Nejm 2000;343:938; 1997;337:1604

Cause:Perhaps autoimmune; perhaps precipitated by EB virus infection (Jama 2005;293:2496; 2003;289:1533; 2002;286:3083). Genetic component indicated by 25% concordance with monozygotic twins but only 2% with dizygotic twins and siblings (Nejm 1986;315:1638)

Pathophys:Autoimmune attack of myelin basic protein by CD4 or CD8 T cells (Nejm 2006;354:943) or by tumor necrosis factor-, which is measurable in CSF (Nejm 1991;325:467). Axonal demyelination and ultimately transection (Nejm 1998;338:278)

Transmissible somehow (eg, Faroe Island epidemic after WWII troop occupation); increased incidence with birth and/or childhood distance from equator; equal sex ratios, although females get at younger age; onset at age 10-50 yr, bell-shaped curve; 1/1000 of population have disease (probably tip of carriers). Higher incidence at higher latitudes even w same populations probably due to vit D levels (Jama 2006;296:2832)

Sx: Motor (most often ataxia) nearly always hyperreflexia and positive Babinski's; and sensory tract (most often visual) sx, confusion, depression

Si:

Diagnose by 2 or more attacks of neurologic deficits in different parts of CNS that last >24 h, not by CSF or MRI lesions (Nejm 1993;329:1764, 1808)

Loss of abdominal reflexes early, in contrast to ALS

Lhermitte's si: electric shock sensation to extremities with neck flexion (posterior column stretch); r/o any disease involving cervical or thoracic cord

Worse with hot climate, late onset; slightly fewer relapses in pregnancy and slightly more relapses postpartum (Nejm 1998;339:285); 25% are benign, with 1-2 episodes and minimal disability

Types:

• Acute attack
• Initially remitting/relapsing (80-90%), but many evolve to progressive; M/F = 1/2
• Initially progressive (10-20%); M = F; superimposed subsequent relapse/remit cycles don't improve prognosis (Nejm 2000;343:1430, 1486)
• Stable (Nejm 1987;317:442)

Pain, neuralgia including trigeminal (Nejm 1969;280:1395)

Optic neuritis; 40% of MS pts will have it sometime; up to 75% of women and 34% of men with isolated optic neuritis will develop MS up to 15 yr later (Neurol 1988;38:185)

Lab:

CSF:Oligoclonal bands (90%), present throughout disease; IgG/albumin ratio elevated (70%); positive antimyelin antibodies (2 types) 77% sens, 95% specif when both pos? (Nejm 2003;349:139 vs 2007;352:371)

Noninv:Brain stem evoked potentials, no false positives except for other similar diseases like Friedreich's ataxia; ~10% false negatives in early MS

Xray:MRI, 25% false negatives (Neurol 1993;43:905; Jama 1993;269:3146), and many false positives

Rx:

Avoid flu shots in pts w definite MS

of remitting/relapsing (not chronic progressive):

• Interferon-ß1b (Betaseron) 250 µgm sc qod or interferon-ß1a (Avonex, Rebif) 30-44 µgm im/sc qd or tiw × years, decreases relapse rate and severity by 50%; $1000/mo (Lancet 1998;352:1491, 1498; Ann Neurol 1996;39:285; Neurol 1995;43:641, Med Let 1996;38:63). Weekly im Avonex × yrs w 3 d of iv then 11 d of po steroids, given on 1st demyelinating si/sx and UBOs on MRI, decr MS × 1/3 (Nejm 2000;343:898); NNT = 9 (Lancet 2001;357:1576)
• Glatiramer (Copaxone) (copolymer I) (Med Let 1997;38:61; Neurol 1995;45:1268) 20 mg sc qd, reduces recurrences from 85% to 60%/yr; $1000/mo
• Mitoxantrone perhaps, iv q3mos (Lancet 2002;360:2018)
• Natalizumab perhaps (Nejm 2006;354:899, 911, 924); may cause progressive multifocal leukoencephalopathy (p 416) in 0.1%
• Azathioprine perhaps (Arch Neurol 2005;62:1843); need lymphocyte-suppressing doses; reduces new brain lesions
• Fingolimod po? (Nejm 2010;362:387, 402, 456), better than interferon, NNT 1/14, alemtuzamab? (Nejm 2008;359:1786), rituximab? (Nejm 2008;358:676)
• Cladribine po, NNT 1:600, SE rash, nausea, anemia (Nejm 2010;362:416)

of progressive MS: mtx, cyclophosphamide, cyclosporine

of acute attack: (hyperbaric and plasmapheresis rx no longer thought useful)

• Cyclophosphamide (Cytoxan) 400-500 mg iv qd × 7-10 d; alone, but many disagree with its use, eg, Canadian multicenter study (Lancet 1991;337:441)
• ACTH 25 U-tapering to 5 U iv qd × 2 wk, then 40 U-tapering to 20 U im × 1 wk, then stop; or short course of steroids, eg, methylprednisolone 1000 mg iv in 3 h qd × 3, then taper in 7-14 d.

of incontinence (Incontinence)

of neuralgias, with carbamazepine, phenytoin (Nejm 1969;280:1395)

of muscle spasms (Med Let 1997;39:62; Nejm 1981;304:29, 95), in order of efficacy:

• Baclofen, a GABA agonist, 5-20 mg po tid, or even chronically intrathecally via pump (Nejm 1989;320:1517); or
• Tizanidine (Zanaflex) (Med Let 1997;39:62) 4 mg hs to 6+ mg tid; adv effects: dry mouth, sedation, dizziness, hypotension, rare visual hallucinations and hepatitis; or
• Diazepam (Valium), but makes sleepy; or
• Dantrolene 300 mg qd, but causes weakness of fatigue: amantadine, methylphenidate (Ritalin), modafinil (Provigil)