Atlas of pathophysiology, 2 Edition

Part II - Disorders

Neurologic disorders

Amyotrophic lateral sclerosis

Commonly called Lou Gehrig's disease, after the New York Yankees first baseman who died of this disorder, amyotrophic lateral sclerosis (ALS) is the most common of the motor neuron diseases causing muscular atrophy. A chronic, progressively debilitating disease, ALS may be fatal in less than 1 year or continue for 10 years or more, depending on the muscles affected. More than 30,000 Americans have ALS; the disease affects three times as many men as women.

Age Alert

The average age of ALS onset is mid-50s but can range from the late teen years to the 80s.

Causes

The exact cause is unknown. A genetic (familial ALS [FALS]) link is seen in 5% to 10% of all ALS cases. Multiple gene mutations (most autosomal dominant) have been identified in about 20% of FALS cases. Several theories have been proposed that explain why motor neurons die, including:

·         glutamate excitotoxicity

·         oxidative injury

·         protein aggregates

·         axonal strangulation

·         autoimmune-induced calcium influx

·         viral infections

·         deficiency of nerve growth factor

·         apoptosis (programmed cell death)

·         trauma

·         environmental toxins.

Pathophysiology

Current research suggests an excess accumulation of glutamate (an excitatory neurotransmitter) in the synaptic cleft. The affected motor units are no longer innervated, and progressive degeneration of axons causes loss of myelin. Some nearby motor nerves may sprout axons in an attempt to maintain function but, ultimately, nonfunctional scar tissue replaces normal neuronal tissue.

Signs and symptoms

·         Fasciculations, spasticity, atrophy, weakness, and loss of functioning motor units (especially in forearms and hands)

·         Impaired speech, chewing, and swallowing; choking; drooling

·         Difficulty breathing, especially if the brain stem is affected

·         Muscle atrophy

·         Reactive depression

Diagnostic test results

·         Electromyography shows abnormalities of electrical activity in involved muscles.

·         Muscle biopsy shows atrophic fibers interspersed between normal fibers.

·         Cerebrospinal fluid analysis by lumbar puncture reveals elevated protein levels.

·         Nerve conduction studies show normal results.

Treatment

·         Riluzole

·         Baclofen or diazepam

·         Trihexyphenidyl or amitriptyline

·         Physical therapy

·         Percutaneous feeding tubes

·         Tracheostomy

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MOTOR NEURON CHANGES IN ALS

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