Demyelinating diseases

Multiple sclerosisCentral pontine myelinolysis

Transverse myelitisGuillain-Barre syndrome

Characteristic

InflammatoryMostly acute onset

Commonly relapsing-remitting course

Multiple sclerosis An inflammatory demyelinating disease Affects brain & spinal cord Common in young- ~40 years, females Classification- based on course Relapsing-remitting- accretive deficits over long-term 2° progressive- progressive neurologic decline,

following relapsing-remitting course 1° progressive- relentless progression without remission Progressive relapsing- steady neurologic decline with few

relapses

Cause & pathophysiology Cause- exactly not known Genetic propensity- HLA-DR15 & DQ6 increase risk Infection- possible trigger of inflammatory response- HHV, MMR Other- decreased sunlight exposure,

smoking, stress, vaccinations, toxins Pathophysiology- Plaques in white matter of brain, rarely peripheral,

due to damage to oligodendrocytes Inflammation, mediated predominantly by T-cells

that enter CNS through permeable blood-brain barrier

Clinical Manifestation- gradually progressive Paresthesias, weakness, ataxia Dysarthria, dysphagia, diplopia, impaired vision Acute/chronic pain, cognitive impairment Depression & mood changes Dx- MRI- plaques, specially at multiple sites CSF- oligoclonal bands of IgG, s/o inflammation Impaired visual or sensory evoked potantials

Treatment Aims- returning function after an acute attack,

preventing new attacks, preventing disability Acute attack- IV methylprednisolone ± plasmapheresis Disease modifiers- Interferon β-1a/1b Glatiramer Mitoxantrone Natalizumab Supportive treatment Px- mean years to death since onset is ~30 years;

Females, relapsing-remitting type, early age & optic neuritis at onset, fewer attacks are associated with a better course

Central pontine myelinolysis Osmotic demyelination syndrome Causes- Rapid correction of hyponatremia, specially chronic Associated with alcoholism, hyperemesis gravidarum, SCT s/s- due to myelinolysis of corticobulbar & corticospinal tracts,

in pons- LOC, quadriparesis, dysarthria, dysphagia, diplopia etc. Dx- clinical + MRI Rx- supportive only Prevention- slow correction of hyponatremia-

~0.5 mEq/L/hr

Transverse myelitis Acute demyelination of spinal cord,

following viral infection or vaccination s/s- depend on site of spinal cord involvement-

sensory level & radicular pain define level DDx- trauma, epidural metastasis, infarction Dx- MRI Rx- high-dose steroids + supportive Px- poor in majority

Guillain-Barre syndrome An autoimmune disease affecting peripheral

nerves- ~80% myelin, ~20% axon Triggers- C.jejuni, influenza virus/vaccine Classification- AIDP- ascending LMN type paralysis, most common Miller-Fisher- descending paralysis; presents with

ophthalmoplegia, ataxia, areflexia AMAN- acute motor axonal neuropathy AMSAN- acute motor sensory axonal neuropathy Acute panautonomic neuropathy Bickerstaff brainstem encephalitis- altered sensorium,

ophthalmoplegia, ataxia, hyperreflexia

Clinical- classic AIDP s/s- progression over days- <4 weeks Symmetrical ascending palsy, legs upwards; with areflexia May affect lower cranial nerves- dysphagia Facial weakness common, eyes spared Deep, dull-aching pain, with numbness & tingling Transient bladder dysfunction Dx- CSF-raised protein, normal cells; EMG & NCV Rx- IVIG- 400 mg/kg/d x 5 days or

plasmapheresis- 50 ml/kg exchange, 4 times over a week Px- ~80% complete recovery, ~10%- severe disability,

~10%- CIDP; poor Px- age >40, preceding diarrhea, requiring mechanical ventilation, high anti-GM1 titres

CIDP- Chronic inflammatory demyelinating polyneuropathy A progressive inflammatory neuropathy over >8

weeks s/s- symmetrical Weakness, numbness/tingling, dull aching pain Autonomic- orthostatic hypotension,

bowel-bladder dysfunction, arrythmia Muscle atrophy, fasciculation, areflexia Dx- clinical + EMG/NCV ± sural nerve biopsy Rx- steroids, IVIG, plasmapheresis &

immunosuppressives- cyclophosphamide, azathioprine, mycophenolate mofetil, rituximab