Atlas of pathophysiology, 2 Edition

Part II - Disorders

Neurologic disorders

Multiple sclerosis

Multiple sclerosis (MS) causes demyelination of the white matter of the brain and spinal cord and damage to nerve fibers and their targets. Characterized by exacerbations and remissions, MS is a major cause of chronic disability in young adults and its prognosis varies. MS may progress rapidly, disabling the patient by early adulthood or causing death within months of onset. However, 70% of patients lead active, productive lives with prolonged remissions.

Age Alert

MS usually produces symptoms between ages 20 and 40 (the average age of onset is 27).

Types of MS include:

·         elapsing-remitting—clear relapses (or acute attacks or exacerbations) with full recovery or partial recovery and lasting disability (The disease doesn't worsen between the attacks.)

·         primary progressive—steady progression from the onset with minor recovery or plateaus (This form is uncommon and may involve different brain and spinal cord damage than other forms.)

·         secondary progressive—begins as a pattern of clear-cut relapses and recovery (This form becomes steadily progressive and worsens between acute attacks.)

·         progressive relapsing—steadily progressive from the onset, but also has clear acute attacks. (This form is rare.)

Causes

·         Exact cause unknown

Possible causes

·         Autoimmune response to a slow-acting or latent viral infection

·         Environmental or genetic factors

Pathophysiology

Evidence suggests that activation of T lymphocytes against the myelin antigens, axons, and oligodendrocytes triggers an immunologic cascade. Recruitment of inflammatory cells and local release of lymphokines and cytokines results in injury to the myelin and the underlying axon. Axon demyelination and nerve fiber loss occur in patches throughout the central nervous system. The damaged myelin sheath can't conduct normally, and the partial loss or dispersion of the action potential causes neurologic dysfunction.

Signs and symptoms

·         Optic neuritis, diplopia, ophthalmoplegia, blurred vision, and nystagmus

·         Sensory impairment, such as burning, pins and needles, and electrical sensations

·         Fatigue (usually the most debilitating symptom)

·         Weakness, paralysis ranging from monoplegia to quadriplegia, spasticity, hyperreflexia, intention tremor, and ataxia

·         Incontinence, frequency, urgency, and frequent urinary tract infections

·         Involuntary evacuation or constipation

·         Poorly articulated or scanning speech (syllables separated by pauses)

·         Dysphagia

Diagnostic test results

Diagnosis of MS requires evidence of two or more neurologic attacks. These tests may also be useful:

·         Magnetic resonance imaging reveals multifocal white matter lesions.

·         EEG reveals abnormalities in brain waves in one-third of patients.

·         Lumbar puncture shows normal total cerebrospinal fluid (CSF) protein but elevated immunoglobulin (Ig) G (gamma globulin); IgG reflects hyperactivity of the immune system due to chronic demyelination. An elevated CSF IgG is significant only when serum IgG is normal. CSF white blood cell count may be elevated.

·         CSF electrophoresis detects bands of IgG in most patients, even when the percentage of IgG in CSF is normal. Presence of kappa light chains provides additional support of the diagnosis.

·         Evoked potential studies (visual, brain stem, auditory, and somatosensory) reveal slowed conduction of nerve impulses in most patients.

Treatment

The aim of treatment is threefold: treat the acute exacerbation, treat the disease process, and treat the related signs and symptoms.

·         I.V. methylprednisolone followed by oral therapy

·         Interferon and glatiramer acetate

·         Stretching and range-of-motion exercises, coupled with correct positioning, adaptive devices, and physical therapy

·         Baclofen and tizanidine

·         Frequent rest periods, aerobic exercise, and cooling techniques (air conditioning, breezes, water sprays)

·         Amantidine, pemoline, or methylphenidate

·         Low-dose tricyclic antidepressants, phenytoin, or carbamazepine

·         Beta-adrenergic blockers, sedatives, and diuretics

·         Antihistamines

·         Speech therapy, vision therapy, and adaptive lenses

·         Bladder problems (failure to store urine, failure to empty the bladder or, more commonly, both) managed by such strategies as drinking cranberry juice or inserting an indwelling catheter and suprapubic tubes (intermittent self-catheterization and postvoid catheterization programs are helpful, as are anticholinergic medications in some patients)

·         Bowel problems (constipation and involuntary evacuation) managed by such measures as increasing dietary fiber, using bulking agents, and bowel-training strategies, such as daily suppositories and rectal stimulation

P.147

MYELIN DESTRUCTION IN MULTIPLE SCLEROSIS

image

image