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Lou Gehrig’s Disease: A Closer Look at the Genetic Basis of Amyotrophic Lateral Sclerosis

 

Nariman Malik, BSc
Contributing Author,
Geriatrics & Aging.

Lou Gehrig: A Brief History
Lou Gehrig was born June 19, 1903 in New York City. He played for the New York Yankees from 1923 to 1939 and was one of the most famous first basemen in the history of major league baseball.1 The man known as the 'iron horse of baseball' and 'Columbia Lou' was originally recruited for only two games in 1923.2 However, this durable athlete went on to play in 2,130 consecutive games.3 In fact, he never missed a game until he voluntarily benched himself on May 2, 1939.

Gehrig had an impressive career. He had a lifetime batting average of .340, hit 493 home runs and was a four-time winner of the Most Valuable Player award.3 He was also inducted into the Baseball Hall of Fame. The 1938 season had proven to be a bad one for Gehrig as he was not playing up to his usual standard. During spring training for the 1939 season, he began having trouble getting power behind the ball and had difficulty with his movements.2 Unhappy with his performance, Gehrig voluntarily benched himself.

Six weeks later, Gehrig was referred to the renowned Mayo Clinic where he was diagnosed with amyotrophic lateral sclerosis (ALS). Gehrig was never told his true diagnosis and was unaware that the outcome was fatal. Only his wife and a few of her confidantes knew the true nature of Gehrig's illness. Both he and the public were told that he suffered from a chronic form of poliomyelitis, which would prevent him from playing baseball.

The deadly disease slowly took its toll on Gehrig. It steadily progressed from limb weakness to difficulties with swallowing and respiration during the last days of his life.2,3 Lou Gehrig died June 2, 1941. The true nature of his illness was only revealed after his death, after which amyotrophic lateral sclerosis became known as 'Lou Gehrig's Disease'.

Introduction
Amyotrophic lateral sclerosis was originally described by Charcot in 1874.4 Also known as motor neuron disease, ALS is among the most dire of the neuro- degenerative diseases. The disease is characterized by the slow, progressive loss of motor neurons of the cerebral cortex, brainstem and spinal cord.5,6 The disease usually begins asymmetrically involving the muscles of one or more limbs, speech or deglutition.7 Asymmetric muscle weakness is the most common presenting feature; it may present as problems in dexterity or in gait, due to muscle weakness in the upper or lower limbs.4,9 Typically, the disease begins focally and then spreads to become bilateral and symmetrical.8

In most cases, there is concurrent involvement of upper and lower motor neurons.5 The clinical features, therefore, are a combination of sign and symptoms of upper and lower motor neuron degeneration. Signs of lower motor neuron degeneration include weakness, muscle wasting, hyporeflexia, muscle cramps and fasciculations.4,8 Signs associated with upper motor neuron degeneration include spasticity, hyperreflexia, extensor plantar responses, hyperactive jaw jerk and emotional lability.4,9 Dysarthria, dysphagia and respiratory insufficiency are usually caused by a combination of lower and upper motor neuron degeneration.4 The symptom of pain is unusual in ALS until late in the course of the disease when limited mobility results in muscle discomfort and adhesive capsulitis.4 Over a period of months or years, there is severe progressive muscular weakness that ultimately leads to death.9

Pathology
Pathologically, the progressive degeneration and loss of motor neurons characterize ALS. Early pathological changes in the motor neuron include fragmentation of the Golgi apparatus, attenuation of the dendrites, hyperaccumulation of phosphorylated neurofilaments, basophilic inclusions, ubiquitin, Lewy-body-like inclusions and swellings in the proximal axonal segments.9-11 The term amyotrophic lateral sclerosis refers to the