Atlas of pathophysiology, 2 Edition

Part II - Disorders

Neurologic disorders

Myasthenia gravis

Myasthenia gravis is an autoimmune disorder that causes sporadic but progressive weakness and abnormal fatigability of striated (skeletal) muscles. Muscle weakness is exacerbated by continuing activity and repeated movement and is relieved by rest.

Myasthenia gravis follows an unpredictable course of periodic exacerbations and remissions. There's no known cure. Drug treatment has improved the prognosis and allows patients to lead relatively normal lives, except during exacerbations. When the disease involves the respiratory system, it may be life-threatening.

Age Alert

Women are most commonly affected in their 20s and 30s while men are usually affected in their 60s and 70s.

Causes

·         Exact cause unknown

Possible causes

·         Autoimmune response

·         Ineffective acetylcholine release

·         Inadequate muscle-fiber response to acetylcholine

Pathophysiology

Myasthenia gravis is an autoimmune disease of the neuromuscular junction resulting from the production of antibodies against the acetylcholine receptor protein of skeletal muscles. Musclelike (myoid) cells in the thymus gland bear surface acetylcholine receptors, and a break in immune regulation interferes with tolerance and initiates antibody production. The site of action is the postsynaptic membrane. The antibodies reduce the number of acetylcholine receptors available at each neuromuscular junction and thereby impair muscle depolarization necessary for movement.

Scientists believe the thymus gland may give incorrect instructions to developing immune cells, ultimately resulting in autoimmunity and the production of the acetylcholine receptor antibodies and thereby allowing for the attack on neuromuscular transmission.

Signs and symptoms

·         Weak eye closure, ptosis, and diplopia

·         Skeletal muscle weakness and fatigue, increasing through the day but decreasing with rest (in the early stages, easy fatigability of certain muscles may appear with no other findings; later, it may be severe enough to cause paralysis)

·         Progressive muscle weakness and accompanying loss of function depending on the muscle group affected; becoming more intense during menses and after emotional stress, prolonged exposure to sunlight or cold, or infections

·         Blank, expressionless facial appearance and nasal vocal tones

·         Frequent nasal regurgitation of fluids; difficulty chewing and swallowing

·         Weak neck muscles (may become too weak to support the head without bobbing); patient must tilt head back to see

·         Weak respiratory muscles; low tidal volume and vital capacity

Clinical Tip

Respiratory muscle weakness seen in myasthenic crisis may be severe enough to require emergency intubation and mechanical ventilation.

Diagnostic test results

·         Tensilon test confirms diagnosis—temporarily improved muscle function within 30 to 60 seconds after I.V. injection of edrophonium or neostigmine and lasting up to 30 minutes.

·         Electromyography with repeated neural stimulation shows progressive decrease in muscle-fiber contraction.

·         Blood chemistry studies reveal elevated serum antiacetylcholine antibody titer.

·         Chest X-ray reveals thymoma (in about 15% of patients).

Treatment

·         Anticholinesterase drugs, such as neostigmine and pyridostigmine

·         Immunosuppressant therapy with corticosteroids, azathioprine, cyclosporine, and cyclophosphamide used in a progressive fashion

·         Immunoglobulin G during acute relapses or plasmapheresis in severe exacerbations

·         Plasmapheresis

·         Thymectomy

·         Tracheotomy, positive-pressure ventilation, and vigorous suctioning

·         Discontinuation of anticholinesterase drugs in myasthenic crisis until respiratory function improves

P.149

FAILURE OF NERVE IMPULSE TRANSMISSION

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