Amyotrophic Lateral Sclerosis (ALS)

1. Amyotrophic Lateral Sclerosis(ALS)

2. Lou Gehrig’s Story • Gehrig played the first eight games of the 1939 season, but he managed only four hits. On a ball hit back to pitcher Johnny Murphy, Gehrig had trouble getting to first in time for the throw. When he returned to the dugout, his teammates complimented him on the "good play." Gehrig knew when his fellow Yankees had to congratulate him for stumbling into an average catch it was time to leave. He took himself out of the game. On May 2, 1939, as Yankee captain, he took the lineup card to the umpires, as usual. But his name was not on the roster. Babe Dahlgren was stationed at first. The game announcer intoned, "Ladies and gentlemen, Lou Gehrig's consecutive streak of 2,130 games played has ended.“ • Doctors at the Mayo Clinic diagnosed Gehrig with a very rare form of degenerative disease: amyotrophic lateral sclerosis (ALS), which is now called Lou Gehrig's disease. There was no chance he would ever play baseball again.

3. At a Glance • Is a progressive, fatal, neurodegenerative disease caused by the degeneration of motor neurons • In the United States, the condition is often referred to as Lou Gehrig's Disease, • Causes muscle weakness and atrophy throughout the body

4. At a Glance Cont… • "a" for without • "myo" for muscle • "trophic" for nourishment • "lateral" for side (of the spinal cord) • "sclerosis" for hardening or scarring

5. Motor Neurons Lou Gehrig • Nerve cells that control muscle movement • Upper motor neurons send messages from the brain to the spinal cord • Lower motor neurons send messages from the spinal cord to the muscles

6. Other Names • ALS • Charcot disease • Lou Gehrig Disease • Motor Neuron Disease, Amyotrophic Lateral Sclerosis

7. Incidence • Up to seven out of every 100,000 people get ALS. It's more common in men than women, with symptoms usually appearing between the ages of 50 and 75. About 10% of people with ALS have a family history of the disease. Life expectancy averages two to five years after diagnosis

8. Prognosis • There is progressive loss of ability to function or care for oneself. • Death often occurs within 3 to 5 years of diagnosis, about 20% of patients survive more than 5 years after diagnosis

9. Causes of The Disorder • Mutations in the ALS2, SETX, SOD1, and VAPB genes cause amyotrophic lateral sclerosis. • Variations of the ANG, DCTN1, NEFH, PRPH, SMN1, and SMN2 genes increase the risk of developing amyotrophic lateral sclerosis. • Each type of familial amyotrophic lateral sclerosis is caused by mutations in a specific gene. Type 1 is caused by mutations in the SOD1 gene, type 2 by ALS2 mutations, type 4 by mutations in the SETX gene, and type 8 by VAPB mutations • It is unclear how mutations in these genes contribute to the death of motor neurons, which leads to muscle weakness and atrophy. • Research findings suggest that these mutations lead to the production of toxic substances or clumps (aggregates) of misshapen proteins that accumulate and damage motor neurons

10. Causes Cont. • About 90 percent of amyotrophic lateral sclerosis cases are sporadic and are not inherited. • Among the estimated 10 percent of familial cases of this disorder, the pattern of inheritance varies with the type of amyotrophic lateral sclerosis. • Type 2 amyotrophic lateral sclerosis is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. • Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

11. Symptoms • Symptoms usually do not develop until after age 50. Persons with ALS have a loss of muscle strength and coordination that eventually gets worse. This eventually makes one unable to do routine tasks such as going up steps, getting out of a chair, or swallowing. • Breathing or swallowing muscles may be the first muscles affected. As the disease gets worse, more muscle groups develop problems. • ALS does not affect the senses (sight, smell, taste, hearing, touch), bladder or bowel function, or a person's ability to think or reason. • Difficulty breathing • Difficulty swallowing • Gagging • Chokes easily • Head drop due to weak spinal and neck muscles • Muscle cramps • Muscle weakness that slowly gets worse • Commonly involves one part of the body first, such as the arm or hand • Eventually leads to difficulty lifting, climbing stairs, and walking

12. Treatment • There is no known cure for ALS. The first drug treatment for the disease is a medicine called riluzole. Riluzole may prolong life, but does not reverse or stop the disease from getting worse. • Physical therapy, rehabilitation, use of braces or a wheelchair, or other orthopedic measures may be needed to maximize muscle function and general health.

13. Diagnosis • An exam of the nerves and muscles shows weakness, often beginning in one area. There may be muscle tremors, spasms, twitching, or loss of muscle tissue (atrophy). Atrophy and twitching of the tongue are common. • The person's walk may be stiff or clumsy. Reflexes may be abnormal and may include loss of the gag reflex. Some patients have trouble controlling crying or laughing. This is sometimes called "emotional incontinence." • Tests that may be done include: • Blood tests to rule out other conditions • Breathing test to see if lung muscles are affected • EMG to see which nerves do not work properly • Genetic testing, if there is a family history of ALS • Head CT or MRI of head to rule out other conditions • Swallowing studies • Spinal tap (lumbar puncture)

14. Quality of Life Support Groups • Although a person's physical state worsens, his or her mental capacity does not. • To cope with the progression of the disease, good emotional support from family and friends is important. • Support groups can also be helpful • ALS Society of Canada can be contacted by phone (1-800-267-4257), by e-mail (alscanada@als.ca), or accessed online at www.als.ca. • ALS Association http://www.alsa.org/

15. Bibliography • "Amyotrophic lateral sclerosis." Genetics home reference. august 07. 18 May 2009 <http://ghr.nlm.nih.gov/condition=amyotrophiclateralsclerosis#treatment>.