June 29, 2015-July 24, 2015

ATLAS OF NEURORADIOLOGICAL FINDINGS IN NEUROFIBROMATOSIS TYPE 1 Hasan Khosravi, Harvard Medical School Year III Gillian Lieberman, MD

Hasan Khosravi, 2015 Gillian Lieberman, MD

Agenda Overview of Neurofibromatosis Type 1 (NF1): • Pathogenesis • Diagnosis • Other Radiological Findings • Menu of Tests Neuroradiological Findings • Case 1: Astrocytoma • Case 2: Moyamoya Syndrome • Case 3: Orbital Plexiform Neurofibroma • Case 4: Spine Plexiform Neurofibroma Hasan Khosravi, 2015 Gillian Lieberman, MD

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Pathogenesis

From Neurofibromatosis Therapeutic Acceleration Program (NTAP)

• Neurofibromatosis Type 1 is an autosomal dominant genetic disorder caused by mutation of

NF1, tumor suppressor gene, on chromosome 17 • NF1 gene produces Neurofibromin protein – a GTPase Activating Protein – that negatively regulates Ras pathway • Mutation of NF1  reduced functional protein Hasan Khosravi, 2015 Gillian Lieberman, MD

Korf, Bruce R. "Neurofibromatosis Type 1 (NF1): Pathogenesis, Clinical Features, and Diagnosis." Neurofibromatosis Type 1 (NF1): Pathogenesis, Clinical Features, and Diagnosis. UpToDate, 19 June 2015. Web. 18 July 2015. .

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Agenda Overview of Neurofibromatosis Type 1 (NF1): • Pathogenesis • Diagnosis • Other Clinical Findings • Menu of Tests Neuroradiological Findings • Case 1: Astrocytoma • Case 2: Moyamoya Syndrome • Case 3: Orbital Plexiform Neurofibroma • Case 4: Spine Plexiform Neurofibroma Hasan Khosravi, 2015 Gillian Lieberman, MD

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Diagnosis ≥2 of the following: ≥6 café-au-lait (flat, uniformly pigmented) macules 2. >2 neurofibromas or 1 plexiform neurofibroma 3. Freckling in the axillary or inguinal areas 4. Optic glioma 5. Two or more iris hamartomas (Lisch nodules) 6. Distinctive bony lesion • Thinning of the long bone cortex • Sphenoid dysplasia 7. A first-degree relative with NF1 1.

Figure 1. Neurofibromas

Figure 2. Axillary Freckling

Figure 4. Plexiform Neurofibroma Hasan Khosravi, 2015 Gillian Lieberman, MD

Figure 3. Lisch Nodules

Images from UpToDate

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Other Clinical Findings What else should we look for? • Intracranial neoplasms • Astrocytomas • Brainstem gliomas • Soft tissue sarcomas • Malignant peripheral nerve sheath tumor • Rhabdoymosarcoma • Gastrointestinal stromal tumor • Glomus Tumor • Bone abnormalities • Bone dysplasia • Pseduoarthrosis • Short stature • Scoliosis • Cognitive deficits and Learning disabilities • Seizures • Macrocephaly • Peripheral neuropathy • Hypertension • From Renovascular Disease or Pheocromocytoma • Moyamoya Syndrome • Pulmonary artery stenosis, bullous emphysema, and interstitial lung disease • Arterial dissection

Hasan Khosravi, 2015 Gillian Lieberman, MD

Korf, Bruce R. "Neurofibromatosis Type 1 (NF1): Pathogenesis, Clinical Features, and Diagnosis." Neurofibromatosis Type 1 (NF1): Pathogenesis, Clinical Features, and Diagnosis. UpToDate, 19 June 2015. Web. 18 July 2015. .

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Agenda Overview of Neurofibromatosis Type 1 (NF1): • Pathogenesis • Diagnosis • Other Clinical Findings • Menu of Tests Neuroradiological Findings • Case 1: Astrocytoma • Case 2: Moyamoya Syndrome • Case 3: Orbital Plexiform Neurofibroma • Case 4: Spine Plexiform Neurofibroma Hasan Khosravi, 2015 Gillian Lieberman, MD

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Menu of Tests How can we evaluate for NF1 radiologically? • Plain Films: • Bony changes/pain

• Bony erosions from neurofibromas • Scoliosis • CT/MRI: • Deep Plexiform Neurofibromas • Neoplasms

• Astrocytoma

• Optic Glioma • Conventional Angiogram:

• Moyamoya syndrome Hasan Khosravi, 2015 Gillian Lieberman, MD

Korf, Bruce R. "Neurofibromatosis Type 1 (NF1): Pathogenesis, Clinical Features, and Diagnosis." Neurofibromatosis Type 1 (NF1): Pathogenesis, Clinical Features, and Diagnosis. UpToDate, 19 June 2015. Web. 18 July 2015. .

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Agenda Overview of Neurofibromatosis Type 1 (NF1): • Pathogenesis • Diagnosis • Other Clinical Findings • Menu of Tests Neuroradiological Findings • Case 1: Astrocytoma • Case 2: Moyamoya Syndrome • Case 3: Orbital Plexiform Neurofibroma • Case 4: Spine Plexiform Neurofibroma Hasan Khosravi, 2015 Gillian Lieberman, MD

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Our Patient 1: History CC: 25 year-old female with vertigo for 3 days HPI: •Sits down at times and feels world is spinning •Sensation of lightheadedness when she gets up from a seated position •ROS: no double vision, tinnitus, facial droop, dysphagia, dysarthria, or change in taste

PMH: •NF 1 diagnosed due to prior • Neurofibromas • Opitc glioma •ADHD •Migraine headaches •Restless Leg Syndrome Clinical Examination: •No deficits in sensation or strength •Normal gait •No intention tremor, dysdiadochokinesia, or dysmetria •Negative Dix-Hallpike

Hasan Khosravi, 2015 Gillian Lieberman, MD

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Our Patient 1: Clinical Differential for Vertigo Central:

Peripheral:

• Vestibular migraine

• Benign paroxysmal positional vertigo

• Brainstem ischemia

• Vestibular neuritis

• Cerebellar infarction and hemorrhage • Herpes zoster oticus • Chiari malformation

• Meniere disease

• Multiple sclerosis

• Labyrinthe concussion

• Episodic ataxia type 2

• Perilymphatic fistula • Semicircular canal dehiscence • • • • •

Hasan Khosravi, 2015 Gillian Lieberman, MD

syndrome Cogan’s syndrome Recurrent vestibulopathy Acoustic Neuroma Amnioglycoside toxicity Otitis Media

Furman JM. Pathophysiology, etiology, and differential diagnosis of vertigo. Pathophysiology, etiology, and differential diagnosis of vertigo 2015.

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Menu of Tests How can we evaluate for vertigo radiologically? 1. CT: • Evaluate osseous component in bony labyrinth, hemorrhage

2. T2 MRI: • Endolymphatic and perilymphatic spaces

3. DWI: • Acute Ischemic Changes

4. Gadolinium MRI: • Neoplastic and Inflammatory lesions

Hasan Khosravi, 2015 Gillian Lieberman, MD

Connor, S.e.j., and N. Sriskandan. "Imaging of Dizziness." Clinical Radiology 69.2 (2014): 111-22. Web.

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Overview of Computed Tomography (CT)

From Keith Gibbs

•

An X-ray source rotates around a patient with multiple detectors on the opposite side, forming 2 dimensional image slices Radiodensity is measured in Hounsfield Units Key imaging pointers:

• • • • •

Bone is most dense at +1000 Acute blood is hyperdense between +55 to +70 White matter is less dense than gray matter – parenchyma ranges from +20 to +40 Hasan Khosravi, 2015 Gillian Lieberman, MD

Imaging Techniques - Neuroradiology. Imaging Techniques - Neuroradiology 2011. Available at: https://sites.google.com/a/wisc.edu/neuroradiology/image-acquisition. Accessed July 27, 2015.

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Our Patient 1: Mass on CT Findings: • Hyperdense lesion with hypodense center • Surrounding vasogenic edema

PACS, BIDMC

Axial CT Without Contrast Index Patient 1

Hasan Khosravi, 2015 Gillian Lieberman, MD

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Overview of Magnetic Resonance Imaging MRI: Patient lies on table with all protons aligning with established magnetic field. Radiofrequency pulses excite hydrogen atoms and their realignment gives off a radio signal that generates tissue contrast. Key imaging pointers on MRI of the Head: •T1:

Image courtesy of Aaron Field MD PhD

• CSF – dark, White matter – white, Gray matter – gray, Vessels - dark

•T1 with contrast: • CSF – dark, White matter – white, Gray matter – gray, Vessels – bright • Contrast evaluates for blood-brain barrier breakdown

•T2: • CSF – bright, White matter – gray, Gray matter – white, Vessels – dark • Watery, cystic material – bright

Hasan Khosravi, 2015 Gillian Lieberman, MD

Imaging Techniques - Neuroradiology. Imaging Techniques - Neuroradiology 2011. Available at: https://sites.google.com/a/wisc.edu/neuroradiology/image-acquisition. Accessed July 27, 2015.

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Our Patient 1: Mass on T1 MRI

PACS, BIDMC

T1 Axial MRI Without Contrast Index Patient 1

Hasan Khosravi, 2015 Gillian Lieberman, MD

PACS, BIDMC

T1 Axial MRI With Contrast Index Patient 1

Findings: • 3.1 x 3.1cm isointense lesion on T1 with heterogenous postcontrast enhancement

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Our Patient 1: Mass on T2 MRI

Frontal Lobe Frontal Horn of Lateral Ventricle Caudate Nucleus Putamen

Findings: • Hyperintense lesion • Broad based with ill-defined borders • Small cystic internal changes • Small zone of edema and mass effect effacing adjacent sulci

Thalamus

Occipital Horn of Lateral Ventricle

Splenium of Corpus Callosum

PACS, BIDMC

T2 Axial MRI Without Contrast Index Patient 1 Hasan Khosravi, 2015 Gillian Lieberman, MD

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Our Patient 1: Imaging Differential Differential Diagnosis for Isointense T1 and Hyperintense T2 Lesions: •Cerebritis •Glial Tumor •Nonhemorrhagic Infarction •Lymphoma

•Meningioma •Metastasis •Pituitary Adenoma

Hasan Khosravi, 2015 Gillian Lieberman, MD

Reeder, Maruice M. "Gamuts in Radiology." Gamuts in Radiology. N.p., 2010. Web. 18 July 2015.

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Our Patient 1: Diagnosis, Treatment, Prognosis, and Outcome Diagnosis: Report from biopsy showed a Grade IV Glioblastoma Prognosis: For grade IV glibolastomas diagnosed in the US in 1995 to 2008, 1 year and 5 year survival rates were 35 and 5 percent, respectively. Treatment: Right frontal craniotomy with tumor resection Outcome: Vertigo improved but did not resolve completely

Hasan Khosravi, 2015 Gillian Lieberman, MD

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Our Patient 1: Overview of Glioblastoma Findings 1. • • • • 2.

3.

CT: 4. Hyperdense Irregular hypodense center representing necrosis Mass effect 5. Vasogenic edema around lesion

MRI T1: • Hypo/isointense mass • Central heterogenous signal representing necrosis

6.

T2/FLAIR: • Hyperintense • Surrounded by vasogenic edema DWI/ADC • Elevated signal due to diffusion restriction PET: • FDG accumulation

MRI T1 with Contrast: • Variable ehancement with blood-brain barrier breakdown

Hasan Khosravi, 2015 Gillian Lieberman, MD

Knipe, Henry, and Frank Gaillard. "Neurofibromatosis Type 1 | Radiology Reference Article | Radiopaedia.org." Radiopaedia. N.p., n.d. Web. 18 July 2015. .

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Agenda Overview of Neurofibromatosis Type 1 (NF1): • Pathogenesis • Diagnosis • Other Clinical Findings • Menu of Tests Neuroradiological Findings • Case 1: Astrocytoma • Case 2: Moyamoya Syndrome • Case 3: Orbital Plexiform Neurofibroma • Case 4: Spine Plexiform Neurofibroma Hasan Khosravi, 2015 Gillian Lieberman, MD

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Patient 2: History CC: 34 year-old female presents for routine follow-up imaging of NF1 HPI: •No new complaints, doing well PMH: •NF1 with Lisch nodules, café-au-lait spots, and neurofibromas over bilateral upper and lower extremities, trunk, and back. She has bilateral axillary freckling. Clinical Examination: •Normal neurologic exam

Hasan Khosravi, 2015 Gillian Lieberman, MD

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Patient 2: 34-year-old female with history of NF1 presents for follow up MRI Imaging Results: •FLAIR/T2 hyperintensities involving periventricular and subcortical white matter on left •Attenuated Internal Carotid Arteries bilaterally Follow-up MR Angiogram showed: •Diminutive distal left M1 segment of Middle Cerebral Artery (MCA) •M2 branches of MCA were opacified from collateral circulation •These findings raised suspicion for Moyamoya Syndrome

Hasan Khosravi, 2015 Gillian Lieberman, MD

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Patient 2: 34-year-old female with history of NF1 presents for follow up Need better evaluation of vasculature! Answer: conventional angiography What is conventional angiography? •Visualization of vessels after injection of radio-opaque contrast with subsequent fluoroscopy

Hasan Khosravi, 2015 Gillian Lieberman, MD

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Our Patient 2: Moyamoya Imaging

Occluded supraclinoid ICA Tortuous vessels

Ophthalmic artery PACS, BIDMC

Left Internal Carotid Artery Angiogram Companion Patient 2

Hasan Khosravi, 2015 Gillian Lieberman, MD

Normal Segments of Internal Carotid Artery for Comparison Case courtesy of Dr Frank Gaillard, Radiopaedia.org

Findings: •Extensive tortuous collateral vascular formation •Supraclinoid segment of ICA is occluded •Less collateral filling of ACA and MCA territories •Classification - Suzuki Stage IV Moyamoya

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Our Patient 2: Moyamoya Imaging

Middle Cerebral Artery (MCA) Anterior Cerebral Artery (ACA)

Anterior Cerebral Artery (ACA)

Tortuous vessels

Ophthalmic artery Stenotic ICA Ophthalmic artery

PACS, BIDMC

Right Internal Carotid Artery Angiogram Companion Patient 2

Hasan Khosravi, 2015 Gillian Lieberman, MD

Normal Image from NEJM for Comparison

Findings: •Multiple small tortuous collateral vessels •ICA is stenotic prior to bifurcation •MCA is not well visualized •Classification Suzuki Stage III Moyamoya

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Moyamoya & NF1 Overview • Moyamoya: Japanese for “something hazy, like a puff of cigarette

smoke” • Idiopathic stenosis of internal carotid artery and development of collateral vasculature • Predisposes to ischemic symptoms, transient ischemic attacks, seizure, hemorrhage, headache, or aneurysm development • Prevalence in NF1 = 0.6%

From getthesmokeout.com

Hasan Khosravi, 2015 Gillian Lieberman, MD

Scott, R. Michael, and Edward R. Smith. "Moyamoya Disease and Moyamoya Syndrome." New England Journal of Medicine N Engl J Med 360.12 (2009): 1226-237. Web.

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Suzuki Staging for Moyamoya Grading system used to monitor progression of Moyamoya based off conventional angiography:

Image from NEJM

Hasan Khosravi, 2015 Gillian Lieberman, MD

Scott, R. Michael, and Edward R. Smith. "Moyamoya Disease and Moyamoya Syndrome." New England Journal of Medicine N Engl J Med 360.12 (2009): 1226-237. Web.

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Treatment for Moyamoya Goal: Revascularize areas that are not well-perfused by the ICA, preventing future ischemic stroke Treatment Modalities: •Medical Therapy: 1. Antiplatelet agents 2. Calcium channel blockers especially for headaches •Surgery: 1. Direct • A branch of the external carotid artery is anastomosed to a cortical artery. 2. Indirect • Placing vascularized tissue, by the external carotid artery, near the brain • Examples: Pial synangiosis, encephaloduroarteriosynangiosis, encephalomyoarteriosynangiosis

Hasan Khosravi, 2015 Gillian Lieberman, MD

Korf BR. Neurofibromatosis type 1 (NF1): Management and prognosis. Neurofibromatosis type 1 (NF1): Management and prognosis 2015.

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What is pial synangiosis?

Surgeons suture the superior temporal artery to the pia mater to reestablish blood flow as demonstrated on the right.

Image from Dartmouth Hitchcock Hasan Khosravi, 2015 Gillian Lieberman, MD

Singer RJ. Moyamoya. Cerebrovascular Disease and Stroke Program 2014. Available at: http://www.dartmouth-hitchcock.org/cerebrovascular/moyamoya.html. Accessed July 27, 2015.

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Our Patient 2: Prognosis and Treatment • Prognosis: • Review of 143 patients • Incidence of stroke before pial synangiosis: 67% • Incidence of stroke perioperatively: 7.7% • Incidence of stroke after 1 year follow-up: 3.2% • Long-term risk of stroke: 4%

• Treatment: • No treatment until patient became symptomatic and started experiencing headache and word-finding difficulty. • Pial synangiosis was performed. • Our patients’ symptoms were resolved, and she has had no seizures or complications.

Hasan Khosravi, 2015 Gillian Lieberman, MD

Scott, R. Michael, and Edward R. Smith. "Moyamoya Disease and Moyamoya Syndrome." New England Journal of Medicine N Engl J Med 360.12 (2009): 1226-237. Web.

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Our Patient 2: Menu of Tests 1.

CT: • Hypodensity – stroke

2.

MRI: • Reduced flow voids in internal, middle, and anterior cerebral arteries with prominent flow voids from collateral vessels

3.

FLAIR: • Diminished blood flow

4.

DWI: • Acute infarct, hyperintense

5.

Angiography – Definitive Diagnosis: • Stenosis of distal intracranial ICA, extensive collaterals at the base of the brain (“puff of smoke”)

Hasan Khosravi, 2015 Gillian Lieberman, MD

Knipe, Henry, and Frank Gaillard. "Neurofibromatosis Type 1 | Radiology Reference Article | Radiopaedia.org." Radiopaedia. N.p., n.d. Web. 18 July 2015. .

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Agenda Overview of Neurofibromatosis Type 1 (NF1): • Pathogenesis • Diagnosis • Other Clinical Findings • Menu of Tests Neuroradiological Findings • Case 1: Astrocytoma • Case 2: Moyamoya Syndrome • Case 3: Orbital Plexiform Neurofibroma • Case 4: Sacral Plexiform Neurofibroma Hasan Khosravi, 2015 Gillian Lieberman, MD

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Our Patient 3: History CC: 39-year-old male with history of NF 1 who presents with large head on examination and blindness in the right eye. HPI: •He was born with a blind right eye. •He has had multiple neurofibromas on his neck, chest, and thighs. •ROS: Occasional vertigo PMH: NF1, renal tumor with hematuria

Clinical Examination: •Visual acuity is normal on left and blind on right. •Visual field is full on left. •Optic disk on the left is normal, and the right optic disk is white and atrophic. •Extraocular movements are intact. •Pupils react normally to light, both directly and consensually. Hasan Khosravi, 2015 Gillian Lieberman, MD

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Case 3: 39-year-old male with history of NF 1 who presents with large head on examination and blindness in right eye Optic Glioma

What are we most concerned about?

Hasan Khosravi, 2015 Gillian Lieberman, MD

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Case 3: 39-year-old male with history of NF 1 who presents with large head on examination and blindness in right eye Optic Glioma

What are we most concerned about?

Possible Optic Glioma

Hasan Khosravi, 2015 Gillian Lieberman, MD

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Clinical Presentation and Imaging of Optic Glioma What is an Optic Glioma? •Low grade pilocytic astrocytoma Typical Clinical Presentation: •Decreased vision •Proptosis •Raised intracranial pressure

Optic Glioma

Menu of Tests for Optic Glioma: 1.CT •Enlarged optic nerve 2.T1 with Contrast •Hypointense/isointense relative to optic nerve •Fusiform enlargement 3.T2 MRI •Hyperintense with low signal peripherally

Hasan Khosravi, 2015 Gillian Lieberman, MD

Example Patient with Fusiform Optic Glioma on T2 Axial MRI Case courtesy of Dr Arthur Daire, Radiopaedia.org

Knipe, Henry, and Frank Gaillard. "Neurofibromatosis Type 1 | Radiology Reference Article | Radiopaedia.org." Radiopaedia. N.p., n.d. Web. 18 July 2015. .

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Our Patient 3: Imaging of Orbital Mass Plexiform Neurofibroma

Plexiform Neurofibroma

Optic Nerve

Optic Nerve

Temporal Lobe

Optic Nerve

Optic Nerve

Uncus Basilar Artery Pons

Aqueduct of Sylvius

PACS, BIDMC

Vermis

Axial T1 MRI Pre Contrast Companion Case 3

Hasan Khosravi, 2015 Gillian Lieberman, MD

PACS, BIDMC

Axial T1 MRI Post Contrast Companion Case 3

Findings: • Infiltrating extraconal mass (5.6 x 2.9 cm) in right periorbital area, extending posteriorly to orbital apex • Hypointense T1 with heterogeneous post contrast enhancement. • Symmetric bilateral optic nerves

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Our Patient 3: Imaging Differential Differential Diagnosis for Extraconal Periorbital Mass on Imaging: • Neurofibroma • Bone Neoplasm • Lymphoma

• Orbital Abcess • Osteomyelitis • Pagets • Trauma

Hasan Khosravi, 2015 Gillian Lieberman, MD

Reeder, Maruice M. "Gamuts in Radiology." Gamuts in Radiology. N.p., 2010. Web. 18 July 2015.

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What are plexiform neurofibromas? • Benign tumor composed of Schwann cells, fibroblasts, perineural cells, and mast cells • Major cause of morbidity and disfigurement • Prevalence in NF1 = 50%

Plexiform Neurofibroma Image from UpToDate

Hasan Khosravi, 2015 Gillian Lieberman, MD

Korf, Bruce R. "Neurofibromatosis Type 1 (NF1): Pathogenesis, Clinical Features, and Diagnosis." Neurofibromatosis Type 1 (NF1): Pathogenesis, Clinical Features, and Diagnosis. UpToDate, 19 June 2015. Web. 18 July 2015. .

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Our Patient 3: Diagnosis, Prognosis, Treatment, and Outcome Diagnosis: Patient had a plexiform neurofibroma that extended into the right optic canal causing optic neuropathy.

Prognosis: Optic neuropathy was irreversible. Treatment: Patient had a right anterior oribtotomy with debulking of the right upper eyelid and anterior orbit lesion. Outcome: Plexiform neurofibroma was resected; however, the patient still experiences blindness in right eye.

Hasan Khosravi, 2015 Gillian Lieberman, MD

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Appearance of Plexiform Neurofibroma on Imaging 1.

Plain film: • Widening of neural foramina

2.

CT: • Soft tissue masses of hypodensity due to endoneural myxoid matrix

3.

T1: • Hypointense mass with hyperintense septations from myelinated axons

4.

T2: • Hyperintense due to myxoid matrix with occasional hypointense central focus

Hasan Khosravi, 2015 Gillian Lieberman, MD

Knipe, Henry, and Frank Gaillard. "Neurofibromatosis Type 1 | Radiology Reference Article | Radiopaedia.org." Radiopaedia. N.p., n.d. Web. 18 July 2015. .

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Agenda Overview of Neurofibromatosis Type 1 (NF1): • Pathogenesis • Diagnosis • Other Clinical Findings • Menu of Tests Neuroradiological Findings • Case 1: Astrocytoma • Case 2: Moyamoya Syndrome • Case 3: Orbital Plexiform Neurofibroma • Case 4: Spine Plexiform Neurofibroma Hasan Khosravi, 2015 Gillian Lieberman, MD

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Our Patient 4: History CC: 31-year-old male with several months of right side lower back pain radiating to his buttock, posterior thigh, and calf HPI: •Treating chronic pain with carbamazepine, duloxetine, gabapentin, pregabalin, and topiramate with little results •ROS: No bowel or bladder incontinence. PMH: •NF1 with seizures Physical Examination: •Normal gait with full range of motion and some stiffness. •Straight leg test is negative bilaterally. •No tenderness to palpation of sacroiliac joint. •No pain with manipulation of hip. Hasan Khosravi, 2015 Gillian Lieberman, MD

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Our Patient 1: Clinical Differential for Lumbosacral Radiculopathy • Herniated disc • Neurofibroma • Nonradicular back pain

• Spinal stenosis • Cauda equina syndrome • Diabetic amyotrophy • Lumbosacral plexopathy • Mononeuropathy

Hasan Khosravi, 2015 Gillian Lieberman, MD

Hsu PS, Armon C, Levin K. Lumbosacral radiculopathy: Pathophysiology, clinical features, and diagnosis. Lumbosacral radiculopathy: Pathophysiology, clinical features, and diagnosis 2015.

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Our Patient 4: Enlarged Nerve Roots on T1 MRI

Iliacus

Sacroiliac Joint Sacrum

Ala of Sacrum

Expanded Intervertebral Foramina

PACS, BIDMC

T1 Axial MRI Companion Case 4

PACS, BIDMC

T2 Axial MRI Companion Case 4

Findings: • Multiple enhancing masses along exiting spinal nerve roots • Hypointense on T1 and hyperintense on T2 with central hypointensity. • Bilateral foraminal masses with extraforaminal extension along anterior sacrum and superficial iliacus

Hasan Khosravi, 2015 Gillian Lieberman, MD

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Our Patient 4: Imaging Differential Differential for Enlarged Nerve Roots: •Neurofibromas •Charcot-Marie-Tooth •Guillain Barré •Langerhans cell histiocytosis •Leptomeningeal carcinomatosis •Leukemia

•Lymphoma •Neuritis •Sarcoidosis

•Toxic Neuropathy Hasan Khosravi, 2015 Gillian Lieberman, MD

Reeder, Maruice M. "Gamuts in Radiology." Gamuts in Radiology. N.p., 2010. Web. 18 July 2015.

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Our Patient 4: Diagnosis, Prognosis, and Treatment Diagnosis: Multiple plexiform neurofibromas Prognosis: May transform into malignant peripheral nerve sheath tumors Treatment: Patient referred to pain clinic and physical therapy. Patient was lost to follow up.

Hasan Khosravi, 2015 Gillian Lieberman, MD

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Treatment for Plexiform Neurofibroma Goal: Surgical removal if significantly disfiguring or compressing airway Limited studies on medical therapies such as chemotherapy Current clinical trials include: •Carboplatin •Imatinib •Pegylated Interferon •Sirolimus •Pirfenidone •Farnesyl transferase inhibitors

Hasan Khosravi, 2015 Gillian Lieberman, MD

Korf BR. Neurofibromatosis type 1 (NF1): Management and prognosis. Neurofibromatosis type 1 (NF1): Management and prognosis 2015.

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Summary 1.

You saw an atlas of neuroradiological findings in NF1 including: • Grade IV Glioblastoma • Moyamoya syndrome • Plexiform Neurofibromas • Optic Glioma

2.

You looked at three imaging modalities including: • CT • MRI • Conventional Angiography

3.

You reviewed anatomy on imaging including: • Neuroanatomy • Neurovasculature and anatomy of the Internal Carotid Artery Hasan Khosravi, 2015 Gillian Lieberman, MD

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Image Gallery Case Companion 2: Moyamoya Syndrome

Example Image: Optic Glioma

Index Patient 1: Glioblastoma

Case Companion 3/4: Plexiform Neurofibromas Hasan Khosravi, 2015 Gillian Lieberman, MD

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References 1. 2. 3.

4. 5. 6.

7. 8. 9.

10.

11. 12. 13.

Biology of Plexiform Neurofibromas - The Neurofibromatosis Therapeutic Acceleration Program (NTAP). The Neurofibromatosis Therapeutic Acceleration Program NTAP RSS. Available at: http://www.n-tap.org/plexiform-neurofibromas/biology-of-plexiform-neurofibromas-in-neurofibromatosis-type-1/. Accessed July 18, 2015. Connor S, Sriskandan N. Imaging of dizziness. Clinical Radiology 2014;69(2):111–122. doi:10.1016/j.crad.2013.10.013. Furman JM. Pathophysiology, etiology, and differential diagnosis of vertigo. Pathophysiology, etiology, and differential diagnosis of vertigo 2015. Available at: http://www.uptodate.com/contents/pathophysiology-etiology-and-differential-diagnosis-ofvertigo?source=search_result&search=vertigo%2Bdifferential&selectedTitle=1~150. Accessed July 27, 2015. Get The Smoke Out Smoke Eaters. Get The Smoke Out Smoke Eaters. Available at: http://www.getthesmokeout.com/. Accessed July 18, 2015. Gibbs K. Computerised axial tomography (CAT or CT). schoolphysics 2015. Available at: http://www.schoolphysics.co.uk/age1619/Medical%20physics/text/CT_scanning/index.html. Accessed July 27, 2015. Hsu PS, Armon C, Levin K. Lumbosacral radiculopathy: Pathophysiology, clinical features, and diagnosis. Lumbosacral radiculopathy: Pathophysiology, clinical features, and diagnosis 2015. Available at: http://www.uptodate.com/contents/lumbosacral-radiculopathy-pathophysiology-clinical-features-and-diagnosis#H31. Accessed July 27, 2015. Imaging Techniques - Neuroradiology. Imaging Techniques - Neuroradiology 2011. Available at: https://sites.google.com/a/wisc.edu/neuroradiology/image-acquisition. Accessed July 27, 2015. Knipe H, Gaillard F. Neurofibromatosis type 1 | Radiology Reference Article | Radiopaedia.org. Radiopaedia. Available at: http://radiopaedia.org/articles/neurofibromatosis-type-1. Accessed July 18, 2015. Korf BR. Neurofibromatosis type 1 (NF1): Management and prognosis. Neurofibromatosis type 1 (NF1): Management and prognosis 2015. Available at: http://www.uptodate.com/contents/neurofibromatosis-type-1-nf1-management-andprognosis?source=search_result&search=Neurofibromatosis%2Btype%2B1%2B%28NF1%29%3A%2BManagement%2Band%2Bprognosis&selectedTitle=1~74. Accessed July 27, 2015. Korf BR. Neurofibromatosis type 1 (NF1): Pathogenesis, clinical features, and diagnosis. Neurofibromatosis type 1 (NF1): Pathogenesis, clinical features, and diagnosis 2015. Available at: http://www.uptodate.com/contents/neurofibromatosis-type-1-nf1-pathogenesis-clinical-features-anddiagnosis?source=machineLearning&search=neurofibromatosis%2Btype%2B1&selectedTitle=1~74§ionRank=1&anchor=H20886007#H19620723. Accessed July 18, 2015. Reeder MM. Gamuts in Radiology. Gamuts in Radiology 2010. Available at: http://gamuts.acr.org/gamuts/data/index.html. Accessed July 18, 2015. Scott RM, Smith ER. Moyamoya Disease and Moyamoya Syndrome. New England Journal of Medicine N Engl J Med 2009;360(12):1226–1237. doi:10.1056/nejmra0804622. Singer RJ. Moyamoya. Cerebrovascular Disease and Stroke Program 2014. Available at: http://www.dartmouth-hitchcock.org/cerebrovascular/moyamoya.html. Accessed July 27, 2015. Hasan Khosravi, 2015 Gillian Lieberman, MD

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Acknowledgements Thank you for your teaching, guidance, and support. Dr. Ning Lu Dr. Gillian Lieberman

Hasan Khosravi, 2015 Gillian Lieberman, MD

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