A Case Presentation & Discussion

1. Bobbye Thompson, MD University of Texas Medical Branch, Galveston Division of Neurosurgery A Case Presentation & Discussion

2. History • 51yo F w/several months progressive BLE weakness; pain greater in LLE • Bilateral numbness just above breasts & inferiorly • Muscle aches cramps spasms falls • Urinary incontinence & saddle anesthesia • Constipation 2wks (manual disimpaction) • No history of spinal operation, injury, or trauma • No F/C/N/V

3. Physical Exam • Sensory deficit inferior to T1 bilaterally • Decreased rectal tone • Motor: LLE 2/5, RLE 5/5 • Increased tone/spasticity • Hyperreflexia • Babinski: Bilateral upgoing toes • Gait: Able to stand with asisstance; drags LLE, circumduction

4. Sag T1 FS MRI Post Sag T2 MRI

5. Labs/CSF • Gram stain & culture: rare monocytes, no organisms isolated • CSF glucose: 69 • CSF protein: 31 • Oligoclonal bands: negative

6. Differential Diagnosis • Tumor • Astrocytoma • Ependymoma • Demyelinating lesion: • Multiple sclerosis • Neuromyelitis optica • Transverse myelitis • ADEM

7. Impression • Progressive LE weakness • Imaging consistent with Intramedullary tumor at T1 • Oligoclonal bands negative • Probable tumor, likely glioma • Proceed with C6-T2 laminectomy with biopsy and/or resection • Midline myelotomy firm, tan tissue • Frozen section: gliosis vs. low-grade glioma • Inflammatory infiltrate

8. Surgical Pathology

9. CD68

10. CD45

12. Diagnosis • Inflammatory demyelinating lesion • Multiple Sclerosis • No further surgical intervention • Neurology for management of MS • Follow up in clinic 2 months postop • Motor LLE improved • MRI Brain & C-spine

13. MRI 2 mos Post Op

14. Multiple Sclerosis (MS) Neuromyelitis Optica (NMO) Transverse Myelitis Acute Disseminated Encephalomyelitis (ADEM) Demyelinating Diseases Mimicking Tumors

15. Multiple Sclerosis • Relapsing-remitting MS (RRMS): • Most common • 85% of MS initially diagnosed • Partial or total recovery between attacks • Secondary-progressive MS (SPMS): • RRMS course, but becomes gradually progressive • Attacks & partial recoveries may continue to occur • Over 60% initially RRMS progress to SPMS in 10 yrs

16. Multiple Sclerosis • Primary-progressive MS (PPMS): • Progressive from onset • Symptoms generally do not remit • Progressive disability w/o acute attacks • 15% of MS initially diagnosed • Primary-relapsing MS (PRMS): • Same as PPMS, but with acute attacks

17. Multiple Sclerosis • Clinical: Episodic, relapsing-remitting neurologic symptoms in a young adult (typically) • Neurological symptoms disseminated in time & space • Common presentations: monocular visual disturbances (optic neuritis), paresthesias/weakness (myelitis), incoordination (cerebellar), and/or diplopia (brainstem) • Labs: Oligoclonal bands positive, MBP elevated • Not specific, new tests improving sensitivity/specificity • Early MS vs Clinically definite • MBP elevated in various disease processes • MRI: T2 intense foci in white matter (UBOs), juxtacortical (G-W junction involving U-fibers), periventricular lesions, involve corpus collosum (perpendicular extensions)

19. MS C-spine

20. Neuromyelitis Optica/Devic • Clinical: Visual loss eye(s) w/myelopathy, usually over several months; may occur simultaneously. Course can be monophasic, but ~2/3 relapsing. • In children: usually monophasic & preceded by infection. Recovery is often complete. ADEM variant. • Labs: Oligoclonal bands negative. NMO-IgG serum can be sent (indirect immunofluorescence assay) • MRI: Spinal cord lesions extend > 3 levels, w/o brain lesions. SC lesions are cavitating, necrotic, w/acute axonal pathology.

21. NMO MRI T2

22. Transverse Myelitis • Clinical: focal inflammatory disorder of spinal cord; acute or subacute combination of motor, sensory, and autonomic deficits. • Up to 50% pt will have LE paralysis/paresis • >80% have numbness, paresthesias, or dysesthesias, often with a well-defined sensory level • vast majority experience impaired bladder function. • 1/3 complete recovery, 1/3 moderate disability, 1/3 severe disability. • Labs/MRI/Treatment: Variable

23. Transverse Myelitis • Findings that herald diagnosis of MS: • asymmetric clinical findings • predominance of sensory deficits • MRI lesions <3 spinal cord segments, • MRI Brain: occult white matter lesions (“dirty white matter”) • CSF: Oligoclonal bands positive

24. Acute Disseminated Encephalomyelitis(ADEM) • Clinical: “Postinfectious Encephalomyelitis” • Presents as ACUTE neurological symptoms • Fever, nausea, vomiting, positional vertigo, and altered consciousness (drowsy or lethargic) • Children following viral infxn or immunization • Labs: ESR, CRP, CSF pleocytosis • MRI: extensive lesions, many enhance w/gad (ring-enhancing lesions) • Basal ganglia and/or thalami involvement • Spares corpus collosum • Molecular mimicry: viral epitope & myelin epitope

25. ADEM MRI - Brain

26. ADEM MRI - Spine

27. Other Differentials • Sjögren’s syndrome: mimics MS by producing recurrent multifocal neurological manifestations; white-matter lesions on MRI and oligoclonal bands in CSF. • Differentiate by: systemic manifestations (sicca-dry eyes, mouth & rheumatic features), abnormal serology (antinuclear, SSA-Ro, or SSB-La antibodies), and findings of inflammatory foci on salivary gland biopsy.

28. Other Differentials • Behçet’s disease: Most common CNS presentation is a subacute brainstem syndrome. • Differentiate by: recurrent oral ulcerations (at least 3 times in 12 months), MRI in Behçet’s disease: brain abnormalities tend to be large, diffuse lesions confined to the brainstem.

29. Red Flags Atypical features that may portend alternative diagnosis (not MS): • Onset: too early/late (before 15-20y, after 50y) • Early onset may point to a genetic etiology • Family history: less likely MS (weak genetic assoc) • Normal CSF, MRI, and/or Evoked potential studies • Systemic signs • Anemia • Angiokeratomas • Cardiomyopathy • Proteinuria • Metabolic acidosis

30. Summary

31. Summary • History & Physical Exam, Labs & MRI findings, AND exclusion of alternative diagnoses. • ~90% of patients ultimately diagnosed with MS initially present with a clinically isolated syndrome (CIS), such as optic neuritis. • MRI can be valuable in differentiating. • American Academy of Neurology: on value of MRI predicting eventual conversion of a clinically isolated syndrome to clinically definite MS: • >3 white-matter lesions in T2 MRI is sensitive predictor (>80%) of clinically definite MS within 7-10 years • In Normal MRIs, <20% will have 2nd attack w/in 10y

32. The Future • Development of more highly specific criteria for this spectrum of diseases. • Development of more reliable biomolecular markers. Always consider demyelinating diseases in the differential diagnosis of enhancing intramedullary lesions. • If index of suspicion is high, further testing may be warranted.

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