1/27/2012

Myelin Abnormal T2 in white matter

70% lipid and 30% glycoprotein “Nonspecific T2 hyperintensities in the T2 short (relative to gray matter) cerebral white matter which, given the T1 short (relative to gray matter) patient’s age, may suggest demyelinating disease…”

Outline White Matter Disease

Differential Illustrative case for each disease category – Demyelinating: Multiple sclerosis, Balo, Devics, Marburg, Schilder’s – Acute disseminated encephalomyelitis (ADEM) Brief looks at other members of that – Viral ( PML, HIV, SSPE) – Rheumatologic (SLE, Sarcoid, Sjogren’s, Susac’s, Behcet’s, category Wegener’s, PAN, PACNS) – Vascular (CADASIL, leukoaraiosis, PRES, postanoxic An idea of what is typical encephalopathy) – Metabolic (central pontine myelinosis) Then an idea of the variety of disease – Toxic (ETOH, radiation, Marchiafava-Bignami disease, disseminating necrotizing leukoencephalopathy, chemotherapy drugs, lead, Tips to narrow an adequate differential mercury) – Traumatic ( diffuse axonal injury) Dysmyelinating disease – (Alexander’s dx, Krabbe’s dx, Pelizaeus – Merzbacher dx, Caravan’s dx, adrenoleukodystrophy, metachromatic leukodystrophy)

1 1/27/2012

Case #1

39 yo male “Can’t walk” For the past six months or so, having problems with erectile dysfunction and urine retention 2 months ago, he was getting out of his car and legs gave out. He crawled into his house, went to bed, and has been crawling ever since.

Case #1 HIV/AIDS encephalopathy

CNS involved in 75% of MRI changes AIDS patients – White matter and gray PML, lymphoma, and matter involved infections should be – Marked cortical considered atrophy Clinically associated with – No enhancement subcortical dementia and – More central or deep other deficits white matter ?HIV directly or – U-fiber sparing vasculopathy HAART may stabilize MRI changes

2 1/27/2012

PML Infectious etiologies

Viral 2-5% AIDS patients – Progressive Multifocal Leukoencephalopathy (PML) Caused by JC virus (polyomavirus) – HIV/AIDS encephalopathy – SSPE (subacute sclerosing – 50% of the population infected in childhood panencephalitis): primarily children – Remains latent in kidneys – HHV-6 – JCV Ab status test available – Herpes simplex – EBV Demyelination related to reactivation of JC TB virus and lysis of oligodendrocytes Fungal Highly fatal without immune reconstitution

Neurology 2007;69:156-165.

Natalizumab-associated PML MRI features in PML

Similar clinical symptoms May be multi-focal or solitary lesions – There are no definitive pathognomic signs or symptoms – Cognitive, motor, language, and visual symptoms are most Parieto-occipital predominance, but can be common anywhere – Seizures and paroxysmal events are not uncommon presenting *Rapidly expanding lesions syndromes Associated T1 hypointensity Known risk factors: Duration of therapy, JCV Ab status, *Usually do not enhance Prior use of chemotherapy – Inflammatory lesions can be seen in both HIV positive New MRI lesions rare after six months of natalizumab and HIV negative patients treatment (N-Ab negative) Spares cortex After six months of natalizumab therapy, any new MRI lesions in a N-Ab-negative patient should be considered Evolves to IRIS with immune reconstitution suspicious for PML

3 1/27/2012

PML Case #2 presentation Post-gad 58 yo woman presented with acute onset of RUE extremity weakness that resolved over hours. PMH of longstanding DM and HTN 3 months later

Case #2: MRI SVID/leukoaraiosis

Results from longstanding hypertension and small vessel atherosclerosis Frequently asymptomatic MRI – Deep white matter affected – External capsule – Posterior horns of lateral ventricle preference – Spare corpus callosum – U fiber sparing – Do not abut the ventricle

JNNP 1998;64:S4

4 1/27/2012

Vascular etiologies Migraine

Stroke Virchow-Robin White matter hyperintensities found to Migraine CADASIL: Cerebral be more common in Leukoaraiosis (SVID) Autosomal Dominant migraine pts Arteriopathy with – 4X more likely to show Subcortical Infarcts and changes than age and Leukoencephalopathy sex matched controls Stable over time Remains controversial whether migraine patients at increased risk of stroke

Swartz et al. Archives of Neurology 2004;61:1366-1368

Virchow-Robin/perivascular spaces CADASIL

Mutations in Notch 3 gene on ch 19 Suspect in young patients with FH – Stroke-like episodes in absence of other vascular risk factors – Psychiatric symptoms common MRI: – Large confluent lesions or small subcortical WM – Likes frontal lobes, anterior temporal region* – External capsule lesions higher sens/spec – Lesions often become hypointense on T1 – No enhancement

5 1/27/2012

CADASIL Case #3

34 year-old Romanian man with one year of progressive headaches, unilateral vision loss, relapsing axillary/inguinal adenopathy, and pustular skin lesions. Presents for question of MS

MRI MRI

6 1/27/2012

Further questioning Behçet’s Disease

Relapsing oral aphthous ulcers and genital Lesion distribution in 65 patients: ulcers over the last 8-12 months. – Mesodiencephalic junction – 30/65 – Pons – 26/65 – Hypothalamus/thalamus – 15/65 – Basal ganglia/internal cap – 12/65 – Cervical cord – 3/65 – Cerebellum – 3/65 – Optic nerve – 1/65 – Hemispheric white matter – 4/65

Kocer et al. AJNR 1999; 20:1015–1024.

Rheumatologic causes of Systemic Lupus Erythematosis white matter disease MRI in 85 patients with definite SLE Behcet’s - history – Normal (34%) SLE – Ab testing, multiorgan involvement – White-matter lesions (60%) Sarcoid – biopsy, pulmonary workup – Volume loss (43%) Sjogren’s – SSA/SSB, sicca sx – Infarcts (21%) Wegener’s – ANCAs, biopsy – Hemorrhage (5%) – Contrast enhancement (9%) Other vasculitides – ESR, CRP, CSF – Diffusion abnormality (18%)

Jennings JE et al. Neuroradiology 2004 46: 15–21.

7 1/27/2012

SLE and MRI changes Sarcoidosis Thromboembolic Prototype is meningeal or perimeningeal, Pure inflammatory with enhancement involving the Inflammatory- hypothalamus and pituitary stalk. vasculitic If parenchymal, tends to have a higher prediliction for the brainstem SARCOID CAN LOOK LIKE ANYTHING!

Jennings JE et al. Neuroradiology 2004; 46: 15–21.

Sarcoidosis – meningeal based Sarcoidosis - parenchymal

8 1/27/2012

Rheumatologic causes of Inflammatory/Vasculitic Mechanisms white matter disease

Pia Behcet’s - history SLE – Ab testing, multiorgan involvement Sarcoid – biopsy, pulmonary workup Sjogren’s – SSA/SSB, sicca sx Wegener’s – ANCAs, biopsy Other vasculitides – ESR, CRP, CSF

Dumas JL et al. Radiology 2000; 214:411-420.

Sjogren’s Syndrome Differentiating Sjögren’s from MS •Often very similar in appearance to MS or leukoaraiosis. Can be difficult to differentiate based on •Callosal lesions notably absent imaging alone. Prominent neurologic events
MS Anti-SSA/Anti-SSB
Sjögren’s Keratoconjunctivitis sicca, xerostomia, sialadenitis
Sjögren’s

Coates T, et al. J Rheumatol 1999; 26: 1301-5.

9 1/27/2012

Susac syndrome Pearl: Corpus callosum lesions

DDx: Rare, self limited – MS Hearing loss, Encephalopathy, retinal – Tumor: GBM or lymphoma artery occlusion – Susac syndrome CSF with elevated – Marchiafava-Bignami protein, no bands MRI predilection for – Diffuse axonal injury corpus callosum and deep white matter Microangiopathy of retina, brain, and inner ear Xu MS et al. Magnetic Resonance Imaging 2004: 22;1295-1298. Halloran HS et al. Ophthalmology 1998:105 (6);1038-1044.

Case #4 Case #4

50 year-old woman with encephalopathy and intermittent focal deficits that were steroid-responsive over 3 hospital admissions.

CSF cytology: malignant lymphocytes Body PET: diffuse marrow and lymph node hypermetabolism

10 1/27/2012

Primary CNS lymphoma CNS Lymphoma

100 immunocompetent patients with PCNSL Location – Cerebral hemispheres (38%) – Basal ganglia or thalamus (16%) – Corpus callosum (23%) – Intraventricular/choroid plexus(20%) Most (65%) had a solitary lesion All but one with contrast enhancement Edema present in all but 6 patients with hemispheric lesions

Kuker W, et al. J Neuroonc 2005; 72: 165-177.

Primary CNS lymphoma Other neoplastic mimics

Beware in immunocompromised patients: Vasogenic edema in a patient with known – Necrosis, edema, and enhancement are less MS. prominent Beware in steroid-treated patients – A response to steroids and resolution of enhancement can mimic demyelination MRS may help: – Absent NAA, decreased Cr, massive Cho

Can. J. Neurol. Sci. 2005; 32: 349-351.

11 1/27/2012

Other neoplasms Case #5

Gliomatosis cerebri 29 year-old woman with onset over days Metastases of headache and encephalopathy. Primary glioma (esp. multicentric GBM) Progressed to lethargy, requiring a feeding tube CSF: WBC=6, OCB+, MBP elevated, IgG index=1.2

Can. J. Neurol. Sci. 2005; 32: 349-351.

August 2004 August 2004

12 1/27/2012

November 2004 followup February 2006

Almost resolved!

Diagnosis: Mitochondrial Disease

Any age Any CNS phenotype Polymerase-gamma mutation= Other organ system involvement Classically: basal ganglia, optic nerve, and Mitochondrial Cytopathy brainstem lesions Lactic acidosis Abnormal ETC activity on muscle bx

13 1/27/2012

PRES Central pontine myelinolysis

Extreme hypertension •Nonenhancing T2 signal in the basis pontis Meds: Cyclosporine, tacrolimus, •Recent rapid correction of hyponatremia interferon-alfa

Hypothyroidism Toxic leukoencephalopathy

Hashimoto’s Encephalopathy: Chemo (MTX, cisplatin, 5FU, fludarabine, Diffuse subcortical white matter hyperintensity interferon alfa, etc.) Immunosuppressants (cyclosporine, tacrolimus) XRT Drugs (toluene, EtOH, heroin, MDMA) Environmental (CO, arsenic, CCl4)

Filley CM et al. NEJM 2001; 345: 425-432.

Osborn AG. Diagnostic Imaging Brain. 2005 Prockop LD et al. J Neuroimaging 2005; 15: 144.

14 1/27/2012

Pearl: Confluent white matter Inhaled heroin abuse changes Vasculopathy/Vasculitis ADEM or longstanding MS SSPE HIV Metabolic/mitochondrial Toxic leukoencephalopathy Leukodystrophies (Genetic)

Vella S et al. Neuropediatrics 2003; 34: 100-104.

Leukodystrophies Leukodystrophies

Alexander Canavan Krabbe Pelizeus-Merzbacher Adrenoleukodystrophy (ALD) Metachromatic leukodystrophy (MLD) Sialidosis Mitochondrial Disease ALD MLD

15 1/27/2012

MRI hints: leukodystrophy Metabolic disease in adults

Asymmetric disease: P-M or mitochondrial Increasing number of late-onset and U-fiber involvement: Canavan’s or P-M atypical phenotypes. Frontal-predominant: Alexander Parietal/splenium corpus callosum: ALD ALD: Enhances Posterior: Krabbe Anterior to posterior progression: MLD

Pearl: Bilat MCP Lesions

Neurodegenerative (Fragile X premutation, MSAs, SCAs) Metabolic diseases (ALD, Wilson’s, Hepatic enceph, hypoglycemic injury) Thank You! Cerebrovascular (PRES, HTN-enceph) Demyelinating (MS, ADEM, Behcet’s, HIV) Neoplasms (Lymphoma, glioma, meningeal carcinomatosis)

AJNR 2003; 24:1946–1954.

16 1/27/2012

Balo’s concentric sclerosis

Historically thought to be monophasic and rapidly progressive Unique pattern of Backup alternating layers of normal myelin and myelin destruction Center of lesion thought to represent significant tissue destruction Leading edge of inflammation often enhances and shows DWI positivity

Multiple Sclerosis 2007;13:471-482

Balo’s Schilder’s disease

Symptoms atypical for MS early in disease (predominately psychiatric) CSF normal Bilateral large areas of demyelination No preceding illness, infection, or vaccination Normal VLCFA (rule out ALD)

Neuroradiology 2007;49:393-409 Poser et al. Acta Neurol Scand 1992;86.

17 1/27/2012

Schilder’s disease

Neuroradiology 2007;49:393-409

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