ATLAS OF Neuroradiological findings in neurofibromatosis ...eradiology.bidmc.harvard.edu/LearningLab/central/Khosravi.pdf · •Neurofibromatosis Type 1 is an autosomal dominant genetic

Hasan Khosravi, 2015 Gillian Lieberman, MD

ATLAS OF NEURORADIOLOGICAL FINDINGS IN NEUROFIBROMATOSIS TYPE 1

Hasan Khosravi, Harvard Medical School Year III

Gillian Lieberman, MD

June 29, 2015-July 24, 2015


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

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Pathogenesis

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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

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. <http://www.uptodate.com>.


Agenda


• Pathogenesis

• Diagnosis

• Other Clinical Findings

• Menu of Tests






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≥2 of the following:

1. ≥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

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Figure 1. Neurofibromas

Figure 2. Axillary Freckling

Figure 3. Lisch Nodules

Images from UpToDate

Diagnosis

Figure 4. Plexiform Neurofibroma


• 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

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Other Clinical Findings

What else should we look for?


Agenda


• Pathogenesis

• Diagnosis


• Menu of Tests






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• Plain Films:

• Bony changes/pain

• Bony erosions from neurofibromas

• Scoliosis

• CT/MRI:

• Deep Plexiform Neurofibromas

• Neoplasms

• Astrocytoma

• Optic Glioma

• Conventional Angiogram:

• Moyamoya syndrome

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Menu of Tests

How can we evaluate for NF1 radiologically?


Agenda


• Pathogenesis

• Diagnosis


• Menu of Tests






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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

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Our Patient 1: Clinical Differential for Vertigo

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Central:

• Vestibular migraine

• Brainstem ischemia

• Cerebellar infarction and hemorrhage

• Chiari malformation

• Multiple sclerosis

• Episodic ataxia type 2

Peripheral:

• Benign paroxysmal positional vertigo

• Vestibular neuritis

• Herpes zoster oticus

• Meniere disease

• Labyrinthe concussion

• Perilymphatic fistula

• Semicircular canal dehiscence 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.


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

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Menu of Tests

How can we evaluate for vertigo radiologically?

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


• 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

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Overview of Computed Tomography (CT)

From Keith Gibbs

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


Our Patient 1: Mass on CT

Findings:

• Hyperdense lesion with hypodense center

• Surrounding vasogenic edema

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PACS, BIDMC Axial CT Without Contrast Index Patient 1


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.

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Overview of Magnetic Resonance Imaging

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

Image courtesy of Aaron Field MD PhD Key imaging pointers on MRI of the Head:

•T1: • 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


Our Patient 1: Mass on T1 MRI

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Findings:

• 3.1 x 3.1cm isointense lesion on T1 with heterogenous post-contrast enhancement

PACS, BIDMC PACS, BIDMC T1 Axial MRI Without Contrast Index Patient 1

T1 Axial MRI With Contrast Index Patient 1


Our Patient 1: Mass on T2 MRI

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Findings:

• Hyperintense lesion

• Broad based with ill-defined borders

• Small cystic internal changes

• Small zone of edema and mass effect effacing adjacent sulci

PACS, BIDMC

Caudate Nucleus

Thalamus

Putamen

Splenium of Corpus Callosum

Frontal Horn of Lateral Ventricle

Occipital Horn of Lateral Ventricle

Frontal Lobe

T2 Axial MRI Without Contrast Index Patient 1


Our Patient 1: Imaging Differential

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Differential Diagnosis for Isointense T1 and Hyperintense T2 Lesions:

•Cerebritis

•Glial Tumor

•Nonhemorrhagic Infarction

•Lymphoma

•Meningioma

•Metastasis

•Pituitary Adenoma

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


Our Patient 1: Diagnosis, Treatment, Prognosis, and Outcome

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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


1. CT:

• Hyperdense

• Irregular hypodense center representing necrosis

• Mass effect

• Vasogenic edema around lesion

2. MRI T1:

• Hypo/isointense mass

• Central heterogenous signal representing necrosis

3. MRI T1 with Contrast:

• Variable ehancement with blood-brain barrier breakdown

4. T2/FLAIR:

• Hyperintense

• Surrounded by vasogenic edema

5. DWI/ADC

• Elevated signal due to diffusion restriction

6. PET:

• FDG accumulation

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Knipe, Henry, and Frank Gaillard. "Neurofibromatosis Type 1 | Radiology Reference Article | Radiopaedia.org." Radiopaedia. N.p., n.d. Web. 18 July 2015. <http://radiopaedia.org/articles/neurofibromatosis-type-1>.

Our Patient 1: Overview of Glioblastoma Findings


Agenda


• Pathogenesis

• Diagnosis


• Menu of Tests






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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

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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

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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

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Our Patient 2: Moyamoya Imaging

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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

PACS, BIDMC Normal Segments of Internal Carotid Artery for Comparison

Case courtesy of Dr Frank Gaillard, Radiopaedia.org

Tortuous vessels

Ophthalmic artery

Occluded supraclinoid ICA

Left Internal Carotid Artery Angiogram Companion Patient 2


Our Patient 2: Moyamoya Imaging

Findings:

•Multiple small tortuous collateral vessels

•ICA is stenotic prior to bifurcation

•MCA is not well visualized

•Classification Suzuki Stage III Moyamoya 26

Normal Image from NEJM for Comparison PACS, BIDMC

Tortuous vessels

Ophthalmic artery

Anterior Cerebral Artery (ACA)

Ophthalmic artery

Anterior Cerebral Artery (ACA)

Middle Cerebral Artery (MCA)

Right Internal Carotid Artery Angiogram Companion Patient 2

Stenotic ICA


• 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%

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From getthesmokeout.com

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.

Moyamoya & NF1 Overview


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

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Suzuki Staging for Moyamoya

Image from NEJM


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

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Treatment for Moyamoya

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


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

What is pial synangiosis?

Image from Dartmouth Hitchcock

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


• 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.

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Our Patient 2: Prognosis and Treatment


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”)

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Our Patient 2: Menu of Tests



Agenda


• Pathogenesis

• Diagnosis


• Menu of Tests





• Case 4: Sacral Plexiform Neurofibroma

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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.

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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

What are we most concerned about?

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Optic Glioma


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

What are we most concerned about?

Possible Optic Glioma

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Optic Glioma


What is an Optic Glioma?

•Low grade pilocytic astrocytoma

Typical Clinical Presentation:

•Decreased vision

•Proptosis

•Raised intracranial pressure

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

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Optic Glioma

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


Clinical Presentation and Imaging of Optic Glioma


Our Patient 3: Imaging of Orbital Mass

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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

Uncus

Pons

Vermis

Basilar Artery

Plexiform Neurofibroma

Aqueduct of Sylvius

Optic Nerve

Optic Nerve

PACS, BIDMC PACS, BIDMC

Temporal Lobe

Plexiform Neurofibroma

Optic Nerve

Optic Nerve

Axial T1 MRI Pre Contrast Companion Case 3

Axial T1 MRI Post Contrast Companion Case 3


Differential Diagnosis for Extraconal Periorbital Mass on Imaging:

• Neurofibroma

• Bone Neoplasm

• Lymphoma

• Orbital Abcess

• Osteomyelitis

• Pagets

• Trauma

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• Benign tumor composed of Schwann cells, fibroblasts, perineural cells, and mast cells

• Major cause of morbidity and disfigurement

• Prevalence in NF1 = 50%

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Plexiform Neurofibroma Image from UpToDate

What are plexiform neurofibromas?



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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.


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

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Appearance of Plexiform Neurofibroma on Imaging


Agenda


• Pathogenesis

• Diagnosis


• Menu of Tests






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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.

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Our Patient 1: Clinical Differential for Lumbosacral Radiculopathy

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• Herniated disc

• Neurofibroma

• Nonradicular back pain

• Spinal stenosis

• Cauda equina syndrome

• Diabetic amyotrophy

• Lumbosacral plexopathy

• Mononeuropathy

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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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

PACS, BIDMC PACS, BIDMC

Sacroiliac Joint

Sacrum

Iliacus

Ala of Sacrum

Expanded Intervertebral Foramina

T1 Axial MRI Companion Case 4

T2 Axial MRI Companion Case 4

Our Patient 4: Enlarged Nerve Roots on T1 MRI


Differential for Enlarged Nerve Roots:

•Neurofibromas

•Charcot-Marie-Tooth

•Guillain Barré

•Langerhans cell histiocytosis

•Leptomeningeal carcinomatosis

•Leukemia

•Lymphoma

•Neuritis

•Sarcoidosis

•Toxic Neuropathy

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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.


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

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

Treatment for Plexiform Neurofibroma


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

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Image Gallery

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Case Companion 2: Moyamoya Syndrome

Index Patient 1: Glioblastoma

Example Image: Optic Glioma

Case Companion 3/4: Plexiform Neurofibromas


References 1. 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.

2. Connor S, Sriskandan N. Imaging of dizziness. Clinical Radiology 2014;69(2):111–122. doi:10.1016/j.crad.2013.10.013.

3. 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-of-vertigo?source=search_result&search=vertigo%2Bdifferential&selectedTitle=1~150. Accessed July 27, 2015.

4. Get The Smoke Out Smoke Eaters. Get The Smoke Out Smoke Eaters. Available at: http://www.getthesmokeout.com/. Accessed July 18, 2015.

5. Gibbs K. Computerised axial tomography (CAT or CT). schoolphysics 2015. Available at: http://www.schoolphysics.co.uk/age16-19/Medical%20physics/text/CT_scanning/index.html. Accessed July 27, 2015.

6. 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.

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

8. 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.

9. 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-and-prognosis?source=search_result&search=Neurofibromatosis%2Btype%2B1%2B%28NF1%29%3A%2BManagement%2Band%2Bprognosis&selectedTitle=1~74. Accessed July 27, 2015.

10. 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-and-diagnosis?source=machineLearning&search=neurofibromatosis%2Btype%2B1&selectedTitle=1~74&sectionRank=1&anchor=H20886007#H19620723. Accessed July 18, 2015.

11. Reeder MM. Gamuts in Radiology. Gamuts in Radiology 2010. Available at: http://gamuts.acr.org/gamuts/data/index.html. Accessed July 18, 2015.

12. 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.

13. 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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Acknowledgements Thank you for your teaching, guidance, and support.

Dr. Ning Lu

Dr. Gillian Lieberman

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Documents

ATLAS OF Neuroradiological findings in neurofibromatosis ...eradiology.bidmc.harvard.edu/LearningLab/central/Khosravi.pdf · •Neurofibromatosis Type 1 is an autosomal dominant genetic