Amyotrophic Lateral Sclerosis (Lou Gehrig's Disease)
Classification and external resources
This MRI (parasagittal FLAIR) demonstrates increased T2 signal within the posterior part of the internal capsule and can be tracked to the subcortical white matter of the motor cortex, outlining the corticospinal tract, consistent with the clinical diagnosis of ALS.
ICD-10	G12.2
ICD-9	335.20
OMIM	105400
DiseasesDB	29148
MedlinePlus	000688
eMedicine	neuro/14 emerg/24 pmr/10
MeSH	D000690

Amyotrophic lateral sclerosis (ALS), also referred to as motor neuron disease in British English, is the most common form of the motor neuron diseases. The condition is sometimes called Lou Gehrig's disease in North America, after the New York Yankees baseball player who was diagnosed with the disease in 1939. The disorder is characterized by rapidly progressive weakness, muscle atrophy and fasciculations, muscle spasticity, difficulty speaking (dysarthria), difficulty swallowing (dysphagia), and decline in breathing ability.

Signs and symptoms[link]

The disorder causes muscle weakness and atrophy throughout the body caused by degeneration of the upper and lower motor neurons. Unable to function, the muscles weaken and atrophy. Affected individuals may ultimately lose the ability to initiate and control all voluntary movement, although bladder and bowel sphincters and the muscles responsible for eye movement are usually, but not always, spared.

Cognitive function is generally spared for most patients although some (~5%) also have frontotemporal dementia.^[1] A higher proportion of patients (~30-50%) also have more subtle cognitive changes which may go unnoticed but are revealed by detailed neuropsychological testing. Sensory nerves and the autonomic nervous system, are generally unaffected meaning the majority of people with ALS will maintain sight, hearing, touch, smell, and taste. Bladder and bowel functions are also rarely affected by ALS.^[2]

Initial symptoms[link]

The earliest symptoms of ALS are typically obvious weakness and/or muscle atrophy. Other presenting symptoms include muscle fasciculation (twitching), cramping, or stiffness of affected muscles; muscle weakness affecting an arm or a leg; and/or slurred and nasal speech. The parts of the body affected by early symptoms of ALS depend on which motor neurons in the body are damaged first. About 75% of people contracting the disease experience "limb onset" ALS i.e. first symptoms in the arms or legs. Patients with the leg onset form may experience awkwardness when walking or running or notice that they are tripping or stumbling, often with a "dropped foot" which drags gently along the ground. Arm-onset patients may experience difficulty with tasks requiring manual dexterity such as buttoning a shirt, writing, or turning a key in a lock. Occasionally, the symptoms remain confined to one limb for a long period of time or for the whole length of the illness; this is known as monomelic amyotrophy.

About 25% of cases are "bulbar onset" ALS. These patients first notice difficulty speaking clearly or swallowing. Speech may become slurred, nasal in character, or quieter. Other symptoms include difficulty swallowing, and loss of tongue mobility. A smaller proportion of patients experience "respiratory onset" ALS where the intercostal muscles that support breathing are affected first. A small proportion of patients may also present with what appears to be frontotemporal dementia, but which later progresses to include more typical ALS symptoms.

Over time, patients experience increasing difficulty moving, swallowing (dysphagia), and speaking or forming words (dysarthria). Symptoms of upper motor neuron involvement include tight and stiff muscles (spasticity) and exaggerated reflexes (hyperreflexia) including an overactive gag reflex. An abnormal reflex commonly called Babinski's sign also indicates upper motor neuron damage. Symptoms of lower motor neuron degeneration include muscle weakness and atrophy, muscle cramps, and fleeting twitches of muscles that can be seen under the skin (fasciculations). Around 15–45% of patients experience pseudobulbar affect, also known as "emotional lability", which consists of uncontrollable laughter, crying or smiling, attributable to degeneration of bulbar upper motor neurons resulting in exaggeration of motor expressions of emotion. To be diagnosed with ALS, patients must have signs and symptoms of both upper and lower motor neuron damage that cannot be attributed to other causes.

Disease progression and spread[link]

Although the order and rate of symptoms varies from person to person, eventually most patients are not able to walk, get out of bed on their own, or use their hands and arms. The rate of progression can be measured using an outcome measure called the "ALS Functional Rating Scale (Revised)", a 12-item instrument administered as a clinical interview or patient-reported questionnaire that produces a score between 48 (normal function) and 0 (severe disability). Though there is a high degree of variability and a small percentage of patients have much slower disease, on average, patients lose about 1 FRS point per month. Regardless of the part of the body first affected by the disease, muscle weakness and atrophy spread to other parts of the body as the disease progresses. In limb-onset ALS, symptoms usually spread from the affected limb to the opposite limb before affecting a new body region, whereas in bulbar-onset ALS symptoms typically spread to the arms before the legs.

Disease progression tends to be slower in patients who are younger than 40 at onset^[3], have disease restricted primarily to one limb, and those with primarily upper motor neuron symptoms.^[4]. Conversely, progression is faster and prognosis poorer in patients with bulbar-onset disease, respiratory-onset disease, and frontotemporal dementia. ^[5]

Late stage disease symptoms[link]

Difficulty swallowing and chewing making eating normally very difficult and increase the risk of choking or aspirating food into the lungs. In later stages of the disease, aspiration pneumonia and maintaining a healthy weight can become a significant problem and may require insertion of a feeding tube. As the diaphragm and intercostal muscles (rib cage) that support breathing weaken, measures of lung function such as forced vital capacity and inspiratory pressure diminish. In respiratory onset ALS, this may occur before significant limb weakness is apparent. External machines such as bilevel positive pressure ventilation (frequently referred to by the tradename BiPAP) are frequently used to support breathing, first at night, and later during the daytime as well. BiPAP is only a temporary remedy, however, and it is recommended that long before BiPAP stops being effective, patients should decide whether to have a tracheotomy and long term mechanical ventilation. At this point, some patients choose palliative hospice care. Most people with ALS die of respiratory failure or pneumonia.

Although respiratory support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Most people with ALS die from respiratory failure, usually within three to five years from the onset of symptoms. The median survival time from onset to death is around 39 months, and only 4% survive longer than 10 years. ^[6] The best-known person with ALS, Stephen Hawking, has lived with the disease for more than 40 years, though his is an unusual case.^[7]

Cause[link]

For patients without a family history of the disease, which includes ~95% of cases, there is no known cause for ALS. Potential causes for which there is inconclusive evidence includes head trauma, military service, and participation in elite sports. Many other potential causes including chemical exposure, electromagnetic field exposure, occupation, physical trauma, and electric shock have been investigated but without consistent findings. ^[8]

There is a known hereditary factor in familial ALS (FALS), where the condition is known to run in families. Recently, a genetic abnormality known as a hexanucleotide repeat was found in a region called C9ORF72, which is associated with ALS combined with frontotemporal dementia ALS-FTD ^[9], and accounts for some 6% of cases of ALS among white Europeans. ^[10] The high degree of mutations found in patients that appeared to have "sporadic" disease, i.e. without a family history, suggests that genetics may play a more significant role than previously thought and that environmental exposures may be less relevant.

A defect on chromosome 21 (coding for superoxide dismutase) is associated with approximately 20% of familial cases of ALS, or about 2% of ALS cases overall.^[11][12][13] This mutation is believed to be autosomal dominant, and has over a hundred different forms of mutation. The most common ALS-causing SOD1 mutation in North American patients is A4V, characterized by an exceptionally rapid progression from onset to death. The most common mutation found in Scandinavian countries, D90A, is more slowly progressive than typical ALS and patients with this form of the disease survive for an average of 11 years. ^[14]

Mutations in several genes have also been linked to various types of ALS, and the currently identified associations are shown in the table below:

Pathophysiology[link]

The defining feature of ALS is the death of both upper and lower motor neurons in the motor cortex of the brain, the brain stem, and the spinal cord. Prior to their destruction, motor neurons develop proteinaceous inclusions in their cell bodies and axons. This may be partly due to defects in protein degradation.^[15] These inclusions often contain ubiquitin, and generally incorporate one of the ALS-associated proteins: SOD1, TAR DNA binding protein (TDP-43, or TARDBP), or FUS.

SOD1[link]

The cause of ALS is not known, though an important step toward determining the cause came in 1993 when scientists discovered that mutations in the gene that produces the Cu/Zn superoxide dismutase (SOD1) enzyme were associated with some cases (approximately 20%) of familial ALS. This enzyme is a powerful antioxidant that protects the body from damage caused by superoxide, a toxic free radical generated in the mitochondria. Free radicals are highly reactive molecules produced by cells during normal metabolism again largely by the mitochondria. Free radicals can accumulate and cause damage to both mitochondrial and nuclear DNA and proteins within cells. To date, over 110 different mutations in SOD1 have been linked with the disease, some of which have a very long clinical course (e.g. H46R), while others, such as A4V, being exceptionally aggressive. Evidence suggests that failure of defenses against oxidative stress up-regulates programmed cell death (apoptosis), among many other possible consequences. Although it is not yet clear how the SOD1 gene mutation leads to motor neuron degeneration, researchers have theorized that an accumulation of free radicals may result from the faulty functioning of this gene. Current research, however, indicates that motor neuron death is not likely a result of lost or compromised dismutase activity, suggesting mutant SOD1 induces toxicity in some other way (a gain of function).^[16][17]

Studies involving transgenic mice have yielded several theories about the role of SOD1 in mutant SOD1 familial amyotrophic lateral sclerosis. Mice lacking the SOD1 gene entirely do not customarily develop ALS, although they do exhibit an acceleration of age-related muscle atrophy (sarcopenia) and a shortened lifespan (see article on superoxide dismutase). This indicates that the toxic properties of the mutant SOD1 are a result of a gain in function rather than a loss of normal function. In addition, aggregation of proteins has been found to be a common pathological feature of both familial and sporadic ALS (see article on proteopathy). Interestingly, in mutant SOD1 mice (most commonly, the G93A mutant), aggregates (misfolded protein accumulations) of mutant SOD1 were found only in diseased tissues, and greater amounts were detected during motor neuron degeneration.^[18] It is speculated that aggregate accumulation of mutant SOD1 plays a role in disrupting cellular functions by damaging mitochondria, proteasomes, protein folding chaperones, or other proteins.^[19] Any such disruption, if proven, would lend significant credibility to the theory that aggregates are involved in mutant SOD1 toxicity. Critics have noted that in humans, SOD1 mutations cause only 2% or so of overall cases and the etiological mechanisms may be distinct from those responsible for the sporadic form of the disease. To date, the ALS-SOD1 mice remain the best model of the disease for preclinical studies but it is hoped that more useful models will be developed.

Other factors[link]

Studies also have focused on the role of glutamate in motor neuron degeneration. Glutamate is one of the chemical messengers or neurotransmitters in the brain. Scientists have found that, compared to healthy people, ALS patients have higher levels of glutamate in the serum and spinal fluid.^[12] Riluzole is currently the only FDA approved drug for ALS and targets glutamate transporters. It only has a modest effect on survival, however, suggesting that excess glutamate is not the sole cause of the disease.

Diagnosis[link]

No test can provide a definite diagnosis of ALS, although the presence of upper and lower motor neuron signs in a single limb is strongly suggestive. Instead, the diagnosis of ALS is primarily based on the symptoms and signs the physician observes in the patient and a series of tests to rule out other diseases. Physicians obtain the patient's full medical history and usually conduct a neurologic examination at regular intervals to assess whether symptoms such as muscle weakness, atrophy of muscles, hyperreflexia, and spasticity are getting progressively worse.

MRI (axial FLAIR) demonstrates increased T2 signal within the posterior part of the internal capsule, consistent with the clinical diagnosis of ALS.

Because symptoms of ALS can be similar to those of a wide variety of other, more treatable diseases or disorders, appropriate tests must be conducted to exclude the possibility of other conditions. One of these tests is electromyography (EMG), a special recording technique that detects electrical activity in muscles. Certain EMG findings can support the diagnosis of ALS. Another common test measures nerve conduction velocity (NCV). Specific abnormalities in the NCV results may suggest, for example, that the patient has a form of peripheral neuropathy (damage to peripheral nerves) or myopathy (muscle disease) rather than ALS. The physician may order magnetic resonance imaging (MRI), a noninvasive procedure that uses a magnetic field and radio waves to take detailed images of the brain and spinal cord. Although these MRI scans are often normal in patients with ALS, they can reveal evidence of other problems that may be causing the symptoms, such as a spinal cord tumor, multiple sclerosis, a herniated disk in the neck, syringomyelia, or cervical spondylosis.

Based on the patient's symptoms and findings from the examination and from these tests, the physician may order tests on blood and urine samples to eliminate the possibility of other diseases as well as routine laboratory tests. In some cases, for example, if a physician suspects that the patient may have a myopathy rather than ALS, a muscle biopsy may be performed.

Infectious diseases such as human immunodeficiency virus (HIV), human T-cell leukaemia virus (HTLV), Lyme disease,^[20] syphilis^[21] and tick-borne encephalitis^[22] viruses can in some cases cause ALS-like symptoms. Neurological disorders such as multiple sclerosis, post-polio syndrome, multifocal motor neuropathy, CIDP, and spinal muscular atrophy can also mimic certain facets of the disease and should be considered by physicians attempting to make a diagnosis.

Because of the prognosis carried by this diagnosis and the variety of diseases or disorders that can resemble ALS in the early stages of the disease, patients should always obtain a second neurological opinion.

Treatment[link]

Slowing progression[link]

Riluzole (Rilutek) as of 2011 is the only treatment that has been found to improve survival but only to a modest extent.^[23] It lengthens survival by several months, and may have a greater survival benefit for those with a bulbar onset. It also extends the time before a person needs ventilation support. Riluzole does not reverse the damage already done to motor neurons, and people taking it must be monitored for liver damage (occurring in ~10% of people taking the drug).^[24] It is approved by Food and Drug Administration (FDA) and recommended by the National Institute for Clinical Excellence (NICE).

Disease management[link]

Other treatments for ALS are designed to relieve symptoms and improve the quality of life for patients. This supportive care is best provided by multidisciplinary teams of health care professionals working with patients and caregivers to keep patients as mobile and comfortable as possible.

Pharmaceutical Treatments[link]

Medical professionals can prescribe medications to help reduce fatigue, ease muscle cramps, control spasticity, and reduce excess saliva and phlegm. Drugs also are available to help patients with pain, depression, sleep disturbances, dysphagia, and constipation. Baclofen and diazepam are often prescribed to control the spasticity caused by ALS, and trihexyphenidyl or amitriptyline may be prescribed when ALS patients begin having trouble swallowing their saliva.^[2]

Physical, Occupational, & Speech Therapy[link]

Physical therapists and occupational therapists play a large role in rehabilitation for individuals with ALS. Specifically, physical and occupational therapists can set goals and promote benefits for individuals with ALS by delaying loss of strength, maintaining endurance, limiting pain, preventing complications, and promoting functional independence.^[25]

Occupational therapy and special equipment such as assistive technology can also enhance patients' independence and safety throughout the course of ALS. Gentle, low-impact aerobic exercise such as performing activities of daily living (ADL's), walking, swimming, and stationary bicycling can strengthen unaffected muscles, improve cardiovascular health, and help patients fight fatigue and depression. Range of motion and stretching exercises can help prevent painful spasticity and shortening (contracture) of muscles. Physical and occupational therapists can recommend exercises that provide these benefits without overworking muscles. They can suggest devices such as ramps, braces, walkers, bathroom equipment (shower chairs, toilet risers, etc.) and wheelchairs that help patients remain mobile. Occupational therapists can provide or recommend equipment and adaptations to enable people to retain as much safety and independence in activities of daily living as possible.

ALS patients who have difficulty speaking may benefit from working with a speech-language pathologist. These health professionals can teach patients adaptive strategies such as techniques to help them speak louder and more clearly. As ALS progresses, speech-language pathologists can recommend the use of augmentative and alternative communication such as voice amplifiers, speech-generating devices (or voice output communication devices) and/or low tech communication techniques such as alphabet boards or yes/no signals.

Feeding and nutrition[link]

Patients and caregivers can learn from speech-language pathologists and nutritionists how to plan and prepare numerous small meals throughout the day that provide enough calories, fiber, and fluid and how to avoid foods that are difficult to swallow. Patients may begin using suction devices to remove excess fluids or saliva and prevent choking. Occupational therapists can assist with recommendations for adaptive equipment to ease the physical task of self-feeding and/or make food choice recommendations that are more conducive to their unique deficits and abilities. When patients can no longer get enough nourishment from eating, doctors may advise inserting a feeding tube into the stomach. The use of a feeding tube also reduces the risk of choking and pneumonia that can result from inhaling liquids into the lungs. The tube is not painful and does not prevent patients from eating food orally if they wish.

Researchers have stated that "ALS patients have a chronically deficient intake of energy and recommended augmentation of energy intake."^[26] Both animal ^[27] and human research ^[26][28] suggest that ALS patients should be encouraged to consume as many calories as possible and not to restrict their calorie intake.

Breathing support[link]

When the muscles that assist in breathing weaken, use of ventilatory assistance (intermittent positive pressure ventilation (IPPV), bilevel positive airway pressure (BIPAP), or biphasic cuirass ventilation (BCV)) may be used to aid breathing. Such devices artificially inflate the patient's lungs from various external sources that are applied directly to the face or body. When muscles are no longer able to maintain oxygen and carbon dioxide levels, these devices may be used full-time. BCV has the added advantage of being able to assist in clearing secretions by using high-frequency oscillations followed by several positive expiratory breaths.^[29] Patients may eventually consider forms of mechanical ventilation (respirators) in which a machine inflates and deflates the lungs. To be effective, this may require a tube that passes from the nose or mouth to the windpipe (trachea) and for long-term use, an operation such as a tracheostomy, in which a plastic breathing tube is inserted directly in the patient's windpipe through an opening in the neck.

Patients and their families should consider several factors when deciding whether and when to use one of these options. Ventilation devices differ in their effect on the patient's quality of life and in cost. Although ventilation support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Patients need to be fully informed about these considerations and the long-term effects of life without movement before they make decisions about ventilation support. Some patients under long-term tracheostomy intermittent positive pressure ventilation with deflated cuffs or cuffless tracheostomy tubes (leak ventilation) are able to speak, provided their bulbar muscles are strong enough. This technique preserves speech in some patients with long-term mechanical ventilation.

Palliative care[link]

Social workers and home care and hospice nurses help patients, families, and caregivers with the medical, emotional, and financial challenges of coping with ALS, particularly during the final stages of the disease. Social workers provide support such as assistance in obtaining financial aid, arranging durable power of attorney, preparing a living will, and finding support groups for patients and caregivers. Home nurses are available not only to provide medical care but also to teach caregivers about tasks such as maintaining respirators, giving feedings, and moving patients to avoid painful skin problems and contractures. Home hospice nurses work in consultation with physicians to ensure proper medication, pain control, and other care affecting the quality of life of patients who wish to remain at home. The home hospice team can also counsel patients and caregivers about end-of-life issues.

Epidemiology[link]

ALS is one of the most common neuromuscular diseases worldwide, and people of all races and ethnic backgrounds are affected. One or two out of 100,000 people develop ALS each year.^[30] ALS most commonly strikes people between 40 and 60 years of age, but younger and older people can also develop the disease. Men are affected slightly more often than women.

Although the incidence of ALS is thought to be regionally uniform, there are three regions in the West Pacific where there has in the past been an elevated occurrence of ALS. This seems to be declining in recent decades. The largest is the area of Guam inhabited by the Chamorro people, who have historically had a high incidence (as much as 143 cases per 100,000 people per year) of a condition called Lytico-Bodig disease which is a combination of ALS, Parkinsonism, and dementia.^[31] Two more areas of increased incidence are West Papua and the Kii Peninsula of Japan.^[32][33]

Although there have been reports of several "clusters" including three American football players from the San Francisco 49ers, more than fifty football players in Italy,^[34] three football-playing friends in the south of England,^[35] and reports of conjugal (husband and wife) cases in the south of France,^{[36][37][38][39][40]} these are statistically plausible chance events^{[citation needed]}. Although many authors consider ALS to be caused by a combination of genetic and environmental risk factors, so far the latter have not been firmly identified, other than a higher risk with increasing age.

Etymology[link]

Amyotrophic comes from the Greek language: A- means "no", myo refers to "muscle", and trophic means "nourishment"; amyotrophic therefore means "no muscle nourishment," which describes the characteristic atrophication of the sufferer's disused muscle tissue. Lateral identifies the areas in a person's spinal cord where portions of the nerve cells that are affected are located. As this area degenerates it leads to scarring or hardening ("sclerosis") in the region.

History[link]

Clinical research[link]

A number of clinical trials are underway globally for ALS; a comprehensive listing of trials in the US can be found at ClinicalTrials.gov.

KNS-760704 (Dexpramipexole) is under clinical investigation in ALS patients. It is hoped that the drug will have a neuroprotective effect. It is one enantiomer of pramipexole, which is approved for the treatment of Parkinson's disease and restless legs syndrome.^[44] The single-enantiomer preparation is essentially inactive at dopamine receptors, is not dose limited by the potent dopaminergic properties of pramipexole.^[45] Results of a Phase II clinical trial conducted by Knopp Neurosciences and involving 102 patients were reported in 2010; the trial found a dose-dependent slowing in loss of function.^[46] A larger phase II trial conducted by Biogen found the drug to be safe, well-tolerated, and associated with a dose-dependent slowing in the decline of ALS.^[47]

Talampanel is being tested in ALS by Teva Pharmaceutical Industries; a Phase II trial was completed in April 2010.^[48]

See also[link]

• ALS Association
• ALS Society of Canada
• ALS Therapy Development Institute
• Motor Neurone Disease Association
• Muscular Dystrophy Association

References[link]

Further reading[link]

External links[link]

• Medline Plus article on ALS

Lou Gehrig
First baseman
Born: (1903-06-19)June 19, 1903 Yorkville, New York City, New York
Died: June 2, 1941(1941-06-02) (aged 37) Riverdale, New York City, New York
Batted: Left	Threw: Left
MLB debut
June 15, 1923 for the New York Yankees
Last MLB appearance
April 30, 1939 for the New York Yankees
Career statistics
Batting average	.340
Home runs	493
Hits	2,721
Runs batted in	1,995
Teams
New York Yankees (1923–1939)
Career highlights and awards
7× All-Star (1933, 1934, 1935, 1936, 1937, 1938, 1939) 6× World Series champion (1927, 1928, 1932, 1936, 1937, 1938) 2× AL MVP (1927, 1936) Hit four home runs in one game on June 3, 1932 New York Yankees team captain (1935–1939) New York Yankees #4 retired Major League Baseball All-Century Team Major League Baseball All-Time Team Other accomplishments
Member of the National
Baseball Hall of Fame
Induction	1939
Vote	Special Election (results unknown)

Henry Louis "Lou" or "Buster"^[1] Gehrig (June 19, 1903 – June 2, 1941) was an American baseball first baseman who played 17 seasons in Major League Baseball (MLB) for the New York Yankees (1923–1939). Gehrig set several major league records,^[2] including most career grand slams (23)^[3] and most consecutive games played (2,130). Gehrig is chiefly remembered for his prowess as a hitter and his durability, a trait which earned him his nickname "The Iron Horse", as well as the pathos of his farewell from baseball at age 36, when he was stricken with amyotrophic lateral sclerosis (ALS). Gehrig was elected to the Baseball Hall of Fame in 1939. In 1969 he was voted the greatest first baseman of all time by the Baseball Writers' Association,^[4] and was the leading vote-getter on the Major League Baseball All-Century Team, chosen by fans in 1999.^[5]

A native of New York City, he played for the Yankees until his career was cut short by ALS, a disorder now commonly known in the United States and Canada as Lou Gehrig's disease.^[6] Over a 15-season span from 1925 through 1939, he played in 2,130 consecutive games. This streak ended only when Gehrig became disabled by the fatal neuromuscular disease that claimed his life two years later. His streak, long considered one of baseball's few unbreakable records,^[7] stood for 56 years, until finally broken by Cal Ripken, Jr., of the Baltimore Orioles on September 6, 1995.

Gehrig accumulated 1,995 runs batted in (RBIs) in 17 seasons, with a career batting average of .340, on-base percentage of .447, and slugging percentage of .632. Three of the top six RBI seasons in baseball history belong to Gehrig. He was selected to each of the first seven All-Star games (though he did not play in the 1939 game, as he retired one week before it was held),^[8] and he won the American League's (AL) Most Valuable Player (MVP) Award in 1927 and 1936. He was also a Triple Crown winner in 1934, leading the AL in batting average, home runs, and RBIs.^[9]

Early life[link]

Gehrig was born in the East Harlem section of Manhattan at 1994 Second Avenue,^[10] weighing almost 14 pounds (6.4 kg) at birth, the second child out of four to German immigrants.^[11] His father Heinrich was a sheet metal worker by trade, but frequently unemployed due to alcoholism, and his mother Christina was a maid, the main breadwinner and disciplinarian in the family.^[12] His two sisters died from whooping cough and measles at an early age; another son also died in infancy.^[13] Young Gehrig helped his mother with her work, doing tasks such as folding laundry and picking up supplies from the local stores.^[14] In 1910, Gehrig lived with his parents at 2266 Amsterdam Avenue in Manhattan.^[15] In 1920 the family resided at 2079 8th Avenue in Manhattan.^[16]

Gehrig on the Columbia University baseball team

Gehrig first garnered national attention for his baseball ability while playing in a game at Cubs Park (now Wrigley Field) on June 26, 1920. Gehrig's New York School of Commerce team was playing a team from Chicago's Lane Tech High School, in front of a crowd of more than 10,000 spectators.^[17] With his team winning 8–6 in the top of the ninth inning, Gehrig hit a grand slam completely out of the major league park, an unheard-of feat for a 17-year old.^[17][18]

Lou Gehrig attended PS 132 in the Washington Heights section of Manhattan, then to Commerce High School, graduating in 1921.^[19][20] Gehrig then studied at Columbia University for two years, although he did not graduate.^[21] While attending Columbia, he was a member of Phi Delta Theta fraternity.^[22] Initially, Gehrig could not play intercollegiate baseball for the Columbia Lions because he had played baseball for the minor-league Hartford Senators of the Eastern League in the summer before his freshman year.^[22] At the time, he was unaware that doing so jeopardized his eligibility to play any collegiate sport. However, Gehrig was ruled eligible to play on the Lions' football team and was a standout fullback. Later, he gained baseball eligibility and played on the Lions team.

On April 18, 1923, the same day that Yankee Stadium opened for the first time and Babe Ruth inaugurated the new stadium with a home run, Columbia pitcher Gehrig struck out seventeen Williams College batters to set a team record; however, Columbia lost the game. Only a handful of collegians were at South Field that day, but more significant was the presence of Yankee scout Paul Krichell, who had been trailing Gehrig for some time. It was not Gehrig’s pitching that particularly impressed him; rather, it was Gehrig’s powerful left-handed hitting. During the time Krichell had been observing the young Columbia ballplayer, Gehrig had hit some of the longest home runs ever seen on various Eastern campuses, including a 450-foot (137 m) home run on April 28 at Columbia's South Field which landed at 116th Street and Broadway.^[23] Within two months, Gehrig had signed a Yankee contract.^[22] Gehrig returned to minor-league Hartford to play parts of two seasons, 1923 and 1924, batting .344 and crushing 61 home runs in 193 games. (It was the only time Lou ever played any level of ball—sandlot, high school, collegiate or pro—for a non-New York City-based team.)

Major League career[link]

Gehrig joined the New York Yankees midway through the 1923 season and made his debut on June 15, 1923, as a pinch hitter. In his first two seasons, he saw limited playing time, mostly as a pinch hitter — he played in only 23 games and was not on the Yankees' 1923 World Series roster. In 1925, he batted .295, with 20 home runs and 68 runs batted in (RBIs).^[24]

Babe Ruth and Lou Gehrig in exhibition game at West Point, New York (May 6, 1927)

The 23-year-old Yankee first baseman's breakout season came in 1926, when he batted .313 with 47 doubles, an American League-leading 20 triples, 16 home runs, and 112 RBIs.^[24] In the 1926 World Series against the St. Louis Cardinals, Gehrig hit .348 with two doubles and 4 RBIs. The Cardinals won a seven-game series four games to three.^[25]

In 1927, Gehrig put up one of the greatest seasons by any batter in history, hitting .373, with 218 hits: 52 doubles, 18 triples, 47 home runs, a then-record 175 runs batted in (surpassing teammate Babe Ruth's 171 six years earlier), and a .765 slugging percentage.^[24] His 117 extra-base hits that season are second all-time to Babe Ruth’s 119 extra-base hits in 1921^[24] and his 447 total bases are third all-time, after Babe Ruth's 457 total bases in 1921 and Rogers Hornsby's 450 in 1922.^[24] Gehrig's production helped the 1927 Yankees to a 110–44 record, the AL pennant, and a four-game sweep of the Pittsburgh Pirates in the 1927 World Series. Although the AL recognized his season by naming him league MVP, it was overshadowed by Babe Ruth’s 60 home run season and the overall dominance of the 1927 Yankees, a team often cited as having the greatest lineup of all time — the famed Murderers' Row.^[26]

Despite playing in the shadow of the larger-than-life Ruth for two-thirds of his career, Gehrig was one of the highest run producers in baseball history: he had 509 RBIs during a three-season stretch (1930–32). Only two other players, Jimmie Foxx with 507 and Hank Greenberg with 503, have surpassed 500 RBIs in any three seasons; their totals were non-consecutive. (Babe Ruth had 498.)^[27] Playing 14 complete seasons, Gehrig had 13 consecutive seasons with 100 or more RBIs (a major league record shared with Foxx until eclipsed in 2010 by Alex Rodriguez). Gehrig had six seasons where he batted .350 or better (with a high of .379 in 1930), plus a seventh season at .349. He had seven seasons with 150 or more RBIs, 11 seasons with over 100 walks, eight seasons with 200 or more hits, and five seasons with more than 40 home runs.^[28] Gehrig led the American League in runs scored four times, home runs three times, and RBIs five times. His 184 RBIs in 1931 remain the American League record as of 2010 and rank second all-time to Hack Wilson's 191 RBIs in 1930. On the single-season RBI list, Gehrig ranks second, fifth (175), and sixth (174), with four additional seasons over 150 RBI. He also holds the baseball record for most seasons with 400 total bases or more, accomplishing this feat five times in his career.^[28] He batted fourth in the lineup to Ruth's third in the order, making it impractical to give up an intentional walk to Ruth.

During the 10 seasons (1925–1934) in which Gehrig and Ruth were both Yankees and played a majority of the games, Gehrig had more home runs than Ruth only once, in 1934, when he hit 49 compared to Ruth’s 22 (Ruth played 125 games that year). They tied at 46 in 1931. Ruth had 424 home runs compared to Gehrig’s 347. However, Gehrig outpaced Ruth in RBI, 1,436 to 1,316. Gehrig had a .343 batting average, compared to .338 for Ruth.^[29]

Gehrig 1933 Goudey baseball card.

In 1932, Gehrig became the first player of the 20th century to hit four home runs in a game, accomplishing the feat on June 3 against the Philadelphia Athletics.^[30] He narrowly missed getting a fifth home run in the game when Athletics center fielder Al Simmons made a leaping catch of another fly ball at the center field fence. After the game, manager Joe McCarthy told him, "Well, Lou, nobody can take today away from you." On the same day, however, John McGraw announced his retirement after thirty years of managing the New York Giants. McGraw, not Gehrig, got the main headlines in the sports sections the next day.^[31] The following year, in September 1933, Gehrig married Eleanor Twitchell, the daughter of Chicago Parks Commissioner Frank Twitchell.^[24]

In a 1936 World Series cover story about Lou Gehrig and Carl Hubbell, Time proclaimed Gehrig "the game's No. 1 batsman", who "takes boyish pride in banging a baseball as far, and running around the bases as quickly, as possible".^[32]

2,130 consecutive games[link]

Seven of the American League's 1937 All-Star players, from left to right Lou Gehrig, Joe Cronin, Bill Dickey, Joe DiMaggio, Charlie Gehringer, Jimmie Foxx and Hank Greenberg. All seven would eventually be elected to the Hall of Fame.

On June 1, 1925, Gehrig entered the game as a pinch hitter, substituting for shortstop Paul "Pee Wee" Wanninger. The next day, June 2, Yankee manager Miller Huggins started Gehrig in place of regular first baseman Wally Pipp. Pipp was in a slump, as were the Yankees as a team, so Huggins made several lineup changes to boost their performance. Fourteen years later, Gehrig had played 2,130 consecutive games. In a few instances, Gehrig managed to keep the streak intact through pinch hitting appearances and fortuitous timing; in others, the streak continued despite injuries. For example:

• On April 23, 1933, a pitch by Washington Senators pitcher Earl Whitehill struck Gehrig in the head. Although almost knocked unconscious, Gehrig remained in the game.
• On June 14, 1933, Gehrig was ejected from a game, along with manager Joe McCarthy, but he had already been at bat and received credit for playing the game.
• On July 13, 1934, Gehrig suffered a "lumbago attack" and had to be assisted off the field. In the next day's away game, he was listed in the lineup as "shortstop", batting lead-off. In his first and only plate appearance, he singled and was promptly replaced by a pinch runner to rest his throbbing back, never taking the field. A&E's Biography speculated that this illness, which he also described as "a cold in his back", might have been the first symptom of his debilitating disease.^[33]

In addition, X-rays taken late in his life disclosed that Gehrig had sustained several fractures during his playing career, although he remained in the lineup despite those previously undisclosed injuries.^[34] On the other hand, the streak was helped when Yankees general manager Ed Barrow postponed a game as a rainout on a day when Gehrig was sick with the flu—even though it was not raining.^[35]

Gehrig's record of 2,130 consecutive games played stood until September 6, 1995, when Baltimore Orioles shortstop Cal Ripken, Jr. broke it.^[36]

Illness[link]

Although his performance in the second half of the 1938 season was slightly better than in the first half, Gehrig reported physical changes at the midway point. At the end of that season, he said, "I tired mid-season. I don't know why, but I just couldn't get going again." Although his final 1938 statistics were above average (.295 batting average, 114 RBI, 170 hits, .523 slugging percentage, 689 plate appearances with only 75 strikeouts, and 29 home runs), they were significantly down from his 1937 season, in which he batted .351 and slugged .643. In the 1938 World Series, he had four hits in 14 at-bats, all singles.^[37]

When the Yankees began their 1939 spring training in St. Petersburg, Florida, it was clear that Gehrig no longer possessed his once-formidable power. Even Gehrig's base running was affected, and at one point he collapsed at Al Lang Field, then the Yankees' spring training park.^[38] By the end of spring training, Gehrig had not hit a home run.^[39] Throughout his career, Gehrig was considered an excellent baserunner, but as the 1939 season got under way, his coordination and speed had deteriorated significantly.^[40]

By the end of April, his statistics were the worst of his career, with one RBI and a .143 batting average. Fans and the press openly speculated on Gehrig's abrupt decline. James Kahn, a reporter who wrote often about Gehrig, said in one article:

I think there is something wrong with him. Physically wrong, I mean. I don't know what it is, but I am satisfied that it goes far beyond his ball-playing. I have seen ballplayers 'go' overnight, as Gehrig seems to have done. But they were simply washed up as ballplayers. It's something deeper than that in this case, though. I have watched him very closely and this is what I have seen: I have seen him time a ball perfectly, swing on it as hard as he can, meet it squarely — and drive a soft, looping fly over the infield. In other words, for some reason that I do not know, his old power isn't there... He is meeting the ball, time after time, and it isn't going anywhere.^[41]

He was indeed meeting the ball, with only one strikeout in 28 at-bats; however, Joe McCarthy found himself resisting pressure from Yankee management to switch Gehrig to a part-time role. Things came to a head when Gehrig had to struggle to make a routine put-out at first base. The pitcher, Johnny Murphy, had to wait for Gehrig to drag himself over to the bag so he could field the throw. Murphy said, "Nice play, Lou."^[41]

On April 30, Gehrig went hitless against the Washington Senators. Gehrig had just played his 2,130th consecutive major league game.^[29]

On May 2, the next game after a day off, Gehrig approached McCarthy before the game in Detroit against the Tigers and said, "I'm benching myself, Joe," telling the Yankees' skipper that he was doing so "for the good of the team."^[42] McCarthy acquiesced, putting Ellsworth "Babe" Dahlgren in at first base, and also said that whenever Gehrig wanted to play again, the position was his. Gehrig himself took the lineup card out to the shocked umpires before the game, ending the fourteen-year streak. Before the game began, the Briggs Stadium announcer told the fans, "Ladies and gentlemen, this is the first time Lou Gehrig's name will not appear on the Yankee lineup in 2,130 consecutive games." The Detroit Tigers' fans gave Gehrig a standing ovation while he sat on the bench with tears in his eyes.^[37] A wire service photograph of Gehrig reclining against the dugout steps with a stoic expression appeared the next day in the nation's newspapers. Other than his retirement ceremony, it is one of the most-reproduced and best-remembered visual images of Gehrig.

Gehrig stayed with the Yankees as team captain for the rest of the season, but never played in a major league game again.^[37]

Diagnosis[link]

As Lou Gehrig's debilitation became steadily worse (he stumbled over curbs, mishandled fielding plays, and fell while running the bases), his wife, Eleanor, called the famed Mayo Clinic in Rochester, Minnesota. Her call was transferred to Charles William Mayo, who had been following Gehrig's career and his mysterious loss of strength. Mayo told Eleanor to bring Gehrig as soon as possible.^[37]

Eleanor and Gehrig flew to Rochester from Chicago, where the Yankees were playing at the time, arriving at the Mayo Clinic on June 13, 1939. After six days of extensive testing at Mayo Clinic, the diagnosis of amyotrophic lateral sclerosis (ALS) was confirmed on June 19, Gehrig's 36th birthday.^[11] The prognosis was grim: rapidly increasing paralysis, difficulty in swallowing and speaking, and a life expectancy of less than three years, although there would be no impairment of mental functions. Eleanor Gehrig was told that the cause of ALS was unknown but it was painless, non-contagious and cruel — the motor function of the central nervous system is destroyed but the mind remains fully aware to the end.^[43][44]

At Eleanor's request, the Mayo doctors intentionally withheld his grim prognosis from Gehrig. He often wrote letters to Eleanor, and in one such note written shortly afterwards, said (in part):

The bad news is lateral sclerosis, in our language chronic infantile paralysis. There isn't any cure... there are very few of these cases. It is probably caused by some germ...Never heard of transmitting it to mates... There is a 50–50 chance of keeping me as I am. I may need a cane in 10 or 15 years. Playing is out of the question...^[45]

Following Gehrig's visit to the Mayo Clinic, he briefly rejoined the Yankees in Washington, D.C. As his train pulled into Union Station, he was greeted by a group of Boy Scouts, happily waving and wishing him luck. Gehrig waved back, but he leaned forward to his companion, a reporter, and said, "They're wishing me luck — and I'm dying."^[11]

"The Luckiest Man on the Face of the Earth"[link]

Lou Gehrig's number 4 was retired by the New York Yankees in 1940.

On June 21, the New York Yankees announced Gehrig's retirement and proclaimed July 4, 1939, "Lou Gehrig Appreciation Day" at Yankee Stadium. Between games of the Independence Day doubleheader against the Washington Senators, the poignant ceremonies were held on the diamond. In its coverage the following day, The New York Times said it was "perhaps as colorful and dramatic a pageant as ever was enacted on a baseball field [as] 61,808 fans thundered a hail and farewell."^[46] Dignitaries extolled the dying slugger and the members of the 1927 Yankees World Championship team, known as "Murderer's Row", attended the ceremonies. New York Mayor Fiorello La Guardia called Gehrig "the greatest prototype of good sportsmanship and citizenship" and Postmaster General James Farley concluded his speech by predicting, "For generations to come, boys who play baseball will point with pride to your record."^[46]

Yankees Manager Joe McCarthy, struggling to control his emotions, then spoke of Lou Gehrig, with whom there was a close, almost father and son-like bond. After describing Gehrig as "the finest example of a ballplayer, sportsman, and citizen that baseball has ever known", McCarthy could stand it no longer. Turning tearfully to Gehrig, the manager said, "Lou, what else can I say except that it was a sad day in the life of everybody who knew you when you came into my hotel room that day in Detroit and told me you were quitting as a ballplayer because you felt yourself a hindrance to the team. My God, man, you were never that."^[47]

The Yankees retired Gehrig's uniform number "4", making him the first player in Major League Baseball history to be accorded that honor.^[48] Gehrig was given many gifts, commemorative plaques, and trophies. Some came from VIPs; others came from the stadium's groundskeepers and janitorial staff. Footage of the ceremonies shows Gehrig being handed various gifts, and immediately setting them down on the ground, because he no longer had the arm strength to hold them.^[11] The Yankees gave him a silver trophy with their signatures engraved on it. Inscribed on the front was a special poem written by The New York Times writer John Kieran.^[49] The trophy cost only about $5, but it became one of Gehrig's most prized possessions.^[50] It is currently on display at the National Baseball Hall of Fame and Museum.

After the presentations and remarks by Babe Ruth, Gehrig addressed the crowd:

The crowd stood and applauded for almost two minutes. Gehrig was visibly shaken as he stepped away from the microphone, and wiped the tears away from his face with his handkerchief.^[50] Babe Ruth came over and hugged him as a band played "I Love You Truly" and the crowd chanted "We love you, Lou." The New York Times account the following day called it "one of the most touching scenes ever witnessed on a ball field", that made even hard-boiled reporters "swallow hard."^[46]

In December 1939, Lou Gehrig was elected to the National Baseball Hall of Fame and Museum in a special election by the Baseball Writers Association.^[52] At age 36, he was the second youngest player to be so honored (behind Sandy Koufax).^[53]

Final years[link]

"Don't think I am depressed or pessimistic about my condition at present," Lou Gehrig wrote following his retirement from baseball. Struggling against his ever-worsening physical condition, he added, "I intend to hold on as long as possible and then if the inevitable comes, I will accept it philosophically and hope for the best. That's all we can do."^[11]

Lou Gehrig Way in New Rochelle, NY

In October 1939, he accepted Mayor LaGuardia's appointment to a ten-year term as a New York City Parole Commissioner and was sworn into office on January 2, 1940.^[52] The Parole Commission commended the ex-ballplayer for his "firm belief in parole, properly administered", stating that Gehrig "indicated he accepted the parole post because it represented an opportunity for public service. He had rejected other job offers – including lucrative speaking and guest appearance opportunities – worth far more financially than the $5,700 a year commissionership." Gehrig visited New York City's correctional facilities, but insisted that the visits not be covered by news media.^[54] Gehrig, as always, quietly and efficiently performed his duties. He was often helped by his wife Eleanor, who would guide his hand when he had to sign official documents. About a month before his death, when Gehrig reached the point where his deteriorating physical condition made it impossible for him to continue in the job, he quietly resigned.^[55]

On June 2, 1941, at 10:10 p.m., sixteen years to the day after he replaced Wally Pipp at first base and two years after his retirement from baseball, Lou Gehrig died at his home in the Riverdale section of the Bronx, New York.^[56][57]

Upon hearing the news, Babe Ruth and his wife Claire went to the Gehrig house to console Eleanor. Mayor LaGuardia ordered flags in New York to be flown at half-staff, and Major League ballparks around the nation did likewise.^[58]

Following the funeral at Christ Episcopal Church of Riverdale, Gehrig's remains were cremated and interred on June 4 at Kensico Cemetery in Valhalla, New York. Lou Gehrig and Ed Barrow are both interred in the same section of Kensico Cemetery, which is next door to Gate of Heaven Cemetery, where the graves of Babe Ruth and Billy Martin are located.^[59]

Lou Gehrig's headstone in Kensico Cemetery (the year of his birth was inscribed erroneously as 1905)

The Gehrigs had no children. Eleanor, who never remarried, dedicated the remainder of her life to supporting ALS research. She died on March 6, 1984, on her 80th birthday.^[18]

The Yankees dedicated a monument to Gehrig in center field at Yankee Stadium on July 6, 1941, the shrine lauding him as, "A man, a gentleman and a great ballplayer whose amazing record of 2,130 consecutive games should stand for all time." Gehrig's monument joined the one placed there in 1932 to Miller Huggins, which would eventually be followed by Babe Ruth's in 1949.^[29]

Gehrig's birthplace in Manhattan, at 1994 Second Avenue (near E. 103rd Street), is memorialized with a plaque marking the site, as is another early residence on E. 94th Street (near Second Avenue). (As of 26/12/2011, the first mentioned plaque is not present due to ongoing construction. The second mentioned plaque is present, but ascribes to his birthplace, not early residence.) The Gehrigs' white house at 5204 Delafield Avenue in the Riverdale section of the Bronx, where Lou Gehrig died, still stands today on the east side of the Henry Hudson Parkway and is likewise marked by a plaque.^[24]

Records, awards, and accomplishments[link]

Sixty years after his farewell to baseball, Gehrig received the most votes of any baseball player on the Major League Baseball All-Century Team, chosen by fan balloting in 1999.^[5]

Records[link]

Gehrig sliding into home plate in 1925.

Awards and honors[link]

Other accomplishments[link]

Film and other media[link]

Gehrig in "Rawhide"

Lou Gehrig starred in the 1938 20th Century Fox movie Rawhide playing himself in his only feature film appearance.^[64] In 2006, researchers presented a paper to the American Academy of Neurology, reporting on an analysis of Rawhide and photographs of Lou Gehrig from the 1937–1939 period, to ascertain when Gehrig began to show visible symptoms of amyotrophic lateral sclerosis. They concluded that while atrophy of hand muscles could be detected in 1939 photographs of Gehrig, no such abnormality was visible at the time Rawhide was made in January 1938. "Examination of Rawhide showed that Gehrig functioned normally in January 1938", the report concluded.^[65]

In 1942, the life of Lou Gehrig was portrayed in the movie The Pride of the Yankees, starring Gary Cooper as Gehrig and Teresa Wright as his wife Eleanor. It received 11 Academy Award nominations and won in one category, Film Editing. Real-life Yankees Babe Ruth, Bob Meusel, Mark Koenig and Bill Dickey (then still an active player) played themselves, as did sportscaster Bill Stern.

Later, in 1978, a TV movie, A Love Affair: The Eleanor and Lou Gehrig Story was released, starring Blythe Danner and Edward Herrmann as Eleanor and Lou Gehrig. It was based on the 1976 autobiography My Luke and I, written by Eleanor Gehrig and Joseph Durso.

In an episode of the PBS series Jean Shepherd's America, the Chicago-born Shepherd told of how he and his father (Jean Shepherd, Sr.) would watch Chicago White Sox games from the right field upper deck at Comiskey Park in the 1930s. On one occasion, the Sox were playing the Yankees, and Shepherd Sr. had been taunting Gehrig, yelling at him all day. In the top of the ninth, with Sox icon Ted Lyons holding a slim lead, Gehrig came up with a man on base, and the senior Shepherd yelled in a voice that echoed around the ballpark, "Hit one up here, ya bum! I dare ya!" Gehrig did exactly that, hitting a screaming liner, practically into the heckler's lap, for the eventual game-winning home run. Shepherd's father was booed mercilessly, and he never again took junior Jean to a game. He apparently told this story originally when Gehrig's widow was in the audience at a speaking engagement.^[66]

See also[link]

	Biography portal
	Baseball portal
	New York City portal

References[link]