Demyelinating Disease
Authors: Flaherty, Alice W.; Rost, Natalia S.
Title: Massachusetts General Hospital Handbook of Neurology, The, 2nd Edition
Copyright 2007 Lippincott Williams & Wilkins
> Table of Contents > Adult Neurology > Demyelinating Disease
Demyelinating Disease
A. Multiple sclerosis
Multiple CNS demyelinating attacks, disseminated in time and space.
1. Definitions:
a. Attack (exacerbation, relapse): Inflammatory and demyelinating lesion lasting >24 h, objective clinical findings, separated by 30 d between onset of attacks.
b. Course: Relapsing-remitting, secondary progressive, primary progressive.
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Figure 6. Cranial nerve nuclei. (Reprinted with permission from Duus P. Topical Diagnosis in Neurology. New York: Thieme; 1983:105.)
c. MRI Criteria: Three of the following: at least one gad+ lesion or nine T2 lesions, one infratentorial lesion, one juxtacortical lesion, at least three periventricular lesions. Spinal cord lesions considered equivalent to infratentorial lesion, enhancing brain lesion, and T2 lesion.
d. % criteria: Diagnostic criteria for MS, possible MS, and not MS.
2. H&P:
a. Common presenting sx: Optic neuritis, weakness and numbness, diplopia, vertigo, myelitis, urinary retention. Sx worse with heat (Uthoff's phenomenon).
b. Other MS sx: Urinary retention, pain, fatigue, Lhermitte's phenomenon (tingling on neck flexion), internuclear ophthalmoplegia, cognitive changes. Weakness frequently worst in hands and hips.
c. MS flare: Usually subacute (>1 wk) deterioration. Acute (1-3 d) deterioration suggests an infection that is briefly exacerbating MS sx. Does the pt. use catheters?
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Table 6. McDonald criteria for diagnosis of MS.
MCDONALD CRITERIA FOR DIAGNOSIS OF MS Clinical Presentation Additional Data Needed for DX 2 attacks, and 2 lesions with
objective clinical evidenceNone 2 attacks and 1 lesion with
objective clinical evidenceDissemination in space, by MRI or 2
MRI lesions plus + CSF or 2nd clinical
attack at different site1 attack, and 2 lesions with
objective clinical evidenceDissemination in time, by MRI or 2nd
clinical attack1 attack, and 1 lesion with objective
clinical evidence (clinically
isolated syndrome)Dissemination in space, by MRI or 2
MRI lesions plus + CSF and
dissemination in time (disseminated by
MRI or second clinical attack)Insidious neurological
progression suggestive of MSOne year of progression and 2 of the
following 3: (A) + Brain MRI (9 T2
lesions or 4+T2 lesions with +VEP);
(B) + spinal cord MRI (2 T2 lesions);
(C) + CSF3. Tests:
a. Initial workup:
1) MRI brain + contrast: see p. 188. Pts. with a first MS-like neurological event and significant white matter lesions on MRI have a 5-year incidence of MS of about 80%. If no lesions, risk is about 5%.
2) MRI spinal cord + contrast only if clinically suspicious.
3) If unusual clinical picture or criteria not fulfilled: CSF for elevated IgG index or oligoclonal bands (WBC should be <50) and VEP (delayed but preserved wave form).
4) Consider Lyme titer, RPR, B12 level, HIV, ESR, ANA, ACE, HTLV.
b. MS attack: CBC, urinalysis, CXR and ESR to help r/o infection that could mimic an attack; consider tests to r/o disc herniation or entrapment neuropathy.
4. DDx:
a. DDx of MS: Acute disseminated encephalomyelitis, antiphospholipid syndrome, carotid dissection, cervical cord compression, CNS lymphomas and gliomas, vasculitis, lupus, myelitis, infection (HIV, Lyme, HTLV, syphilis), neurosarcoid, Chiari malformations, B12 deficiency, arylsulfatase or hexosaminidase A deficiencies, CADASIL, paraneoplastic syndrome, mitochondrial dzs .
b. Neuromyelitis optica (Devic's syndrome): Severe opticospinal recurrent demyelinating disease, either variant of MS or separate disease. Serum NMO antibody is sensitive and specific.
c. DDx of MS attack in pt. with known MS: Infection (bladder > teeth > URI), cervical or lumbar disc herniation, entrapment neuropathy .
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5. Rx of MS:
a. Immunomodulators: Approved for relapsing-remitting MS. Reduce clinical and MRI indicators of disease activity, possibly may alter course.
1) Avonex ( -IFN 1a): 30 g IM q wk. May delay progression.
2) Rebif (high-dose -IFN 1a): 22 or 44 g SC qod. Possible dose-related benefit, much higher rate of neutralizing antibodies.
3) Betaseron ( -IFN 1b): 8 MIU IU SC qod. May delay progression in active relapsing-remitting or secondary progressive MS.
4) Glatiramer (Copaxone): Fragments of myelin basic protein. 20 g SC qd.
5) Mitoxantrone: FDA approved for active relapsing-remitting or secondary progressive MS. Has a lifetime dose limit.
6) Cyclophosphamide (Cytoxan): Controversial. For aggressively progressive MS.
b. MS attack: High-dose steroids (methylprednisolone IV 1,000 mg 3 d, prednisone taper) speed clinical recovery but no long-term benefit. For prevention of steroid side effects, see p. 173.
c. Rx of secondary sx: See rx for spasticity, p. 176; pain, p. 155; tremor, p. 79; and spastic bladder or bladder-sphincter dyssynergia, p. 126. Fatigue: modafinil 100-200 mg in AM and at noon. Brief, painful, focal seizures sometimes resolve after a few weeks of low-dose ACD.
B. Other CNS demyelinating conditions
1. Transverse myelitis: Isolated spinal cord inflammation without compressive lesion.
a. H&P: Back pain, sudden paresthesias, myelopathy (see Spinal Cord Disorders, p. 113) over hours to weeks.
b. Tests: CSF, MRI spine with gado, consider MRA or CTA spine, CT myelogram more sensitive for dural AVF, infectious workup, ANA, ESR, ANCA, SSA/SSB, ACE, B12 and Vit E levels.
c. Causes: Idiopathic, postinfectious (M. pneumonia, otitis media, skin infections, Lyme, VZV, HSV, CMV, TB, HTLV, HIV, syphilis, influenza, echovirus, hepatitis A, rubella, schistosomiasis), postvaccine. Associated with SLE, Sj gren's, sarcoid. Can be first attack of MS, may be secondary to ischemia.
d. DDx: Some infections, e.g., TB. Structural myelopathy, infarct, hemorrhage, AVM, dural AV fistula, cord contusion, vasculitis, vitamin B12 and E deficiency.
e. Rx: Steroids (1 g methylprednisolone IV or 100 mg dexamethasone IV for at least 3 days), consider IVIg.
f. Prognosis: Rarely recurs. Recovery starts in 2-12 wk, up to 2 years. 1/3 good recovery, 1/3 can walk but have deficits, 1/3 paraplegic.
2. Acute disseminated encephalomyelitis (ADEM): Multifocal demyelination similar to MS but acute, monophasic, sometimes postinfectious.
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a. H&P: Recent viral infection or vaccination.
b. DDx: Infectious encephalomyelitis.
c. Rx: Consider steroids, plasmapheresis.
3. Acute hemorrhagic leukoencephalitis: A hyperacute ADEM, often with fever, seizures, obtundation.
4. Cerebellitis: see p. 145.
5. Brainstem (Bickerstaff) encephalitis: Adolescents and young adults.
C. Guillain-Barr syndrome
AKA acute idiopathic demyelinating polyradiculoneuritis (AIDP, as opposed to CIDP).
1. GBS is an emergency: There is danger of sudden respiratory collapse, even in pts without severe limb weakness. 25% of pts. need intubation.
2. H&P: Infection (1/4 have prior Campylobacter jejuni), vaccination, or surgery in previous 1-3 wk; pregnancy. Rapid (days to 1 mo) symmetric weakness, weak or absent DTRs, facial diplegia, poor swallowing or breathing, stocking/glove numbness in hands and feet. Sometimes proximal > distal (vs. other peripheral neuropathies), ANS instability, diffuse back pain.
3. Variants:
a. Miller Fisher variant: Areflexia, sensory ataxia, ophthalmoparesis. GQ1b Ab is sensitive and specific.
b. Axonal variants: Can be pure motor or motor + sensory. EMG shows the axon damage. Ganglioside antibodies, e.g., GM1, are common.
c. Polyneuritis cranialis: A variant that often presents with bifacial weakness.
d. Acute pandysautonomia: ANS dysfunction, papilledema, upgoing toes. No meningeal signs.
4. Tests:
a. Respiratory: Vital capacity tid. Remember that O2 saturation is not sensitive; pt will become hypercarbic before becoming hypoxic.
b. Blood: -HCG, heterophile Ab and EBV titers, Campylobacter, HIV, CMV, RF, ANA, hepatitis titers, serum GM1 and GQ1b antibodies.
c. NCS: Conduction block, usually low velocity, high latency, decreased F-wave conduction (poor correlation with sx, can be nl early in dz).
d. Biopsy: Focal demyelination. Biopsy only if dx unclear.
e. CSF: Protein usually up after first few days. Cell count usually normal; sometimes 10-100 monocytes.
5. DDx of GBS: CIDP, other neuropathies (see p. 93); neuromuscular problem, e.g., myasthenia or botulism, Lyme, MS, foramen magnum or other spine tumor, polio, hypophosphatemia (during long TPN course), tick paralysis .
6. Rx: Intubate if vital capacity <15 cc/kg or 0.6 L, or higher if falling fast. Plasmapheresis (ANS instability is a relative contraindication) and IVIg are equally effective, limit severity and hasten recovery. No role for steroids (although help CIDP). Protect eyes from drying. Back pain may require narcotics. Watch for SIADH.
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a. Prognosis: Fatal in 4-15%, 20% disabled, and 35% have permanent deficit. 10% relapse. 50% nadir in 1 wk; 90% in 1 mo. Poorer outcomes with axonal variants, elderly, bed-bound or intubated, more rapid onset, prior diarrheal illness, motor amplitude <250.
D. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
1. CIDP vs. GBS: CIDP progresses or relapses for 2 months or more; usually legs > arms; incidence peaks at age 50-60. Like GBS, it is probably autoimmune.
2. Tests: NCS show demyelination, CSF protein >45 mg/dL, cell count <10/ L, sural nerve biopsy shows de- and remyelination with perivascular inflammation.
3. DDx: Other neuropathies, e.g., DM, metabolic, toxic, infectious (HIV, HCV), paraneoplastic, paraproteinemias, lymphoma, vasculitis.
4. Rx: Steroids, plasma exchange, and IVIg are equally effective; 60% respond. Second line = combinations of these or immunosuppressants (cyclosporine, mycophenolate, etc.).
5. Multifocal motor neuropathy (MMN): Purely motor variant of CIDP.
a. H&P: Age 20-50 at onset, progressive, asymmetric weakness in distribution of individual nerves, upper > lower limbs, multifocal conduction block, GM1 Ab.
b. Rx of MMN: Long-term IVIg; 80% respond but dose lasts only few weeks. Plasma exchange and steroids do not work. Immunosuppressants for refractory dz.
EAN: 2147483647
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