Demyelinating Disorders

DEMYELINATING DISORDERS

Multiple sclerosis (MS) is a chronic relapsing-remitting disorder of probable auto-immune origin characterized by recurrent episodes of demyelination in the brain (including optic nerves) and spinal cord; it results in progressive neurological deficits.

•         The overall prevalence of MS is 1/1,000, with higher prevalence in northern countries.

•         Those who emigrate age >15 from areas of high prevalence to areas of low prevalence maintain their original risk.

•         Women have 2x the risk of men.

Genetic and environmental factors contribute to the pathogenesis. HLA DR 15 con-fers genetic susceptibility. Environmental factors include viral infection, vitamin D deficiency, and smoking.

•         Acute lesions on gross examination show well-circumscribed gray lesions (plaques), with bilateral distribution that is frequently periventricular. His-tology shows chronic inflammation with phagocytosis of myelin by macro-phages; axons are initially preserved.

•         Chronic lesions have no inflammation, with axons showing remyelination. Remyelination is defective because myelin sheaths are thinner with shorter internodes.

During an acute attack, nerve conduction is entirely blocked, leading to acute neuro-logical deficits. Chronic plaques are associated with slower nerve conduction, allowing for partial recovery. Recurrent attacks cause progressive neurological deterioration.

Clinical onset is typically in decades 3–4. About 85% of cases show a relapsing-remitting course; a minority of cases show primary progressive (slow deteriora-tion) or progressive-relapsing (slow progression punctuated by acute exacerbations) course. Recovery from each episode of demyelination occurs in weeks or months.

Early symptoms include sensory problems, paresis, and visual dysfunction. As the disease progresses, other symptoms include fatigue, bladder dysfunction, spasticity and ataxia. Neuropsychological symptoms affect 40–60% of patients.

Diagnosis of MS requires the demonstration of the dissemination of disease in space and time. Clinical history, MRI, CSF studies and electrophysiological stud-ies are important. Treatment is immunomodulatory drugs (e.g., interferon beta), immunosuppressive therapies (e.g., mitoxantrone), and monoclonal antibodies (e.g., natalizumab). The latter is used as monotherapy in cases of relapsing MS; its use is linked to PML.

Central pontine myelinolysis (CPM) is a focal demyelination of the central area of the basis pontis. It probably derives from rapid correction of hyponatremia, and the condition is very often fatal. Patients at risk include the severely malnourished and alcoholics with liver disease.