Differential Diagnosis of MS vs. Connective Tissue Disease

MSCoE Case Teleconference October 2006

M. Wallin, MD, MPH

Assoc. Director, Clinical Care MSCoE-East

Associate Prof. of Neurology, Georgetown University

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History

58 year old male veteran who presented to the neurology clinic with a history of multifocal neurologic symptoms:-1995: Right V2-3 trigeminal neuralgia-2000: Tingling and numbness in right upper extremity-2000: Dysarthria & V2-3 sensory loss s/p trigeminal rhizotomy-2004: Difficulties with balance and walking-2005: Double vision and blurred vision OD-2006: Significant decline in cognitive function that started 4 years prior according to family-deficits in recent memory, expressive speech, & slowing. Several MVAs over the past 4 years.

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History (cont)

PMH: 1) Hypopigmented scalp patches 1980s-1990s; bx performed

2) Alopecia areata3) Sicca syndrome, lip mucosal bx VAMC-DC4) Hypertension5) Depression and PTSD6) Trigeminal neuralgia, s/p R V2-3 rhizotomy

2000 MEDS: Verapamil, Atenolol, HCTZ, Trazodone, Paroxetine,

eye lub. gtts

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Physical Exam

GEN: hypopigmented scalp patch, sclera dry/clear, a few scattered cervical lymph nodes; lungs: clear; cv: rrr, no murmurs; no joint swelling, erythema or warmth

NEURO: MSt: alert, dysarthric speech, moderate psychomotor slowing,

disorientated to time, place and date, 22/30 MMSt, depressed moodCN: VA with corr-OD: 20/40, OS: 20/30, no APD, saccadic pursuits, full

EOM, R V1-3 hypoesthesia to pp & lt, R lower facial weaknessReflexes: ¾ in UE, 4/4 knees and ankles, Babinski reflex pos. bilaterallyMotor: diffuse atrophy, spastic LE>UE, 5/5 power for bulk in all 4 ext Sensory: loss of vibration in distal LE bilaterallyCSG: dysmetria on FNF, ataxic HKS, wide-based spastic gait

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Laboratory

CBC, Chem 7, liver enz, ua, spep, tsh, HIV, B12, HTLV1/2 were normal or negative

11/05 CSF: clear, colorless, gluc: 66, protein: 36, 1.0 wbc/cmm, positive OCB, IgG/alb nl, neg vdrl, bact and fungal cx negative, viral and lyme pcr negative

FANA: pos, speckled 1:1280; SM-RNP: positive SSA and SSB Ab: negative; Cryoglob: neg; anti-

DNA neg, RF: neg; CRP <0.5

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Cognitive Testing 7-05

Diffuse cognitive dysfunction scoring well below average on standardized tests in the following domains:

• Orientation• Verbal fluency• Attention• Verbal & Visual Learning• Confrontational naming• Spatial functioning• Working memory

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Axial T1 3-06

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Axial FLAIR 3-06

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Sagittal T1 3-06

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T1 with Gd 3-06

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Axial T1 9-06

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Axial FLAIR 9-06

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Sagittal FLAIR 9-06

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Cervical Spine MRI 3-06

• Cervical spondylosis (moderate) without cord compression or intramedullary lesions

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Differential Diagnosis

– Discoid Lupus/Lupoid sclerosis

– Sjoegren’s syndrome

– HTLV1/2

– Multiple sclerosis

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Management and Follow-up

• Further work-up

• Immune modulating therapy

• Symptomatic therapy

• Rehabilitation

• Counseling

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Systemic Lupus Erythematosis

• Neuropsychiatric manifestation seen in up to 60% of patients with SLE

• Lupoid sclerosis

• ANA 1:40 or greater

• MRI– Brain: High signal subcortical T2 lesions– Spinal cord: > 4 segments, swelling

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Antiphospholipid Syndrome

• Recurrent venous or arterial thrombosis with Abs to membrane phospholipids

• Primary APS vs. Secondary APS

• Nonthrombotic neurologic symptoms: migraine headaches, seizures, TM, GBS

• Brain MRI: high signal T2 subcortical lesions

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Primary Sjoegren’s Syndrome

• Chronic Autoimmune exocrinopathy

• SSA-SSB, RF, ANA

• Shirmer test, parotid gland flow

• Neurologic manifestations seen in 20%– Often precedes diagnosis– CNS & PNS involvement (ON and TM)– May mimick RR MS or PP MS

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Behcet’s Disease

• Inflammatory multisystem disorder characterized by:– Uveitis– Erythema nodosum– Oral and genital ulcers

• CNS affected 10-49%• CSF: IgG index ↑, +/- OCB• MRI: brainstem, basal ganglia, deep white

matter lesions (high T2, low T1)

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Demyelination in Rheumatic Disease(Theodoridou A, JNNP 2006;77:290-5)

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Conclusions

• Assessment for systemic connective tissue disease should be included in all patients presenting with CNS demyelinating disease

• Long term follow-up of patients may be required to confirm diagnosis

• Suspect systemic connective tissue disease in patients presenting with MRI lesions or CSF atypical for MS

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References

Theodoridou A, et al. Demyelination in rheumatic disease. JNNP;2006:77:290-295.

Csepany T, et al. MRI findings in central nervous systemic lupus erythematosis are associated with immunoserological parameters and hypertension. J Neurol 2003;1348-54.

Alexander, EL, et al Anti-Ro autoantibodies in central nervous system disease associated with Sjögren’s syndrome. Neurology 1994;44:899-908.