J Neurosurg Pediatrics 10:315–319, 2012
Intraventricular baclofen as an alternative to intrathecal baclofen for intractable spasticity or dystonia: outcomes and technical considerations Clinical article Michael Turner, M.D., Ha Son Nguyen, B.S., and Aaron A. Cohen-Gadol, M.D., M.Sc. Goodman Campbell Brain and Spine, Indiana University Department of Neurological Surgery, Indianapolis, Indiana Object. The aim of this study was to identify the benefits of intraventricular baclofen (IVB) therapy for the treatment of intractable spasticity or dystonia in a subset of patients who had experienced multiple revisions while receiving intrathecal baclofen (ITB) therapy. Methods. The authors reviewed the charts of 22 consecutive patients with intractable spasticity or dystonia who initially underwent ITB therapy, subsequently suffered multiple revisions during ITB therapy, and ultimately received IVB therapy, all during a 12-year period from November 1998 to October 2010. The intraventricular catheters were positioned in the lateral ventricle, aided by stereonavigation. Results. The surgical revision rate (the average number of surgical revisions per average number of follow-up years) during ITB therapy was 0.84, and was 0.50 during IVB therapy. The most frequent complication requiring surgical revision during ITB therapy was catheter occlusion, followed by pump malfunction/pump pocket issues, and infection. The most frequent complication requiring surgical revision during IVB therapy was infection, followed by catheter misplacement/migration. Four patients suffered infection that required removal of their intraventricular catheter, and currently have no baclofen system. Conclusions. Some of these patients had a history of increasing revisions with increasing frequency during ITB therapy. Such a history puts them at risk for spinal arachnoiditis, a condition that complicates further ITB therapy. For such patients, the authors believe that IVB therapy may be a beneficial therapeutic option, given that the surgical revision rate was lower for IVB than for ITB. Intraventricular baclofen may be a cost-effective option for patients with mounting revisions during ITB therapy. (http://thejns.org/doi/abs/10.3171/2012.6.PEDS11456)
Key Words • intrathecal baclofen • intraventricular baclofen • spasticity • cerebral palsy • functional neurosurgery
S
the mid-1980s, ITB has been used to treat medically refractory spasticity caused by various conditions, including cerebral palsy, traumatic brain and spinal cord injury, and multiple sclerosis.19,24–26 Subsequently, ITB became a therapeutic option for dystonia in the 1990s.3–5,15,16 Several studies have described beneficial outcomes from ITB systems, reporting patient satisfaction,11 patient goal attainment,34 and cost effectiveness.13 Nevertheless, ITB systems are associated with ince
Abbreviations used in this paper: ITB = intrathecal baclofen; IVB = intraventricular baclofen.
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numerous catheter (fracture, occlusion), pump (malfunction, rotation), and wound complications (infection, dehiscence).22,32,33 These issues necessitate additional surgical intervention, leading to multiple revisions. Recently, a few studies have reported the use of IVB in refractory spasticity or dystonia. Albright and Ferson7 reported the use of IVB for dystonia with favorable results.7 Haranhalli et al.19 used IVB in 2 patients after multiple complications from ITB. In the present study, the authors report the outcomes of a series of 20 patients who were treated with IVB therapy after increasing revisions during ITB therapy. 315
M. Turner, H. S. Nguyen, and A. A. Cohen-Gadol Methods
Surgical Procedure for IVB
Patient Selection
We reviewed the charts of 22 consecutive patients with intractable spasticity or dystonia who initially underwent ITB therapy, subsequently suffered multiple complications from their ITB therapy, and ultimately received IVB therapy, all during a 12-year period from November 1998 to October 2010 (Table 1). We could not retrieve follow-up information for 2 patients, and their data were excluded from the study. The 20 other patients included 6 females and 14 males. The patients’ ages ranged from 4 to 65 years (mean 23 years) during the initial intrathecal catheter placement, and from 6 to 68 years (mean 27 years) during the initial intraventricular catheter placement. The causes of the spasticity/dystonia of the patients included cerebral palsy (n = 11), spinal cord injury (n = 4), traumatic brain injury (n = 2), cerebrovascular accident (n = 1), mitochondrial dystrophy (n = 1), and iron deposition disorder (n = 1). The follow-up period ranged from 0.5 to 121 months (mean 62 months) for ITB and from 2 to 57 months (mean 20 months) for IVB. Four patients (Cases 2, 6, 9, and 14) had a concomitant ventriculoperitoneal shunt, whereas 2 patients (Cases 19 and 20) had a history of spinal fusion.
The patient was placed supine and a surgical navigation system was calibrated using tracer technology. An entry point in the right or left posterior parietal region was identified near Keen’s point. Subsequently, the abdominal incision over the previous ITB pump was reopened and dissected down to the old catheter, which was disconnected from the pump. The spinal segment of the previous ITB catheter was then ligated and returned to the pump pocket. A bur hole was then made at Keen’s point and the new catheter was tunneled subcutaneously between the bur hole and the abdominal incisions. The ventricular catheter was directed into the ventricle using stereotactic neuronavigation. Once good CSF flow was determined, the ventricular catheter was trimmed and connected to the other catheter, which was tunneled subcutaneously between the incisions using a connector. The other end of the catheter was attached to the pump. The pump was then programmed to prime the catheter.
Results
There were a total of 82 complications noted in these 20 patients while using ITB (Table 2). Catheter-related complications constituted 67.1% (n = 55) of the total complications, whereas pump-related complications consti-
TABLE 1: Characteristics of 20 consecutive patients with intractable spasticity or dystonia who initially underwent ITB therapy and eventually received IVB therapy* ITB
IVB
Case No.
Sex
Indication
Age (yrs)
No. of Revisions
F/U (mos)
Age (yrs)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 average
M M M M M M M F M M M M F F F F M M M F
CP CP IDD TBI SCI CP TBI CP CP CP SCI SCI CP CP CP CVA CP MD SCI CP
19 15 4 13 65 9 20 20 16 5 37 34 56 7 14 37 9 8 37 28 22.65
6 5 4 1 3 5 3 3 3 3 4 2 6 2 12 7 1 6 6 5 4.35
113.6 59.9 121.4 33.4 39.6 65.5 48.2 79.8 110.9 15.0 34.6 9.2 93.4 83.4 48.2 66.7 0.5 21.0 87.7 107.9 62.0
28 20 14 16 68 14 24 27 26 6 40 34 64 14 8 42 9 10 44 37 27.25
No. of Revisions 0 4 0 1 0 1 1 0 2 0 0 0 2 1 0 0 1 3 1 0 0.85
F/U (mos)
Baclofen Dose (μg/day)†
4.6 6.9 2.2 6.3 48.7 46.9 14.6 35.5 32.4 6.3 26.3 18.1 19.9 39.2 57.1 2.5 2.2 6.5 19.5 11.4 20.4
1045 none 481.9 none 300 762 1440 399.7 350 165 500 342.2 400 none 1589.5 100 644.5 180 none 170 554.4
* CP = cerebral palsy; CVA = cerebrovascular accident; F/U = follow-up; IDD = iron deposition disorder; MD = mitochondrial dystrophy; SCI = spinal cord injury; TBI = traumatic brain injury. † Cases 2, 4, 14, and 19 did not have a final baclofen dose because their intraventricular catheters were removed.
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A comparison of intraventricular and intrathecal baclofen TABLE 2: Numbers and types of complications in each group* Complication
ITB
IVB
catheter occlusion pump malfunction/pump pocket issues infection catheter fracture/leak catheter misplacement/migration catheter kink baclofen withdrawal catheter disconnection seroma total
31 13 10 9 9 4 3 2 1 82
1 3 7 0 6 1 0 0 0 18
* Includes catheter tip loculations, subdural catheters, and catheter malfunctions without identifiable causes.
tuted 15.9% (n = 13). Spiral computed tomography with contrast injection, as outlined in our previous article,31 was used as indicated to diagnose some of these complications. The most common complication was catheter occlusion, followed by pump complications, infection, and catheter fracture. The average time before the first ITB system experienced any complication was 27.6 months. The average time between the last ITB revision and the initial intraventricular catheter placement was 12.9 months. There were a total of 18 complications noted in 10 of 20 patients while using IVB. Catheter-related complications constituted 44% (n = 8) of the total complications, whereas pump-related complications constituted 16.7% (n = 3). The most common complication was infection, followed by catheter migration/misplacement. The first complication occurred, on average, 7.4 months after placement of the initial intraventricular catheter. Overall, 87 surgical revisions occurred during ITB therapy and 17 during IVB therapy. The revision rate (the average number of surgical revisions per average number of follow-up years) during ITB therapy was 0.84, and was 0.50 during IVB therapy. Currently, 4 patients (Cases 2, 4, 14, and 19) have no IVB system due to infection. One patient (Case 15) received globus pallidus internus deep brain stimulation while under treatment with IVB.
Illustrative Case
This 28-year-old man (Case 1, Table 1) presented with a history of intractable spasticity secondary to cerebral palsy. The patient underwent placement of an initial ITB system when he was 19 years old. After that time, he had chronologically encountered 2 infections, a catheter extrusion, and 3 catheter occlusions (1 instance associated with a fracture). Due to his recurrent complications with ITB, it was believed that IVB would be a better alternative. After placement of the intraventricular catheter, the pump was programmed at 1442 μg/day, the same rate as when the patient was on ITB. On postoperative Day 1, the patient was very sleepy; he would respond to touch, but would nod off if he had no stimulation. For the next few days, the dose was decreased sequentially to 1161 μg/ J Neurosurg: Pediatrics / Volume 10 / October 2012
day and then to 1045 μg/day, at which point the patient became more responsive. At discharge, the patient was awake and alert. Currently, the patient has been on IVB therapy for 4.6 months with no complications.
Discussion
In the 1980s, Penn et al.24,26,27 first reported the usage of ITB in humans. Since that time, ITB has been employed to treat spasticity caused by spinal cord injury,25,26,27 multiple sclerosis,25,26,27 cerebral palsy,6 and traumatic brain injury.10,17 Benefits using ITB have also been attained for patients with dystonia.3–5,15,16 Sampson et al.29 determined that continuous ITB provided a suitable cost-benefit ratio for select patients who had not gained adequate relief from less invasive therapy, who were bedridden due to severe spasticity, or who were dependent on a wheelchair while suffering from severe spasm-related pain. The percentage of patients with complications from ITB requiring surgical management has ranged from 16%–33% in various studies.11,19,22,32 Of these patients, 18%–47%19,22,33 suffered from more than 1 complication. Common issues included infection, catheter-related problems (catheter disconnections, fractures, and malfunctions), and CSF leaks.22,33 Our patients suffered from multiple complications related to continuous ITB; the majority of these complications were catheter- or pump-related. A cost analysis of continuous ITB for severe spinal spasticity demonstrated that approximately two-thirds of the costs can be attributed to pump implantation and related hospitalization, while roughly one-fifth can be attributed to complications.28 Savings originated from withdrawal of oral medication, job preservation, and avoidance or delay of admission to a nursing home.28 Obviously, a method to reduce the incidence of these complications, especially for patients with a history of past complications, would effectively reduce the total cost of baclofen therapy. Our surgical revision rate was lower for IVB than for ITB, suggesting that IVB may be a costeffective option for patients with increasing revisions during ITB therapy. Recently, Albright and his colleagues reported the use of IVB for the treatment of 10 patients with either severe secondary generalized dystonia or degenerative dystonia.2,5,7 Their indications for IVB included a lack of response to ITB, spinal deformity, and/or clinical impression that IVB would elicit a better response than ITB. They noted that patients with a history of intraventricular hemorrhage or meningitis should undergo a flow study to assess the benefits of IVB. Haranhalli et al.19 reported on 2 patients with dystonia who underwent IVB therapy after multiple catheter-related complications from ITB therapy; the cause of these complications was linked to severe writhing from excessive truncal dystonic movements. Similarly, our indications for IVB therapy included spasticity refractory to ITB and/or a history of increasing complications. Albright and colleagues endoscopically positioned the catheter within the third ventricle.1,7 Past studies have suggested that baclofen acts at the cerebral convexities when treating generalized dystonia, inhibiting the stimu317
M. Turner, H. S. Nguyen, and A. A. Cohen-Gadol lation of the premotor and supplementary motor cortex.30 Infusion into the lateral ventricles might introduce baclofen into regions of stagnate flow and cause regional toxicities; on the other hand, infusion within the third ventricle may disseminate with CSF via the aqueduct and fourth ventricle, while maintaining a high concentration once CSF reaches the cerebral convexities.1,7 Albright and colleagues reported an average IVB dosage of 303 μg/day, although a value of 2012 μg/day was considered an outlier and consequently was excluded from analysis.1,7 Moreover, 2 of the patients did not respond to IVB infusion; they also had not responded to high-dose ITB infusion. Our average IVB dosage was 554.4 μg/day (Table 1). One possible explanation for the different values between the 2 studies may be the different patient populations (patients with dystonia compared with patients with spasticity). Albright and Ferson7 reasoned that IVB may be less efficacious for patients with spasticity, because baclofen needs to reach the spinal cord level, whereas it needs to reach the cerebral convexities for dystonia. This theory would support the need for a higher average dose among our patients. In another study, 5 the ITB dosage was noted to be higher for patients with generalized dystonia compared with those with spasticity. Overall, there may not be a correlation between ITB dose and corresponding CSF baclofen level;8 therefore, inferring patterns from IVB dosages may be inconsequential. Park23 did caution against the potential toxicities of baclofen, noting the deaths of 2 beagles at high doses of IVB in a prior study.2 Albright agreed that the deaths were likely due to obtundation and profound systemic hypotonia that occur with severe baclofen overdosing.23 Nevertheless, similar to our findings, Albright reported that no patient exhibited any sign of overdose while on IVB therapy.23 Catheter occlusions constituted the majority of complications during ITB therapy in our patient population. Arachnoiditis may explain the high incidence of catheter occlusions. Baclofen itself does not induce inflammation.14 However, our patients harbored preexisting neurological disease, infection, and trauma and had undergone previous surgical spinal interventions, which are risk factors for arachnoiditis.9 Recently, a rat model for spinal cord injury demonstrated that inflammatory cells and connective tissue could occlude chronic intrathecal tubing in the setting of active inflammation.20,34 Placement of the catheter within the spacious ventricle, a proximal CSF site lined by ependyma, rather than within the spinal canal and arachnoid-lined cavity, may decrease the risk of arachnoiditis. Catheter occlusions by choroid plexus or ependymal tissue have been reported.12,18,21 The high incidence of infection during IVB therapy may be attributable to the presence of a ventriculoperitoneal shunt. Five of the 7 infections associated with IVB therapy occurred in 2 of the 4 patients with a concomitant ventriculoperitoneal shunt. The same 2 patients currently do not harbor a baclofen system. Accurate catheter placement—typically ipsilateral to the shunt catheter—is a more prominent issue for IVB therapy. The ventricular catheter had to be revised for migrations to the choroidal fissure and perimesencephalic region. Catheter placement 318
was difficult for these patients due to their very small ventricles, which may be a limiting factor for IVB therapy. Of note, IVB dosing required some additional adjustments for the patients who harbored a ventriculoperitoneal shunt. This adjustment was necessary only during the initial period of IVB therapy, and these patients’ baclofen requirement reached a “steady state” after 1–2 months similar to those of other patients without a ventriculoperitoneal shunt. Our study has several limitations. We did not use a standard score to assess the level of spasticity or dystonia in our patients (such as the Ashworth scale and others). Furthermore, the follow-up period for ITB was significantly longer than that for IVB, affecting the rate of complications detected in the 2 groups. With time, our patients may endure more complications with IVB. In addition, with time, our threshold for considering IVB decreased; this phenomenon potentially provides a selection bias in our series.
Conclusions
The patients reviewed in this series had a history of revisions with increasing frequency during ITB therapy. Such a history puts them at risk for spinal arachnoiditis, a condition that further complicates ITB therapy. According to our data from this study, IVB therapy may afford a lower surgical revision rate. For select patients, we believe that IVB therapy may be a beneficial therapeutic option. Disclosure Dr. Turner serves as a consultant to Medtronic. Author contributions to the study and manuscript preparation include the following. Conception and design: Cohen-Gadol, Turner. Acquisition of data: Cohen-Gadol, Turner. Analysis and interpretation of data: all authors. Drafting the article: all authors. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Cohen-Gadol. References 1. Albright AL: Intraventricular baclofen infusion for dystonia. Report of two cases. J Neurosurg 105 (1 Suppl):71–74, 2006 2. Albright AL: Long-term intraventricular baclofen infusion in beagles. J Neurosurg 107 (3 Suppl):225–227, 2007 3. Albright AL, Barry MJ, Fasick P, Barron W, Shultz B: Continuous intrathecal baclofen infusion for symptomatic generalized dystonia. Neurosurgery 38:934–939, 1996 4. Albright AL, Barry MJ, Painter MJ, Shultz B: Infusion of intrathecal baclofen for generalized dystonia in cerebral palsy. J Neurosurg 88:73–76, 1998 5. Albright AL, Barry MJ, Shafton DH, Ferson SS: Intrathecal baclofen for generalized dystonia. Dev Med Child Neurol 43: 652–657, 2001 6. Albright AL, Cervi A, Singletary J: Intrathecal baclofen for spasticity in cerebral palsy. JAMA 265:1418–1422, 1991 7. Albright AL, Ferson SS: Intraventricular baclofen for dystonia: techniques and outcomes. Clinical article. J Neurosurg Pediatr 3:11–14, 2009 8. Albright AL, Thompson K, Carlos S, Minnigh MB: Cerebrospinal fluid baclofen concentrations in patients undergoing continuous intrathecal baclofen therapy. Dev Med Child Neurol 49:423–425, 2007
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A comparison of intraventricular and intrathecal baclofen 9. Aldrete JA: Neurologic deficits and arachnoiditis following neuroaxial anesthesia. Acta Anaesthesiol Scand 47:3–12, 2003 10. Becker R, Alberti O, Bauer BL: Continuous intrathecal baclofen infusion in severe spasticity after traumatic or hypoxic brain injury. J Neurol 244:160–166, 1997 11. Borowski A, Littleton AG, Borkhuu B, Presedo A, Shah S, Dabney KW, et al: Complications of intrathecal baclofen pump therapy in pediatric patients. J Pediatr Orthop 30:76–81, 2010 12. Collins P, Hockley AD, Woollam DH: Surface ultrastructure of tissues occluding ventricular catheters. J Neurosurg 48: 609–613, 1978 13. de Lissovoy G, Matza LS, Green H, Werner M, Edgar T: Costeffectiveness of intrathecal baclofen therapy for the treatment of severe spasticity associated with cerebral palsy. J Child Neurol 22:49–59, 2007 14. Deer TR, Raso LJ, Coffey RJ, Allen JW: Intrathecal baclofen and catheter tip inflammatory mass lesions (granulomas): a reevaluation of case reports and imaging findings in light of experimental, clinicopathological, and radiological evidence. Pain Med 9:391–395, 2008 15. Diederich NJ, Comella CL, Matge G, Becker G, Schiltz F, Metz H: Sustained effect of high-dose intrathecal baclofen in primary generalized dystonia: a 2-year follow-up study. Mov Disord 12:1100–1102, 1997 16. Ford B, Greene P, Louis ED, Petzinger G, Bressman SB, Goodman R, et al: Use of intrathecal baclofen in the treatment of patients with dystonia. Arch Neurol 53:1241–1246, 1996 17. François B, Vacher P, Roustan J, Salle JY, Vidal J, Moreau JJ, et al: Intrathecal baclofen after traumatic brain injury: early treatment using a new technique to prevent spasticity. J Trauma 50:158–161, 2001 18. Guevara JA, La Torre J, Denoya C, Zúccaro G: Microscopic studies in shunts for hydrocephalus. Childs Brain 8:284–293, 1981 19. Haranhalli N, Anand D, Wisoff JH, Harter DH, Weiner HL, Blate M, et al: Intrathecal baclofen therapy: complication avoidance and management. Childs Nerv Syst 27:421–427, 2011 20. Jones LL, Tuszynski MH: Chronic intrathecal infusions after spinal cord injury cause scarring and compression. Microsc Res Tech 54:317–324, 2001 21. Kaufman BA, Park TS: Ventricular anatomy and shunt catheters. Pediatr Neurosurg 31:1–6, 1999 22. Motta F, Buonaguro V, Stignani C: The use of intrathecal baclofen pump implants in children and adolescents: safety and complications in 200 consecutive cases. J Neurosurg 107 (1 Suppl):32–35, 2007 23. Park TS: Editorial. Intraventricular baclofen. J Neurosurg 107 (3 Suppl):224, 2007
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24. Penn RD: Drug pumps for treatment of neurologic diseases and pain. Neurol Clin 3:439–451, 1985 25. Penn RD, Kroin JS: Continuous intrathecal baclofen for severe spasticity. Lancet 2:125–127, 1985 26. Penn RD, Kroin JS: Intrathecal baclofen alleviates spinal cord spasticity. Lancet 1:1078, 1984 (Letter) 27. Penn RD, Savoy SM, Corcos D, Latash M, Gottlieb G, Parke B, et al: Intrathecal baclofen for severe spinal spasticity. N Engl J Med 320:1517–1521, 1989 28. Postma TJ, Oenema D, Terpstra S, Bouma J, Kuipers-Upmeijer H, Staal MJ, et al: Cost analysis of the treatment of severe spinal spasticity with a continuous intrathecal baclofen infusion system. Pharmacoeconomics 15:395–404, 1999 29. Sampson FC, Hayward A, Evans G, Morton R, Collett B: Functional benefits and cost/benefit analysis of continuous intrathecal baclofen infusion for the management of severe spasticity. J Neurosurg 96:1052–1057, 2002 30. Siebner HR, Dressnandt J, Auer C, Conrad B: Continuous intrathecal baclofen infusions induced a marked increase of the transcranially evoked silent period in a patient with generalized dystonia. Muscle Nerve 21:1209–1212, 1998 31. Turner MS: Assessing syndromes of catheter malfunction with SynchroMed infusion systems: the value of spiral computed tomography with contrast injection. PM R 2:757–766, 2010 32. Vender JR, Hester S, Waller JL, Rekito A, Lee MR: Identification and management of intrathecal baclofen pump complications: a comparison of pediatric and adult patients. J Neurosurg 104 (1 Suppl):9–15, 2006 33. Ward A, Hayden S, Dexter M, Scheinberg A: Continuous intrathecal baclofen for children with spasticity and/or dystonia: goal attainment and complications associated with treatment. J Paediatr Child Health 45:720–726, 2009 34. Zhang SX, Huang F, Gates M, White J, Holmberg EG: Extensive scarring induced by chronic intrathecal tubing augmented cord tissue damage and worsened functional recovery after rat spinal cord injury. J Neurosci Methods 191:201–207, 2010
Manuscript submitted October 20, 2011. Accepted June 28, 2012. Please include this information when citing this paper: published online August 3, 2012; DOI: 10.3171/2012.6.PEDS11456. Address correspondence to: Aaron A. Cohen-Gadol, M.D., M.Sc., Goodman Campbell Brain and Spine, Indiana University Department of Neurological Surgery, 1801 North Senate Boulevard #610, Indianapolis, Indiana 46202. email:
[email protected].
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