperative ECoG is an interictal recording. Therefore, intraoperative ECoG is restricted to the definition of the irritative zone and has thus limitations for sufficiently delineating the epileptogenic zone or eloquent cortices (Zentner, Hufnagel et al. 1997). Complete yet safe resection close to motor areas in medically intractable epilepsy requires functional information. New deficits may occur despite preservation of motor cortex, e.g., through vascular compromise. Continuous motor-evoked potential (MEP) monitoring in focal epilepsy surgery may provide additional 84
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safety, and should be used in cases close to the motor strip as an alternative or additionally to extraoperative motor cortex mapping via chronically implanted subdural electrodes. It has been shown that MEP changes predict occurrence and permanence of new pareses. Successful MEP monitoring correlates with unimpaired motor outcome and full seizure control. (Neuloh, Bien et al. 2010) Different types of ETLE Most experience is available for the treatment of frontal lobe epilepsy (FLE)(Jeha, Najm et al. 2007) The importance of detection of focal epileptogenic lesions is of major importance for patient counseling and treatment, because the presence of a focal lesion in MR imaging is the most important prognostic factor. Cases with focal FLE can be treated with good success rates, in some series comparable to results after treatment for TLE.(Janszky, Jokeit et al. 2000; Kral, Kuczaty et al. 2001; Schramm, Kral et al. 2002; Yun, Lee et al. 2006; Jeha, Najm et al. 2007) The necessity of frontal lobectomies implies a more widespread epileptogenic lesion and zone, with the consequence of less promising results.(Kral, Kuczaty et al. 2001) Higher cognitive functions and visual fields are the main concerns when operating on patients with parietal (PLE) and occipital lobe epilepsies (OLE). There are patient series available for parietal, occipital, and multilobar epilepsies (Urbach, Binder et al. 2007). Invasive monitoring is required in a substantial number of cases, in order to provide reliable information on the cortical areas that should be spared. However, OLE and PLE can be operated on with good success rates.(Rasmussen 1991; Williamson, Boon et al. 1992; Olivier and Boling 2000; Kun Lee, Young Lee et al. 2005; Binder, Von Lehe et al. 2008; Binder, Podlogar et al. 2009) Even rarer forms of ETLE arise from the insular cortex or the cingulate cortex. These areas are considered to be difficult for evaluation, due to their distance to the cortical surface and the variable symptoms that can be associated with cingulate and insular epilepsies.(Roper, Levesque et al. 1993; Isnard, Guenot et al. 2000; von Lehe, Wellmer et al. 2009) 4. Future Questions and Directions Limits and perspectives of epilepsy surgery With increasing use of the developing chances, one has to be consciously aware of the limits of epilepsy surgery. First of all, with few exceptions (e.g. inferior 3.5 cm of motor strip), no resection in functional important areas is recommended, due to intolerable neurological side effects. Unsolved is the increasing notion that even complete seizure control does not per se lead to social and socio-economic reintegration.(Oxbury, Oxbury et al. 1997; Helmstaedter 2004; von Lehe, Lutz et al. 2006; Buschmann, Wagner et al. 2009) The use of limited resections will probably contribute to reduce the neurological and cognitive morbidity. Whether more precise preoperative evaluation will allow “superselective resections” remains unclear, especially, because from a theoretical standpoint a certain amount of tissue-removal will always be necessary to remove or disconnect the “epileptogenic zone”. Improvements in intraoperative orientation and increased completeness of intended resections will be achieved 85
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by increased availability of intraoperative MR imaging and improvements of intraoperative neuronavigation, including correction of the inevitable brain –shift. (Nimsky, Ganslandt et al. 2004) The availability of functional, electrophysiological and morphological data when displayed in the microscope will aid the surgeon in addition to more sophisticated preoperative imaging, for example with high-field (3 or 7 Tesla) MRI.(Madan and Grant 2009) 5. Conclusion 1.
Modern diagnostic techniques enable more focused hypotheses of the epileptogenic zone, thus enabling precisely directed resection.
2.
Focal cortical dysplasia (especially Palmini and Lüders Type IIb) can be successfully resected with minimal rim, close to or even within eloquent cortex.
3.
Risc – benefit ratio is crucial, thus all means to reduce potential morbidity should be regularly applied (neuronavigation, intraoperative monitoring, awake craniotomy, etc.)
4.
Focal pathology bears a better prognosis than more widespread or diffuse lesions, except for holo-hemispheric especially porencephalic defects treated with hemispherectomy.
6. Key References, Recommended Reading Binder, D. K., M. Podlogar, et al. (2009). “Surgical treatment of parietal lobe epilepsy.” J Neurosurg 110(6): 1170-1178. Jeha, L. E., I. Najm, et al. (2007). “Surgical outcome and prognostic factors of frontal lobe epilepsy surgery.” Brain 130(Pt 2): 574-584. Kun Lee, S., S. Young Lee, et al. (2005). “Occipital lobe epilepsy: clinical characteristics, surgical outcome, and role of diagnostic modalities.” Epilepsia 46(5): 688-695. Neuloh, G., C. G. Bien, et al. (2010). “Continuous motor monitoring enhances functional preservation and seizure-free outcome in surgery for intractable focal epilepsy.” Acta Neurochir (Wien) 152(8): 1307-1314. Ojemann, G. A., J. Ojemann, et al. (1989). “Cortical language localization in left, dominant hemisphere. An electrical stimulation mapping investigation in 117 patients.” J Neurosurg 71(3): 316-326. Palmini, A. and H. O. Luders (2002). “Classification issues in malformations caused by abnormalities of cortical development.” Neurosurg.Clin.N.Am. 13(1): 1-16, vii. Schramm, J. (2002). “Hemispherectomy techniques.” Neurosurg.Clin.N.Am. 13(1): 113-134. Rosenow, F. and H. Luders (2001). “Presurgical evaluation of epilepsy.” Brain 124(Pt 9): 1683-1700.
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Schramm, J. and H. Clusmann (2008). “The surgery of epilepsy.” Neurosurgery 62 Suppl 2: 463-481; discussion 481. Yun, C. H., S. K. Lee, et al. (2006). “Prognostic factors in neocortical epilepsy surgery: multivariate analysis.” Epilepsia 47(3): 574-579.
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OUTCOME AND LONG-TERM PERSPECTIVES IN EPILEPSY SURGERY Ulrich Sure, Dorothea Miller Department of Neurosurgery, University Hospital Essen, Germany Objective The present paper describes the (long-term) outcome of the below mentioned resective epilepsy surgery techniques (table 1). Table 1 Type 1:
Temporal epilepsy patients without focal lesions*.
Type 2:
Extratemporal epilepsy patients without focal lesions.
Type 3:
Lesionectomy for a a. Vascular lesion. b. Non-vascular lesion.
*Lesion defined as either vascular or tumour lesion. When the outcome of epilepsy surgery is assessed, it is usually evaluated whether the patient is either suffering no more or rarely disabling seizures, or experiences at least a worthwhile improvement. A classification addressing these criteria was introduced into the literature by Engel et. al. in 1993 (see table 2) [1]. Table 2 (Engel´s classification) Class I: Free of disabling seizures A: Completely seizure free since surgery B: Non-disabling simple partial seizures only since surgery C: Some disabling seizures after surgery, but free of disabling seizures for the last 2 years D: Generalized convulsions only with antiepileptic drug (AED) discontinuation. Class II: Rare disabling seizures (“almost seizure free“) A: Initially free of disabling seizures but has rare seizures now B: Rare disabling seizures since surgery C: More than rare disabling seizures since surgery, but rare seizures fort he last 2 years D: Nocturnal seizures only Class III: Worthwhile improvement A: Worthwhile seizure reduction
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B: Prolonged seizure free intervals amounting to greater than half the follow-up period, but not 35%) is about 50%, and mean YBOCS score decrease varies from 7 to 30 points (out of 40). Efficacy of STN-DBS and NAcc-DBS has been confirmed in comparative blinded studies 14, 15. Major Depression Major depression (MD) is one of the most prevalent mental illnesses (lifetime prevalence rates 17%) and is associated with a high rate of mortality (1% /year). Pathophysiology of MD is probably related to the dysfunction of a neural network involved in the control of mood in response to health events 16. Neuroimaging studies have identified the cortical (dorsolateral prefrontal cortex, anterior cingulum (Cg24)), basal ganglia (NAcc, thalamus, …) and limbic (subgenual cingulum (Cg25), insula, …) structures belonging network, and their respective implications. Several prospective open studies have shown that 50-60% of the patients suffering from medically-refractory MD respond (depression score decrease >50%) to DBS targeting the subgenual portion of the cingulum (Cg25) 17, 18 or the nucleus accumbens (NAcc) 19. Other targets (ventral striatum, habenula, inferior thalamic peduncle) have been proposed too 20, 21. Conclusion These results are encouraging but need to be confirmed in large comparative studies before to discuss the place of surgery in the management of these affections. The mechanisms of action and the predictive factors of DBS efficacy have not been identified yet. The ethical aspects of this approach have to be discussed too. 1.
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2.
Limousin P, Krack P, Pollak P. Electrical stimulation of the subthalamic nucleus in advanced Parkinson’s disease. N Engl J Med. 1998;339:11051111
3.
Vidhailet M, Vercueil L, Houeto J et al. Bilateral deep brain stimulation of the globus pallidus in primary generalized dystonia. N Engl J Med. 2005;352:459-467
4.
Alexander G, DeLong M, Strick P. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci. 1986;9:357-381
5.
Obeso J, Rodrıguez-Oroz M, Benitez-Temino B et al. Functional Organization of the Basal Ganglia: Therapeutic Implications for Parkinson’s Disease. Mov Disord. 2008 23:S548–S559
6.
Mink J. The basal ganglia and involuntary movements: impaired inhibition of competing motor patterns. Arch Neurol. 2003;60:1365-1368
7.
Temel Y, Visser-Vandewalle V. Surgery in Tourette Syndrome. Mov Disord. 2004;91:3–14
8.
Mataix-Cols D, Wooderson S, Lawrence N et al. Distinct neural correlates of washing, checking, and hoarding symptom dimensions in obsessivecompulsive disorder. Arch Gen Psychiatry. 2004;61:564-576
9.
Aouizerate B, Martin-Guehl C, Cuny E et al. Deep brain stimulation of the ventral striatum in the treatment of obsessive-compulsive disorder and major depression. Am J Psychiatry. 2005;21:811-813
10.
Fontaine D, Mattei V, Borg M et al. Effect of subthalamic nucleus stimulation on obsessive-compulsive disorder in a patient with Parkinsosn disease. J Neurosurg. 2004;100:1084-1086
11.
Nuttin B, Gabriels L, Cosyns P et al. Long-term electrical capsular stimulation in patients with obsessive-compulsive disorder. Neurosurgery. 2003;52:1263-1274
12.
Sturm V, Lenartz D, Koulousakis A et al. The nucleus accumbens: a target for deep brain stimulation in obsessive-compulsive and anxiety-disorders. Journal of Chemical Neuroanatomy. 2003;26:293-299
13.
Greenberg B, Malone D, Friehs G et al. Three years outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder. Neuropsychopharmacology. 2006;31:2384-2393
14.
Denys D, Mantione M, Figee M et al. Deep brain stimulation of the nucleus acccumbens for treatment refractory obsessive compulsive disorder. Arch Gen Psychiatr 2010;67:1061-1068
15.
Mallet L, Polosan M, Jaafari N et al. Subthalamic Nucleus Stimulation in Severe Obsessive Compulsive Disorder. N Eng J Med. 2008;359:2121-2134
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16.
Mayberg H. Defining neurocircuits in depression. Psychiatric Annals. 2006;36:259–269
17.
Kennedy S, Giacobbe P, Rizvi S et al. Deep brain stimulation for treatmentresistant depression: follow-up after 3 to 6 years. Am J Psychiatr. 2011;168: 502–510
18.
Mayberg H, Lozano A, Voon V et al. Deep Brain Stimulation for TreatmentResistant Depression. Neuron. 2005;45:651–660
19.
Bewernick B, Kayser S, Sturm V, Schlaepfer T. Long-term effects of nucleus accumbens deep brain stimulation in treatment-resistant depression: evidence for sustained efficacy. Neuropsychopharmacology. 2012;(Epub aheadof print).1–11
20.
Anderson R, Frye M, Abulseoud O et al. Deep brain stimulation for treatment-resistant depression: Efficacy, safety and mechanisms of action. Neurosci Biobehavior Rev. 2012;36:920–1933
21.
Malone D, Dougherty D, Rezai A et al. Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression. Biological Psychiatry. 2009;65:267–275
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PSYCHOSURGERY HISTORY AND EHICOLEGAL REFLECTIONS J. Verlooy M.D.,Ph.D. University of Antwerp, Belgium Ehicolegal committee EANS Objective This lecture tries to give an insight in the problems neurosurgeons might encounter when dealing with ethical issues in psychosurgery, and how to cope with them. History It is very important to remember the history of psychosurgery because it explains why neurosurgeons should pay attention the ethical issues in psychosurgery. The famous case of Phineas Cage (1848) indicated that the frontal lobe might be related with behaviour. In 1892 the first attempts of psychosurgery was done by Gottlieb Burkhardt in Zwitserland. Jacobson and Fulton presented 2 cases in London in 1935. It was not until the publication of Egas Moniz and Almeida Lima (1936) that psychosurgery was introduced Egas Moniz (1874-1955) was awarded the Nobel Prize for the leukotomy in 1949. Interestingly enough ElectroConvulsive Therapy (ECT) was introduced in 1938. Walter Freeman (1895-1972) popularised the transorbital leucotomy and personally performed about 2500 surgeries with questionable indications and desastrous outcome. This was the main reason why psychosurgery was completely abandoned since the 1960’s. Another reason was the introduction of chlorpromazine as a drug. We mention also the cerberal stimulation in animals by Dr Jose Delgado in 1965. Guidelines When deep brain stimulation (DBS) for OCD (Obsessive Compulsive Disorders) was introduced in the 90’s the OCD-DBS collaborative Group introduced guidelines that should be respected. In Flanders, patient assessment committee was installed in order to judge on the indications for DBS. In some instances, legal regulations exist. Future Developments Not only psychosurgery, but also neurocognitive enhancement , “cosmetic neurology”, might become an issue in future neurosurgical practice. 131
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Some objections can be formulated : t
Risk of an unknown future harm outweighs any short-term intellectual benefit (nonmaleficence).
t
Unnatural (beneficence)
t
Anti-egalitarian (costly) unless society chooses to subsidese enhancement (distributive justice)
t
Threat of individuals being pressured into unwanted enhancement (autonomy)
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RADIOSURGICAL MANAGEMENT OF TRIGEMINAL NEURALGIA Jean Regis MD(1), Constantin Tuleasca MD(1,2,4.) 1. Aix-Marseille University, INSERM, UMR 1106 and Timone University Hospital, Functional and Stereotactic Neurosurgery Service and Gamma Knife Unit, Marseille, France 2. Lausanne University Hospital (CHUV), Neurosurgery Service and Gamma Knife Center 3. Neurology Department, Aix-Marseille University and Timone University Hospital, Marseille, France 4. University of Lausanne, Faculty of Biology and Medicine, Lausanne, Switzerland Address for correspondence: Pr Jean Régis Head of Functional Neurosurgery Dept Timone University Hospital Aix Marseille Univ
[email protected] Introduction Trigeminal neuralgia (TN), also known as “tic douloureux”, is a serious health problem with a prevalence rate of 4 to 5 per 100.000 people. Medically refractory TN may be treated by microvascular decompression (MVD), percutaneous procedures (glycerol injection, balloon microcompression or thermocoagulation), and Gamma Knife radiosurgery (GKR). Methods We describe the historical evolution and concept of GKR for TN, and review the clinical results in the framework of the large experience of pioneering groups. We also present and discuss technical nuances that are of importance for analyzing and understanding this approach. Results In 1951, Leksell performed the first radiosurgical procedure for TN by targeting the gasserian ganglion, as identified on X-rays. GKR was implemented in 1968, and gained further interest for the treatment of TN in the early 1990s, with the use of MRI and limitations of other more invasive techniques. In 1993, Rand proposed to move the target from the gasserian ganglion to the cisternal segment of the nerve. Lindquist promoted short time afterwards the idea of targeting the nerve at its emergence from the brainstem (DREZ), with a dose of 70 Gy. We then reported the first 5 cases successfully treated in Marseille with a more anterior target (plexus triangularis target) and a higher dose of 90 Gy. In 1996, the multi-centric trial published by Kondziolka et al. demonstrated the safety-efficacy of GKR with a maximum doses between 70 and 90 Gy. In the only prospective trial published in 2006, we demonstrated a high efficacy/safety rate using an average high dose of 85 Gy and the anterior cisternal target, comparing favorably with the series using a DREZ target and a lower radiation doses. Long-term results have been reported in two series with 22% of patients painfree at 7 years (Dhople et al, 2009) and 30% of patients pain-free at 10 years 133
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(Kondziolka et al, 2010), respectively, both using the DREZ and quite low radiation doses. The large series of Marseille (Tuleasca et al., work in progress) is the only study reporting long-term results for the anterior cisternal target. From a series of 737 consecutive patients, we analyzed 497 cases with more than one year of follow-up: 45.3% remained pain free at 10 years; the hypoesthesia rate was low, with only 21.1%, being somewhat bothersome in only 8 cases (1.6%) and very bothersome in 3 cases (0.6%). Nuances in the radiosurgical technique make significant differences in clinical results. For example, the Pittsburgh group demonstrated that increasing the volume of the treated nerve leads to dramatic increase in the risk of toxicity with no clear benefit in efficacy. Our work comparing treatment variables between 2 centers (Marseille and Brussels) demonstrated a dramatic increase of toxicity when using channel blocking. More recently the dose received by the brainstem has been demonstrated to be a negative prognostic factor for trigeminal function injury. Conclusion Even if MVD remains the reference technique for the treatment of refractory TN, the current evidence for the long-term safety-efficacy of the GKR is sufficient to propose this method of treatment as a first intervention. Technical nuances should be taken into account, as they have major impact on the results of this approach. 1. Introduction Trigeminal neuralgia (TN), also known as “tic douloureux”, a name given by the French surgeon Nicholas André (1), is a serious health problem with a prevalence rate of 4 to 5 per 100.000 people (2). Patients typically describe a brutal, intense pain in the face, with “electrical shock-like” characteristics (3). Several etiologies are considered to be involved possibly in TN, and vascular compression at the emergence from the pons is one of the major pathogenic factors (4-6). Usually, vessels component of the neurovascular conflict are rather small, such as arteries (superior cerebellar or anterior inferior cerebellar) or, less frequently, prominent veins (petrosal vein, draining veins in the brainstem) (7, 8). Microvascular decompression (MVD) treats this hypothetic cause, by separating the vascular loop from the trigeminal nerve; MVD is nowadays considered as the reference technique in the drug-resistant TN, with long-term cure rates varying between 69% and 96% (9-18). Trigeminal pain can be treated with percutaneous techniques also, aiming at the gasserian ganglion via the foramen ovale, producing a partial lesion on the nerve by different mechanisms of action, that are thermic in thermocoagulation, mechanic in microcompression, and chemical in glycerol injection (19-23). Nevertheless, surgery as a treatment in idiopathic TN is not a new concept, being one of the most ancient indications in neurosurgery and started far before the medical therapies in this disease (see first gasserectomy done by Wears in 1885). The concept of stereotactic radiosurgery was first introduced by the Swedish neurosurgeon Lars Leksell in 1951, when treating a patient suffering from 134
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essential TN using a prototype guiding-device linked to a dental X-ray machine for performing a “stereotactic gangliotomy” (24). Gamma Knife radiosurgery (GKR) with 201 Cobalt sources was finally adopted in 1968. Nevertheless, the efficacy of the GKR to treat other type of pathologies, as well as the discovery by Leksell of the glycerol injection, the absence of a high-quality neuroradiological examination and also the appearance of the effective drugs against TN, made GKR to temporarily be abandoned. During the nineties, due to the clear limitations of other surgical therapeutic options, as well as the possibility of accurate direct targeting of the cisternal portion of the nerve, regained interest of GKR for TN (25, 26). None of these treatment strategies is perfect, but neurosurgeons shall adapt each technique to individual context, as no surgery for TN will provide definitive alievement for all patients (26). Without any doubt, the heterogeneity of the clinical results in different GKR series (table 1) is suggesting an important impact of the preoperative and perioperative parameters, both part of the dose planning strategy (26). 2. Methods Between July 1992 and November 2010, 737 patients presenting with intractable trigeminal neuralgia were treated with GKR and prospectively followed-up in the Timone University Hospital in Marseille, France. Our main objective was to evaluate if one single treatment with a target on the cisternal portion of the nerve (“retrogasserian target” or “far-anterior target”) alleviates or cures the trigeminal pain, as compared to pre-therapeutic clinical assessment. As secondary objectives, we estimated the changes within the intensity of the pain, the number of attacks before and after the treatment, the neurological exam as well as the influence of the preoperative and perioperative parameters on the safety and efficacy. We excluded patients with TN secondary to multiple sclerosis, those with second GKR treatment and also those presenting with megadolichobasilar artery compression (a special anatomical condition), which are reputed to have more variable response to radiosurgery. Thus, safety and efficacy is reported in this present chapter in 497 patients with medically refractory classical TN, never previously treated by GKR and having a follow-up of at least one year. All the patients were fulfilling the criteria’s of the International Headache Society (3). Evaluation of the type of the trigeminal pain was made according to the classification proposed by Eller et al. (27) into idiopathic TN1 and TN2. TN1 is described as typical sharp, shooting, electrical shock-like, with pain-free intervals between the attacks, that is present for more than 50% of the time; TN2 is described as an aching, throbbing, or burning pain, present for more than 50% of the time and that is constant in nature (constant background pain being the most significant attribute). Were included only patients fulfilling the criteria of the TN1 type. We would also like to underline the fact that when referring to atypical pain in our series, it is to describe patients with slights characteristics of atipicity, and not with those features from the previous classification, as TN2 is described. Our patients presenting “atypical” pain had still a trigeminal neuralgia and not a different facial pain syndrome, as someone can presume from the name if misinterpreted. We
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included no patient that had secondary TN due to a lesion or compressive element on the nerve (3). During the 18 years of the study, various models of the Gamma Knife were successively used (models B, C, 4C and Perfexion; Elekta Instruments, AB, Sweeden). After application of the Leksell Model G stereotactic frame (Elekta Instruments AB, Sweden) under local anesthesia, all patients underwent stereotactic magnetic resonance imaging (MRI) and computer tomography (CT) for target definition. The MRI sequences used to identify the trigeminal nerve are T2-type CISS without contrast, and contrast-enhanced T1-weighted images. Bone CT always supplements the neuroradiological investigation in order to correct any distortion errors on the MRI images. A single 4-mm isocenter is positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range 4.5-14) anteriorly to the emergence of the nerve (retrogasserian target, figure 1). The theoretical maximal dose (100%) to be administrated with a 4-mm shot was 90 Gy. This had been adapted to the individual anatomy, taking into account the dose to the brainstem (maximum 15 Gy received by the first 10 mm3) and also the condition of the patient (lower dose had been administrated in multiple sclerosis cases) (26, 28). The final median value of the maximum dose delivered in this series was 85 Gy (70 to 90). All the procedures have been performed by the senior author (J.R.). Patients continued their medication unchanged for one month after GKR and then were able to diminish the drug doses progressively depending on the treatment efficacy. Patients were seen for a neurological examination including facial sensibility, corneal reflex and jaw motility at 3 months, 6 months, and one year after the treatment and then regularly after, once a year. The study was designed as an open, self-controlled, non-comparative prospective study. Ethics committee (CPPRB1) permission was obtained for this study. Follow-up information was obtained in two ways: direct clinical evaluation and telephone interview by one author (CT) who was not involved in the selection of the cases for treatment. Outcome measures included initial pain freedom, the onset of the sensory disturbance and the recurrence. The results have been evaluated as follows (29): Class I: pain free without medication; Class II: pain free with medication; Class III: pain frequency reduction superior to 90%; Class IV: Pain frequency reduction between 50 and 90%; Class V: no significant reduction in pain frequency; Class VI: pain worsening. A recurrence is defined as the change from class I to a lower outcome class. Thus the situation of a patient who had been pain free without medication (Class I) and who then restarted taking specific drugs but who remained pain free on medication (Class II) was considered as a recurrence. A minor recurrence was defined as well tolerated by the patient (lower frequency and intensity of the pain) and not requiring a new surgical therapy. A major recurrence was defined as requiring further surgical procedure (29). The degree of hypoesthesia is reported using the BNI facial hypoesthesia scale, which uses the following grades: I, no facial numbness; II, mild facial numbness but not bothersome; III, facial numbness that is somewhat bothersome; and IV, facial numbness that is very bothersome.
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For patients presenting facial sensory dysfunction, we also inquired about their quality of life related to trigeminal neuralgia and whether this sensory problem was bothering them or not. We have asked whether or not they have mastication difficulties. The latency intervals to become pain free or to develop a recurrence or a sensory disturbance, the date of medication changes, the date of further surgical procedures, were also cautiously monitored. 3. Results As previously stated, in the present chapter we analyze 497 patients with medically refractory, classical TN, never treated previously by GKR and having a follow-up of at least one year. We present the results by evaluating the widely recognized parameters in the literature: initially pain freedom, sensory disturbance onset and probability of maintaining pain relief. The median age was 68.3 years (range 28.1-93.2). The median follow-up period was 43.8 months (range 12-174.4). Three hundred and eighty-six, 296, 227, 191, 130, 99, 77, 61, and respectively 24 patients had at least 2, 3, 4, 5, 7, 8, 9, 10 and respectively 12 years of follow-up. Two hundred and twenty-five were men and 272 were women. The median duration of symptoms was 68.3 months (range 1- 531). Twenty- six patients (5.2%) died but were not excluded from the study as they had at least one year of follow- up. Preoperative MRI revealed the presence of a vascular conflict in 278 cases (55.9%). One hundred and seventy three (34.8%) patients had a prior surgical procedure, of which 102 (20.5%) patients had only one previous intervention, 41 (8.2%) patients had two and 30 (6%) had three or more previous surgeries (as described in table 6). The preoperative surgery technique used was radiofrequency lesion in 99 (19.9%) patients, balloon microcompression in 64 (12.9%), MVD in 45 (9.1%) and glycerol rhizotomy in 6 (1.2%) patients. GKR was the first surgical procedure in 324 patients (65.2%). The median maximal dose (100%) was 85 Gy (range 70-90). The median distance between the DREZ and the isocenter was of 7.6 mm (range 4.5-14). Four hundred and fifty-four patients (91.75%) were initially pain-free in a median time of 10 days (range 1-459). The probability of remaining pain-free at 3, 5, 7 and 10 years was 71.8%, 64.9%, 59.7% and 45.3%, respectively. The hypoesthesia actuarial rate at 5 years was 20.4% and at 7 years reached 21.1% and remained stable till 14 years with a median delay of onset of 12 months (range 1-65). A facial hypoesthesia somewhat (8 cases, 1.6%) or very (3 cases, 0.6%) bothersome was reported in a total of 11 patients (2.2%). Interestingly, the hypoesthesia rate was higher in cases with latter pain free (after 30 days), compared to those alleviated within the first 48 hours, or between 48 hours and 30 days (30). One hundred and fifty seven (34.4%) patients initially pain free experienced a recurrence with a median delay of 24 months (range 0.62-150.06). The rate of recurrence sufficiently severe to require a new surgery was 67.8% at 10 years. 137
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Postoperative hypoesthesia was a positive predictive factor both for maintaining pain relief as well as for recurrence without further surgery. 4. Discussion 4.1. Historical perspective Leksell performed the first radiosurgical procedure for TN by targeting the retrogasserian ganglion (“stereotactic radiogangliotomy”) in 1951, using X-ray films (24). The series published by Lindquist in 1991, using this target included 46 patients from whom 18% maintained pain relief at 2 years. In 1993, Rand proposed to move the target from the ganglion to the cisternal segment of the nerve (the so-called retrogasserian or far-anterior target). We then reported the first 5 cases successfully treated in Marseille with the same target and a high dose of 90 Gy. Lindquist promoted short time afterwards the idea of targeting the DREZ, at the emergence of the nerve from the brainstem, with a lower dose of 70 Gy (2). In 1996, the multicentric trial published by Kondziolka et al. demonstrated that the maximal dose plays a major role in the efficacy, without any effect on the safety, in presuming that the target was located in the same place in all the patients (31). This trial gathered together the first cases from several centers: Los Angeles, Marseille, Pittsburg, Rhode Island and Seattle. It advocated that the maximal radiation dose plays a major role on the efficacy, with no effect on its safety, by identifying short and long-term outcomes, the cut-off of a necessary radiation dose and the risk of complications. More precisely, patients treated with less than 70 Gy were rarely found to become pain-freedom (31). In the light of this fact, the maximal dose of 70 Gy became a standard for all the centers using the technique used by the Pittsburgh group. The results were encouraging, with 72% of the patients pain-free, 84% with good or excellent results and with only 6% hypoesthesia. Even if this multicentric trial was a pioneering study on the topic, there was clearly heterogeneity of the targets and dose planning strategies between these different groups, which is the main bias of this study, and may have led to some confusion in interpreting the results of further studies (29, 32, 33). In the only prospective trial published in 2006 (29), we compared favorably our results, using an average high dose of 85 Gy and the retrogasserian target, to that of the series with a lower radiation doses and the DREZ target. As we were preoccupied by the potential risk of irradiating the brainstem with high doses, we decided to use a more anterior cisternal target, at the level of the plexus triangularis (figure 2 and figure 3, A), which is more in agreement with the target classically used for microsurgical rhizotomy and thermocoagulation (34, 35). 4.2. Far anterior and DREZ targets The far anterior target refers to the placement of a unique, 4-mm shot, on the cisternal portion of the trigeminal nerve, at around 7-8 mm or more anteriorly from the brainstem emergence of the nerve (figure 3, B). At the opposite, the DREZ (posterior) target refers at placing the 4-mm shot at the emergence of the
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trigeminal nerve at the level of the pons, with heterogeneous definitions about the isodose that is supposed to cover the brainstem depending on centers (figure 3, C). No level 1 or 2 evidence exists in favor of anterior versus posterior target. Although this remains a subject of controversy in the literature, our experience oriented us to use an optimal distance between 7.5 and 8 mm, as it showed clear benefit in terms of efficacy, toxicity and long-lasting pain relief (25, 26, 33). What accounts for the difference between the two anatomical targets? The dose to the DREZ and the dose to the brainstem, more precisely the dose to the trigeminal nerve pathway in the brainstem, are dramatically increased with the DREZ target. The DREZ, also known as the Obersteiner-Redlich zone, is histologically defined as the zone where the peripheral myelination (Schwann cells) leaves places to the central type of myelination (oligodendrocytes). There are two issues that must be kept in mind. One is related to the variability of the limit between the Schwann cells and the glial environment of the nerve as it exits the brainstem, classically located 3 mm from the emergence of the nerve. The second one is related to the fact that this zone can be variable in length and may extend further more in the distal portion of the nerve (13). As there is no in vivo possibility to individually evaluate the extent of the DREZ in the nerve, this makes the term “DREZ target” inappropriate. Beside this anatomical issue, there is also a dose planning-related definition given for the DREZ by Christer Lindquist: “a 4-mm collimator centered on the trigeminal root entry zone treated with a dose of 70 Gy at the center, including the nerve root and the adjacent brainstem within the 50% isodose surface (35 Gy)” (figure 4) (2). This first definition had changed in current clinical practice and the authors are now reporting that no more than the 20% isodose line should irradiate the brainstem (2), or even 30%, if we are considering the Pittsburgh group technique. So, the so-called DREZ target continues to evolve as a concept. A recent paper of Arai et al. placed it “at the midposterior portion of the trigeminal nerve, anterior to the pons” (36), which could be also be considered equivalent to the far anterior target in some cases. There are many clinical implications related to the anatomical aspect of dose planning. One is that the DREZ target is suggested to yield more toxicity than the far anterior target. The more severe complication of radiosurgery for TN is the “dryeye”, reported by Matsuda et al. (37) and present in 3 of 41 cases of TN treated with 80 Gy at the DREZ target in their series. This complication was significantly related to the irradiated volume of the brainstem (37). Also, 77 patients out of 104 treated have been found to have hyper intensities on the region of the DREZ on follow-up MRI (37). We never had this complication in our series using a much higher irradiation dose but the far-anterior target, neither in the prospective trial published in 2006, nor in the results reported in the present chapter (26, 29). In another paper, including 47 patients in a retrospective study, we recommended a minimal distance of 5 mm and an optimal distance of 8 mm for the placement of a unique shot (38). A recent study made by Park et al. (39) compared both targets (far anterior and the DREZ) and found much more bothersome complication in the DREZ target group (3 cases, 13.1% compared to 0 cases). Other studies also suggested that a target placed at the DREZ or close to it seems to be associated
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with higher risk of hypoesthesia (including bothersome hypoesthesia) (32, 40, 41). 4.3. Outcome after radiosurgery: pain freedom, hypoesthesia and recurrence There is an important discrepancy between the results that have been published in the literature (table 1). Also, very frequently, different groups report results using heterogeneous methodology. Globally, a good initial outcome on pain relief is present in most of the radiosurgical papers and varies between 35% and 100%; the risk of recurrence ranges between 0 and 46%; the risk of trigeminal nerve dysfunction varies between 0 to 57% (28, 29, 38-40, 42-61). Pain freedom Different concepts are employed to define pain freedom after radiosurgery, as due to its delayed efficacy, these can be interpreted differently according to different study groups: complete or with more than 90% alleviation, with or without medication etc. In our opinion, it is mandatory to clearly and separately report all nuances of this specific outcome. Multiple sclerosis (25, 29, 54, 62-70), previous surgical treatment on the same side (29, 71, 72) or atypical TN (73) are considered to be negative predictors. The presence of a neurovascular compression has been suggested to have no influence by Sheehan (60), a predictor of failure by Shaya (74) and of a success by Brismann (75). We have recently shown that previous MVD is also a negative predictor for pain freedom (76), but this finding needs further cautious analysis. Patient related parameters and operative technical nuances give different results. In this sense, the maximal dose is considered related to the initial pain freedom (see table 1). Pollock et al. published a study comparing the 70 Gy maximal dose in 27 patients and the 90 Gy maximal dose in 41 patients (41). The target was the DREZ. They concluded that a high dose of radiosurgery is associated with higher chances of pain relief (41). A study published by the Stanford University group advocated that with a maximal dose higher than 75 Gy, patients had a much higher chance of being pain free (77). Park et al. (39) published recently a retrospective study opposing the DREZ and the retrogasserian target. Patients treated with the retrogasserian target were more likely to become pain free (BNI classes I-IIIb) than those with the DREZ target (93.8% compared to 87%). The time of response was also shorter in the first group than in the second (mean of 4.1 weeks compared to 6.4 weeks). All these findings are in line with our personal experience (78). Dhople et al. (47), used the DREZ target and a median prescription dose of 75 Gy (range 70-80 Gy), and reported a series of 102 patients with a median follow-up of 5.6 years. They reported an initial pain relief of 81%, new bothersome facial numbness in 6% of the cases and a recurrence rate of 56%. The maintenance of pain relief was of 22% at 7 years. Matsuda et al. (79) reported a series of 104 patients, treated with GKR, a unique 4-mm shot, doses of 80 or 90 Gy and the target at the trigeminal nerve root. They found 98% initial pain relief with 49% new trigeminal nerve dysfunction, appearing between 4 and 68 months after the treatment. Kondziolka et al. (52) published recently a series of 503 patients with 107 cases having more than 5 years of follow-up. A single 4 mm isocenter was used
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in 99% of the cases and two isocenter in 1%. The target was located at around 3 to 8 mm anterior from the emergence of the trigeminal nerve from the pons. The isocenter was usually situated so that the brainstem surface was irradiated at the 20% isodose line or less. The majority of the patients (92%) received doses of at least 80 Gy with a maximum of 90 Gy. They had 89% initial pain relief with 10.5% hypoesthesia and a recurrence rate of 42.9%. One patient (0.2%) developed deafferentation pain. Only 29% were still controlled with or without medications at 10 years. Verheul et al. (69) reported a series of 450 treatments in 365 patients with a median follow-up of 28 months. They were all treated with a maximal dose of 80 Gy and a unique 4 mm shot at the DREZ; 6% of the patients presented a somewhat bothersome hypoesthesia with only 0.5% very bothersome hypoesthesia. The pain relief at 5 years was of 75%. Loescher et al. (54) reported a series of 72 patients, 58 with essential and 14 with secondary TN (8 with multiple sclerosis). They were all treated with a 4 mm isocenter at the DREZ and a maximal dose of 80 Gy. The initial pain relief in essential trigeminal neuralgia was quite low, 71% at 6 months, with a rather high hypoesthesia rate of 31%. Hypoesthesia We advocated earlier in this chapter the role that is played by the anatomical localization of the target in the appearance of hypoesthesia and its degree of severity (37, 39). The UCLA group reported their results in 126 patients treated between with a 4 mm shot and the target being placed at the emergence of the nerve (DREZ), with 90 Gy at the center (80). The rate of numbness was very high (58.3%), with 19.4% very bothersome, 30.5% subjective dry eyes and 30.5% decreased corneal reflex. In patients with hypoesthesia, Marshall et al. (55) found a significantly higher dose to the DREZ (57.6 compared to 47.3 Gy). The anatomical location of the target is not the only dose planning strategy factor of major importance. The integrated dose to the nerve (i.e. the volume of the nerve that is irradiated and the total dose received by the nerve) has been reported to correlate to the risk of trigeminal nerve dysfunction. Flickinger et al. demonstrated that increasing the volume of the treated nerve leads to a dramatic increase of the risk of toxicity (i.e. bothersome hypoesthesia), with no clear benefit on efficacy (49). The Stanford University team reported the results of 83 patients treated with maximal doses varying between 71.4 and 86.4 Gy, with a special strategy, covering all the nerve (important integrated dose) (77). Due to the volume of the treated nerve, the hypoesthesia rate was high (74%) with 39% severe numbness. Moreover, the authors demonstrated that a longer length of nerve treatment resulted in higher rates of numbness. We also focused on this issue and published a paper about using the far-anterior cisternal target and a median dose of 90 Gy, as used in Brussels at that time (38). We found increased trigeminal nerve injury associated with increased nerve length included in the 50% isodose in patients in which the 90 Gy dose prescription necessitated source plugging. So, the efficacy was similar with the series in Marseille, but the toxicity was much higher (43% of hypoesthesia in Brussels’s series instead of 15% in Marseille’s series). After a cautious analysis, we showed that in cases of a 141
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narrow cistern with too high dosage delivered to the brainstem, the attitude of the 2 teams was not the same. In Marseille, we lowered the maximal dose and then, if still necessary, we would have used shielding (figure 5); in Brussels, the dose of 90 Gy was kept a priori, and shielding of the sources was first done in order to reduce the dose to the brainstem. At that time, we maintained that this plugging strategy accounted for the different rates of toxicity (the hypoesthesia rose from 15% with no bothersome hypoesthesia to 50% including 10% bothersome hypoesthesia) (38). A comparative, retrospective study gathering together the patients treated in Marseille and in Brussels, established that in patients with a large cistern, our methods were similar and results homogenous, with around 20% of trigeminal nerve disturbance. In patients with narrow cistern, the Brussels shielding strategy led to dramatic increase of the mean dose (42.86 Gy compared to 38.01 Gy) and also of the integrated dose (3.28 Gy instead of 2.76 Gy) to the nerve. We concluded that there is no significant benefit with increasing of the volume of the treated nerve (81). Our attitude was of saying that radiosurgery, unlike percutaneous treatment, should offer very good pain control without any hypoesthesia for the majority of the patients. Maybe also in the case of trigeminal neuralgia radiosurgery could act by a neuromodulator mechanism, which remains a matter of speculation and debate (82). A correlation between hypoesthesia and pain response does exist and hypoesthesia has been reported in some studies as a positive predictor for pain relief (59, 83). We have also found similar results in our present series both for the recurrence and the recurrence without further surgery (78). This postoperative hypoesthesia was not mandatory for long-term pain relief. Park et al. (39) found much more bothersome complication in the DREZ target compared to the far anterior one (3 cases, 13.1% compared to 0 cases). Moreover, there were huge differences regarding the frequency of bothersome facial numbness and dry-eye syndrome (13.1%, 8.7% compared to o%, 0%). Dhople et al. (47) reported new bothersome facial numbness in 6% of the cases. In the series of Matsuda et al. (79), they found 49% of new trigeminal nerve dysfunction, appearing between 4 and 68 months after the treatment. Also, recently, they made a comparison between the posterior and anterior target affirming that the first one is safer. On cautious analysis, the posterior target is closed to the far anterior one (that we also use) and the anterior is actually the historical, plexus triangularis target. Matsuda et al. (37) also reported higher toxicity with higher dose rate. Kondziolka et al. (52) reported 10.5% hypoesthesia. One patient (0.2%) developed deafferentation pain. Only 29% were still controlled with or without medications at 10 years. Verheul et al. (69) found 6% of the patients presenting a somewhat bothersome hypoesthesia, with only 0.5% a very bothersome hypoesthesia. In the series of Loescher et al. (54) the hypoesthesia rate was 31%. In our series (Tuleasca et al., work in progress), the hypoesthesia actuarial rate at 5 years was 20.4% and at 7 years reached 21.1% and remained stable till 14 years with a median delay of onset of 12 months (range 1-65). A facial hypoesthesia somewhat (8 cases, 1.6%) or very (3 cases, 0.6%) bothersome was reported in a total of only 11 patients (2.2%).
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An “evidence-based” review (84) published recently establishes the fact that the hypoesthesia rate currently reported with GKR is not significantly different than after the MVD and is also much less frequent than after percutaneous techniques. Recurrence As for pain freedom, recurrence is reported using heterogeneous methodologies, which makes sometimes difficult to appreciate the results on long-term basis. Papers should report pain freedom at precise intervals, such as 1, 3, 5, 7, 10 years instead of the status at the last follow-up. Depending on studies, the recurrence rate varies between 0 to 42%. Also, if two studies reported long-term follow-up concerning the DREZ target (47, 52), there is no such a paper concerning the far anterior one. Dhople et al. (47) and Kondziolka et al. (52) used the DREZ target and quite low doses and reported a quite steady rate of failures: 22% at 7 years for the first one and 30% for the second one. We analyzed recently our series of 737 patients operated with GKR, at a far anterior target and using high-doses of irradiation (the median dose of 85 Gy) (30, 76, 78, 85). The probability of remaining pain relief was of 45.3% at 10 years. Furthermore, the rate of recurrence that was sufficiently severe to require a new surgery was of 67.8% at 10 years. In our series (Tuleasca et al., work in progress), patients with multiple sclerosis related trigeminal neuralgia were found to have much more recurrence than the idiopathic cases. 4.4. Radiosurgery in the context of other surgical methods The surgical treatment of medically refractory TN consists of percutaneous ablative techniques, MVD and GKR. Thermocoagulation, balloon micro-compression and glycerol injection have in common the fact that they act through an ablative mechanism of action and are usually performed under a brief general anesthesia. Very high rates of trigeminal nerve dysfunction, which is classically necessary for complete and prolonged efficacy, are found. They are simple techniques and easy to repeat and readily suitable for the elderly. The efficacy is immediate and they very useful in patients with resistant and devastating pain. Microvascular decompression is performed under general anesthesia, with craniotomy, and it is established as a technique of choice. It has been first performed on the basis of the observations made by Dandy (86), with a technique developed initially by Gardner and Miklos and perfected by Janetta. Even if accepted frequently as a first line treatment, its rate of failure vary between 15 to 35% (10, 11, 13, 8789) and its long-term cure rate in 69% to 96% (12, 13, 15, 16, 87, 90). It has the major advantage of treating the probable cause of disease as well as offering a very low risk of subsequent trigeminal nerve dysfunction (10, 13, 16, 64, 87-89, 91-93). Major complications include dead, brainstem infarction, intracerebral hematoma, cerebellar edema, hydrocephalus, facial palsy, ipsilateral hearing loss, severe facial numbness, cerebrospinal fluid leak, meningitis, and others (10, 13, 16, 64, 87-89,
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91-95), never encountered with GKR. However, if both MVD and GKR have very similar rate of long-term recurrences, the probability of being pain free without medication looks better with MVD (15, 96). The majority of the authors (among those who have at their disposal the technical and human resources allowing them to perform both MVD and GKR, as well as percutaneous techniques) are agreeing on the fact that the evidence for long-term safety and efficacy of GKR is nowadays sufficient for proposing it as first intention (29, 47, 97, 98). Advantages and disadvantages of each technique must be loyally exposed to the patient according to the data provided by the reliable peer-reviewed series published during these last 20 years. No definitive answer can be given to the question of the superiority of one technique on the other. Radiosurgery has the advantage of being the least invasive technique available and is performed under local anesthesia. Additionally, the rate of trigeminal dysfunction is remarkably low and comparable to that occurring with MVD. Postoperative GKR hypoesthesia increases the probability of pain cessation but the majority of the patients experience pain freedom without sustaining any trigeminal nerve dysfunction. It appears as late as 5 years after the treatment, as reported in recent series (52). Our results confirm an actuarial rate at 5 years of 20.4% and at 7 years of 21.1%, which remained stable until 14 years and had a median delay of onset of 12 months (range 1-65). A facial hypoesthesia somewhat (8 cases, 1.6%) or very (3 cases, 0.6%) bothersome was reported in a total of 11 patients (2.2%). In the meta-analysis of Gronseth et al. (99), the rate of hypoesthesia reported after radiosurgery is similar to the rate of hypoesthesia after MVD, and much lower than the rate of hypoesthesia reported after percutaneous procedures. This observation is suggestive for the fact that radiosurgery may involve neuromodulator mechanisms and not only a pure destructive effect (82). Technical nuances play a major role and their impact on current clinical practice may explain the large variability of safety and efficacy reported in the literature. 4.5. Curent indications of radiosurgery in trigeminal neuralgia According to the current literature, GKR is frequently proposed in everyday practice, including in candidates for MVD (72). Some authors use the very good safety-efficacy ratio of radiosurgery as an argument for promoting this treatment as a first-line alternative to conventional methods. We still recommend MVD in young patients with clear evidence of neurovascular compression on preoperative MRI as it remains, in our opinion, the gold-standard treatment for this particular group. However, if young patients decline MVD, radiosurgery shall be offered as the alternative choice, on the grounds that it results in a very low rate of numbness, rarely bothersome, for a similar rate of efficacy as compared to percutaneous methods. As in our centers all the main surgical techniques are available and currently practiced, this diminishes the bias in terms of optimal treatment choice for an individual patient at a particular moment at her/his medical history. In our experience, a high radiation dose (median maximal dose 85 Gy), on a retrogasserian target (at a median 7.6 mm distance from the emergence form the brainstem) and with a unique 4 mm shot offers a high probability of pain-freedom
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of 91.75, a hypoesthesia rate of 21.1% with only 0.6% being very bothersome, a rate of recurrence of 34.4% and a probability of maintaining pain relief of 45.3% at 10 years. Even if MVD remains the reference technique for the treatment of refractory TN, the current evidence for the long-term safety-efficacy of the GKR is sufficient to propose this method of treatment as a first intervention in medically refractory TN. Technical nuances should be taken into account, as they have major impact on the results of this approach. Acknowledgments Supported by Timone University Hospital (Assistance Publique des Hopitaux de Marseille) and Aix-Marseille University Figures: Figure 1: A single 4-mm isocenter is positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range 4.5-14) anteriorly to the emergence of the nerve (retrogasserian target). The theoretical maximal dose (100%) to be administrated with a 4-mm shot is 90 Gy. This has to be adapted to the individual anatomy, taking into account the dose to the brainstem (maximum 15 Gy received by the first 10 mm3) and also the condition of the patient (e.g. multiple sclerosis)
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Figure 2: Plexus triangularis target as published in 1995 (100). The 4 mm shot is positioned on the nerve at the level of the trigeminal incisura of the petrous bone apex. The targeting is based both on CISS MR and CT bone window.
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Figure 3: targeting in radiosurgery for trigeminal neuralgia: the plexus triangularis (figure 3, A); the far anterior target refers to the placement of a unique, 4-mm shot, on the cisternal portion of the trigeminal nerve, at around 7-8 mm or more anteriorly from the brainstem emergence of the nerve (figure 3, B); at the opposite, the DREZ (posterior) target refers at placing the 4-mm shot at the emergence of the trigeminal nerve at the level of the pons, with heterogeneous definitions about the isodose that is supposed to cover the brainstem depending on centers (figure 3, C).
Figure 4: DREZ target according to Christer Lindquist published in 1993 (2); the 50% isodose (35 Gy) line “must” generously overlap the brainstem
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Figure 5: Shielding (figure 5A) vs no shielding (figure 5B) in radiosurgery for trigeminal neuralgia; the theoretical maximal dose (at the 100% isodose) to be administrated with a 4-mm shot is 90 Gy; this has to be adapted to the individual anatomy, taking into account the dose to the brainstem- maximum 15 Gy received by the first 10 mm3; if this dose shall be higher than 15 Gy, we would start by decreasing the maximal dose to the nerve to 85 Gy instead of 90 Gy; if still the first 10 mm3 would receive more than 15 Gy, we would use shielding, as shown in the figure 5A; figure 5B shows a 15 Gy isodose line in contact- but not overlapping- the brainstem, which requires no shielding of sources
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knife surgery for trigeminal neuralgia: outcome, imaging, and brainstem correlates. Int J Radiat Oncol Biol Phys. 2004 Oct 1;60(2):537-41. 47.
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TRAUMATIC BRAIN INJURY Andras Buki M.D., Ph.D., D.Sc Department of Neurosurgery, Medical Faculty of Pecs University, Pecs, Hungary, H-7624 1. Objective The aim of this work is to provide a brief summary of the most important features of traumatic brain injury primarily focusing on classification of injuries as well as the injured. 2. Modern Literature Review Traumatic brain injury (TBI) represents a major yet under- recognized health care problem frequently referred to the silent epidemic. This phrase reflects that TBI is the leading cause of death in the first four decades and estimated to become the third most frequent cause of death at 2020 worldwide. While Hippocrates have already highlighted its significance stating that no injury to the skull can be as trivial or so severe to deny treatment, the care for TBI is characterized with major regional inequalities particularly as far as guideline-compliance is considered. While moderate/severe head injury harbors surgical consequence the significance of mild head injury should not be underestimated either: the number of these cases can be enormous, 15-30 times outnumbering the former entities and the consequences can alter quality of life (QOL) and also may end up with medico-legal complications and issues. 3. Recent Clinical and Research Developments Unfortunately despite of intensive research and promising experimental therapeutic results at the preclinical phase, none of those interventions or drugs that had worked at the lab did actually prove successful in the clinical setting. While the care for injuries dates back to the prehistoric ages, almost all aspects of TBI research and care are rather controversial. i., Classification, definitions To cover all aspects of TBI-classifications would be well beyond the scope of this mini-paper, thereby the author refers to excellent reviews in this field(1;2). In sum, TBI can be classified upon the mechanism of injury (static vs. dynamic, impact vs. inertial), pathoanatomy (location of injury), pathophysiology (primary vs. secondary, diffuse vs. focal), imaging features as well as clinical symptoms and signs, including the classification upon injury severity. To this end, a neurosurgery resident should be confident to classify her/his patients to identify those cases purportedly requiring neurosurgical attention. Upon this triage the most important aid is the Glasgow Coma Score (GCS). A postresuscitation GCS under 9 defines severe TBI, 9-12 is characteristic of moderate-, and 13-15 mild head injury. It is of note however that GCS does not reflect the complexity of TBI and some studies dispute the ground for this kind of distinction between various groups of the injured (3). 157
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For practical reasons, the triage should reflect the probability of intracranial complications following TBI thereby the group of patients who should undergo CT/ close observation on the floor have to be defined. Table-1 summarizes some criteria that may characterize those patients with medium risk for post-TBI intracranial lesion (low risk patients lack such criteria, and can go home with an information sheet about their injury, while high risk patients are easily classified upon GCS under 13, focal neurological signs, indirect/direct signs of skull fracture, polytrauma purportedly including head injury.(2)) Table-1 Criteria identifying patients with medium risk for post-TBI intracranial lesion 1.
Witnessed loss of consciousness
2.
Progressive headache
3.
Alcohol/drug intoxication
4.
Seizure
5.
Unreliable history
6.
Age under 2y
7.
Repeated vomiting
8.
Amnesia
9.
Injury mechanism or circumstances indicative of major mechanical forces
10.
Repeated trauma
11.
Severe maxillo-facial trauma
12.
Child abuse
13.
Significant subgaleal swelling/collection
14.
Coagulopathy/liver dysfunction/altered hemostasis
15.
Diabetes or any other significant metabolic alteration
In this “suspicious” group a negative CT is enough to discharge a patient, yet intracranial bleeding may show up after an ultra-early, negative CT particularly in patients with altered hemostasis. This latter group requires additional observation of 12-16 hours just as the group of abused/intoxicated patients with a chance for repeated/additional injury. ii., Diagnostics As other abstracts cover this field extensively, the author only intends to highlight the importance of extracranial injuries. At least 4% of patients with severe brain injury harbors associated spine injury, particularly at the cranio-cervical junction (CCJ) and nearly every second severe TBI patient requires attention for extracranial injury. It is of note that an adult patient can practically never be in hemorrhagic shock because of TBI only, so a prompt search for additional injuries is mandated. 158
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The optimal solution to exclude purported multiple injuries is the execution of the trauma-CT protocol with a CT scanner of at least 16 slices. In case of diffuse brain/axonal injury (DAI) clinically characterized by GCS under 9, minimal lesions on CT and normal intracranial pressure (ICP) values, MRI with susceptibility weighted imaging (swi) or hemogradient imaging can be of aid. Similarly, diffusion tensor imaging with fractional anisotropy measurement may provide additional information about the extent of DAI(4). MRI is also useful in cases where the indication of decompressive surgery is elucidated. As far as the mild/minimal-head-injury group is considered more liberal use of CT was found cost efficient by various studies. iii.,Therapeutic interventions and strategies Both in the US (AANS, AITKEN) and in the EU (EANS, EBIC) several attempts were made to establish scientific evidence based guidelines for the treatment of the head injured(5;6). These efforts are summarized in other abstracts. It is of note that to date only organized trauma care and application of guidelines focused on the maintenance of cerebral perfusion pressure (CPP)/ICP management proved efficient to reduce the burden of TBI. To this end, removal of all space occupying lesions with monitoring of the CPP (mean arterial blood pressure/MABP) and ICP in conjunction with intraparenchymal pCO2/temperature/blood flow/ electrophysiological monitoring aiming at the reversion/prevention of secondary brain injury is the gold standard of treatment(5). iv. Follow-up The sequelae of TBI is not over with the acute phase: additional late deterioration may be associated with post-TBI hydrocephalus, cognitive deficit, hypopituitarism primarily affecting the growth hormone (GH) axis and neuropsychological alterations also troubling the life of patients undergone mild TBI. A close follow-up is required to identify and, if possible, solve these issues in a timely fashion. 4. Future Questions and Direction To date there is no targeted therapy for TBI. Those issues preclinical and clinical trials both should face are complex but need to be resolved in order to help the injured to a better care. These are the following: i.
to identify common pathophysiological endpoints for trials. To this end, sophisticated imaging tools and novel biomarkers (UCHL-1, GFAP, protein breakdown products) both provide promising perspectives (7;8).
ii.
to define prognostic models for the identification of target-populations. The Common Data Element project and the IMPACT-project represent groundbreaking progress in this field (9;10).
iii.
with the aid of the above tools and the scientific merit of our successes and failures in the past decades in the field of translational research novel therapeutic strategies and substances should be identified and tested, aiming at “polypharmacia” in our approaches including early post-injury application of mild hypothermia, slow rewarming with proteolysis159
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inhibitors and other pathophysiology-targeted therapeutic interventions. 5. Conclusion Neurosurgeons operate in an extremely cost-efficient field of health care while treating TBI with saving life and restoring quality of living. Residents usually get their first impressions in patient management both at the ER and the OR while taking care of the injured. Neurotrauma is the field, which will always belong to neurosurgeons regardless how prestigious this field is considered to be. In the future we hope to see more enthusiasm in guideline development and application, more success in translational research and a far better quality of care all culminating in a better outcome of the head injured. 6. Key References, Recommended Reading 1.
SAATMAN KE, DUHAIME AC, BULLOCK R, MAAS AI, VALADKA A, MANLEY GT. Classification of traumatic brain injury for targeted therapies. J Neurotrauma 2008; 25:719-738.
2.
GREENBERG MS. Handbook of Neurosurgery. 6th ed. Thieme, New York, 2006.
3.
COMPAGNONE C, D’AVELLA D, SERVADEI F et al. Patients with moderate head injury: a prospective multicenter study of 315 patients. Neurosurgery 2009; 64:690-696.
4.
LE TH, GEAN AD. Neuroimaging of traumatic brain injury. Mt Sinai J Med 2009; 76:145-162.
5.
BULLOCK MR, POVLISHOCK JT. Guidelines for the management of severe traumatic brain injury. Editor’s Commentary. J Neurotrauma 2007; 24 Suppl 1:2.
6.
Surgical management of penetrating brain injury. J Trauma 2001; 51:S16-S25.
7.
KOVESDI E, LUCKL J, BUKOVICS P et al. Update on protein biomarkers in traumatic brain injury with emphasis on clinical use in adults and pediatrics. Acta Neurochir (Wien ) 2009.
8.
MONDELLO S, ROBICSEK SA, GABRIELLI A et al. alphaII-spectrin breakdown products (SBDPs): diagnosis and outcome in severe traumatic brain injury patients. J Neurotrauma 2010; 27:1203-1213.
9.
MAAS AI, HARRISON-FELIX CL, MENON D et al. Standardizing data collection in traumatic brain injury. J Neurotrauma 2011; 28:177-187.
10.
LINGSMA HF, ROOZENBEEK B, STEYERBERG EW, MURRAY GD, MAAS AI. Early prognosis in traumatic brain injury: from prophecies to predictions. Lancet Neurol 2010; 9:543-554.
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PATHOPHYSIOLOGY OF TRAUMATIC BRAIN INJURY AND NEUROPROTECTION Martin Smrcka Neurosurgical Department, University Hospital Brno, Czech Republic The important terms in this topic are: 1) primary and secondary brain injury and 2) focal and diffuse brain injury. Primary injury is a structural damage to the brain parenchyma, which occurs in the moment of injury. Primary injury in its focal appearance is for example cerebral contusion and traumatic intracerebral hematoma. Primary diffuse injury is cerebral concussion and diffuse axonal injury. Currently there is no possibilty to repaire this type of damage. Therefore a great attention is payed to study the secondary brain injury. Here we take into consideration some systemic influence (hypotension, hypoxia) and then the issues of brain edema, intracranial and perfusion pressures,molecular and biochemical mechanisms after the brain injury. 1. Primary Injury In terms of biomechanics primary brain injury is usually caused by a hit of a subject to the head by a dynamic force in a very short time interval (20-200 ms). This is addressed as a contact mechanism. Small subject may cause impressive fractures or an open injurie, large contact surfaces cause more frequently linear fractures. Besides fractures also contusions develop, usually in the site of the impact but even in the opposite site, so called „par contre coup“ mechanism. Sometimes the brain injury may arise also without the contact with the head by a pulse mechanism on the basis of acceleration and deceleration, for example during the abrupt movement of the cervical spine, so called inertial injury. The longer the time of the acceleration, the deeper the forces propagace into the brain tissue and various types of diffuse axonal injury may evolve. In short-term accelerations the stress occurs mainly on the brain surface with the development of focal injuries and subdural hematomas due to torn bridging veins. In penetrating gun shot injuries the most important issue is the projectile velocity. There is an increasing tissue distruction with the increasing kinetic energy. There are cavitations and shock waves in these rapid shots due to compression and decompression of the adjacent tissues. Thus primary necrosis evolves which reaches far from the shooting canal. Both closed and penetrating head injuries might be complicated by various types of hematomas. Epidural and subdural hematoma, however, affects the brain tissue secondarily, on the basis of cerebral compression. Intracerebral hematomas are in 80-90% located in the frontal and temporal white matter. The pathophysiology of so called „delayed“ traumatic intracerebral hematoma is not completely clear. This type of hematoma affects 0,6-7,4% of head trauma patients and mortality rate of this complication is as high as 35-40%. It occurs in the interval from 6 hours to 30 days after the injury and might appeare both in contusion tissue as well as in CT
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scan intact brain. Traumatic subarachnoidal hematoma belongs also among the primary focal lesions. Trauma is the most common cause of this type of hematoma. Considering diffuse injurie we usually talk about cerebral concussion and the diffuse axonal injury. The term concussion is used to describe the reversible traumatic cerebral disfunction. There is typically a short-term unconsciousness (within 10 minutes), after which the neurological function returns to normal. There is a normal CT scan. The concussion is now considered to be the mildest type of diffuse axonal injury. The severity of the diffuse axonal injury depends according to the biomechanical studies on the extent of the acceleration and deceleration mechanisms. There is a disruption of axons and vessel tearing in the brain stem and in corpus callosum in the severe diffuse axonal injuries 2. Secondary Injury Secondary (ischemic) brain injury after the head trauma is often enhanced by the presence of systemic hypoxia and hypotension. Hypoxia occurs frequently in the link with the aspiration to the breathing pathways and in the chest injury. Hypotension is usually defined as a systolic pressure lower than 90 mmHg. Its occurence in the connection with the severe head injury practically doubles the mortality (55% versus 27%) Often the hypotension occurs secondarily on the basis of the shock state, particularly in the bleeding to the chest, abdomen or pelvis. In the context with posttraumatic intracranial hypertension, the hypotension means a further decrease of cerebral perfusion pressure. There are other systemic variables with negative influence, such as hypercapnia, which increases cerebral edema due to vasodilatatory effect. On the other hand hypocapnia (pCO2 less then 30 mmHg) is also undesirable, because of vasoconstriction and the restriction of blood flow. Highly unwanted systemic insult is from hypothermia, especially above 39 ºC, due to increased release of excitatory aminoacids and an impaired function of proteinkinase C. Hyperglycemia and hypoglycemia have also a negative effect on the brain metabolism. Except for systemic insults there are also intracranial pathophysiological mechanisms which influence the development of secondary brain injury. Cerebral edema is very frequent after the severe head injury. The most important types of cerebral edema are vasogenic and cytotoxic edema. Vasogenic edema arises primarily in the white matter. Mechanical trauma of the cerebral tissue and vascular endothelium disturbs the integrity of the bloodbrain barier. Therefore there is a leak of the fluid and plasmatic proteins into the extracellular space. These proteins further worsen the edema on the basis of the changed oncotic gradient. Cytotoxic edema is mostly expressed in the gray matter. Sometimes it is called ischemic because it usually developes due to disturbed cerebral blood flow. The cerebral metabolism is therefore deteriorated and the function of the membrane ion channels is disturbed. Water enters into the intracellular space 162
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together with sodium and edema evolves. Cerebral hyperemia (swelling) might be another cause of increased intracranial pressure. The reason is probably the damage of vasoregulatory centres in hypothalamus and brain stem. Vasoparalysis leads to increased cerebral blood flow (CBF) and cerebral blood volume which then increases intracranial pressure and decreases the venous outflow. Very important factor in the pathophysiology of traumatic brain injury is intracranial hypertension. It may be caused by cerebral edema, by the presence of intracranial hematoma or by the disturbance in cerebrospinal fluid passage. The normal values of intracranial pressure (ICP) in the adult in the horizontal position are between 7 – 15 mmHg. The values above 20 mm Hg are generaly considered as pathological. According to the so called Monro-Kellie´s hypothesis the skull cavity is a rigid case of a fixed volume which consists of three non-compressible compartments: brain tissue, blood and cerebrospinal fluid. If there is an increase in the volume of some of these compartments, the volume of some other has to be decreased to maintain the ICP stationary. The influence of the volume changes inside the skull on the ICP depends on the state of the compensatory mechanisms. It matters how much cerebrospinal fluid can be moved from the skull cavity to the spinal canal, how much can be decreased the cerebral blood volume in the cerebral vessels and what is the state of the brain tissue elasticity. According to so called pressure-volume curve the ICP raises after the exhaustion of these compensatory mechanisms exponentially. Picture 1: Pressure-volume curve. First raise of volume does not mean increase in ICP, with further volume increase the raise of ICP is exponential. From Youmans, Neurological Surgery, 4. edition, 1996.
After the exhaustion of these mechanisms may rapidly increasing ICP cause movements of brain tissue and a formation of so called cerebral herniation. If the expansive forces work unilaterally, the midline shift appears. So called subfalcine (cingulate) herniation evolves, when the brain tissue of the frontal or parietal lobe 163
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is stuck under the free edge of the falx. Even ischemia in the area of pericallosal arteries may develop. Very frequent is temporal lobe herniation into the tentorial incisura (transtentorial herniation, conus temporalis). The transtentorial herniation was first described by Meyer in 1920. Picture 2.: The principle of transtentorial herniation. Temporal lobe is pushed into the tentorial incisura with the pressure on the brain stem, oculomotor nerve and posterior cerebral artery. From Youmans, Neurological Surgery, 4. edition, 1996.
In posterior fossa lesions or as a continuation of the shift from the supratentorial compartment so called tonsilar herniation may develop. Cerebellar tonsils get bellow the level of foramen magnum, the great cistern is obliterated and there is a direct pressure on the brain stem. This mechanism may lead very rapidly to the breathing arrest and death. Many authors think that cerebral perfussion pressure (CPP) is much more important then ICP. CPP is defined as MABP – ICP (MABP = mean arterial blood pressure). In patients with severe head injury we try to keep the CPP above 70 mmHg. The importace of CPP is in its relation with CBF. The relation between CBF and CPP is expressed by so called autoregulatory curve. Normally CBF is not changed if CPP is between 40 and 160 mmHg, bellow 40 mmHG CBF dramatically 164
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decreases. In patients with severe head injury the autoregulation may be disturbed. Picture 3: Autoregulatory curve.Normal autoregulation. Between 40 to 160 mmHg of CPP there are no changes in CBF.
Let is the secondary brain damage after the head injury started by mechanical axonal damage, ischemia and hypoxia of the brain tissue, vasogenic edema or increased ICP, there are common pathophysiological manifestations on the cellular and subcellular level which lead finally to the cell death. The fundamental role in the cell pathophysiology of the traumatised brain belongs to so called excitatory aminoacids (glutamate, aspartate), which are released after the mechanical brain damage. According to this concept the hyperstimulation of the neurons leads finally to their death. These amins activate the sodium and calcium intracellular influx and activate the phospholipase C. The pathological increase in the intracellular calcium concentration is usually considered to be the key mechanism leasing to the cell death. The increased level of intracellular calcium leads then to disturbed oxydative phosphorylation and to inappropriate activation of intracellular enzymes. The lipolysis is started leasing to disturbed membrane functions with the formation of diacylglycerids, lipophospholipids, free fatty acids and the platlet activating factor. The disturbance of protein phosphorylation leads to disrupted gene transcription and to activation of apoptosis. Proteolysis leads also to desintegration of microtubules and the cytoskeleton. Calcium further activates some enzymatic systems with formation of free radicals. Their main source is the arachidonic acid. The hydroxyl radicals then start to oxidise the membranes in the process known as lipid peroxidation. There is a chain oxidative reaction among the lipids in the membranes which spreads also to the membrane lipoprotiens, which means the ion channel damage. A destruction of a large part of cerebral parenchyma, which was not primarily disturbed, may occur. 165
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Moreover in the phase of secondary ischemia there is a decrease of an oxidative phosphorylation and the energy is gained from the anaerobic glycolysis. The result is an excessive accumulation of lactate and there is not enough energy for proteosynthesis.
Picture 4: The basic biochemical mechanisms leading to the cell destruction
caused by the brain trauma. Mechanical damage
Activation of excitatory aminoadids Activation of AMPA, NMDA and metabotropic receptor
Disturbance of membrane and BBB
permeability
Activation of lipolysis
Activation of proteolysis
Gene transcription failure
Formation of free radicals, lipid peroxydation of membranes
Disintegration of cytoskeleton
Apoptosis
Cell death
Neuroprotection The strategies for neuroprotection approaches are basically pharmacollogical and non-pharmacological. Unfortunately, even though many of these approaches
have shown a beneficial effect in animal models, practically all of the phase III clinical studies have failed. The pharmacological approaches which are currently under investigation are targeting excitotoxicity, oxidative stress, inflammation, mitochondrial dysfunction, blood-brain barier disruption, edema, apoptosis and others. The drugs studied are: statins, progesterone, cyclosporine A, erythropoetin, cell cycle inhibitors, cannabinoids, magnesium, citicoline and many others. The non-pharmacological approaches include for example cell/gene therapy, vaccines, hyperbaric oxygen therapy, deep brain stimulation, hypothermia. None of these approaches and drugs is being used widely clinically except for hypothermia. Mild hypothermia 33-35°C has minimal side affects and has been proved to lower ICP. 166
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Recommended Reading Neurotrauma: New insights into patology a treatment: John T.Weber, Andrew I.R.Maas, Elsevier, 2007 Head injury: Pathophysiology and management: Peter L. Reilly, Ross Bullock. Hodder Arnold, 2005. Neuroprotection for traumatic brain injury: translational challenges and emerging therapeutic strategie. David J. Loane, Alan I.Faden. Trends in Pharmacological Science, vol. 31(12), 2010, p. 596-604. Neuroprotection in traumatic brain injury: a complex struggle against the biology of nature.Joost W. Schoulen, Curr Opin Crit Care 13:134–142. 2007 Lippincott Williams & Wilkins.
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NOVEL IMAGING IN NEUROTRAUMA: SPINAL CORD INJURY Shekar N. Kurpad MD, PhD Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, USA Objective In this paper, we review the literature on spinal cord DTI in both animal models and humans. We provide a summary of the use of DTI in patients with spinal cord injury (SCI). We hope that by providing a review on the current role of DTI in SCI we may be able to better direct future efforts in this field. Modern literature review Diffusion MRI provides a measure of the displacement of water molecules in tissues. Displaced water molecules produce an attenuated signal during diffusion MR scanning. By its nature, the axonal architecture in CNS white matter promotes diffusion of water molecules in a direction predominantly parallel, rather than perpendicular, to axon fibers.1-3 Diffusion perpendicular to the fibers seems to be limited by cell membranes more than myelin sheaths.4, 5 This direction-dependent diffusion is described as ‘anisotropic’ and is used by DTI to infer the orientation of surrounding axonal fibers and to delineate anatomical boundaries. DTI uses a tensor framework to characterize molecular motion in multiple directions in a three-dimensional space. The diffusivities along the three principle axes are defined by the eigenvectors where 1 (primary eigenvector) represents the direction and magnitude of the longitudinal diffusion vector, while 2 and 3 represent vectors along the minor axes. The magnitudes of these vectors are used to calculate a number of indices: fractional anisotropy (FA), mean diffusivity (MD), longitudinal apparent diffusion coefficient (lADC) and transverse apparent diffusion coefficient (tADC). FA, which ranges from 0 -1, defines the degree of anisotropy and tissues with high anisotropy have a value closer to 1. While the lADC of the spinal cord represents rostro-caudal diffusivity along white matter fibers, the tADC is a measure of axial/radial diffusivity. The eigenvalues are affected by microstructural alterations that affect the diffusion of water molecules and this forms the basis for using DTI indices to identify spinal cord pathology. Animal studies One of the important applications of DTI is the evaluation of SCI in animal models. In one of the earliest studies that used a rat SCI model, Ford et al6 described significant decreases in lADC and increases in tADC at the level of injury as well as in areas of the cord that were apparently normal on conventional T2-weighted images. Experimental SCI leads to disruption of cell membranes and increased membrane permeability at the level of the lesion which results in increased diffusivity and lower anisotropy.7-9 In hyperacute SCI (0-6 hours), diffusion measurements are able to distinguish SCI based on severity.10 The unique feature of DTI is its ability to detect changes in diffusion metrics at regions remote from the lesion.8, 11-13 An overall reduction in lADC throughout the cord and a decrease in MD remote from the lesion has been described during recovery from SCI.12 These findings are 168
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possibly related to cytotoxic edema, axonal loss or chronic atrophy.14-16 Several authors have reported histological correlations to DTI changes following SCI in rat models.10, 17-20 DTI metrics have also been correlated with electophysiological measures, so as to identify which diffusion measures could act as predictors of neurological function. Since axonal structure and integrity have been closely linked to MR diffusion measurements9, 21 the above correlations emphasize the utility of DTI to mirror both the structural and functional properties of axons. Human studies In acute human SCI, both the FA and ADC are decreased around the injured level. Facon et al22 showed that although ADC decreased in the majority of SCI patients. Shanmuganathan et al23 reported that ADC was uniformly decreased in patients with cervical spine trauma. DTI metrics at the injury site correlated with ASIA motor score in patients with non-hemorrhagic cord contusions.24 . In chronic SCI, MD, tADC, and lADC have been shown to be significantly greater in injured patients compared to corresponding levels in neurologically intact controls. The FA value at the site of the lesion is greatly reduced and appears to depend on both the level of injury and the completeness of the injury.25 The role of DTI in human SCI, however, needs to be explored further to deterimine definitive functional correlates and clinical applications. Recent clinical and research developments Animal studies DTI studies in animal models of SCI have recently focused on evaluating changes in diffusivity within the brain after SCI.26 We have recently shown that changes in diffusivity within the corticospinal tracts at the brainstem and internal capsule correspond to injury severity, and further provide evidence for diffuse changes in the neuraxis after SCI (unpublished data). DTI is also being used to delineate microstructural changes within the spinal cord after experimental stem cell transplants for SCI. In rats with thoracic SCI, stem cell transplants produce characteristic increases in MD at the cervical level that are significantly different as compared to placebo treatments (unpublished data). While the physiological basis of these changes needs to be evaluated, these findings provide encouraging evidence that DTI may be used as a biomarker to determine viability and efficacy of stem cell transplants. Human studies At our center, we have shown that axial FA maps and tractography are sensitive to asymmetric cord damage in acute SCI and can supplement conventional MR imaging in this setting.27 We have also found that FA decreased and tADC increased both at the level of injury as well as at the high cervical level in patients (n=11) after acute SCI (submitted for publication). We have therefore shown that DTI can detect retrograde changes in spinal cord architecture that are not visualized on conventional MRI. The use of high cervical DTI as a imaging biomarker of SCI will enable us to obviate imaging artifacts created by spinal instrumentation around the injury site. This approach has been utiilzed in a few studies in patients with 169
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chronic SCI. High cervical DTI showed significant reduction in anisotropy in patients with chronic cervical SCI, and the FA at the C2 level correlated with tibial SSEPs as well as ASIA scores.28 Recent studies have also demonstrated that high cervical DTI metrics correlate with spinal cord area and upper limb function in patients with chronic SCI.29 Moreover, changes in diffusivity are also visualized in the brain within the corticospinal tracts.30, 31 Overall, DTI is emerging as a useful technique to delineate pathophysiological changes within the neuraxis after spinal cord injury. These findings may help us better understand neural reorganization and plasticity, and thereby enable us to better plan therapeutic and rehabilitative strategies. Future questions and direction Spinal cord DTI in humans still has a number of limitations. Adequate spatial resolution remains a problem and it is difficult to visualize the individual funiculi on diffusion-weighted images, particularly in the lower thoracic cord.32 DTI of these segments is affected more by artifacts arising from cardiac and respiratory motion as well as CSF pulsation.33 The use of faster imaging techniques such as parallel imaging, single shot echo-planar imaging as well as the use of cardiac pulse-gating have helped to reduce these artifacts. However, scan acquisition time is still a limitation for patients with acute SCI since these patients cannot withstand even 30 minutes of additional scanning time in the MRI suite. The signal to noise ratio in human SCI is sub-optimal in most studies and can lead to overestimation of anisotropy measures, particularly in low-anisotropic tissues such as the central gray matter.34 The use of 3T MR scanners does improve the SNR,35 but is still not used universally. The use of DTI postoperatively is hampered significantly by the use of spinal instrumentation, which creates numerous artifacts and this issue is currently unresolved. Additionally, standardized software to process tensor images is essential to make this a feasible option for routine clinical use. The current limitations of spinal cord DTI need to be addressed in future studies, and overcoming these will improve the reliability and utility of this technique. Human SCI studies that use longitudinal imaging to determine the temporal profile of DTI metrics after SCI are needed. Also, it will be important to correlate DTI metrics in acute SCI to functional outcome at a future timepoint. Such studies will establish spinal cord DTI as a prognostic biomarker of SCI that can be used in the clinic. Conclusion 1.
DTI gives us a unique insight into the pathophysiology and microstructural alterations associated with spinal cord disorders.
2.
DTI in animal SCI models has demonstrated definitive histological and functional correlates that make this a potential non-invasive biomarker for SCI.
3.
DTI studies in human SCI have shown characteristic changes in acute and chronic SCI and DTI shows considerable potential as a clinical tool in the evaluation and treatment of these patients.
4.
Future studies should focus on overcoming the current technical limitations of spinal cord DTI and attempt to establish its utility in the clinic.
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Key references, recommended reading. 1.
Basser PJ, Mattiello J, LeBihan D. MR diffusion tensor spectroscopy and imaging. Biophys J 1994; 66: 259-67.
2.
Basser PJ, Pierpaoli C. Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. J Magn Reson B 1996; 111: 209-19.
3.
Basser PJ. Inferring microstructural features and the physiological state of tissues from diffusion-weighted images. NMR Biomed 1995; 8: 333-44.
4.
Beaulieu C, Allen PS. Determinants of anisotropic water diffusion in nerves. Magnetic Resonance in Medicine 1994; 31: 394-400.
5.
Beaulieu C. The basis of anisotropic water diffusion in the nervous system – a technical review. NMR in Biomedicine 2002; 15: 435-455.
6.
Ford JC, Hackney DB, Alsop DC, Jara H, Joseph PM, Hand CM et al. MRI characterization of diffusion coefficients in a rat spinal cord injury model. Magn Reson Med 1994; 31: 488-94.
7.
Shi R, Pryor JD. Pathological changes of isolated spinal cord axons in response to mechanical stretch. Neuroscience 2002; 110: 765-77.
8.
Deo AA, Grill RJ, Hasan KM, Narayana PA. In vivo serial diffusion tensor imaging of experimental spinal cord injury. J Neurosci Res 2006; 83: 801-10.
9.
Ford JC, Hackney DB, Lavi E, Phillips M, Patel U. Dependence of apparent diffusion coefficients on axonal spacing, membrane permeability, and diffusion time in spinal cord white matter. J Magn Reson Imaging 1998; 8: 775-82.
10.
Loy DN, Kim JH, Xie M, Schmidt RE, Trinkaus K, Song S-K. Diffusion Tensor Imaging Predicts Hyperacute Spinal Cord Injury Severity. Journal of Neurotrauma 2007; 24: 979-990.
11.
Schwartz ED, Shumsky JS, Wehrli S, Tessler A, Murray M, Hackney DB. Ex vivo MR determined apparent diffusion coefficients correlate with motor recovery mediated by intraspinal transplants of fibroblasts genetically modified to express BDNF. Exp Neurol 2003; 182: 49-63.
12.
Ellingson BM, Kurpad SN, Schmit BD. Ex vivo diffusion tensor imaging and quantitative tractography of the rat spinal cord during long-term recovery from moderate spinal contusion. J Magn Reson Imaging 2008; 28: 1068-79.
13.
Sundberg LM, Herrera JJ, Narayana PA. In vivo longitudinal MRI and behavioral studies in experimental spinal cord injury. J Neurotrauma 2010; 27: 1753-67.
14.
Loubinoux I, Volk A, Borredon J, Guirimand S, Tiffon B, Seylaz J et al. Spreading of vasogenic edema and cytotoxic edema assessed by quantitative diffusion and T2 magnetic resonance imaging. Stroke 1997; 28: 419-26; discussion 426-7.
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15.
Lu H, Sun SQ. A correlative study between AQP4 expression and the manifestation of DWI after the acute ischemic brain edema in rats. Chin Med J (Engl) 2003; 116: 1063-9.
16.
Ellingson BM, Ulmer JL, Prost RW, Schmit BD. Morphology and morphometry in chronic spinal cord injury assessed using diffusion tensor imaging and fuzzy logic. Conf Proc IEEE Eng Med Biol Soc 2006; 1: 1885-8.
17.
Ellingson BM, Schmit BD, Kurpad SN. Lesion growth and degeneration patterns measured using diffusion tensor 9.4-T magnetic resonance imaging in rat spinal cord injury. J Neurosurg Spine 2010; 13: 181-92.
18.
Zhang J, Jones M, DeBoy CA, Reich DS, Farrell JA, Hoffman PN et al. Diffusion tensor magnetic resonance imaging of Wallerian degeneration in rat spinal cord after dorsal root axotomy. J Neurosci 2009; 29: 3160-71.
19.
Kozlowski P, Raj D, Liu J, Lam C, Yung AC, Tetzlaff W. Characterizing white matter damage in rat spinal cord with quantitative MRI and histology. J Neurotrauma 2008; 25: 653-76.
20.
Farrell JA, Zhang J, Jones MV, Deboy CA, Hoffman PN, Landman BA et al. q-space and conventional diffusion imaging of axon and myelin damage in the rat spinal cord after axotomy. Magn Reson Med 2010; 63: 1323-35.
21.
Schwartz ED, Cooper ET, Fan Y, Jawad AF, Chin CL, Nissanov J et al. MRI diffusion coefficients in spinal cord correlate with axon morphometry. Neuroreport 2005; 16: 73-6.
22.
Facon D, Ozanne A, Fillard P, Lepeintre J-F, Tournoux-Facon C, Ducreux D. MR Diffusion Tensor Imaging and Fiber Tracking in Spinal Cord Compression. AJNR Am J Neuroradiol 2005; 26: 1587-1594.
23.
Shanmuganathan K, Gullapalli RP, Zhuo J, Mirvis SE. Diffusion tensor MR imaging in cervical spine trauma. AJNR Am J Neuroradiol 2008; 29: 655-9.
24.
Cheran S, Shanmuganathan K, Zhuo J, Mirvis SE, Aarabi B, Alexander MT et al. Correlation of MR Diffusion Tensor Imaging Parameters with ASIA Motor Scores in Hemorrhagic and Nonhemorrhagic Acute Spinal Cord Injury. J Neurotrauma 2011; 28: 1881-92.
25.
Ellingson BM, Ulmer JL, Kurpad SN, Schmit BD. Diffusion tensor MR imaging in chronic spinal cord injury. AJNR Am J Neuroradiol 2008; 29: 1976-82.
26.
Ramu J, Herrera J, Grill R, Bockhorst T, Narayana P. Brain fiber tract plasticity in experimental spinal cord injury: diffusion tensor imaging. Exp Neurol. 2008; 212: 100-7.
27.
Vedantam A, Jirjis MB, Schmit BD, Budde MD, Ulmer JL, Wang MC et al. Diffusion tensor imaging and tractography in brown-sequard syndrome. Spinal Cord 2012; 50: 928-30.
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28.
Petersen JA, Wilm BJ, von Meyenburg J, Schubert M, Seifert B, Najafi Y et al. Chronic cervical spinal cord injury: DTMRI correlates with clinical and electrophysiological measures. J Neurotrauma 2012; 29: 1556-66.
29.
Freund P, Schneider T, Nagy Z, Hutton C, Weiskopf N, Friston K et al. Degeneration of the injured cervical cord is associated with remote changes in corticospinal tract integrity and upper limb impairment. PLoS One 2012; 7: e51729.
30.
Freund P, Weiskopf N, Ward NS, Hutton C, Gall A, Ciccarelli O et al. Disability, atrophy and cortical reorganization following spinal cord injury. Brain 2011; 134: 1610-22.
31.
Freund P, Wheeler-Kingshott CA, Nagy Z, Gorgoraptis N, Weiskopf N, Friston K et al. Axonal integrity predicts cortical reorganisation following cervical injury. J Neurol Neurosurg Psychiatry 2012; 83: 629-37.
32.
Ellingson BM, Ulmer JL, Kurpad SN, Schmit BD. Diffusion tensor MR imaging of the neurologically intact human spinal cord. AJNR Am J Neuroradiol 2008; 29: 1279-84.
33.
Thurnher MM, Law M. Diffusion-weighted imaging, diffusion-tensor imaging, and fiber tractography of the spinal cord. Magnetic resonance imaging clinics of North America 2009; 17: 225-44.
34.
Bastin ME, Armitage PA, Marshall I. A theoretical study of the effect of experimental noise on the measurement of anisotropy in diffusion imaging. Magnetic resonance imaging 1998; 16: 773-85.
35.
Carballido-Gamio J, Xu D, Newitt D, Han ET, Vigneron DB, Majumdar S. Single-shot fast spin-echo diffusion tensor imaging of the lumbar spine at 1.5 and 3 T. Magnetic resonance imaging 2007; 25: 665-70.
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MANAGEMENT OF THE POLYTRAUMA PATIENT PJ Hutchinson Academic Division of Neurosurgery, University of Cambridge Introduction Trauma is the commonest age of death under the age of 40 years in the developed world. Death following trauma is trimodal. Patients may succumb immediately following trauma due to devastating injuries such as massive head injury, cardiac rupture or aortic transection (first peak), die in the acute stages from hypotension, thoracic complications (e.g. haemopneumothorax), cerebral complications (e.g. extradural / subdural haematomas) (second peak), or die several days or weeks later due to complications e.g. multi-organ failure and sepsis (third peak). Only prevention can reduce the incidence of first peak deaths but optimising trauma care from the scene through to definitive treatment reduces the incidence of second and third peak deaths. The goal of management of the polytrauma trauma patient is therefore to provide optimal care to reduce mortality while aiming for the best quality of life for survivors. The priorities for the initial management of the patient with multiple injuries follows the same principles whether the patient has sustained a head injury or not. The treatment of severely injured polytrauma patients has improved with the introduction of protocol-driven approaches such as Advanced Trauma Life Support (ATLS) developed by the American College of Surgeons (1) and the European Trauma Course (ETC) , a joint initiative of the European Resuscitation Council (ERC), The European Society of Anaesthesiology (ESA), the European Society of Trauma and Emergency Surgery (ESTES) and the European Society of Emergency Medicine (EuSEM). Overview of Management While conventional medicine relies on taking a history, examining the patient and ordering appropriate investigations the priorities for the trauma patient are different with the immediate implementation of treatment. Primary survey and resuscitation The first priority is the airway. A patent airway can be achieved or maintained using two maneouvres: the chin thrust and jaw lift. In addition, the oral cavity should be cleared of debris that may obstruct the airway and secretions e.g. blood and vomit removed with suction. High flow oxygen should be administered. In the unconscious patient the airway can be initially protected with an oropharngeal airway. If a patent airway cannot be achieved using these measures and in the unconscious patient intubation is indicated, both to protect the airway and provide adequate ventilation. If intubation is not possible, for example, with major maxillofacial injuries a surgical airway (cricothyroidotomy) should be considered. While controlling the airway measures should be applied simultaneously to protect the cervical spine; classically hard collar, sandbags and tapes. The hard collar needs to be appropriately sized. 174
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The second priority is the breathing. The chest should be examined for adequate and equal air entry. Life threatening injuries e.g. tension pneumothorax require immediate management. The diagnosis of tension pneumothorax is made on the basis of respiratory distress, tachycardia, hypotension, unilateral reduced air entry and tracheal deviation. Treatment is by needle decompression with a large caliber needle placed into the chest via the second intercostal space (midclavicular line). Following needle decompression and in patients with simple pneumothorax / haemothorax a chest drain should be inserted into the chest in the fifth intercostal space anterior to the mid-axillary line. The drain should be connected to an underwater seal. The chest should then be re-examined. The third priority is the circulation. Intravenous access should be obtained ideally in the antecubital fossa. At the same time bloods should be taken for full blood count, urea and electrolytes, coagulation profile and group and save / cross match (quantity depends on extent of injury and blood loss). Intravenous fluid should be administered. ATLS recommends crystalloid e.g. Ringer’s Lactate solution (2 litres rapid infusion for major trauma). With significant blood loss early administration of blood is recommended. If venous access cannot established via the antecubital fossa the options include central venous access via the neck (internal jugular/ subclavian line) or groin (femoral line). In children interosseous needles into the tibia are an option. A further option is via a venous cutdown usually into the saphenous vein. Haemorrhage from open wounds should be controlled by direct pressure or if necessary haemorrhage from the limbs can be controlled using tourniquets. The fourth priority is assessment of disability (the neurological status of the patient). This should be undertaken following assessment and treatment of the airway (with cervical spine control), breathing and circulation (with haemorrhage control). The simple AVPU method (alert, responds to speech, responds to pain, unresponsive) has been superceded by early assessment of the Glasgow Coma Score which is a more accurate measure of the patient’s neurological status. In addition the pupils should be assessed for size and reactivity to light. The final part of the primary survey is to expose the patient while preventing hypothermia to enable examination of the whole patient, including logroll to examine the spine. Monitoring In parallel to clinical assessment and treatment, monitoring should be applied to the patient including pulse oximetry, ECG monitoring, end-tidal carbon dioxide monitoring and blood pressure monitoring initially by cuff and if indicated using arterial line. Arterial puncture also enables blood gases to be taken to assess both the partial pressure of oxygen (critical to avoid hypoxia) and carbon dioxide (critical in terms of head injury). The stomach should be decompressed by passing a nasogastric tube (caution in patients with skull base fracture) and a urinary catheter passed (following examination for urethral transection). This decompresses the bladder and enables on-going assessment of hourly urine output.
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History Also in parallel to clinical assessment and treatment a history should be obtained from a witness or member of the ambulance staff. The history should be AMPLE (allergies, medications, past history / pregnancy, last meal, events / environment surrounding the injury). Imaging Two main initial radiological investigations are part of the primary survey. Firstly, a chest X-ray should be undertaken to assess the nature and extent of chest injury. A chest X-ray should also be undertaken following endotracheal intubation and insertion of chest drain. Secondly, a pelvic X-ray should be considered – a pelvic fracture can be a source of substantial haemorrhage. Undertaking a cervical spine X-ray as part of the primary survey has been superceded by CT. When the patient has been assessed and treated as part of primary survey and resuscitation, then further imaging can be undertaken usually by CT. There is increasing application of a complete trauma CT series in the patient with polytrauma – spiral CT enables rapid scanning of the head, neck, thorax, abdomen and pelvis. This approach enables a rapid diagnosis assisting in decision making as to the destination of the patient in terms of definitive care. This destination depends on the nature and extent of the injuries and may be to theatre for laporatomy, thoracotomy, craniotomy, pelvic external fixation or other orthopaedic surgery. If the polytrauma patient does not require urgent surgery transfer to intensive care is indicated for on-going monitoring and resuscitation. Secondary survey Irrespective of the destination and timing of definitive care the patient should undergo a secondary survey (the timing of which is dictated by the nature and extent of injury). The secondary survey is a top – tail examination of the patient to ensure that all injuries are documented and treated. Timing of orthopaedic fracture fixation In terms of the management of the polytrauma patient with head injury controversy exists in terms of the timing of management of other injuries (2). This particularly applies to orthopaedic injuries in the patient with or at risk of intracranial hypertension. There are arguments for both early and delayed fixation of fractures. This decision as to the timing of surgery should be tailored to the individual patient. Recent Developments Tranexamic acid There have been a number of recent developments in the management of the polytrauma patient. These include the administration of tranexamic acid for patients with significant haemorrhage (3). A large randomized study of tranexamic acid versus placebo in 20211 trauma patients with or at significant risk if bleeding showed that tranexamic acid safely reduced the risk of death (CRASH 2 study). The authors recommend that tranexamic acid should be considered for use in bleeding trauma patients. 176
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Primary survey CT There is also increasing interest in the role of very early CT performed as part of the primary survey. This is being investigated by the REACT-2 trial (4); an international, multicenter randomised clinical trial where patients are randomized to direct scanning i.e. receiving a contrast-enhanced total-body CT scan (head to pelvis) during the primary survey versus a control group managed according to local conventional trauma imaging protocols (based on ATLS guidelines) supplemented with selective CT scanning. The primary outcome measure is in-hospital mortality. Summary Management of the patient with polytrauma presents several challenges. The priorties are to avoid hypoxia and hypotension (especially in patients with polytrauma including head injury). Protocol driven therapy addressing the airway, breathing, circulation and disability in parallel with resuscitation provides a logical approach to management giving the patient the best chance of a good in outcome. References 1.
Advanced Trauma Life Support Manual American College of Surgeons Chicago 2008
2.
Nahm NJ, Vallier HAJ Timing of definitive treatment of femoral shaft fractures in patients with multiple injuries: a systematic review of randomized and nonrandomized trials.Trauma Acute Care Surg. 2012 Nov;73(5):1046-63. doi: 10.1097/TA.0b013e3182701ded.
3.
CRASH-2 trial collaborators, Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, El-Sayed H, Gogichaishvili T, Gupta S, Herrera J, Hunt B, Iribhogbe P, Izurieta M, Khamis H, Komolafe E, Marrero MA, Mejía-Mantilla J, Miranda J, Morales C, Olaomi O, Olldashi F, Perel P, Peto R, Ramana PV, Ravi RR, Yutthakasemsunt S.Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010 Jul 3;376(9734):23-32.
4.
Sierink JC, Saltzherr TP, Beenen LF, Luitse JS, Hollmann MW, Reitsma JB, Edwards MJ, Hohmann J, Beuker BJ, Patka P, Suliburk JW, Dijkgraaf MG, Goslings JC; REACT-2 study group.BMC Emerg Med. 2012 Mar 30;12:4. doi: 10.1186/1471-227X-12-4. A multicenter, randomized controlled trial of immediate total-body CT scanning in trauma patients (REACT-2). BMC Emerg Med. 2012 Mar 30;12:4. doi: 10.1186/1471-227X-12-4.
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TRAUMATIC INTRACRANIAL HAEMORRHAGE: INDICATIONS FOR NEUROSURGICAL INTERVENTIONS Professor Miroslav Vukic, MD, PhD and Sergej Marasanov, MD Department of Neurosurgery, Medical School University of Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia Objective Traumatic brain injury (TBI) is estimated to affect up to 2% of the general population per year. It represents the major cause of death and severe disability among young people, and thus causing a both major medical and socioeconomic problem to the society. Several forms of intracranial haematomas (ICH) that develop as a complication of TBI, namely the epidural haematoma, the acute subdural haematoma and traumatic parenchimal lesions/haematomas, will be discussed in this paper with a particular focus on indications for surgical removal. ICH complicate TBI in 25-45% of severe TBI cases, 3-12% of moderate TBI cases and in 1 of approximately 500 cases of mild TBI (1). Modern Literature Review Regardless the vast number of papers concerning TBI management published each year worldwide, it is very difficult to gain strong and relevant clinical evidence, simply due to the fact that there are no controlled clinical trials in the literature to support different forms of surgical management, or conservative versus surgical treatment. Regarding the nature of the disease the later is quite understandable. Therefore, it is virtually impossible to formulate recommendationts of treatment on a level of Class I evidence (evidence from one or more well-designed, randomized, controlled clinical trials, including overviews of such trials). Different groups of authors have tried to overcome such problems by reviews of the literature, issuing Guidelines to present rigorous literature-based recommendations for the surgical management of patients with posttraumatic intracranial haematomas. This paper will focus on the Guidelines published by the Congress of Neurological Surgeons in March 2006, which was based on review of more than 700 manuscripts and is and will be constantly revised and kept up-to-date (1). Recent Clinical and Research Developments Intracranial haemorrhage provoked by trauma can be diffuse or focal, the latter is being the focus of interest of this paper as being amenable to surgery. Epidural haematomas, acute subdural haematomas and traumatic parenchimal lesions/haematomas with special concern on posterior fossa lesions (2). Due to the importance of mass-volumes of intracranial hematomas to surgical management and to surgical decision making process, an easy method for the volume measurement is incorporated in this paper (3). Epidural haematomas (EDH) occur in the range of 2.7 to 4% among TBI patients, and can result from injury to the middle meningeal artery, vein, diploic veins or 178
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venous sinuses, the first being considered the main source of EDH. EDH occurs in all ages, but primariliy in the population younger than 50 years of age. The most frequent locations for EDH are temporoparietal and temporal regions. Indications for Surgery t
An epidural hematoma (EDH) greater than 30 cm3 should be surgically evacuated regardless of the patient’s Glasgow Coma Scale (GCS) score.
t
An EDH less than 30 cm3 and with less than a 15-mm thickness and with less than a 5-mm midline shift (MLS) in patients with a GCS score greater than 8 without focal deficit can be managed nonoperatively with serial computed tomographic (CT) scanning and close neurological observation in a neurosurgical center.
Timing t
It is strongly recommended that patients with an acute EDH in coma (GCS score < 9) with anisocoria undergo surgical evacuation as soon as possible.
Methods t
There are insufficient data to support one surgical treatment method. However, craniotomy provides a more complete evacuation of the hematoma.
Acute subdural hematomas (SDH) occur in about 11% of patients with TBI regardless the severity of TBI, and in the range of 12 to 29% in patients suffering from severe TBI. Acute SDH most frequently results from tearing of bridging veins, but can be arterial in origin. The average age of patients sustaining acute SDH is greater than that of patients with EDH. Indications for Surgery t
An acute subdural hematoma (SDH) with a thickness greater than 10 mm or a midline shift greater than 5 mm on computed tomographic (CT) scan should be surgically evacuated, regardless of the patient’s Glasgow Coma Scale (GCS) score.
t
All patients with acute SDH in coma (GCS score less than 9) should undergo intracranial pressure (ICP) monitoring.
t
A comatose patient (GCS score less than 9) with an SDH less than 10mm thick and a midline shift less than 5 mm should undergo surgical evacuation of the lesion if the GCS score decreased between the time of injury and hospital admission by 2 or more points on the GCS and/or the patient presents with asymmetric or fixed and dilated pupils and/or the ICP exceeds 20 mm Hg.
Timing t
In patients with acute SDH and indications for surgery, surgical evacuation should be performed as soon as possible. 179
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Methods t
If surgical evacuation of an acute SDH in a comatose patient (GCS < 9) is indicated, it should be performed using a craniotomy with or without bone flap removal and duraplasty.
Traumatic parenchimal lesions (TPL) occur in about 8,2% of mpatients with TBI and represent up to 20% of posttraumatic intracranial mass lesions treated surgically. Traumatic parenchimal mass lesions amenable to surgery comprehend intracerebral haematomas (ICH), delayed traumatic ICH and contusions. The predilection areas for ICHs and/or contusions are predominantly the inferior frontal and the temporal lobes, however, can be more often diffuse. The amount of blood in a lesion denominates the type of lesion – if blood accounts for at least 2/3 of a lesion it is classified a haematoma in contrast to cerebral contusions (2). Indications for Surgery t
Patients with parenchymal mass lesions and signs of progressive neurological deterioration referable to the lesion, medically refractory intracranial hypertension, or signs of mass effect on computed tomographic (CT) scan should be treated operatively.
t
Patients with Glasgow Coma Scale (GCS) scores of 6 to 8 with frontal or temporal contusions greater than 20 cm3 in volume with midline shift of at least 5 mm and/or cisternal compression on CT scan, and patients with any lesion greater than 50 cm3 in volume should be treated operatively.
t
Patients with parenchymal mass lesions who do not show evidence for neurological compromise, have controlled intracranial pressure (ICP), and no significant signs of mass effect on CT scan may be managed nonoperatively with intensive monitoring and serial imaging.
Timing and Methods t
Craniotomy with evacuation of mass lesion is recommended for those patients with focal lesions and the surgical indications listed above, under Indications.
t
Bifrontal decompressive craniectomy within 48 hours of injury is a treatment option for patients with diffuse, medically refractory posttraumatic cerebral edema and resultant intracranial hypertension.
t
Decompressive procedures, including subtemporal decompression, temporal lobectomy, and hemispheric decompressive craniectomy, are treatment options for patients with refractory intracranial hypertension and diffuse parenchymal injury with clinical and radiographic evidence for impending transtentorial herniation.
Posterior fossa mass lesions represent a specific issue due to the characteristic anatomical relationships and smaller volume of the infratentorial versus the supratentorial space, therefore having its’ own rigorous indications for surgical management. 180
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Indications for Surgery t
Patients with mass effect on computed tomographic (CT) scan or with neurological dysfunction or deterioration referable to the lesion should undergo operative intervention. Mass effect on CT scan is defined as distortion, dislocation, or obliteration of the fourth ventricle; compression or loss of visualization of the basal cisterns, or the presence of obstructive hydrocephalus.
t
Patients with lesions and no significant mass effect on CT scan and without signs of neurological dysfunction may be managed by close observation and serial imaging.
Timing t
In patients with indications for surgical intervention, evacuation should be performed as soon as possible because these patients can deteriorate rapidly, thus, worsening their prognosis.
Methods t
Suboccipital craniectomy is the predominant method reported for evacuation of posterior fossa mass lesions, and is therefore recommended.
Post-traumatic Mass Volume Measurement in Traumatic Brain Injury Patients 1.
Direct volumetric measurement with imaging software using a modern computer tomographic CT scanner is the gold standard.
2.
The ellipsoid method is based on the concept that the volume of an ellipsoid is approximately one-half of the volume of the parallelepiped into which it is placed. By measuring three diameters of a given lesion a parallelepiped is constructed, and its volume, divided in half, is close to the actual volume of the lesion. The ABC method (3) for the measurement of intracerebral hemorrhages is based on the concept of measuring the volume of an ellipsoid. The formula for an ellipsoid is:Ve = 4/3 (A/2) (B/2) (C/2)where A, B, and C are the three diameters.For = 3, the formula becomes Ve = ABC/2
The volume of an intracerebral hemorrhage can be approximated by following the steps listed below: t
Identify the CT slice with the largest area of hemorrhage (Slice 1)
t
A: measure the largest diameter, A.
t
B: measure the largest diameter 90° to A on the same slice, B.
t
C: count the number of 10-mm slices.
t
Compare each slice with slice 1.
t
If the hemorrhage is greater than 75% compared with slice 1, count the slice as 1. 181
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t
If the hemorrhage is 25 to 75%, count the slice as 0.5.
t
If the hemorrhage less than 25%, do not count the slice.
t
Add up the total C.
Future Questions and Directions The imporance of adherence to guidelines resulting in marked improvement in treatment of patients suffering from TBI has been recognised and documented, also the need of statifying different Levels of Trauma centers (4,5). It is of utmost importance to be aware of the impact neurosurgeons can have on the care of patients suffering TBI. The amount of aggressiveness and rapidity provided for the treatment of intracranial haematomas determines the outcome of the patient in an enormous amount, and cannot be overemphasized (1). Key References 1.
Bullock MR, Chesnut R, Ghajar J, Hartl R, Newell DW, Srevadei F, Walters BC, Wilberger JE: Guidelines for the surgical management of traumatic brain injury. Neurosurgery 58, Suppl to March: S2-1 – S2-61.
2.
Zwienenberg-Lee M, Muizelaar JP: Clinical pathophysiology of traumatic brain injury. In: Winn HR (ed): Youmans neurological surgery, 5th edition, Saunders Philadelphia 2004, Vol4, pp 5039-5064.
3.
Kothari RU, Brott T, Broderick JP, Barsan WG, Sauerbeck LR, Zuccarello M, Khoury J: The ABCs of measuring intracerebral haemorrhage volumes. Stroke 27: 1304-1305, 1996.
4.
Hesdorffer DC, Ghajar J: Marked improvement in adherence to traumatic brain injury guidelines in United States Trauma Centers. J Trauma, 2007; 63:841-848.
5.
Vuki M, Negoveti L, Kova D, Ghajar J, Glavi Ž, Gop evi Ž: The effect of implementation of guidelines for the management of severe head injury on patient treatment and outcome. Acta neurochir 1999; 141:1203-8.
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MANAGEMENT / MONITORING IN THE ICU Claudius Thomé Objective Treatment of patients with brain injury due to trauma, intracranial hemorrhage or other causes generally involves neurosurgical intensive care management. An overview should be given on the available management strategies particularly for intracranial hypertension and on the monitoring options both for the cranial compartment but also for potential extracranial organ dysfunction. Modern Literature Review Cardiovascular monitoring is routinely performed online to assess mean arterial pressure, oxygen saturation and other parameters, which can be further supplemented by an extended hemodynamic monitoring (e.g. PICCO®) in selected patients to assess and optimize cardiopulmonary parameters. ICP monitoring is recommended and used to assess cerebral perfusion pressure (CPP = MAP – ICP). For traumatic brain injury a CPP of 60mmHg is considered optimal, but individualized CPP goals can be necessary for other patient groups like subarachnoid hemorrhage. ICP measurement is achieved via external ventricular drains or intraparenchymal pressure probes. Brain edema, space-occupying lesions or CSF obstruction can cause intracranial hypertension after traumatic brain injury or intracranial hemorrhage. The pressure-volume relationship is exponential in nature: there is spatial compensation by outflow of CSF in the early stages followed by a reduction of intracranial blood volume; once the compensatory mechanisms are exhausted the intracranial compliance curve exhibits a steep rise, i.e. a minimal increase in volume causes a dramatic rise in ICP. This rapidly leads to life-threatening cerebral herniation syndromes, first subfalcine, second transtentorial and last transforaminal through the foramen magnum. The entailing hypoperfusion causes neuronal death due to insufficient energy supply and within short periods of time irreversible brain damage. ICP management thus aims at maintaining a normal or only mildly elevated ICP of < 20 mmHg in an attempt to absolutely avoid decompensation of intracranial hypertension. Treatment algorithms encompass different stages of therapeutic intensity with an increasing risk-benefit-ratio: General maneuvers:
Analgosedation Head elevation (up to 30°) Avoidance of jugular venous outflow obstruction Normothermia, Normocapnia CSF drainage via external ventricular drain
1st tier therapies:
Mannitol 20% Hypertonic saline
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Moderate hyperventilation (down to 32mmHg) 2nd tier therapies:
Barbiturates (burst suppression EEG) Decompressive craniectomy Mild hypothermia
Extended neuromonitoring has been implemented in specialized centers including brain tissue oxygenation, microdialysis, cerebral blood flow, electroencephalography and brain temperature. However, no consensus exists concerning the choice of monitoring parameters in individual patients and the location of intraparenchymal probes in relation to parenchymal lesions. Recent Clinical and Research Developments Very recently, a randomized clinical trial did not show superiority of an ICP-guided management in comparison to a management guided by clinical and imaging data after severe traumatic brain injury. Nevertheless, ICP monitoring constitutes the mainstay of assessing the intracranial “black box” in unconscious patients. CPP-guided treatment has been strengthened in recent years, while a somewhat lower optimal CPP than previously assumed has been identified at 60mmHg. The importance of autoregulation has been realized and there is increasing knowledge on the complexity of potential autoregulatory disturbances as well as their importance for prognosis. The neurosurgical community has focused on extended neuromonitoring techniques in an attempt to individualize patient treatment, as, for example, traumatic brain injury may require different strategies than subarachnoid hemorrhage. Particularly brain tissue oxygenation can be reliably measured and used to guide therapies like potential mild hyperventilation. Transcranial Doppler sonography remains an important tool to raise suspicion of cerebral vasospasm after subarachnoid hemorrhage due to its high sensitivity, but its very low specificity. Therefore, it is now considered a poor parameter to assess cerebral perfusion quantitatively, which has led to the introduction of cerebral blood flow monitoring with other devices, e.g. thermal diffusion microprobes. Although still cumbersome in every-day practice and thus not as reliable as brain tissue oxygen monitoring, these methods have been shown to accurately detect cerebral hypoperfusion. Near infrared-spectroscopy is continuously evaluated with variable results. Perfusion imaging using CT or MRI is increasingly used with semiquantitative, but reliable values. Nevertheless, these techniques are limited by their single-shot analysis. The same is true for metabolic imaging like PET. Cerebral microdialysis on the contrary has proven its online feasibility for routine metabolic parameters like glucose and the lactatepyruvate ratio, but is restricted to specialized centers. It is now an established tool for neurochemical research as various analytes including neurotransmitters and inflammatory biomarkers can be investigated. Although all these methods have broadened our knowledge of the pathophysiology of secondary brain injury, there still is no real evidence that they have any impact on patient outcome. For neurosurgeons, the main problem in neurointensive care is therapy-resistant 184
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intracranial hypertension. An incremental treatment algorithm is usually applied as outlined above, which has recently been augmented by controlled lumbar drainage in selected cases of increased ICP. Overall, howver, maybe even more important is pulmonary failure mostly due to ventilator-associated pneumonia. Acute lung injury is a common complication after traumatic brain injury and clearly associated with morbidity and mortality. Thus, it is of upmost importance to (1) prevent lung collapse and/or consolidation, (2) prevent lung infection and (3) accelerate weaning from mechanical ventilation. Ventilation with “best” PEEP, recruitment maneuvers, careful fluid balance and early tracheostomy are some of the currently used methods to achieve these goals. The problem of abdominal hypertension has also recently received more attention in neurocritical care, as it directly influences ICP and impacts outcome. Prevention of intraabdominal hypertension by e.g. early enteral nutrition and careful fluid balance as well as monitoring of intracranial pressure and adequate medical or endoscopic treatment of intraabdominal hypertension or even compartment present a mainstay of contemporary ICU management. Future Questions and Direction The neurosurgical interest will continue to focus on extended neuromonitoring techniques, their integration in routine patient management and their relevance for parameter-guided individualized patient treatment as well as for outcome. Multimodal monitoring seems to slowly evolve to standard care with all its limitations. Online bioinformatics have the potential to rapidly assess parameter constellations and provide useful additional information on , for example, autoregulation. Recent advances in near-infrared spectroscopy in anesthesiology could well be introduced more and more in intensive care medicine. Intensivists will have an important impact on neurocritical care, as extracranial organ failure, sepsis, etc. dramatically influence outcome and improvement of respective care is essential. Conclusion Recent advances in multimodal neuromonitoring have improved our understanding of the pathophysiology of brain injury. As advanced monitoring techniques are increasingly used to guide ICU management, individualized patient management has become possible, although its impact on outcome is unclear. Management of extracerebral organ dysfunction is crucial and recent improvements have been implemented in standard ICU care. Take Home Messages 1.
Treatment of intracranial hypertension is crucial after brain injury and follows an incremental treatment algorithm to sustain an adequate CPP.
2.
Advanced neuromonitoring techniques can increase your knowledge of the patients current situation and allow individualized patient management.
3.
Extracranial organ dysfunction needs to be assessed and treated early and aggressively.
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Key References Brain Trauma Guidelines, J Neurotrauma, Volume 24, Supplement 1, 2007 Chesnut et al., N Engl J Med 367: 2471-2481, 2012 Dagal & Lam, Curr Opin Anesthesiol 24: 131-137, 2011 De Laet et al., Acta Clinica Belg 62: 89-97, 2007 Farahvar et al., Curr Opin Anesthesiol 24: 209-213, 2011 Goodman & Robertson, Curr Opin Crit Care 15: 110-117, 2009 Malbrain et al., Intensive Care Med 30: 822-829, 2004 Pellosi et al., Curr Opin Crit Care 11: 37-42, 2005 Schirmer-Mikalsen et al., Acta Anesthesiol Scand 51: 1194-1201, 2007 Stuart et al., Neurocrit Care 12: 188-198, 2010 Valadka & Robertson, Neurosurgery 61: 203-221, 2007
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MANAGEMENT OF CRANIOFACIAL TRAUMA AND CSF LEAKS Pr Pierre-Hugues Roche Department of Neurosurgery, North Hospital, University of Marseille, France
[email protected] Introduction Craniofacial traumas (CFT) associate concomitant traumatic injuries of the face and skull, particularly the anterior cranial base. They may have potential lethal consequences due to severe haemorrhage or brain injuries. They may also have a major functional impact on vision, olfaction, mastication, and may lead to facial deformities and aesthetic problems. Motor vehicle accidents account for 50% of CFT, assaults for 30% and sporting injuries for 20%. Falls are highly represented in children and elderly patients. CFT are managed by multiple specialities where the neurosurgeon plays a key role, particularly in case of CSF leaks and associated brain injuries. Clinical Presentation There is a need for a careful investigation about the circumstances of the trauma to understand the mechanism and the topography of the lesions. Clinical manifestations depend on the delay of examination and location of the injury. When the patient is seen very early the CFT are responsible of minimal oedema that will increase in the few hours after the trauma and will hamper the clinical checking. Inspection seeks for facial oedema, ecchymosis, deformity of the nose, telecanthus, displacement of the lateral or medial canthus, displacement of the ocular globe. Particular attention will be given to identify liquid exteriorisation namely epistaxis, rhinorrhea, otorrhea. Palpation of the face will search bony irregularities, abnormal motion, crepitus, malocclusion. Cranial nerve function will be systematically assessed and reported on the initial chart. The most frequent deficits encompass anesthesia of the cheek, diplopia, blindness, anesthesia of the forehead, and anosmia. General and vital parameters are assessed at the first examination and spine is also checked for potential concomitant trauma. Initial Radiological Exploration This radiological workup provides the classification of the injuries and gives orientation to the treatment & prognosis. Standard plain radiographs are still done in routine in some centers but the highresolution CT Scan (HRCT) is nowadays the mainstay of the radiological workup. With the use of axial and coronal slides and bone algorithm, the sensitivity of HRCT to detect the skull base defect is above 90% (5). The CT-scan will systematically comprise an exam of the brain and the cranium from the vertex to the foramen magnum. Indications for brain CT are particularly justified in cases of upper face trauma, CSF leaks, neurological signs, penetrating injury. Indications of a head & neck CT-angio are: Skull base fracture – Lefort II-III fractures
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– Unexplained GCS worsening. In case of polytraumatisms or comatous state, there is a need to perform a total body scan with bone windows reconstructions of the spine Classification of Craniofacial Fractures CFT are usually the consequence of a direct impact. Biomechanically speaking, three buttresses allow the face to absorb forces from the impact: a nasomaxillary (medial) buttress, a zygomaticomaxillary (lateral) buttress and a pterygomaxillary buttress (posterior) are described. The fracture is a consequence of an impact perpendicularly orientated to the buttress. The numerous classifications that have been proposed reflect the difficulty to systematize the fractures. Mandible and nasal bone are the most commonly fractured areas but are not under the scope of this chapter because they usually do not involve the neurosurgeon. Roughly we can classify the CFT as lateral and central fractures with several subtypes in this latter group. 1. Lateral fractures comprise t
zygomatic & zygomaticomaxillary (tripod) fractures
t
Orbital fractures:
Involvement of the walls: the typical blow-out fracture involves the inferior wall and damages the infraorbital canal and inferior rectus muscle (muscular entrapment). Fractures of the medial wall affect the medial canthal ligament and the lacrimal duct & sac. Fractures of the orbital rim involve and expose to cosmetic trouble while the fractures of the apex are responsible of multiple oculomotor nerve deficits. Involvement of the optic canal put the optic nerve at high risk of deficit which is usually a unilateral blindness. 2. Central fractures Maxillary fractures Maxillary is capable of resisting considerable violence. Transverses fractures are generated from the weakest areas of midfacial complex when assaulted from a frontal direction at different levels. René Le Fort described a relevant classification in 1901. Le Fort I: Palate-facial disjunction (Transverse maxillary, above the level of the teeth), Le Fort II: Pyramidal disjunction (Pyramidal fractures at the level of the nasal bone, the most common subtype), Le Fort III: Craniofacial dysjunction fractures, at orbital level, the less common. Naso-orbital-Ethmoidal fractures. The nasal bones are forced back into the interorbital space Supraorbital & frontal sinus fractures: Represent 5-12% of craniofacial fractures. Are isolated or associated with naso188
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orbital fractures. There is a frequent association between frontal sinus fracture and naso-orbito-ethmoid fractures. They are associated to a high rate of intracranial injuries: Pneumocephalus, cerebral contusion, dural tear, CSF leak, epidural hematoma.
3. Anterior cranial base fractures. The Classification developed by Sakas & col. (8) describes: t
Type I: cribriform fracture
t
Type II: frontoethmoidal fracture ;
t
Type III: lateral frontal fracture (through the lateral frontal sinus). The brain overlies the area of the bone disruption.
t
Type IV complex fracture. The high risk group included the large type I and type II fractures associated with rhinorrhea exceeding 8 days (infection rate 100%)
Complications Of CFT 1. Cerebrospinal fluid (CSF) leaks Postraumatic CSF leaks account for nearly 90% of all cases of CSF leaks. These leaks occur in 1-3% of all closed head injuries and in 10% to 30% of patients with skull base fractures. There are considerable variations in respective incidences of otorrheas and rhinorrheas. Eighty percent of posttraumatic CSF leaks occur within the first 48 hours after injury. Defect in the cribriform plate and anterior ethmoid sinus represent 75% of all cases of traumatic CSF fistulas. Location (cribriform plate – frontoethmoidal fractures clothe to the midline) and size (more than 1 cm) of the fracture are predisposing factors. Up to two third of
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traumatic CSF leaks close spontaneously but large Sakas type I and type II fractures are significantly correlated to long-lasting duration of the CSF leak with a very high risk of meningitis. Risk of meningitis is comprised between 7 & 30% of patients with CSF leak and Pneumococcus is responsible of more than half of these meningitis. Detection The first step of detection is to confirm that the liquid is actually CSF. High falsepositive rate of glucose level of the draining fluid is well known. The ß2-transferrin is a protein highly specific for human CSF and a positive ß2-transferrin result confirms an active CSF leak (Reisinger 1989). The second step is to target accurately the area where the defect is. Thin-section multidetector CT with reformations (axial and coronal images, bone algorithm) may be all that is necessary for appropriate evaluation in most cases. Bony defects are identified with a reported sensitivity as high as 92% and specificity of 100% (5). However, multiple osseous defects and adjacent opacified sinuses may hamper the identification of the causative defect. In these special circumstances, CT cisternography may be necessary or in cases where ß2-transferrin is positive in the liquid while the CT does not show the defect. CT cisternography is restricted to actively leaking patients. The MR cisternography is a non-invasive and nonionizing technique which is able to localize the actual site of a fistulous tract with a 87% sensitivity and accuracies ranging from 78% to 100% (11). However the major limitation of MR imaging is the lack of osseous detail and decreased ability to visualize subtle fractures or osseous defects. If this extensive workup is still negative, endoscopical examination at the side of prior trauma is then undertaken. The use of fluorescein cisternography and evaluation for the evidence of pulsatile pooling CSF or fluorescein may be recommended during endoscopy (6). Treatment Once a diagnosis of CSF rhinorrhea has been confirmed, conservative treatment should be instigated in first since 68 to 85% of CSF leaks stop spontaneously within 1 week after trauma (1). In case of failure, lumbar drainage is inserted for 7 to 10 days with a recommended drainage rate of 100-150 ml / day(10). In case of failure, surgery is proposed; Dandy (2) described the first case of intracranial repair, by the way of a bifrontal craniotomy. The risks of intracranial procedures are anosmia, epilepsy, and a 20% rate of failure. So far we do not have guidelines about the technique but there is a trend to propose upfront endoscopic repair for small defects (6). Complete exposure of the defect, appropriate selection of a fitting graft as well as accurate placement & stabilization of the graft are essential to get a success rate close to 90%.
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2. Vascular injuries These injuries are mainly dissections of the internal carotid artery or vertebral artery, carotidocavernous fistula (less than 0.2% of craniofacial trauma), thrombosis and pseudoaneurysms. In a series of 71 patients in whom a skull base fracture was diagnosed, a neurovascular injury was found in 6 cases (8.5%) with a statistical trend with clival and sella turcica-sphenoid sinus fractures (3). Others studies have reported a rate of blunt carotid and vertebral artery injury in up to 1.6% of patients admitted for trauma. CT angiography is the main diagnostic technique to detect vascular injury. In a recent series of 100 head and neck injuries including 35 skull base fractures, 24 maxillofacial and 11 cervical spine fractures, a CTA protocol was prospectively conducted and depicted 6 cases of vascular injury (4) The need for systematic CTA is justified by the lack of clinical manifestation at the early stage and by a reported stroke rate of up to 60% in cases of traumatic vascular injury. Treatment options are an open surgical repair, endovascular techniques, anticoagulation therapy. 3. Cranial nerve injuries 4. Other complications t
Cosmetic disturbances: facial deformity, enophtalmos, eyelid problems (blepharoptosis)
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t
Functional problems on masticatio : Ankylosis of the coronoid process
t
Mucocele & pyocele are delayed complications due to an opening of the frontal sinus with secondary disturbance of the sinus ventilation.
t
Lacrimal system injuries
t
Nasal airway obstruction due to deformation and synechiae between the septum and turbinates
t
Associated injuries
Management I. Emergency or initial care 1.
Preserve the Airways. The first consideration is the assurance of a patent airway. An altered level of consciousness is the most common cause of upper airway obstruction. Existence & identification of obstruction is needed (Manually clear of fractured teeth, blood clots, dentures – Endotracheal intubation & packing of oronasal airway. In cases of severe injuries with an airway compromise due to a hematoma, the tracheostomy may be the safest and quickest means of establishing an airway.
2.
Blood. Control of haemorrhage from wounds of the face, scalp and mouth. If the cribriform plate is supposed to be injured, the nasal cavities should not be packed. Prevent or control shock. Prevent and compensate massive blood loss. Monitor vital signs closely
3.
Careful neurological examination. Consider for associated injuries (chest, abdomen, cervical spine, extremity fractures) – Cervical spine stabilization
II. Early care (emergency room) Treatment of life-threatening injuries who have treatment precedence over craniofacial Fractures Exploration (Plain films, CT) Neurosurgical emergency procedures are: Open craniocerebral injury / Tension pneumocephalus / intracranial hematomas Achieve hemostasis – antibiotics – discuss for operative room or emergency room management III. Definitive care Care of soft tissue injuries (contusions, abrasions, lacerations) Care of associated soft tissue injuries (lacrymal system, parotid duct, facial nerve). Orbits evaluated. Principles of the surgical approaches: 192
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Open wounds, large depressed skull base fractures and skull base fractures accompanied by complications such as intracranial hemorrhage or tension pneumocephalus are considered indications for early surgery. Timing and indication for cranial nerve decompressions are individually discussed Treatment of Lefort II and III. As early as the general condition of the patient allow. Exposure and visualization of all fractures. Teeth and occlusion are the key to reconstruction and provide the foundation upon which other facial structures are built. Establishment of the correct occlusion, correct reconstruction of the outer facial frame from proper facial dimensions, correct position for nasoethmoidal complex. Reestablishment of the correct intercanthal distance. Frontal sinus fracture: t
Anterior wall fracture & cosmetic goal – restoration of the preoperative facial aesthetics
t
Posterior wall: the dural integrity must be assured. Cranialization of the sinus means complete removal of the mucosa and the remaining wall and closure of the frontonasal duct.
Conclusions Proper management of craniofacial trauma requires a close co-operation between maxillo-facial, ENT surgeons, ophthalmologists and neurosurgeons. There is a need for a careful clinical and radiological workup where the high resolution CT-scan is the key exam. Complications are mainly represented by occurrence of CSF leakage with posttraumatic meningitis risk. The conservative management should be considered at the initial step. In case of persistence or recurrence of the leak, the exact identification of the defect responsible of the leak via HRCT, CT cisternography or MR cisternography is needed before discussing the less invasive surgical repair with a priority to endoscopic techniques. References 1.
Bell RB, Dierks EJ, Homer L, Potter BE. Management of cerebrospinal fluid leak associated with craniomaxillofacial trauma. J Oral Maxillofac Surg. 2004 Jun;62(6):676-84.
2.
Dandy WD. Pneumocephalus (intracranial pneumocele or aerocele). Arch Surg 1926 ; 12: 949-982
3.
Feiz-Erfan I, Horn EM, Theodore N, Zabramski JM, Klopfenstein JD, Lekovic GP, Albuquerque FC, Partovi S, Goslar PW, Petersen SR. Incidence and pattern of direct blunt neurovascular injury associated with trauma to the skull base. J Neurosurg. 2007 Aug;107(2):364-9.
4.
Langner S, Fleck S, Kirsch M, Petrik M, Hosten N. Whole-body CT trauma imaging with adapted and optimized CT angiography of the craniocervical vessels: do we need an extra screening examination? AJNR Am J Neuroradiol.
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2008 Nov;29(10):1902-7 5.
Lloyd KM, DelGaudio JM, Hudgins PA. Imaging of skull base cerebrospinal fluid leaks in adults. Radiology. 2008 Sep;248(3):725-36.
6.
Maatox DE, Kennedy DW. Endoscopic management of cerebrospinal fluid leaks and cephaloceles. Laryngoscope 1990, 100: 857-862
7.
Reisinger PW, Hochstrasser K. The diagnosis of CSF fistulae on the basis of detection of beta 2-transferrin by polyacrylamide gel electrophoresis and immunoblotting. J Clin Chem Clin Biochem. 1989 Mar;27(3):169-72.
8.
Sakas DE, Beale DJ, Ameen AA, Whitwell HL, Whittaker KW, Krebs AJ, Abbasi KH, Dias PS. Compound anterior cranial base fractures: classification using computerized tomography scanning as a basis for selection of patients for dural repair. J Neurosurg. 1998 Mar;88(3):471-7.
9.
Villalobos T, Arango C, Kubilis P, Rathore M.Antibiotic prophylaxis after basilar skull fractures: a meta-analysis. Clin Infect Dis. 1998 Aug;27(2):3649.
10.
Yilmazlar S, Arslan E, Kocaeli H, Dogan S, Aksoy K, Korfali E, Doygun M. Cerebrospinal fluid leakage complicating skull base fractures: analysis of 81 cases. Neurosurg Rev. 2006 Jan;29(1):64-71
11.
Zapalac JS, Marple BF, Schwade ND. Skull base cerebrospinal fluid fistulas: a comprehensive diagnostic algorithm. Otolaryngol Head Neck Surg. 2002 Jun;126(6):669-76.
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PENETRATING BRAIN INJURY Sandor Szabo, M.D., Ph.D. Department of Neurosurgery, Medical School of University Debrecen, Hungary Objective The aim of this work is to summarize the pathogenesis of injury mechanisms, the clinical features, the diagnostics and the management of penetrating brain injury. Modern Literature Review - Recent Clinical and Research Developments General Considerations 50% of all trauma deaths are secondary to traumatic brain injury (TBI). 35 % of these fatal cases are related to gunshot wounds to the head. Previous efforts to establish treatment protocols for head injury concentrated on blunt trauma and did not address the management of penetrating brain injury (PBI). Majority of references in PBI literature provide evidences type class III, thus available data are not sufficient to support treatment standards. Most of the evidences provide only recommendations and basically one should follow the Guidelines for the Management of Severe Traumatic Brain Injury. Outcome prediction also requires further investigations, prognosis literature must not be used to determine treatment. The most comprehensive review of the literature in PBI was published in The Journal of Trauma in 2001. Classification PBIs are divided into the following categories: penetrating injury, i.e. the foreign body penetrates the skull and dura, but does not leave the cranium, remaining embedded within the intracranial cavity, perforating injury, i.e. through and through injury with an entry and an exit wound, and tangential injury, i.e. the foreign object glances off the skull, mostly resulting impressed skull fracture. Incidence of the different types varies mainly depending on whether it was studied in militarian or civilian circumstances. However, literature agrees that perforating injuries associated with the highest mortality. It is important to differentiate PBIs according to the cause of injury, missile or nonmissile type, the latter is mentioned, as stab wounds. Missile injury Projectiles can cause primary injury to brain parenchyma by different mechanisms, direct laceration and crushing with coagulative necrosis, permanent and temporary cavitation, and shock waves. As a projectile penetrates the head, the destroyed tissue is compressed into the walls of the missile tract. This creates both a permanent cavity that is 3-4 times
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larger than the missile diameter and a pulsating temporary cavity that expands outward. The temporary cavity can be as much as 30 times larger than the missile diameter and causes injury to structures a considerable distance from the actual missile tract. The pathological consequences depend on the properties of the weapon: the energy of the impact, the location and characteristics of the intracranial trajectory. Ballistics, shape of projectile, the caliber, the fragmentation potential are all important factors to determine primary impact. Similarly to the nonpenetrating TBI, following the primary impact, secondary injuries may develop involving all those biochemical cascade and pathophysiological processes which adversely affect the ability of the brain to recover from the primary insult, and propagate further cell damage. Non-missile injury - stab wounds Non missile injuries represent a smaller fraction of penetrating head injuries. They are typically caused by a weapon with a small impact area with low velocity. Unlike missile injuries, there is no concentric zone of coagulative necrosis, there is no additional damage of shock waves and cavitation. Unlike in nonpenetrating TBI, no diffuse shearing injury to the brain occurs. Cerebral damage is largely restricted to the wound tract. Most commonly the injuries occur around the thin bones of the skull, especially the orbital surfaces and the squamous portion of the temporal bone are vulnerable. Patients in whom the penetrating object is left in place at the insult have a significantly lower mortality than those in whom the objects are inserted and then removed. As the causes of stab wounds vary on a large and often bizarre scale, surgery, as well, often requires individualized, inventive and combined operative planning. Investigations in PBI CT scanning is the first radiologic test of choice to evaluate the severity of PBI. Beside the standard views, coronal sections can depict skull base and high convexity injuries. If CT is available plain X ray is not essential. Angiography is recommended when vascular injury can be suspected, i.e. trajectory passes close to Sylvian fissure, near to the clinoids, cavernous sinus, large venous sinuses. Extreme subarachnoid bleeding, development of delayed hematoma may refer to vascular injury. Because in most cases PBI result from metal foreign body, MRI is not generally recommended in the acute management. However, in case of injuries caused by penetrating wooden or other non-magnetic objects MRI may have important role in neuroimaging. Intracranial pressure monitoring Intracranial hypertension (ICH) is a major complication following PBI. Failure of 196
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cerebral pressure autoregulation is the most common source of ICP increase. Lacking exact studies in the field one should follow the guidelines for TBI in the management of ICH. Hyperventilation, /keeping in mind the concern about induced hypoperfusion/, mannitol, cerebrospinal fluid drainage, high dose barbiturate, decompressive craniectomy should be taken into consideration to control ICH. ICP monitoring has the advantage to follow patients with depressed level of consciousness. Surgical management Small entrance wounds without devitalization and significant intracranial damage require local wound care and simple closure. More extensive injury with severely destroyed, nonviable scalp, bone, dura, brain tissue claims more extensive debridement, followed by grafting to secure watertight closure. To remove bone fragments either craniotomy or craniectomy can be applied. If there is no significant mass effect, debridement of the bullet track or removal of deep bone fragments, foreign objects is not recommended. Presently, there is a clear tendency in the literature toward minimizing the degree of debridement. Open-air sinus should be repaired with watertight closure of the dura. Autologous material is preferable for grafting. Effective exenteration and adequate cranialization of the violated sinus are recommended. Indication for surgery beyond wound care is removal of large hematomas with mass effect. ICP monitoring supports decision. Retrieval of any foreign object may have forensic purpose. Timing of surgery: wound care, debridement, and closure should be performed as soon as possible to prevent contamination. Intracranial surgery should be performed also promptly if it is indicated, otherwise ICP monitoring will determine. Decompressive craniectomy Very limited information is available in PBI literature, recent data report a meaningful survival among those patients who underwent early craniectomy under military condition. Decompressive craniectomy should be taken into account to control severe brain swelling and intracranial hypertension, one should follow the guidelines for nonpenetrating TBI patients. Vascular complications Aneurysm Incidence of traumatic intracranial aneurysm (TICA) in PBI is uncertain, it is estimated between 3-6 % of the cases. Angiography is the diagnostic tool to depict these lesions. Delayed appearance of a new aneurysm weeks after the trauma may occur. Both the contact force of a projectile and the shearing forces of the pulsating temporary cavity may result transection of the vessel wall leading to aneurysm 197
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formation. Peripheral branches of middle and anterior cerebral arteries are more vulnerable. High potential risk of bleeding necessitates exclusion. These aneurysms are primarily false aneurysms. Lacking true vessel wall layers the clipping is hazardous, or more often impossible, requiring rather trapping between clips on the parent artery. Endovascular treatment of these false aneurysms has advantage over surgical intervention. Subarachnoid hemorrhage and cerebral vasospasm Incidence of SAH in PBI is extremely high, ranges from 30 to 80 % of the cases. Presence and severity of SAH tends to correlate with mortality. Though the incidence of vasospasm is similarly high, there is no difference in outcome related to vasospasm. There is no proved benefit documented in the literature from treatment of vasospasm. CSF leaks CSF leaks may occur at the sites of injury, or at a remote site because of the skull fracture. There is a significant correlation between the presence of leakage and developing infection. Even the retained bone fragments or foreign objects become infected secondarily as a consequence of persistent CSF leak. Thus surgery should aim vigorous debridement, complete excision of devitalized tissue, watertight closure using grafting if necessary, and wound closure without tension. Rhinorrhea, otorrhea refers to CSF leaks caused by fractures and dural rents far from the entry or exit zones. There is a real chance of spontaneous obliteration, CSF diversion is an optional consideration. Surgical technique is not well documented, exact identification of leak origin can be troublesome, nevertheless mighty close of dural tears by grafting, tissue glue is mandatory. Antibiotic prophylaxis The nature of injury means high risk for intracranial infection. Cultures most often proved Staphylococcus, Acinetobacter and Streptococcus infections, but a wide variety of organisms may act as infectious agent. This diversity supports the prophylactic use of broad spectrum antibiotics. Majority of authors use cephalosporin. Epilepsy prophylaxis Incidence of epilepsy in PBI varies between 30 and 50 %, contrary to the lower figure of 4 to 42 % experienced in nonpenetrating TBI. Epilepsy after head injury is classified into two groups, early and late. Term of early is applied for seizures developing within the first week, but this criteria should not be regarded absolute. 4 to 10 % of seizures occur within the first week, vast majority /80%/ develop during the first two years. Risks markedly decreases with time, 50 % of patients with epilepsy stop having seizures on the long run. Prophylactic anticonvulsive therapy does not prevent the development of late 198
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epilepsy. Present guideline suggests that antiseizure therapy is recommended to prevent early seizure in the acute phase of hospitalization, however prophylactic treatment beyond the first/second week is not recommended. Prognostics Mortality in series including patients who are dead at the scene or on arrival reaches 93%. The most predictive for poor outcome is GCS score, notably postresuscitation GCS score. Bihemispheric injury associated with intraventricular hemorrhage, severe SAH, transventricular injury, track crossing the midline, multilobar injury, basal cisterns effacement, ICP maintained below 20 mmHg also tend to show significant correlation with mortality and morbidity. A survey found that only 23% of neurosurgeons surgically intervene when both pupils are dilated. At the same time another study has reported that 21% of those patients who presented with bilaterally fixed and dilated pupils survived. These figures emphasize that prognostic factors must not be used to determine treatment. Future Questions and Direction Almost all aspects of PBI mentioned above require support by evidences class I-II. Conclusion Most of the evidences provide class III recommendations for the management of PBI. Essentially one should follow the Guidelines for the Management of Severe Traumatic Brain Injury. Majority of PBI result from high energy missile insult with extreme mortality. Postresuscitation GCS score the most predictive for outcome, but none of the prognostic factors can be used to determine therapy. Primary injury involves direct laceration with coagulative necrosis, cavitation and shock waves. In management adequate debridement, watertight CSF control, less aggressive removal of deep foreign objects, complex control of ICH, broad spectrum antibiotic and seizure prophylaxis are the most important issues. Key References, Recommended Reading 1.
Journal of Trauma-Injury Infection & Critical Care, Volume 51 (2) Supplement pgs. S1-S86 August 2001
2.
Guidelines for the management of severe traumatic brain injury. Brain Trauma Foundation, American Association of Neurological Surgeons Joint Section on Neurotrauma and Critical Care, J Neurotrauma 2000; 17: 451– 627.
3.
A national survey of neurosurgical care for penetrating head injury. Kaufman HH, Schwab K, Salazar AM: Surg Neurol 36:370–377, 1991
4.
Military Traumatic Brain and Spinal Column Injury: A 5-Year Study of the 199
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Impact Blast and Other Military Grade Weaponry on the Central Nervous System. Bell, Randy S.; Vo, Alexander H.; Neal, Christopher J.; Tigno, June; Roberts, Ryan; Mossop, Corey; Dunne, James R.; Armonda, Rocco A. Journal of Trauma-Injury Infection & Critical Care. 66(4):S104-S111, April 2009. 5.
Wartime Traumatic Aneurysms: Acute Presentation, Diagnosis, and Multimodal Treatment of 64 Craniocervical Arterial Injuries Bell, Randy S.; Vo, Alexander H.; Roberts, Ryan; Wanebo, John; Armonda, Rocco A.Neurosurgery. 66(1):66-79, January 2010.
6.
Vector Analysis Correlating Bullet Trajectory to Outcome after Civilian Through-and-Through Gunshot Wound to the Head: Using Imaging Cues to Predict Fatal Outcome Kim, K Anthony; Wang, Michael Y.; McNatt, Sean A.; Pinsky, Greg; Liu, Charles Y.; Giannotta, Steven L.; Apuzzo, Michael L.J. Neurosurgery. 57(4):737-747, October 2005.
7.
Management of Severe Traumatic Brain Injury by Decompressive Craniectomy. Münch, Elke; Horn, Peter; Schürer, Ludwig; Piepgras, Axel; Paul, Torsten; Schmiedek, Peter Neurosurgery. 47(2):315-323, August 2000.
8.
A study of a series of wounds involving the brain and its enveloping structures. Harvey Cushing Article first published online: 2 MAR 2006, British Journal of Surgery Volume 5, Issue 20, pages 558–684, 1917
9.
Early decompressive craniectomy for severe penetrating and closed head injury during wartime. Randy S. Bell, Corey M. Moss op, Michael S. Dirks, Frederick L. Stephens, Lisa Mulligan, Robert Ecker, Christopher J. Neal,Anand Kumar, Teodoro Tigno, Rocco A. Armonda, Neurosurg Focus 28 (5): E1, 2010
10.
Interdisciplinary endoscopic assisted surgery of a patient with a complete transorbital intracranial impalement through the dominant hemisphere. Jan-Karl Burkhardt & David Holzmann & Lisa Strobl & Christoph M. Woernle & Martina M. Bosch &Spyros S. Kollias & Robert Reisch. Childs Nerv Syst (2012) 28:951–954
11.
Outcome prediction following penetrating craniocerebral injury in a civilian population: aggressive surgical management in patients with admission Glasgow Coma Scale scores of 6 to 15. Levy M.L.. Neurosurg Focus 8 (1): Article 2, 1999
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LATE COMPLICATIONS OF HEAD INJURIES Panagiotis Selviaridis Professor, AHEPA University Hospital, Thessaloniki, Greece Objective Emerging contemporary data on presentation, characteristics, prevalence and time pattern of late complications of head injuries suggests that delayed problems may be more common and multiplex than previously thought. In order to identify delayed sequelae of head injuries, one ought to define them first. All categories of head trauma are included, regardless of severity. The term complication refers to both surgical and non surgical sequelae. Finally, the definition of late remains in literature somewhat vague, as there is no universal time limit. Modern literature review The incidence of readmissions because of delayed intracranial complications after primarily uncomplicated concussion is generally low. High clinical severity grade and male gender are mentioned as risk factors.(5) The hypothalamic-pituitary structures are vulnerable to damage following TBI and long-term neuroendocrine dysfunction is a potential complication. Anterior pituitary hormone dysfunction may be an important feature of long-term morbidity in survivors of TBI. Pituitary dysfunction, which may be detected months or years after injury, is well recognised as a long-term consequence of TBI in adults. The available paediatric data shows that after both mild and severe TBI, hypopituitarism may occur, with GH and gonadotrophin deficiencies appearing to be most common. (3) Some chronic hormone deficiency occurs in 30 - 40% of selected patients after TBI, more than one deficiency in 10 - 15%, growth hormone in 15 - 20%, gonadal hormones in 15%, and hypothyroidism in 10 - 30%. Chronic adrenal failure and diabetes insipidus are reported over a wide incidence. Prolactin is elevated in 30%. All clinical symptoms respond favorably to replacement therapy.(14) It appears that TBI increases the risk for depression, seizures, psychotic disorders and dementia. Young children are more prone to early seizures, and adolescents and adults, to late posttraumatic seizures.(4) Traumatic brain injury is associated with cognitive, affective, and physical sequelae. Links between trauma and the subsequent onset of premature, psychiatric syndromes and neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease are reported.(9) The most common post concussion symptoms are headache, dizziness, decreased concentration, memory problems, irritability, fatigue, visual disturbances, sensitivity to noise, judgment problems, depression, and anxiety. When this cluster is persistent in nature, it is called the post concussion syndrome.(16) Delayed onset neurological deterioration can be caused by brain oedema and 201
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vasospasm after traumatic brain injury, despite an intervening period of improvement. (10) An emergency decompressive craniectomy may become necessary. Delayed acute subdural hematoma is a relatively neglected entity as opposed to chronic subdural hematoma. The potentially elevated risk among elderly, anticoagulated or anti-aggregated mild traumatic brain injury patients is emphasized in recent literature, even when they present with GCS 15 and normal computed tomographic scans after injury. Perhaps these kind of patients should be admitted for observation.(8) Traumatic delayed epidural hematoma (DEH) can be defined as a hematoma that is insignificant or not present on the initial computerized tomography (CT) scan made after trauma but subsequent CT scan shows sizeable epidural bleeding. DEHs are highly unpredictable and cause diagnostic difficulty. Close observation for signs of clinical deterioration and repeat CT scan are the most important factors for early detection of DEH.(15) Traumatic intracranial aneurysms can occur following blunt or penetrating head trauma and are more common in the pediatric population. They can present in a variety of ways, but are typically associated with an acute episode of delayed intracranial hemorrhage with an average time from initial trauma to aneurysm hemorrhage of approximately 21 days. The mortality rate for patients harboring these aneurysms may be as high as 50%.(11) Delayed glossopharyngeal nerve, vagus nerve, and facial nerve palsies after a head injury are described in literature.(18) Usually a fracture of the petrous part of the temporal bone is responsible. Last but not least, delayed onset hydrocephalus after head injury (from mild to severe and even coma patients) is a well described entity, which needs to be closely followed and offensively treated.(12) Recent clinical and research developments. The most interesting clinical and research developments come from the neuroendocrine and neurobehavioural fields. The post-concussional syndrome is still a topic of research amongst psychiatrists, psychologist and cognitive scientists. Pituitary dysfunction is well recognised after traumatic brain injury (TBI) in adults; however, little except anecdotal evidence was known about this potential complication in childhood and adolescence. Recent analysis highlights few registered cases of TBI-related growth hormone deficiency, suggesting that this may be either an uncommon or an overlooked phenomenon. Given the critical role of anterior pituitary hormones in the regulation of growth and pubertal development in childhood, early detection of hormone abnormalities is vital.(1, 2) Severe TBI associated with basilar skull fracture, hypothalamic edema, prolonged unresponsiveness, hyponatremia, and/or hypotension is associated with a higher occurrence of endocrinopathy. Delayed diagnosis of hypopituitarism is often mistaken for symptoms of residual head injury. Greater awareness of this possible complication of TBI and appropriate testing are encouraged.(14) 202
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Research and the advent of sophisticated imaging have led to progression in the understanding of brain pathophysiology following TBI. Experimental evidence demonstrates links between TBI and the subsequent onset of premature, psychiatric syndromes and neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease.(9) Basal ganglia damage is an important feature in the development of Parkinson’s disease after trauma. Other types of Parkinsonism affect susceptible groups such as career boxers, with dementia pugilistica being caused by repeated blows to the head. Post-traumatic dementia is nowadays diagnosed all the more frequently. Last but not least, the more severe the head injury, the greater risk of developing Alzheimer’s disease. Apolipoprotein E4 carriers play a key role in the pathogenesis after TBI. Risk factors involved in the origin of late posttraumatic seizures in TBI patients and their occurrence, as well as the time of the first late seizures, and influence of these seizures on functional and occupational long-term outcome are a topic for further research. Current research is focusing on epilepsy experimental models and the development of new anti epileptic drugs. Recent developments regarding CSF leaks, their diagnosis and repair include the already well established testing for 2-transferase to detect CSF and the development of sealants. Furthermore, the development of new antibiotics represents a further step to control CNS infections after rhinorrhea or otorrhea. Outflow resistance measuring and technical advances in programmable shunting valves are the main research developments in the management of hydrocephalus in the last decade and consequently in late onset posttraumatic ventricular dilation as well. Finally, redefining CT indications and admission policy is a major discussion. Although the use of computed tomographic scanning in severe head trauma is an accepted practice, the indications for its use in minor injury remain ill defined and subjective. Identification of these patients is important for the occasional case requiring intervention and for the tracking of complications. A liberal policy of CT scanning is warranted for pediatric patients with a high-risk mechanism of injury despite maintenance of normal neurologic status.(17) However the predictive value of CT in late complications is highly disputed. Future questions and direction. Future objectives focus on increasing awareness regarding the long-term delayed consequences. As the patient population is altering, co-morbidity tends to play a key role. Elderly patients under antiaggregation or/and anticoagulation comprise an increasing part of trauma incidents. Posttraumatic epilepsy is an extremely disabling condition and a major clinical problem in need of major advances. Patients are frequently pharmacoresistant and are often not good surgical candidates. Research into the nature of posttraumatic epilepsy deserves a more robust and concentrated effort.(6) When researching late complications of head injury it becomes clear that adult
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pathophysiology and epidemiology is to be differentiated from corresponding mechanisms in children, emphasizing the fact that a child is not just a small adult but a different pahtophysiological entity. A direction towards regular interdisciplinary follow up allows tracking and treating in a more systematic manner. Prospective studies and perhaps even registries could offer much more date on delayed onset complications. Finally, a high clinical suspicion during rehabilitation is probably the future in recognizing delayed sequelae in head injured patients. Conclusion. Late complications of head injuries are often underdiagnosed. High clinical suspicion may help to identify them. The need for an evidence based concensus on how and how long patients ought to be followed becomes evident. Furthermore, the question raised is who is responsible for the treatment of head trauma. The different nature of the delayed sequelae of head trauma requires a multidisciplinary team, involving neurologists, endocrinologists, psychologists, neurosurgeons, neuroradiologists and rehabilitation personnel. The neurosurgeon being the first to encounter the patient is responsible to suggest a close follow up. The incidence of readmissions because of delayed complications is of medical and socioeconomic importance. It represents a public health problem and a major cause for disability. Rehabilitation, reemployment and reintegration are important issues. After all, trauma is a disease, not a single incident! Key references, recommended reading. Valadka AB, Andrews BT: “Neurotrauma: Evidence-based Answers to Common Questions”. Thieme 2005. ISBN 3-13-130781-1. Thiruppathy SP, Muthukumar N: Mild head injury: revisited. Acta Neurochir (Wien) 146:1075-1082; discussion 1082-1073, 2004. 1.
Acerini CL, Tasker RC: Endocrine sequelae of traumatic brain injury in childhood. Horm Res 68 Suppl 5:14-17, 2007.
2.
Acerini CL, Tasker RC: Neuroendocrine consequences of traumatic brain injury. J Pediatr Endocrinol Metab 21:611-619, 2008.
3.
Acerini CL, Tasker RC, Bellone S, Bona G, Thompson CJ, Savage MO: Hypopituitarism in childhood and adolescence following traumatic brain injury: the case for prospective endocrine investigation. Eur J Endocrinol 155:663-669, 2006.
4.
Asikainen I, Kaste M, Sarna S: Early and late posttraumatic seizures in traumatic brain injury rehabilitation patients: brain injury factors causing late seizures and influence of seizures on long-term outcome. Epilepsia 40:584-589, 1999.
5.
de Boussard CN, Bellocco R, af Geijerstam JL, Borg J, Adami J: Delayed intracranial complications after concussion. J Trauma 61:577-581, 2006.
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6.
Garga N, Lowenstein DH: Posttraumatic epilepsy: a major problem in desperate need of major advances. Epilepsy Curr 6:1-5, 2006.
7.
Gualtieri T, Cox DR: The delayed neurobehavioural sequelae of traumatic brain injury. Brain Inj 5:219-232, 1991.
8.
Itshayek E, Rosenthal G, Fraifeld S, Perez-Sanchez X, Cohen JE, Spektor S: Delayed posttraumatic acute subdural hematoma in elderly patients on anticoagulation. Neurosurgery 58:E851-856; discussion E851-856, 2006.
9.
Kiraly M, Kiraly SJ: Traumatic brain injury and delayed sequelae: a review-traumatic brain injury and mild traumatic brain injury (concussion) are precursors to later-onset brain disorders, including early-onset dementia. ScientificWorldJournal 7:1768-1776, 2007.
10.
Kohta M, Minami H, Tanaka K, Kuwamura K, Kondoh T, Kohmura E: Delayed onset massive oedema and deterioration in traumatic brain injury. J Clin Neurosci 14:167-170, 2007.
11.
Larson PS, Reisner A, Morassutti DJ, Abdulhadi B, Harpring JE: Traumatic intracranial aneurysms. Neurosurg Focus 8:e4, 2000.
12.
Licata C, Cristofori L, Gambin R, Vivenza C, Turazzi S: Post-traumatic hydrocephalus. J Neurosurg Sci 45:141-149, 2001.
13.
McHugh T, Laforce R, Jr., Gallagher P, Quinn S, Diggle P, Buchanan L: Natural history of the long-term cognitive, affective, and physical sequelae of mild traumatic brain injury. Brain Cogn 60:209-211, 2006.
14.
Powner DJ, Boccalandro C, Alp MS, Vollmer DG: Endocrine failure after traumatic brain injury in adults. Neurocrit Care 5:61-70, 2006.
15.
Radulovic D, Janosevic V, Djurovic B, Slavik E: Traumatic delayed epidural hematoma. Zentralbl Neurochir 67:76-80, 2006.
16.
Ryan LM, Warden DL: Post concussion syndrome. Int Rev Psychiatry 15:310316, 2003.
17.
Simon B, Letourneau P, Vitorino E, McCall J: Pediatric minor head trauma: indications for computed tomographic scanning revisited. J Trauma 51:231-237; discussion 237-238, 2001.
18.
Yildirim A, Gurelik M, Gumus C, Kunt T: Fracture of skull base with delayed multiple cranial nerve palsies. Pediatr Emerg Care 21:440-442, 2005.
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RESEARCH IN NEUROTRAUMATOLOGY Niklas Marklund, MD, PhD Neurosurgeon, Department of Neurosurgery, Uppsala University Hospital, Uppsala Sweden
[email protected] Objective t
To provide an overview of the pathophysiology of traumatic brain injury (TBI) and its clinical implications
t
To describe ongoing research areas.
Modern Literature Review Traumatic brain injury (TBI) is defined as “an alteration in brain function, or other evidence of brain pathology, caused by an external force”. TBI is commonly named a silent epidemic and in Europe, TBI causes ~60 000 annual deaths. Additionally, the number of TBI victims globally is rising sharply. TBI frequently leads to a loss of decades of productive life due to persistent functional deficits with a huge cost to the patient, his/her family, and society. Common consequences of TBI include personality changes, seizures, cognitive problems, impaired motor function, and a reduced quality of life. A range of psychiatric disorders, where depression may be the most common, also occur after TBI. Improved prehospital management and refined neurocritical care have been associated with a decline in mortality in many Western World countries. However, despite some 20 completed clinical trials of pharmacological treatment options and several ongoing (a recent search for “traumatic brain injury” AND “treatment” at www.clinicaltrials.gov yielded 336 results), there are no pharmacological treatment options currently available. Thus, improved treatment options for TBI patients are needed. The primary injury is markedly worsened during the first hours-days-months following the impact due to numerous secondary injury factors. Some of these secondary factors are well established, summarised in Fig. 1, although our knowledge of many aspects of the pathophysiology of TBI is still incomplete. My talk and this abstract will provide some thoughts on current clinical and experimental questions with important implications for neurotrauma research. Basic Mechanisms to Improve Outcome Following TBI t
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Neuroprotection - All clinical trials thus far used neuroprotective compounds, i.e. compounds that may reduce the secondary injury process and reduce the extent of the final injury. So far, this approach has not been successful due to numerous different reasons such as the inability to achieve high enough brain concentration of the neuroprotective compound in the early time window needed for efficacy. Not even hypothermia, the most “logical” neuroprotectant, has been effective when clinically evaluated in both adults and children. Anti-inflammatory compounds may have a better chance of success due to a more prolonged time course for many factors involved in the post-injury inflammatory cascade.
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Brain repair - Since dead neurons are not replaced to a significant degree and injured axons fail to regenerate in the injured brain, it is surprising that so many patients show a substantial recovery over time. This recovery process may be due to plasticity, e.g. the capacity of uninjured regions to “take over” the function of lost brain regions by structural reorganization, sprouting of axons etc. Promotion of plasticity may be one way to improve outcome of TBI patients. Other options for “brain repair” is promotion of axonal regeneration by targeting the naturally occurring inhibitors for axonal regeneration (e.g. Nogo-A). By promoting endogenous neurogenesis and perhaps also by transplanting e.g. stem cells, lost nerve cells may be replaced.
Fig. 1 Basic and clinical mechanisms that may lead to a gradual worsening of the initial injury. TBI is considered “the most complex disease in our most complex organ” and secondary injury factors continue for long time periods after the initial impact. By targeting some or even all of these secondary injury factors, outcome of TBI patients may be improved. rCBF: regional cerebral blood flow Experimental Research Obviously, there are enormous differences between the brains of rats and mice compared to humans (one example is that rodent brains are lissencehaphalic, i.e. lack gyri). However, several of the commonly used rodent TBI models produce a brain injury with histological features similar to what is observed in human TBI including axonal injury, inflammation and plasticity responses. Rodent behaviour is (should be) commonly evaluated in experimental TBI research and rodent TBI models have been useful when evaluating neuroprotective compounds. Current TBI models include those that produce a focal contusion (such as the weightdrop or the controlled cortical impact, CCI, model), a “mixed” TBI (the lateral fluid percussion model; Fig 2) or a diffuse axonal injury (the central fluid percussion or the impact/acceleration models). Additional models evaluating blast and penetrating TBI are also available. Although rodent models will continue to be widely used, higher species/larger animals such as the pig needs to be increasingly used in the development of pharmacological tools for clinical TBI. 207
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Fig.2 Example of a commonly used rodent TBI model- the fluid percussion injury model. In this model, a pressure wave is created in a fluid-filled cylinder by a falling pendulum. The pressure wave is then transmitted to the brain of the rodent producing a 22ms ICP rise and brain displacement leading to a short apnea, immediate seizures and long-term motor dysfunction and cognitive deficits. Histologically, this model produces an inflammatory response, widespread axonal injury and neuronal cell death e.g. in the hippocampus. Clinical Research
Fig. 3 One basic challenge for neurotrauma research (and management): the marked heterogeneity of TBI. One single treatment or pharmacological compound (“the silver bullet”) will not cure each TBI subtype and more targeted and individualized approaches are needed. There are still numerous unanswered questions of relevance for neurotrauma research and management. It is likely that TBI care can be refined and tailored to the unique pathophysiology of each TBI subtype. Axonal injury - MRI increasingly reveals that widespread axonal injury occurs not 208
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only in patients with severe diffuse axonal injury (DAI) but also in patients with mild TBI or predominately focal TBI. Axonal injury also appears to be evolving during the initial post-injury period suggesting that it could be prevented or at least be attenuated. t
What is the contribution of axonal injury to patient outcome?
t
Can axonal regeneration be promoted by e.g. antibodies against myelinassociated inihibitors and if so, will this lead to improved outcome?
Age - The mortality following TBI more than doubles in the elderly patients compared to in young patients and high age is one of the most negative important predictors of outcome after TBI. The mechanisms leading to brain swelling, neural death, axonal injury and recovery is likely much different in infants, toddlers, adolescents, adults and the elderly patients. t
Why is outcome impaired in elderly patients and should they be managed differently from younger TBI victims?
t
Can age-specific therapies be developed?
Genetics and Premorbid factors - The importance of the patient’s genotype is likely substantial. Genetic influence on outcome has been most widely studied for the Apo 4 genotype due to its connection to neurodegenerative disorders such as Alzheimer’s disease. t
How doed other genotypes (such as BDNF, DRD2, COMT, TP53 and BCL2 and others) influence outcome and how should this knowledge be used in neurotrauma management?
t
How does associated co-morbidities such as substance abuse or significant medical disorders influence outcome and patient management?
Gender - A vast majority of TBI victims are males. Initial reports suggested that women fared better than males following TBI, which however has not been firmly established. Progesterone repeatedly improved outcome in experimental TBI studies and is currently undergoing clinical trial evaluation. t
Is there an important gender difference in the response to TBI and if so, how does it influence outcome and management?
Prehospital refinement and Neurocritical care - time is brain and many secondary injury factors and secondary insults (seizures, high and/or low blood glucose, fever, poor oxygenation, hypotension, high ICP, low/excessive CPP) threaten the vulnerable brain during the early post-injury phase and exacerbate the initial injury. t
Can prehospital management be refined and what is the optimal fluid resuscitation?
t
In the era of multimodality monitoring, what monitoring tools actually make a difference in patient management?
t
Can analysis of autoregulatory status and intracranial compliance guide 209
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optimal ICP and CPP thresholds? Multitrauma management - Many TBI patients also suffer from significant systemic injuries which may lead to e.g. hypotension, which is a highly negative prognostic factor for TBI patients. t
Does systemic injuries alter brain physiology via e.g. blood-derived factors after TBI and in what way?
t
How and when should the systemic injuries be treated and what is the optimal fluid/transfusion protocol to avoid negatively influencing the vulnerable brain?
Decompressive craniectomy (DC) - Although DC is lifesaving in many patients with brain swelling and refractory elevations of ICP, it did not improve clinical outcome when evaluated for diffuse TBI in the (widely criticized) randomized DECRA trial. t
Can the use and timing of DC for patients with severe TBI be defined (the Rescue-ICP trial!)?
Biomarkers - A biomarker should ideally display a close correlation with a pathological process and/or a pharmacological intervention and be easily measured in the CSF or, preferably, serum. t
Can some commonly evaluated biomarkers (e.g. tau, neurofilament light, neuron-specific enolase (NSE), glial fibrillary acid protein (GFAP), S-100b protein, spectrin breakdown products (SBDPs), ubiquitin C-terminal hydrolase-L1 (UCH-L1) and myelin basic protein) be used to predict outcome and be used as surrogate biomarkers?
t
Can novel biomarkers be used to follow the course of the disease (similar to e.g. C-reactive protein in infectious disease)?
Long-term consequences - There is an association between TBI and neurodegenerative disorders such as Alzheimer’s disease. Additionally, many survivors of TBI also suffer from psychiatric problems such as depression, occurring in -50% of TBI survivors. t
What is the post-injury mechanisms resulting in neurodegeneration and can it be prevented?
t
What is the cause and best treatment of the psychiatric disturbances observed in TBI patients?
Outcome evaluation - Although the Glasgow Outcome Scale (GOS) or its extended version eGOS are commonly used outcome measures in clinical TBI research, its use (and/or how it should be used) is debated and they may be too insensitive to enable detection of clinically meaningful differences in clinical trials. t
Is there a benefit of implementing large and detailed neuropsychological tests in clinical trials?
t
Is there a role for Health-Related Quality of Life scales?
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Design of Successful Clinical Trials Thus far, every pharmacological clinical trial in TBI has failed. There has been much debate about of the reasons for this failure where e.g. inclusion criteria, time window of treatment and statistical methods have been criticised. Improved clinical trial design is important when evaluating novel treatments for TBI. t
Can detailed and improved prognostication using the IMPACT outcome prediction tool be implemented in clinical trial design?
t
Can improved classification of TBI help selecting subsets of TBI patients for clinical trials?
t
Can comparative effectiveness research (Maas et al., 2012) be a tool for evaluating new treatment strategies?
Conclusion The complexity of TBI is an ongoing challenge for the neurosurgical community. Although we lack strong scientific evidence for many of our therapies used for TBI patients today, it is expected that advanced understanding of the pathophysiology of TBI may lead to the development of new treatments options, hopefully in the near future. Key References, Recommended Reading Blennow K, Hardy J, Zetterberg H. The neuropathology and neurobiology of traumatic brain injury. Neuron. 2012 Dec 6;76(5):886-99 Endre Czeiter E et al., Brain Injury Biomarkers May Improve the Predictive Power of the IMPACT Outcome Calculator JOURNAL OF NEUROTRAUMA 29:1770–1778 (June 10, 2012) Bryant, RA, O’Donnell, ML, Creamer, M, McFarlane, AC, Clark, CR, Silove, D (2010) The psychiatric sequelae of traumatic injury. Am J Psychiatry 167(3): 312-320. Hutchinson PJ, Corteen E, Czosnyka M, et al., Decompressive craniectomy in traumatic brain injury: the randomized multicenter RESCUEicp study (www. RESCUEicp.com). Acta Neurochir Suppl. 2006;96:17-20 Kövesdi E, Lückl J, Bukovics P, et al., Update on protein biomarkers in traumatic brain injury with emphasis on clinical use in adults and pediatrics. Acta Neurochir (Wien). 2010 Jan;152(1):1-17 Li LM, Timofeev I, Czosnyka M, Hutchinson PJ. Review article: the surgical approach to the management of increased intracranial pressure after traumatic brain injury. Anesth Analg. 2010 Sep;111(3):736-48. Maas, AI, Stocchetti, N, Bullock, R (2008) Moderate and severe traumatic brain injury in adults. Lancet Neurol 7(8): 728-741. Maas AI, Menon DK, Lingsma HF, et al., Re-orientation of clinical research in traumatic brain injury: report of an international workshop on comparative effectiveness research. J Neurotrauma. 2012 Jan 1;29(1):32-46. 211
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Marklund N, Hillered L. Animal modelling of traumatic brain injury in preclinical drug development: where do we go from here? Br J Pharmacol. 2011 Oct;164(4):120729 Masel, BE, DeWitt, DS (2010) Traumatic brain injury: a disease process, not an event. J Neurotrauma 27(8): 1529-1540.’ Murray, GD, Maas, AI (2003) Patient age and outcome following severe traumatic brain injury: an analysis of 5600 patients. J Neurosurg 99(4): 666-673. Roozenbeek B, Lingsma HF, and Maas AI. New considerations in the design of clinical trials for traumatic brain injury Clin Investig (Lond). 2012 February ; 2(2): 153–162 Roozenbeek B, Lingsma HF, Lecky FE, et al., International Mission on Prognosis Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) Study Group; Corticosteroid Randomisation After Significant Head Injury (CRASH) Trial Collaborators; Trauma Audit and Research Network (TARN). Crit Care Med. 2012 May;40(5):1609-17 Saatman KE, Duhaime AC, Bullock R, et al., Workshop Scientific Team and Advisory Panel Members. Classification of traumatic brain injury for targeted therapies. J Neurotrauma. 2008 Jul;25(7):719-38.
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CONCUSSION IN ATHLETES Niklas Marklund, MD, PhD Neurosurgeon, Department of Neurosurgery, Uppsala University Hospital, Uppsala Sweden
[email protected] Objective t
To provide an overview of sports-related brain injuries, concussions, and their management
t
To provide information about the risk and long-term consequences of repeated concussions
Modern Literature Review Although the term mild traumatic brain injury (mTBI) is preferable in a neurotrauma context, the term concussion (from the latin word concutere-to shake violently) is commonly used in sports-related literature. A sports concussion is defined as ‘‘a complex pathophysiological process affecting the brain, induced by traumatic biomechanical forces’”. Until recently, sports concussions were considered to be minor, benign injuries without consequences. Due to an increasing number of highprofile athletes affected with long-term disabilities and early retirement due to concussions, this attitude has rapidly changed. There is an obvious risk for severe or even fatal TBI in e.g. motor sports, skiing, equestrian sports and others and there is an increased risk for repeated mild TBIs in sports such as ice hockey, rugby, football and, in particular, in contact sports such as boxing and mixed martial arts (MMA). As a neurosurgeon, these mild TBIs will not require your surgical skills- however, as a “brain expert” you will likely be asked on your opinion on the acute management of sport-related concussions, return to play decisions and career-ending advice. t
Symptoms include headache, confusion, irritability, dizziness, fatigue, lability, reduced reaction speed (common!) and antero- and/or retrograde amnesia1-2. Observe that loss of consciousness is not a diagnostic criterion for concussion. These symptoms are listed in the sport concussion assessment tool 2 document (SCAT2, the revised SCAT 3 is due 2013), which is a frequently used assessment tool to be used at the time of injury. The previously used grading (e.g. Grade 1-3 or Mild-Severe) of concussions should not be used. The incidence is higher in female than in male athletes in similar sports and the risk of receiving a concussion is much higher in athletes with a previous history of concussions3.
The recovery following a sports concussion typically requires roughly 2–10 days in about 85-90% of athletes1-2, although adolescent or pediatric recovery may take twice as long. Thus, 10-15% of athletes have symptoms beyond 10 day, the postconcussion syndrome4, typically consisting of e.g. headache, irritability, anxiety, depression, personality changes, confusion and memory problems. t
Conventional (CT) imaging rarely shows structural abnormalities following a concussion. However, advanced MR technology including DTI increasingly 213
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reveals white matter tract changes5-7 such as altered diffusivity e.g. within the corpus callosum and corticospinal tract7. There is evidence of a temporal vulnerability of the brain after a concussion, during which a new concussion would cause additional injury to the brain. Thus, the athlete must wait several days before returning to play (see below), typically a minimum of one week. However, when MR spectroscopy was used to evaluate cerebral metabolic changes using e.g. the N-acetylaspartate (NAA)/creatinine ratio following a concussion a more prolonged recovery was suggested8. Although all clinical symptoms had disappeared from 3-15 days post-injury, the metabolic ratio was normalized in only 12% of concussed athletes at two weeks and in 50% at three weeks. First at 30 days post-concussion had the cerebral metabolism normalized in all athletes8. t
Biomarkers studies of Olympic boxers9 showed that CSF levels of brain injury markers (such as T-tau, NFL, GFAP, and S-100B) were increased in .80% of the boxers both acutely (day 1-6) and prolonged (>14d) after a bout. In contrast, controlled heading in football did not result in increased levels of CSF brain injury biomarkers10.
Recent Clinical and Research Developments Much of the recommended guidelines for the management of concussions have emerged from the four Consensus Conferences on Concussion in Sport (Vienna 2001, Prag 2004, Zurich, 2008 and Nov 2012). The publication of the consensus statements from the 4th Consensus Conference is planned for the spring of 2013. t
Prevention is the best cure for concussions and e.g. recently, a strict rule enforcement strategy including harsh penalties and no tolerance on head checking has reduced the incidence of concussions in the National Hockey League. Surprisingly, there is no clear evidence that (currently available) helmets or mouth guards protect against concussion although neck strengthening exercises may help reducing the risk of concussions.
t
Management of concussion: A concussed athlete should NOT be allowed back into play on the same day of injury. A gradual return to activity is suggested; including at least 24h with complete “brain rest” (see Table 1).
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Rehabilitation Steps
Functional exercise
Step 1 - no activity
“Brain rest” - physical and cognitive resting (bed rest? If so, never more than 48h)
Step 2- light aerobic exercise
Walking, swimming etc.
Step 3- sport-specific exercise
E.g. skating drills in ice-hockey, running drills in football (no contact drills with a risk for head injury is allowed)
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Step 4- non-contact training drills
More complex sport-specific training and may start progressive resistance training
Step 5- full contact practice
Participate in normal activities including body contact
Step 6- Return to play
Regular game/competition OK
Table 1 - graded return to play protocol. Return to play - at least 24h without symptoms are needed before the athlete is allowed to proceed to next Step. Thus, a minimum of 24h before first exercise and between each step is required. If the athlete gets symptomatic- he/she should return to Step 1 and when asymptomatic- resume the gradual return to play on the Step lower than the one where symptoms occurred (i.e. if a players gets new symptoms at Step 4, resumes “brain rest” and when asymptomatic he/she may start again on Step 3). In those with prolonged symptoms (>10 days), moderate exercise and a graded exercise program should be commenced after medical evaluation, even if symptoms persist. t
There are no definitive guidelines on how many concussions are too many, e.g. when to recommend retirement of an athlete following concussions.
t
In pediatrics11, concussions symptoms can last longer. The basic strategy is to gradually return the child to learn the skills before return to the sport itself
t
Neuropsychological tests may be more sensitive to detect e.g. cognitive impairment than regular clinical exams and their use has been suggested in the management of concussions. However, although the tests may provide information on cognitive recovery, they may not be necessary in the majority of cases. A suggested use of neuropsychological tests is in the evaluation of athletes with persistent symptoms.
Long-Term Consequences of Repeated Concussions t
Neurophysiological, neuropsychological and motor and cognitive testing has frequently revealed deficits ranging from subclinical neurophysiological changes in young athletes to significantly impaired results in former athletes, up to >30 years following the last concussion (reviewed in12).
t
Former athletes who suffered multiple concussions had a 5-fold prevalence of mild cognitive impairment (MCI) compared with retirees without a history of concussion3. In a cohort of previous players of American football, the risk of e.g. depression was >triple in players with a history of *3 concussions.
t
A punch from a skilled and fit boxer can cause a rotational and/or linear acceleration of the opponent´s head sufficient to induce a concussion and with a high likelihood also some axonal injury. Since 1928, professional boxing has been associated with the “punch-drunk”/“dementia pugilistica”/ 215
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chronic traumatic encephalopathy (CTE)/chronic traumatic brain injury (CTBI) syndrome. CTE manifests as progressive memory deficits, aggression, Parkinsonism, depression and, finally, dementia and was in some studies observed in >20% of old-time professional boxers. These symptoms differ from those observed following a concussion and appear to be caused by an ongoing loss and dysfunction of neurons. At autopsy, a unique feature of neurofibrillary tangles composed by tau (a tau-pathy) is observed in the frontal and temporal lobes where marked brain atrophy may also be found. There are similarities between the brains of CTE and Alzheimer´s patients although there is substantially less beta-amyloid in CTE. CTE is not observed in Olympic boxers and the risk is likely reduced also in modernday professional boxers due to fewer fights and more rigorous controls following a knock-out. t
Only recently has CTE been diagnosed in the brains of athletes from other sports such as ice hockey, rugby and American football. In these athletes, most who have a history of repeated concussions and many dying at a relatively young age, signs of CTE with a marked taupathy and neurofibrillary tangles have been observed at autopsy13-14. It must be noted that there may be a selection bias in these small patient series and other yet unknown factors beside concussions may also contribute.
Future Questions and Directions t
The “minimum” definition for concussion is a matter of debate (e.g. is a “bell ringer” where the player feels stunned for a few seconds and then asymptomatic a concussion?)
t
Can more precise (and safe) return-to-play guidelines be developed?
t
What should the criteria be to end an athlete’s career from a medical perspective?
t
Is there a causative effect by repeated concussions on the development of CTE in athletes? Or have other yet unknown factors (drugs/alcohol abuse or certain medications etc.) been overlooked? What role does genetics, particularly the presence of APOEE4, have in the development of CTE?
Conclusions t
The player should not be allowed to return to play on the day of concussion and a graded, step-wise return to play is suggested.
t
There are no evidence-based guidelines for disqualifying/retiring an athlete from a sport after a concussion or how many concussions should be considered too many. Each athlete must be carefully evaluated and an individualized approach developed for career-ending decisions.
t
Although most concussions “heal” spontaneously, e.g. all symptoms resolve, they may not be benign and long-term evidence for disturbed brain function and persisting symptoms is a reality. Refined MR-technology
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including DTI and MR-spectroscopy increasingly reveal white matter lesions and metabolic disturbances in the brains of concussed athletes. t
Chronic Traumatic Encephalopathy (CTE), classically observed in the brains of old-time professional boxers, has recently been observed also in e.g. ice hockey, rugby and American Football players subjected to concussions during their career which obviously has important implications. However, more data is needed to establish a causative effect by repeated concussions on the development of CTE.
Key References, Recommended Reading. 1.
Paul McCrory et al., . Consensus Statement on Concussion in Sport3rd International Conference on Concussion in Sport. Clin J Sport Med 2009;19:185–200)
2.
Harmon KG et al., ; American Medical Society for Sports Medicine position statement: concussion in sport. Br J Sports Med. 2013 Jan;47(1):15-26.
3.
Guskiewicz KM et al., . Association between recurrent concussion and late-life cognitive impairment in retired professional football players. Neurosurgery. 2005 57(4):719-26.
4.
Jotwani V, Harmon KG. Postconcussion syndrome in athletes. Curr Sports Med Rep. 2010 Jan-Feb;9(1):21-6.
5.
Virji-Babul N et al., Diffusion tensor imaging of sports-related concussion in adolescents. Pediatr Neurol. 2013 Jan;48(1):24-9.
6.
Cubon VA, et al., A diffusion tensor imaging study on the white matter skeleton in individuals with sports-related concussion. J Neurotrauma. 2011 Feb;28(2):189-201.
7.
Acute and chronic changes in diffusivity measures after sports concussion. Henry LC et al., . J Neurotrauma 2011 Oct;28(10):2049-59.
8.
Assessment of metabolic brain damage and recovery following mild traumatic brain injury: a multicentre, proton magnetic resonance spectroscopic study in concussed patients. Vagnozzi R, et al., . Brain. 2010 Nov;133(11):3232-42.
9.
Neurochemical aftermath of amateur boxing. Zetterberg H et al., . Arch Neurol. 2006 Sep;63(9):1277-80
10.
No neurochemical evidence for brain injury caused by heading in soccer. Zetterberg H et al., Br J Sport Med 2007 41(9):574-7.
11.
Guskiewicz KM, Valovich McLeod TC. Pediatric sports-related concussion. PM R. 2011 Apr;3(4):353-64
12.
De Beaumont L, Henry LC, Gosselin N. Long-term functional alterations in sports concussion. Neurosurg Focus. 2012 Dec;33(6):E8.
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13.
Long-term consequences of repetitive brain trauma: chronic traumatic encephalopathy. Stern RA et al., . PM R. 2011 Oct;3(10 Suppl 2):S460-7.
14.
Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. McKee AC, et al., . J Neuropathol Exp Neurol. 2009 Jul;68(7):709-35. Review.
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TRAUMATIC BRAIN INJURY DURING CHILDHOOD J. André Grotenhuis Department of Neurosurgery, Radboud University Medical Centre, Nijmegen, The Netherlands Objective To provide guidelines for the acute neurosurgical and critical care management of traumatic brain injury in infants, children and adolescents, pointing out some specific traumatic events, type of injuries and sequelae that are distinctive for this age group as compared to adults, and to provide a small reference text for residents in training. Aetiology, Pathophysiology and Clinical Context Unfortunately, head injuries are very common during childhood. Although such accidents account for 600,000 emergency room visits and approximately 100,000 hospitalizations annually in the U.S., most cases of paediatric head trauma do not require intervention or result in negative sequelae. But nevertheless, more severe traumatic brain injury (TBI) is still an overwhelmingly large problem and in so-called developed countries, TBI remains one of the most common causes of death and disability in childhood. The Morbidity and Mortality Weekly Report published by the Centers for Disease Control and Prevention listed 84,792 deaths from TBI that occurred in children aged 0-19 years during a 10-year period from 1989-1998. The highest rate (29.6 deaths per 100,000 population) was found in those aged 15-19 years. Prevalence was higher in males than females in all age groups, with a 2.5:1 male-to-female ratio. Although children are susceptible to the same mechanisms of injury as their adult counterparts, a child’s physiologic and psychological responses to trauma are very unique. Thus a thorough understanding of some of the unique anatomic and pathophysiologic differences of children will enhance the quality of care that is provided during the evaluation, stabilization and management of the paediatric trauma patient. A summary of some of the key anatomic differences in children are as follows : t
a) Smaller body size.
t
b) Larger head-to-body ratio.
t
c) Greater body surface ratio.
t
d) Shorter trachea and relatively larger tongue size.
t
e) Glottic opening more anterior and superior.
t
f) Less protective muscle and body fat.
t
g) Abdominal organs more anterior.
t
h) Growth plates of long bones are more susceptible to injury.
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One of the first very obvious physiologic differences between children and adults is the variation of normal paediatric vital signs based on the age of the child. A thorough understanding of paediatric vital signs is imperative in being able to detect very subtle abnormalities in a child’s heart rate and respiratory rate. For example a subtle tachycardia may be the only clue to the possibility of early haemorrhagic shock in a child who otherwise looks stable. A subtle tachypnoea may be the earliest clue to possible intra-thoracic injuries in a child with a normal room air oxygen saturation. Thus, anyone involved in the emergency care of children must be aware of normal vital signs based on a child’s age. A simplified method to easily and quickly recall paediatric vital signs is as follows: Heart rate
Respiratory rate
New-born to 1 year old
140
40
1 to 4 years old
120
30
4 to 12 years old
100
20
>12 years old
80
15
The larger head-to-body ratio of infants and young children makes them more susceptible to head injuries during falls. The larger head size also affects the fulcrum forces along the neck, making upper cervical spine injuries more common in infants and younger children as opposed adults who more commonly sustain injuries to their lower cervical spine. The larger head size as well as the increased body surface area in children make them more susceptible to greater heat loss and hypothermia when they are exposed during the trauma resuscitation. It is extremely important to realize that children will maintain a normal systolic blood pressure for age until they have lost up to 30% of their circulating blood volume ! The circulating blood volume of a child is 70-80 ml/kg as compared to the typical adult circulating blood volume of 60 ml/kg. A normal systolic blood pressure for a child can be calculated via the formula: (Age X 2) + 90 mmHg. The corresponding expected diastolic blood pressure should be 2/3 X (SBP). The initial compensatory mechanism that one should look for during the early stages of haemorrhagic shock is tachycardia. The other compensatory mechanism that occurs to maintain normal perfusion and blood pressure is an increase in the systemic vascular resistance, which is manifested clinically by mottled/cool extremities, weak/thready distal pulses, delayed capillary refill time and a narrowed pulse pressure. If the early clinical signs of haemorrhagic shock are not identified and corrected, the child may progress to a preterminal stage of decompensated shock, which is defined as hypotension for age. Hypotension (systolic) in any aged child is defined via the formula: (Age X 2) + 70 mmHg. Thus a 5 year old child who presents with an initial systolic blood pressure less than or equal to 80 mmHg is already in the phase of decompensated shock and clinical has lost at least 30% of his circulating blood volume. The minimum systolic blood pressures and circulating blood volumes for age are:
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Minimum systolic pressure
Circulating blood volume
New-born to 1 month
> 60 mm Hg
90 ml / kg
1 month to 1 year old
> 70 mm Hg
80 ml / kg
>1 year old
(Age x 2) + 70 mm Hg
70 ml / kg
As a general rule, it is taught that intracranial bleeds in themselves do not result in hypovolaemic/haemorrhagic shock. The one exception to this rule involves head trauma in infants. Because the suture lines of an infant’s skull are not yet fused, the skull has the capability to expand and accommodate large volumes of blood during acute intracranial haemorrhage. TBI involves children of all ages and includes a variety of mechanisms ranging from falls and motor vehicle collisions, bicycle accidents and sporting injuries to child abuse and gunshot wounds. The aetiology of head injury in children also varies according to the age group t
(a) New-borns – birth trauma
t
(b) Infants - falls or possibly child abuse,
t
(c) Pre-school children - falls or passengers in motor vehicle accidents,
t
(d) School-attending children - falls, motor vehicle accidents or sportsrelated accidents, and
t
(e) Adolescents - motor vehicle accidents or sports-related accidents.
Despite the high prevalence of traumatic brain injury in the paediatric population, there are no evidence-based guidelines for the care of victims of this particular trauma. This is in part due to the fact that some treatments, such as mannitol for lowering intracranial pressure, were being used extensively prior to rigorous scientific inquiry. Thus, such measures are commonly accepted as being valid and beneficial, but they are difficult to recommend as evidence-based. Another issue complicating the development of guidelines for paediatric traumatic brain injury are the varying methods and outcomes of research in this area. The authors of the most recently published guidelines tried to overcome these shortcomings by reviewing more than 700 peer-reviewed articles to arrive at their conclusions. Because outcomes from brain injury are observed in cognitive and behavioural dimensions, as well as somatic dimensions, evaluation of the recovery process in children is confounded by cognitive and behavioural changes that occur as a function of normal development. Furthermore, development within each dimension accelerates and decelerates during different developmental phases. Injury severity, and the presence or absence of multiple-system injuries, will also interact with the child’s age to influence outcome. An additional issue specific to paediatric trauma is that of intentional injury. The nature of the trauma and secondary complications are thought to be distinct in ways from many unintentional injuries, requiring corresponding differences 221
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in appropriate treatment. The delay between injury and hospital admission, or between admission and recognition that the injury was intentional, can thwart timely treatment decisions. In review of the literature, no studies provided data of any kind to assist in making distinctions about treatment for intentional injury. Furthermore, certain aspects of brain injury are unique to children. For example, it is more difficult to determine the measure the loss of brain function in a child. In adults there are prior academic records, I.Q. scores, and job histories to rely on. At one time it was assumed that children were more resistant to brain trauma than adults because their developing brains could rewire over time. However, mounting evidence seems to suggest otherwise. In fact, it may be that children are more susceptible than adults to permanent brain damage even when the forces involved are equivalent. In children some neurologic deficits after head trauma may not manifest for many years. Frontal lobe functions, for example, develop relatively late in a child’s growth, so that injury to the frontal lobes may not become apparent until the child reaches adolescence as higher level reasoning develops. Since the frontal lobes control our social interactions and interpersonal skills, early childhood brain damage may not manifest until such frontal lobe skills are called into play later in development. Likewise, injury to reading and writing centres in the brain may not become apparent until the child reaches school age and shows signs of delayed reading and writing skills. The neurosurgical treatment of intracranial hematomas, i.e. extradural hematoma, acute subdural hematoma and intraparenchymal hematoma during childhood is not different from that in adults. But there are some specific items of traumatic events and type of injuries that are distinctive to the paediatric population and that will be discussed first. Brain Injury Due to Birth Trauma Traumatic birth injury is defined by any condition that affects the foetus adversely during labour or delivery, which may be either because of hypoxia or due to mechanical factor. Birth injury falls into 2 categories: (1)
injuries produced by the normal force of labour and
(2)
those produced by obstetric intervention (complication of forceps application!)
Cephalhaematoma, skull bone fracture, intracerebral haematoma, subdural hematoma (SDH) and extradural hematoma (EDH) following cranial birth injury have been mentioned by various authors in different series. Though cases of SDH with intracerebral haematoma are relatively common, EDH is rare. This is because of firm adherence of the dura to overlying skull bone in children. Neonatal EDH is extremely rare. Natelson studied 42 cases of intracerebral hematoma. Not a single case was associated with EDH. Pollina described 41 consecutive cases of cranial birth injuries without a single case of EDH. Pierre described 17 cases of intracranial hematoma in neonates and there was not even a single case of EDH. The proposed mechanism of birth injury during labour is the pressure of the ischial tuberosity against the skull, resulting in bending of the elastic skull of a neonate. 222
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This mechanical force results in injury to draining veins giving rise to subdural and intracranial hematoma. Simultaneously, rupture of emissary vein results in collection of blood in the epidural space. Most of the observers have described that intracranial vascular accidents occurring in the new-born period are related to the venous rather than the arterial system. The reason given is the greater susceptibility of veins to changes in the intracranial pressure and direct injury. Scalp swelling, hypoxia and seizures are the common presentation of intracranial haemorrhage. 37% of the new-borns presented with convulsion and 39% with apnoea in one series of 41 patients of neonatal intracranial hematoma following birth injury. New-borns delivered vaginally and with vertex presentation may have some scalp swelling and in few cases the baby may have a fracture, most common of which is the so-called “ping-pong” fracture that occurs in the region of parietal bossing and is not associated with visible scalp injury. Intra-uterine depressed skull fracture may be the result of pressure against the maternal symphysis pubis or the promontory of the sacrum as described by Potter and Watson-Jones. There is rarely any associated intracranial injury. This condition can be diagnosed on clinical examination. Plain X-ray may show the degree of deformation. An ultrasound of the skull is an easily available bedside tool for the diagnosis and management of intracerebral hematoma in neonates. Ultrasound guided aspiration of the hematoma can be performed in infants but it may precipitate the fresh bleeding also. The hematoma visualized by USG may appear larger on CT Scan as CT can reveal surrounding parenchymal contusion and other multiple small hematoma also. The major indications for obtaining a CT scan in a new-born suspected of having an intracranial haematoma are uncontrolled seizure with normal serum biochemistry (rule out hypoglycemia or hypocalcaemia too!), also seizures with neonatal haemorrhagic disorder, lethargy and progressive neurological deterioration. CT scan is a sensitive radiological tool to diagnose surgically treatable intracranial pathologies in the immediate perinatal period. Small lesions are likely to resolve spontaneously without any surgical intervention. Large lesions (>3cm), which produces mass effect and having midline shift, require corrective surgery. But uncontrolled seizures, progressive neurological deterioration or failure to improve with conservative management are also indications for surgery to decompress the haematoma. Correction of the coagulation profile, if present, should be done before surgery and blood must be made available before taking the new-born baby to the operation theatre. Proper intraoperative neuromonitoring is essential in a new-born with raised intracranial tension. Surgery is this age group is even more delicate than in adults. A pial membrane including the cortical blood supply is easily stripped of by the sucker, which may cause further damage to the normal brain parenchyma. Brain at this age is mostly water and therefore sudden herniation of cerebral tissue may occur when the dura is opened. No effort should be made to remove contused brain tissue because there is a chance of recovery of that damaged tissue. Often the bleeding within the cerebrum is difficult to control because of the fluid nature of brain tissue at this age. The prognosis for children who require surgery is poor with
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10% mortality and 30% poor outcome. Skull Fractures in the Paediatric Population A retrospective analysis of 12,072 paediatric head injury cases revealed 1,297 skull fractures. Patients with skull fractures were divided into four age groups according to the fusion of skull sutures and other developmental radiological skull changes. Results revealed that the patients with open skull sutures (aged 2 years), the children became progressively more susceptible to developing intracranial hematomas if they had a skull fracture. The risk of developing intracranial hematomas was the highest among those patients (>11– 15 years) whose paranasal sinuses had reached adult size and spheno-occipital synchondrosis had begun to fuse. Because a significant number of intracranial injuries occur in the absence of skull fractures, skull radiographs are not generally recommended for screening when CT is readily available. However, when CT is not available, skull radiographs provide some screening information, because the relative risk of intracranial injury is greatly increased in the presence of a skull fracture. Linear skull fractures are the most common fracture in children and account for 80% of all skull fractures. The presence of a fracture reflects significant impact and therefore increased potential for underlying brain injury. Fractures that cross the path of the middle meningeal artery or dural sinuses are at greater risk for intracranial bleed. Simple linear fractures require no surgical intervention. Depressed skull fractures account for 10-20% of fractures in children. A depressed skull fracture occurs when the inner table of the skull is displaced downwards. The bony edges are easily surgically elevated by surgery if the depression is greater than the thickness of the skull. Base of skull fractures are difficult to diagnose radiologically. The diagnosis of a base of skull fracture should be suspected based on clinical findings such as associated cerebrospinal fluid otorrhoea and rhinorrhoea, haemotympanum, Battle’s sign (mastoid ecchymosis), and racoon eyes (periorbital ecchymosis). In addition to the findings of altered mental status, focal neurologic deficits, seizure, signs of a basilar skull fracture, and a palpable depression of the skull, any symptoms related to head injury in an infant should prompt strong consideration for head CT. Although generally skull radiographs are not recommended for most children, they are so in infants younger than 1 year with hematomas or contusions after head injury, because these infants are at greater risk for skull fracture. Documentation of a skull fracture may also be useful in evaluation for non-accidental trauma and in young infants. An infant with an identified skull fracture should warrant in-hospital observation, head CT, or both. Growing Skull Fractures Simple skull fractures usually heal without incident within a few weeks. One potential complication is a “growing skull fracture”. Although most commonly known as a growing skull fracture, it is also referred to as a leptomeningeal cyst or posttraumatic meningocele. The essential features of this condition are a skull fracture in infancy or early childhood, a dural tear at the time of fracture, brain 224
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injury beneath the fracture and subsequent enlargement of the fracture to form a cranial defect. The incidence of growing skull fractures is estimated at about 1% among skull fractures in children. Growing skull fractures occur during the first 3 years of life and almost never after eight years of life. This is due to the rapid increases in brain growth seen only in infancy. A dural laceration is an essential component of a growing skull fracture. The development of a growing skull fracture requires a fracture severe enough to include a tear in the underlying dura and an outward driving force such as a normally growing brain or hydrocephalus. Continued pulsation of the brain and arachnoid is thought to enlarge the fracture over time and herniation of the cerebral tissue or subarachnoid fluid through the fracture line may occur. A leptomeningeal cyst represents an invagination and entrapment of arachnoid into a diastatic fracture with an associated dural tear. This prevents healing of the fracture margins, can cause expansion of the fracture and is a palpable mass on physical exam. Linear fractures can be associated with growing skull fractures while depressed fractures are usually not. A fracture with a diastasis separation of more than 4 mm may be considered at risk of developing a growing fracture. Beneath the lesions of skull and dura matter there is local brain injury which is a constant feature of this syndrome and on acute imaging studies there is usually an indication of a cortical injury immediately beneath the fracture. A growing skull fracture presents as a progressively enlarging pulsatile mass or an enlarging and sunken palpable cranial defect. It may enlarge over months and occur months after the initial skull fracture. Neurological complications related to growing skull fractures include seizures (often intractable), hemiparesis and psychomotor retardation. The majority of cases have shown progressively worsening neurologic deficits over time. Therefore, it is important to examine children with skull fractures 4-6 weeks post injury to ensure adequate healing at the site of the initial fracture. The most common location for the development of a growing fracture is the parietal bone, although it can occur anywhere, including the skull base. Skull radiographs taken at the time of the initial injury will universally demonstrate a diastatic fracture, with the edges separated by more than 3mm. Computed tomography is helpful in identifying underlying intracranial pathology. Imaging done at the time of trauma may show a haemorrhagic contusion or subarachnoid or extraparenchymal haemorrhage. CT scan done months after the injury may also demonstrate unilateral ventricular enlargement and a shift toward the skull defect. Early surgical correction is recommended due to the risk of neurological complications (seizures, hemiparesis). There is no indication that the condition ever improves spontaneously. Intractable seizures in association with a growing skull fracture often respond to surgical correction. Principles of surgery include reconstruction of the dura, reconstruction of the skull and excision of excessive scalp tissue.
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Traumatic Diffuse Axonal Injury A common pathology observed in infants with severe inflicted closed-head injuries is diffuse axonal injury (DAI). DAI involves widespread damage to axons in the white matter of the brain. Hypoxic-ischemic injury, calcium dysregulation, and mitochondrial and cytoskeletal dysfunction are thought to play important roles in axonal damage. DAI is a frequent result of traumatic deceleration injuries and a frequent cause of persistent vegetative state in patients. DAI is the most significant cause of morbidity in patients with traumatic brain injuries, which most commonly are the result of high-speed motor vehicle accidents. DAI is a significant medical problem because of the high level of debilitation of the patient, the stress that the patient’s family must endure when the patient is in a persistent vegetative state, and the staggering medical cost of sustaining an individual in this state. The pathophysiology of DAI first was described by Holbourn in 1943 using 2-dimensional gelatin molds. His work led to the understanding that shear injury is not induced by linear or translational forces but rather by rotational forces. Sudden acceleration-deceleration impact can produce rotational forces that affect the brain. The injury to tissue is greatest in areas where the density difference is greatest. For this reason, approximately two thirds of DAI lesions occur at the gray-white matter junction. Typically, the process is diffuse and bilateral, involving the lobar white matter at the gray-white matter interface. The corpus callosum frequently is involved, as is the dorsolateral rostral brainstem. The most commonly involved area is the frontal and temporal white matter, followed by the posterior body and splenium of the corpus callosum, the caudate nuclei, thalamus, tegmentum, and internal capsule. Internal capsule lesions are associated more frequently with haemorrhage than are the other lesions and are secondary to the proximity of the lenticulostriate vessels. The following stages of involvement have been described by Adams et al. according to the anatomic location of the lesions: t
Stage I: this involves the parasagittal regions of the frontal lobes, periventricular temporal lobes, and, less likely, the parietal and occipital lobes, internal and external capsules, and cerebellum.
t
Stage II: in addition to the white matter areas in stage I, also involvement of the corpus callosum. This is observed in approximately 20% of patients. Most commonly, the posterior body and splenium are involved; however, the process is believed to advance anteriorly with increasing severity of disease. Both sides of the corpus callosum may be involved; however, involvement more frequently is unilateral and may be haemorrhagic. The involvement of the corpus callosum carries a poorer prognosis.
t
Stage III: this involves the areas associated with stage II, with the addition of brainstem involvement. A predilection for the superior cerebellar peduncles, medial lemnisci, and corticospinal tracts is found.
The result of shearing forces in areas of greater density differential is trauma to the axons, which results in oedema and axoplasmic leakage that is most severe during 226
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the first 2 weeks after injury. The exact location of the shear-strain injury depends on the plane of rotation and is independent of the distance from the centre of rotation. Conversely, the magnitude of injury depends on 3 factors, including (1) the distance from the centre of rotation, (2) the arc of rotation, and (3) the duration and intensity of the force. The true extent of axonal injury typically is worse than visualized using current imaging techniques. On the microscopic level, the axon may not be torn completely by the initial force, but the trauma still can produce focal alteration of the axoplasmic membrane, resulting in subsequent impairment of axoplasmic transport. Axoplasmic swelling ensues, and the axon then splits in two. A retraction ball forms, which is a pathologic hallmark of shearing injury. The axon then undergoes Wallerian degeneration. Dendritic restructuring may occur, with some regeneration possible in mild-to-moderate injury. Within the basal ganglia, the effect of DAI produces parenchymal atrophy brought on by shrinkage of astrocytes in the lateral and ventral nuclei, with sparing of the anterior and dorsomedial nuclei, the pulvinar, centromedian nuclei, and lateral geniculate bodies. Cholinergic neurons have been found to be slightly more susceptible to trauma than neurons belonging to other neurotransmitters. Peripheral lesions usually are smaller than central lesions. The lesions typically are ovoid or elliptical, with the long axis parallel to the direction of the involved axonal tracts. A high association is seen between DAI and thalamic injury. DAI classically was believed to represent a primary injury (occurring at the instant of the trauma). Currently, however, it is apparent that the axoplasmic membrane alteration, transport impairment, and retraction ball formation may represent secondary (or delayed) components to the disease process. DAI is suggested in any patient who demonstrates clinical symptoms disproportionate to their CT findings. Although CT scanning may demonstrate findings suggestive for DAI, MRI is the preferred examination (particularly with gradient-echo sequences), although CT is maybe more practical and also more available in today’s medical milieu around the world. DAI results in instantaneous loss of consciousness, and most patients (>90%) remain in a persistent vegetative state, since brainstem function typically remains unaffected. DAI rarely causes death. The chance that a patient will remain in a persistent vegetative state is greater when lesions are observed in the supratentorial white matter, corpus callosum, and corona radiata. The prognosis also worsens as the number of lesions increases. For the almost 10% of patients who experience a return to any form of normal function, this improvement will be seen within the first year. DAI lesions can result in deficits in information transfer between the 2 sides of the corpus callosum, commonly resulting in auditory deficits. Guidelines for the Acute Management of Severe TBI for the Paediatric Population Despite on-going research targeting these mechanisms of secondary brain injury, treatment for children with TBI remains mainly supportive. Numerous multidisciplinary teams have been formed to provide guidelines for management of both adult and paediatric severe TBI. Specific guidelines include Guidelines for the Acute Medical Management of Severe Traumatic Brain Injuries in Infants,
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Children, and Adolescents (The guidelines have been published simultaneously in three medical journals (Paediatric Critical Care Medicine 2003;4(suppl): S1-17; Critical Care Medicine 2003;31(suppl): S417-91; Trauma 2003;54(suppl): S235310)). A second edition of these guidelines have been published in 2012. In this second edition the cohort of authors have also listed changes in recommendations between the first and second edition. For these changes it is advisable to read Paediatric Critical Care Medicine 2012; 13(suppl): S1-82 by Kochanek PM, Carney N, Adelson PD, et al. Treatment of severe TBI (Glasgow Coma Scale 3-8) begins with initial stabilization, including securing the airway, achieving sufficient oxygenation and ventilation, and providing adequate fluid resuscitation. t
Early airway management involves appropriate bag-mask ventilation and endotracheal intubation. Hypercarbia and hypoxia both are potent cerebral vasodilators, resulting in increased cerebral blood flow and potentially increased ICP. Endotracheal intubation allows for airway protection in severely obtunded patients and better control of oxygenation and ventilation. In the initial resuscitation period, efforts should be made to maintain eucapnia at the low end of the reference range (PaCO2 of 35-40 mm Hg) and prevent hypoxia (PaO2 38.0°C) is not uncommon following TBI. Temperature control through the treatment of fever can aide in decreasing systemic and cerebral
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metabolic requirements. Control of metabolism may limit excitotoxicity and inflammation. Fever also decreases the seizure threshold. Efforts should be made to avoid hyperthermia with medications and cooling devices. t
Sedation and analgesia are also important adjuncts to maintaining CPP and minimizing increases in ICP. Painful stimuli and stress increase metabolic demands and increase blood pressure and ICP; however, sedatives and analgesics must be chosen judiciously to prevent unwanted side effects (e.g., hypotension). Short-acting and reversible medications, such as fentanyl, are commonly used. Benzodiazepines, such as midazolam, are also common and have the added benefit of elevating the seizure threshold.
ICP Monitoring The pressure-volume relationship between ICP, volume of CSF, blood, and brain tissue, and cerebral perfusion pressure (CPP) is known as the Monro-Kellie doctrine. It states that the cranial compartment is incompressible, and the volume inside the cranium is a fixed volume. The cranium and its constituents (blood, CSF, and brain tissue) create a state of volume equilibrium, such that any increase in volume of one of the cranial constituents must be compensated by a decrease in volume of another. The principal buffers for increased volumes include CSF and, to a lesser extent, blood volume. These buffers respond to increases in volume of the remaining intracranial constituents. For example, an increase in lesion volume (e.g. epidural hematoma) will be compensated by the downward displacement of CSF and venous blood. These compensatory mechanisms are able to maintain a normal ICP for any change in volume less than approximately 100–120 mL. Normal ICP depends on age and body posture. Normal ICP in a supine healthy adult ranges between 8 and 15 mm Hg. In the vertical position it is negative with an approximate mean of −10 mm Hg but not exceeding −15 mm Hg. Normal values of ICP Normal intracranial pressure New-born
2 mm Hg
Infants
2-5 mm Hg
8 year old
8-15 mm Hg
Intracranial hypertension is associated with poor neurologic outcome. In the neurointensive care unit, continuous ICP monitoring is predominantly used to help target therapies to maintain adequate CPP (mean arterial blood pressure – ICP), minimize intracranial hypertension, and monitor trends in ICP. Although no randomized controlled trials have been conducted to assess the utility of ICP monitoring, it is generally widely accepted as an essential tool in major paediatric centres to guide therapies for the treatment of severe TBI. ICP can be measured through the placement of an external strain gauge transducer, a catheter tip pressure transducer, or a catheter tip fiberoptic transducer. External 229
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strain gauge devices measure ICP via transduction through fluid-filled lines. The external device must be placed with reference to the head for accurate measurements. Complications in measurement most commonly arise from line obstruction. Catheter tip devices are calibrated and then placed in the parenchyma or coupled to a ventricular catheter. They are susceptible to measurement drift after several days of use if not replaced. Choice of measurement device is made on the basis of the mechanism and severity of injury and accessibility of the ventricles. Ventricular devices have the added benefit of CSF drainage. As secondary brain injury occurs, oedema increases and cerebral blood flow decreases with ensuing ischemia. Goals of ICP monitoring revolve around adjusting therapies to maintain CPP greater than 40 mm Hg (and higher for the older child) and ICP less than 20 mm Hg, based on studies showing increased mortality rates at lower CPP and higher ICP. Patients with TBI likewise must continue to maintain normal blood pressure and adequate oxygenation during this time to prevent further ischemic damage. Ct Scanning and Surgical Mass Evacuation Head CT scanning should be performed after initial resuscitation in all patients, regardless their age, with TBI to establish a baseline and assess initial damage. Neurosurgeons evaluate the potential need for surgical intervention, such as evacuation of a mass or clot. The timing of repeat CT scanning is determined by the response to therapy. Repeat CT scanning should be considered whenever significant deterioration in status occurs or increased ICP persists despite interventions. Sedation and Neuromuscular Blockade If initial manoeuvres are unsuccessful in controlling ICP, sedation and neuromuscular blockade should be considered. Paralysis can be facilitated through intermittent boluses versus continuous infusion. Benefits of paralysis include the prevention of shivering, thus decreasing metabolic demands and oxygen consumption; improved cerebral venous drainage through decreased intrathoracic pressure; and ease of ventilation and oxygenation by elimination of competition. Concerns regarding neuromuscular blockade with specific consideration of brain injury include masking of seizure activity, secondary complications due to ineffective pulmonary toilet, and increased stress and ICP related to inadequate sedation and analgesia. In the new guidelines there is a level III recommendation that thiopental may be used and also that etomidate may be considered to control severe intracranial hypertension but that the risk resulting from adrenal suppression should be considered when giving etomidate. Appropriate sedatives and paralytics Sedation
Paralysis
Etomidate 0.3 mg/kg
Rocuronium 1 mg/kg
Thiopental 3-5 mg/kg
Vecuronium 0.3 mg/kg
Fentanyl 2-4 mcg/kg Midazolam 0.1-0.2 mg/kg 230
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Cerebrospinal Fluid Drainage Ventricular drains have long been used for the drainage of cerebrospinal fluid in patients with hydrocephalus. With the advent of ventricular ICP monitoring, ventricular drainage for patients with increased ICP became an interesting concept. With removal of CSF, total intracranial fluid volume is reduced, and subsequently, ICP decreased and cerebral perfusion improved. In addition, in an attempt to optimize CSF drainage, lumbar drains have also been placed in patients who have a ventricular drain already in place and exhibit small ventricles. Of note, to avoid acute herniation, these patients should have open basal cisterns and no mass effect or midline shift prior to placement of the lumbar drain. Hyperosmolar Therapy Mannitol has long been successfully used to treat increased ICP in adult and paediatric populations. More recently, hypertonic saline has been shown to also be an effective therapy for intracranial hypertension. More research in this area is needed to compare the effectiveness of hypertonic saline and mannitol in the paediatric population. Mannitol is an osmolar agent with rapid onset of action via 2 distinct mechanisms. In TBI the dose for mannitol is between 0.25 gram- 1 gram per kg of bodyweight. Initial effects of mannitol result from reduction of blood viscosity and a reflex decrease in vessel diameter to maintain cerebral blood flow through autoregulation. This decrease in vessel diameter contributes to decreasing total cerebral fluid volume and pressure. Patients must be euvolaemic at the time of administration. This mechanism of action is transient and requires repeated dosing for prolonged effect. Mannitol exhibits its second mechanism of action through is osmotic effects. It increases serum osmolality; thus, water is shifted from intracellular compartments to the intravascular space, and cellular oedema is decreased. Although slower in onset (15-30 min), this mechanism lasts up to 6 hours in duration. Pitfalls of mannitol include its potential to accumulate in regions of cerebral damage and to cause a reverse osmotic shift, therefore increasing intracranial oedema and pressure. For this reason, intermittent mannitol boluses rather than continuous infusions are recommended. Also, mannitol has been linked to acute tubular necrosis and renal failure at serum osmol levels greater than 320 mOsm/L. Because mannitol is a potent diuretic, euvolaemia should be maintained to avoid deleterious side effects. Hypertonic saline has been emerging in the literature as a successful therapy in the reduction of ICP. In TBI the effective dose for acute use range between 6.5 ml and 10 ml per kg of bodyweight. Hypertonic saline, typically 3% saline, has an osmolar mechanism of action similar to that of mannitol, without the diuretic effects. Patients with TBI appear to tolerate a higher osmolar load with the use of hypertonic saline rather than mannitol. In recent studies, patients using hypertonic saline have tolerated serum osmolalities of up to 360 mOsm/L. However, reversible renal insufficiency has been noted with the use of hypertonic saline when serum osmolality approached 360 Osm/L. Added theoretical benefits of hypertonic saline include improved 231
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vasoregulation, stimulation of atrial natriuretic peptide release, improved cardiac output, immune modulation, and plasma volume expansion. Risks of hypertonic saline administration include rebound intracranial hypertension after withdrawal of therapy, central pontine myelinolysis with rapidly increasing serum sodium levels, subarachnoid haemorrhage due to rapid shrinkage of the cerebrum and tearing of bridging veins, and renal failure. More investigation is needed to delineate the adverse effects of hypertonic saline. Hyperventilation Although ventilation at the higher end of eucapnia may be beneficial in decreasing ICP, whether further reduction in PaCO2 yields additional benefit and improves outcome is unclear. Hyperventilation has the potential to reduce ICP via reflex vasoconstriction in the presence of hypocapnia. The vasoconstriction leads to decreased cerebral blood flow, decreased overall cerebral fluid volume, and therefore, decreased ICP, improved perfusion, and decreased oedema. In addition, hyperventilation is thought to limit cerebral acidosis and improve metabolism. In cases of refractory intracranial hypertension, mild hyperventilation (PaCO2 of 30-35 mm Hg) may be beneficial in decreasing ICP. It should, however, be avoided in the first 48 hours after the trauma and if it is applied then advanced neuromonitoring for evaluation of cerebral ischemia may be considered. Difference Between Ventilation Rates for Eucapnea and Hyperventilation Eucapnia
Hyperventilation
Infants ( 6 h posttraumatic). Fibrinogen was the most affected coagulation factor in our analysis (52%). The correlation between the initial and follow-up CT scans of patients with early/sustained coagulopathy showed progressive traumatic intracerebral hemorrhages more frequently than in patients with early/short-lasting coagulation and patients with delayed coagulopathy. 12 patients (5.2%) who were not under treatment with anticoagulants or platelet inhibitors demonstrated platelet dysfunction detected using platelet function analyzer (PFA-100). In addition, the in-hospital mortality rate (42 patients, 18.5%) significantly increased in the early coagulopathy patients’ group (27/42 patients, 64.2%) compared to the other groups with delayed coagulopathy or without coagulopathy (15/42, 35.8%). Patients’ functional outcome showed the highest percentage of severe disability – mRS 4 or 5 — occurring in the early/sustained coagulopathy group (75.5% of severe disability cases). Furthermore, patients with early/sustained coagulopathy had the longest ICU stay (18.3 vs. 4 d) and ventilation time (320 vs. 68 h). Conclusions In Patients with TBI early/sustained coagulopathy is more frequently associated with progressive traumatic intracerebral hemorrhage, with longer ICU stay, and unfavorable outcome than delayed or early/short-lasting coagulopathy. These data emphasize the importance of initial comprehensive analysis of the coagulation status. A rapid correction of early coagulopathy has to be an indispensable part of the treatment of TBI patients to improve their short- and long-time prognosis.
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LOCAL FIBRINOLYSIS FOR THE SURGICAL TREATMENT OF TRAUMATIC INTRACRANIAL HEMORRHAGE Horbatyuk Kostyantyn Neurosurgical department of Vinnitsa Regional Phycho-Neurological hospital, Vinnitsa, Ukraine Medvedeva str.36, Vinnitsa, Ukraine 21036
[email protected] phone: 00 38 097 999 47 51 Introduction Over the past few decades conducted search of low-invasive techniques for surgery of traumatic intracranial hematomas. We found that local application of fibrinolytics for intracerebral hypertensive hemorrhage clot lysis is successfully used since middle 80’s, so we applied this method for surgery of traumatic epidural and subdural hematomas. Material and Methods We operated 16 patients with epidural hemorrhage, and 24 with subdural, 32 males and 8 females. All operated patients were between 11 and 15 GCS. Volume of hemorrhage varied from 30 to 100ml, average 58ml. We made burrhole trepanation, and drainage of hematoma. Every 6 hours we infused 50 000 streptokinase or 50 000 urokinase, beforehand aspirated liquid (lysed) part of haematoma through drainage. CT control was performed every 24 hours of lysis procedure. Results As a usual to remove more than 70% of clots we were need 24-36h. We have 2 rebleeding cases with epidural hematomas, and no rebleeding in subdural hematoma patients, there were no signs of system fibrinolytics effect. 39 patients were discharged from hospital with good recovery, 1 with mild disability. Conclusion We found local fibrinolysis application in surgery of traumatic intracranial hematomas promising effective method, wich allows to perform interventions under local anesthesia (31 patients), reduces surgical invasiveness, and surgical risk in elderly and somatic grave patients; also it allows to activate the patients in the shortest possible time after the operation and to reduce the time of their stay in hospital. We suggest that local fibrinolysis is good for subdural hemorrhage aspiration. For draining of epidural hemorrhages it can be used only if standart operation is associated with high risk in somatically grave and elderly patients.
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SURGERY FOR TEMPORAL LOBE EPILEPSY IN CHILDREN: RELEVANCE OF PRESURGICAL EVALUATION AND ANALYSIS OF OUTCOME Anna Miserocchi MD (1), Beatrice Cascardo Dr (2), Chiara Piroddi Dr (2), Dalila Fuschillo MD (1), Francesco Cardinale MD (1), Lino Nobili MD (1), Stefano Francione MD (1), Giorgio Lo Russo MD (1), Massimo Cossu MD (1) 1. C. Munari” Epilepsy Surgery Centre Niguarda Hospital, Milan, Italy 2. Cognitive Neuropsychology Centre, Neuroscience Department, Niguarda Hospital, Milan, Italy. Introduction Increasing evidence suggests the importance of surgical resections to achieve seizure freedom in cases of paediatric focal symptomatic epilepsy. Although less frequent than in adults, temporal lobe epilepsy (TLE) represents a substantial problem also in childhood. The favourable outcome of epilepsy surgery is the result of an appropriate selection of candidates and of an accurate presurgical evaluation, aimed at the identification of the epileptogenic zone. In this study we reviewed the presurgical pathway that led to surgical indication. An exhaustive analysis of electroclinical data, seizure semeiology and MRI data was sufficient in most of the cases to candidate the patient for surgery. Methods We performed a retrospective analysis of the 68 patients (43 males, 25 females) who underwent resective surgery for TLE between 2001 and 2010, with a minimum postoperative follow-up of 12 months. Presurgical investigations included: full clinical evaluation, interictal EEG, Magnetic Resonance Imaging (MRI) in all cases; cognitive evaluation in patients over five years of age; scalp video-EEG in 46 cases and invasive EEG in three cases. Clinical evaluation included a careful assessment of ictal semiology. Microsurgical resections were performed within the anatomical limits of the temporal lobe. Surgical specimens were processed for histological examination. Postoperative assessment of seizure outcome (Engel’s scoring scale) and cognitive performance were conducted at regular intervals. The effect on postoperative seizure outcome (good = Engel’s class I; poor = Engel’s classes II-IV) of several presurgical and surgery-related variables was investigated by bivariate statistical analysis. Results All patients had at least one early sign/symptom suggesting the temporal lobe origin of their seizures. Lateralized interictal or ictal EEG abnormalities were seen in all cases, and in 45 they were localised to the temporal lobe. In all cases MRI demonstrated a structural abnormality. Surgery consisted of a tailored anterior temporal lobectomy in 64 cases, and in a neocortical lesionectomy in four cases. Postoperatively, 58 cases (85%) were in Engel’s class I. Variables significantly associated with a poor outcome were: preoperative sensory motor deficit (p=0,019) or mental retardation (p=0,003), MRI abnormalities extending outside the temporal lobe (p=0,0018), history of generalized seizures (p=0,01) or status epilepticus 251
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(p=0,008), unremarkable histology (p=0,001), immediate postoperative seizures (p=0,00001), ipsilateral epileptiform activity at postoperative EEG (p=0,005). At postoperative neuropsychological assessment, the percentage of patients with a pathological score at the final control invariably dropped compared to the preoperative evaluation in all the considered cognitive domains. Conclusions Surgical management of TLE in children is a safe and effective treatment option and may provides excellent results on seizures. Selection can be achieved with the invaluable information resulting from the rigorous non-invasive electroclinical and neuroimaging evaluation.
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THE WARNING SIGN HIERARCHY BETWEEN QUANTITATIVE SUBCORTICAL MOTOR MAPPING AND CONTINUOUS MOTOR EVOKED POTENTIAL MONITORING DURING SURGERY OF SUPRATENTORIAL BRAIN TUMORS Kathleen Seidel, Jürgen Beck, Lennart Stieglitz, Philippe Schucht, Andreas Raabe Department of Neurosurgery, Inselspital, Bern University Hospital, Switzerland Mapping and monitoring are believed to provide an early warning to avoid damage to the corticospinal tract (CST) during tumor surgery. This study compared subcortical mapping thresholds (MT) with direct cortical stimulation (DCS) motor evoked potential (MEP) monitoring signal abnormalities in 100 patients. Evaluation was done regarding the lowest subcortical MT (monopolar stimulation, train of 5 stimuli, 4.0ms inter-stimulus interval, 0.5ms pulse duration) and signal changes of DCS-MEP (same parameters, 4-contact strip electrode). Motor function was assessed one day after surgery, at discharge, and at 3 months post-operative. Lowest individual motor thresholds (MT) were as follows (MT in mA, number of patients): >20 mA, n=12; 11-20 mA, n=13; 6-10 mA, n=20; 4-5 mA, n=30; 1-3 mA, n=25. DCS showed stable signals in 70 patients, unspecific changes in 18, irreversible alterations in 8, and irreversible loss in 4 patients. At 3 months, 5 patients had a postoperative new motor deficit (lowest mapping MT 20mA, 13mA, 6mA, 3mA, 1mA). All 5 cases presented DCS-MEP alterations (2 sudden irreversible threshold increases and 3 sudden irreversible MEP losses). Of these cases, 2 had vascular lesions (MT 20mA, 13mA) and 3 had mechanical CST damage (MT 1mA, 3mA and 6mA; in the latter two resection was continued after mapping and severe DCS-MEP alterations occurred thereafter). 80% of patients with a mapping MT of 1-3 mA showed stable DCS-MEP or unspecific reversible changes and none had a permanent motor worsening at 3 months. In contrast, 25% of patients with irreversible DCS-MEP changes and 75% of patients with irreversible DCS-MEP loss had permanent motor deficits. Mapping should primarily guide tumor resection adjacent to the CST. DCS-MEP is a useful predictor of deficits, but limited because signal alterations were reversible in only 60% of cases. The true safe mapping MT is lower than previously thought. We postulate a mapping MT of 1mA or less where irreversible DCS-MEP changes and motor deficits regularly occur. The limited spatial and temporal coverage of contemporary mapping may increase error and may contribute to false higher MTs.
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SUBCORTICAL STIMULATION Ehab Shiban(1), Sandro M. Krieg(1), Maria Wostrack(1), Thomas Obermueller(1), Doris Droese(2), Bernhard Meyer(1), Florian Ringel(1) 1. Department of Neurosurgery, Technische Universität München, Munich, Germany; 2. Department of Anesthesiology, Technische Universität München, Munich, Germany Background Subcortical stimulation is a method to evaluate the distance from the stimulation site to the motor tract (CST) and to decide whether the resection should be terminated. A clear correlation between stimulation intensity and the distance to the CST has not been properly substantiated. To date various reports with different stimulation conditions have reached different results. Objective The aim of this study was to investigate various stimulation conditions in order to better define the correlation between the subcortical stimulation and the distance to the CST Methods Monopolar subcortical stimulation (mSCS) was performed in addition to continuous MEP monitoring in 37 consecutive patients with a motor eloquent lesion. The functional boundaries of the resection were identified with the help of subcortical stimulation. At the end of resection, the point at which a MEP response was still measurable with minimal subcortical stimulation intensity was marked with a titanium clip was. At this point different stimulation variants were examined with cathodal or anodal stimulation at 0.3, 0.5 and 0.7 ms pulse duration, respectively. The distance between the CST (based on the postoperative DTI data) and the titanium clip was measured. The correlation between the distance and the mSCS the electric charge (µCoulumb) was calculated. Results mSCS was successful in all patients. One patient developed a postoperative bleed and displacement of the titanium clip and was therefore excluded from the study. There were no new postoperative deficits. Transient new postoperative neurological deficit was observed in 14% (5/36) of cases. Gross total resection was achieved in 75% (27/36) and subtotal resection (>80% of tumor mass) in 25% (9/36) of cases. Current intensity ( mA x ms) was blotted agains the mesuered distance between the CST and the titanium clip. Regression Analysis revield a nonlinear correlation. For anodal stimulation : Current = Distance**0,709 (R2= 0,865). For cathodal stimulation : Current = Distance**0,606 (R2 = 0,889)
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Conclusion The subcortical stimulation is an excellent intraoperative method to determine the distance to the CST during resection of motor eloquent lesions. This should minimize the risk of injuring the CST. There is a nonlinear correlation between stimulation current and the distance to the CST.
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ADDITIONAL TRAINEE ABSTRACTS
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EMERGENCY LUMBAR DISC SURGERY: IS IT SAFE? Shadi Al-Afif, Zafer Cinibulak, Mohammed Jabarin, Kerstin Schwabe, Joachim K. Krauss Department of the Neurosurgery, Medical School Hannover, Hannover, Germany Introduction Lumbar disc surgery is widely practiced and is considered a safe procedure in general. The rate of complications has been low but variable in several studies. It was suggested, that the following factors could represent risk factors for complications: age of the patient, experience of the surgeon, reoperation for recurrent herniation and emergency surgery. Here we evaluated, whether complications rates indeed are higher in emergency operations as compared to elective surgery. Methods Patient data sets from 498 microscopic lumbar disc surgeries were evaluated in a retrospective study design. Recurrent disc herniations were excluded. Age at surgery ranged between 22 and 96 years (mean age 56 years). A total number of 38 patients (7.6%) were operated as an emergency during the day or the night of admission (group N), whereas 460 patients (92.4) were operated electively (group E). The incidence of dural tears, the frequency of intra- and perioperative complications (wound infection, wound hematoma, nerve root injury), the rate of recurrent disc herniation, and the length of hospital stay were evaluated. Results There were no statically significant differences between the tow groups with regard to the incidence of dural tears (in group N 7.9%, in group E 4.3%, P= 0.32), the rate of complications (in group N 2.6%, in group E 2.8%, P=0.95), the rate of recurrent disc herniation (in group N 10.5%, in group E 8.9%, P=0.74) and the length of the hospital stay (P=0.35). Conclusion Emergency lumbar disc surgery has a similar safety profile like the elective surgery. Patients who present with cauda equina syndrome or progressive neurological deficits and need surgery on the day or the night of admission are not exposed to a higher risk of surgery.
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EFFECTIVE MANAGEMENT OF LOWER DIVISIONAL PAIN IN TRIGEMINAL NEURALGIA USING BALLOON TRACTION Mario Teo, Nigel Suttner, P. Barlow Department of Neurosurgery, Institute of Neurological Science, Glasgow, UK Objective Percutaneous balloon compression (PBC) of the trigeminal ganglion uses a differential injury of axons to interfere with the nerve’s ability to transmit signals. Due to the difficulty in achieving effective pain relief for lower divisional pain in trigeminal neuralgia, we described a modification to the technique, and present our experience to date. Design Retrospective analysis of prospectively collected data Subject From 1 January 2000 to 1 January 2010, 155 procedures were performed on 83 patients with trigeminal neuralgia refractory to medical treatment or failure of a previous surgical procedure, using PBC of the trigeminal ganglion. Method In patients with lower divisional pain, controlled traction was applied to the No.4 Fogarty catheter for the duration of the balloon compression. Meticulous examination for facial numbness was performed on day 1, and at follow-up. Retrospective analysis of prospectively collected data was performed. Result 27 males and 56 females, age range 32 to 87 years old (median 72 years), 17 patients (20%) had multiple sclerosis. 13 patients had V3 pain, 35 patients V2 and V3 pain, and all three divisions were affected in 8 patients. 41 patients had previous surgical procedures. Controlled traction was applied in 107 procedures with 74 (69.2%) experiencing V3 numbness and 87% experienced pain relief. This is in contrast to 8 procedures out of 38 (21%) in which no traction was applied, experiencing V3 numbness on day 1 post procedure (p 30% in 9 cases. In those with PLC bigger than 30%, operative time (P=0.02) and blood loss (P=0.05) reduced significantly compared to other groups. The average angle obtained was 33.5º with a median of 33.5º. No significant clinical changes in outcome was observed between groups. Conclusions No relationship was found between PLC and work angle with clinical outcome. Bigger craniotomies seem to reduce operative time and blood loss.
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COMBINED TRANSCRANIAL-ENDONASAL APPROACH FOR AN ESTHESIONEUROBLASTOMA WITH INTRADURAL INVASION ZOIA C. (1), Turri Zanoni M. (2), Tabano A. (1), Castelnuovo P. (2), Tomei G. (1) 1. NEUROSURGICAL CLINIC, UNIVERSITA’ DELL’INSUBRIA, OSPEDALE DI CIRCOLO, VARESE 2. ENT Clinic, Università dell’Insubria , Ospedale di Circolo, Varese Introduction The traditional approach to sinonasal tumors with cranial-base invasion is transcranial-transfacial. In our experience is possible to achieve a total resection of this kind of lesions also with a pure endoscopic approach; the combined transcranialendonasal approach could be necessary in some selected cases, specially when the lesion has an intradural extension. Methods We report an illustrative case of an operation for an Esthesioneuroblastoma with intradural invasion (Hyams III, T4b N0 M0, Kadish C) in wich we used the combined transcranial-endonasal approach. Results Thanks to the transcranial-endonasal tecnique and to the collaboration between neurosurgeons and Ent-surgeons was possbile to achieve a total resection of the lesion and to minimize the operatory risks. Conclusions The combined transcranial-endonasal approach allow to better dominate the sinonasal lesions with intradural extension and to reach, in most of cases, a total resection of them.
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