Amyotrophic Lateral Sclerosis

ALS is a rapidly progressive neuro-degenerative disease. It belongs to a group of disorders known as motor neuron diseases, which are characterized by the gradual degeneration and death of motor neurons. Many people know amyotrophic lateral sclerosis (ALS) as Lou Gehrig's disease, named after the famous New York Yankee baseball player who retired in 1939 because of it. Lou Gehrig died from ALS at the age of thirty seven. Too little is known about what causes this deadly disease.

ALS is a disease that causes nerve cells to stop working and die. This is a serious neurological disease, which leads to muscle weakness, paralysis, disability and eventually death. There are three forms of ALS: familial, which is hereditary and passed through genes; non-hereditary, which is called sporadic; and ALS that targets the brain, called ALS/dementia". No one knows how many people are living with ALS, although scientists estimate 30,000 people in the United States have the disease (CDC, 2011).

Worldwide ALS occurs in one to three people per 100,000. With no known treatment for this paralysis, 50% of all ALS patients die within three years. Current research is about to help change this percentage of deaths.

These neuro-degenerative diseases cause loss of ability to trigger specific muscles, which results in the muscles becoming weak, wasting away, and ultimately leading to paralysis. Early signs and symptoms of ALS include:

• Muscle twitching and weakness in an arm, leg, feet, and ankles
• Difficulty raising the front part of the foot and toes (foot drop)
• Hand weakness or clumsiness
• Muscle cramps and twitching in arms, shoulders, and tongue
• Slurring of speech
• Trouble swallowing

Frequently ALS begins in the hands, feet, or limbs and progressively spreads to the muscles in the rest of the body until they are paralyzed. This affects chewing, swallowing, speaking and breathing, ending in death.

Researchers have suggested several possible causes of ALS which includes:

• Chemical imbalances such as a higher than normal level of glutamate which is a chemical messenger in the brain found around the nerve cells in the spinal fluid. When this chemical increases beyond the cells needs can be toxic to some nerve cells.
  
  Current research found that a faulty breakdown of cellular recycling systems in the neurons of the spinal cord and brain of ALS patients resulted in the nervous systems inability to carry brain signals to the body's muscular system. Northwestern neurological researcher Han-Xiang Deng and Wenjie Chen discovered that when a chemical Ubiquilin 2 is unable to remove or repair damaged proteins, these proteins pile up in the cells, eventually blocking normal transmission of brain signals in the spinal cord and brain, leading to paralysis. Once it is understood what is happening at the cellular level drugs can be developed to combat this process (Los Angeles Times, 2011).
• Gene mutation(s) can lead to an inherited form of ALS, which presently appears identical to the non-inherited forms of ALS. The familial form of ALS usually results from a pattern of inheritance that requires only one parent to carry the gene responsible for the disease. About 20 percent of all familial cases result from a specific genetic defect that leads to mutation of the enzyme known as superoxide dismutase 1 (SOD1). Research on this mutation is providing clues about the possible causes of motor neuron death in Lou Gehrig's Disease. Not all familial ALS cases are due to the SOD1 mutation, therefore other unidentified genetic causes clearly exist.
• Disorganized immune response occurs when a person's immune system begins attacking some of his or her body's own normal cells, and scientists have speculated that this may trigger the process that results in ALS.
• Protein mishandling may occur when there is evidence that mishandled proteins within the nerve cells can lead to a gradual accumulation of abnormal forms of these proteins in the cells, eventually causing the nerve cells to die.

• Heredity is a factor since up to 10 percent of the people with ALS have inherited it from their parents. It is estimated that children of a person with ALS have a 50-50 chance of developing this disease.
• Age is a factor since ALS most commonly occurs in individuals between the ages of 40 and 60.
• Sex may be a factor since before the age of 65, slightly more men than women develop ALS but after age 70 this difference disappears.
• Environmental factors could contribute to some individuals being more prone to developing ALS who already carry a genetic predisposition to the disease. Scientists found numerous genetic variations that individuals with ALS have in common making them more susceptible to ALS.
  
  These Environmental factors under study that may modify a person's individual risk of ALS include:
  • Smoking. Smoking cigarettes may increase a person's risk of ALS to almost twice the risk of nonsmokers. Naturally the longer one spent smoking, the greater the risk. Studies have shown that quitting smoking can eventually lower this increased risk to that of a nonsmoker.
  • Lead exposure. Some evidence suggests that exposure to may be associated with the development of ALS.
  • Military service. Recent studies indicate that individuals who have served in the military are at higher risk of developing ALS. It is uncertain what about military service may trigger the development of ALS. Contributing factors may be due to the exposure to certain metals, chemicals, traumatic injuries, viral infections and intense exertion.

As ALS progresses individuals may develop the following complications.

1. Breathing Problems develop as the disease progresses and the muscles needed to breath become affected. Devices to assist the individual's breathing are worn only at night and are similar to devices used by people who have sleep apnea (for example, continuous positive airway pressure (CPAP) masks). As the disease progress some people choose to have a tracheostomy. This is a surgically created hole at the front of the neck leading to the windpipe (trachea). This enables the full-time use of a respirator that inflates and deflates their lungs. These 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. Patients and their families should consider several factors when deciding whether and when to use one of the above 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 and their significant others need to be fully informed about these considerations and the long-term effects of life without movement before they make decisions about ventilation support.
2. Eating problems occur when the muscles that control swallowing are affected. Individuals with ALS can aspirate, become malnourished and suffer from dehydration. They are at higher risk of aspirating food, liquids or secretions into the lungs, which causes pneumonia. Healthcare providers need to take their time when feeding patients with ALS and place them in an eating position to help eliminate the risks aspiration. Patients and caregivers can learn from speech therapists 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. Able patients can be taught how to use suction devices to remove excess fluids or saliva and prevent choking. 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.
3. Dementia. Some people with ALS experience problems with memory and making decisions, and some are eventually diagnosed with a form of dementia called frontotemporal dementia. ALS/dementia targets the frontal and temporal lobes of the brain, affecting patients' judgment, the ability to understand language and to perform basic tasks like planning what to wear or organizing their day. "These people in the prime of their lives and the peak of their productivity get this devastating illness that kills them," Siddique said. "The people who get ALS/dementia, an even more vicious disease, have a double whammy." (Nature journal, August 2011).

Specific EMG findings can support the diagnosis of ALS. A common test used measures nerve conduction velocity (NCV). Specific abnormalities in the NCV results suggest, that the patient has a form of peripheral neuropathy (damage to peripheral nerves) or myopathy (muscle disease) rather than amyotrophic lateral sclerosis. The physician may order, a magnetic resonance imaging (MRI) 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, a herniated disk in the neck, syringomyelia, or cervical spondylosis (Health Newsflash, 2011).

Based on the patient's symptoms and findings from examination and 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. 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 leukemia virus (HTLV), and Lyme disease can in some cases cause ALS-like symptoms. Neurological disorders such as multiple sclerosis, post-polio syndrome, multifocal motor neuropathy, and spinal muscular atrophy also can mimic certain facets of the disease and are 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 may wish to obtain a second neurological opinion.

In summary tests used primarily to rule out other neurological diseases include the following:

• Electromyogram. This test is mildly uncomfortable and is done to measure the tiny electrical discharges produced in muscles. A fine wire electrode is inserted into the muscles that are being studied. An instrument records the electrical activity in these muscles as they rest and contract.
• Nerve conduction study. Electrodes are attached to the skin above the nerve or muscle to be studied. A small shock, which may feel like a twinge or spasm, is passed through the nerve to measure the strength and speed of nerve signals.
• MRI-magnetic resonance imaging. Using radio waves and a powerful magnetic field, MRI can produce detailed images of the brain and spinal cord. It involves the individual lying on a movable bed that slides into a tube-shaped machine. Some people feel uncomfortable in the confined space and may refuse this test.
• Muscle biopsy. If the physician believes that there is another muscle disease rather than ALS, he may request that a muscle biopsy be done. In this procedure, a small portion of muscle is removed while the individual is under local anesthesia and this portion is sent to a lab for analysis.
• Blood and urine tests. Analyzing samples of blood and urine in the laboratory may help the physician eliminate other possible causes of the signs and symptoms demonstrated by the individual.

Currently there is no reversing the course of ALS and treatments and drugs are used to slow the progression of the symptoms enabling the individual to be as independent and comfortable as possible.

Brandon is forty three years old and is a veteran who just returned from Iraq and Afghanistan. He was eager to enjoy his young family of two boys who were two and five years of age. Making the service his career he would be working stateside. After being home two months he started having muscle twitching and weakness in his right arm, both legs, feet, and ankles. When a neurologist evaluated Brandon he was not able to raise the front part of his feet and exhibited signs of foot drop. He gradually became clumsy, and started dropping cups of coffee and other drinks. He would wake up with muscle cramps, twitching in his shoulders and arms. What scared him was that his tongue started twitching and acting peculiar and when he started to eat and drink he had difficulty swallowing. He and his family did not know what to do. Brandon was dying before their eyes.

Tests were done to determine his diagnosis and to eliminate those diseases which could cause these symptoms.

• The doctors felt that the neurological signs could be due to the exposure to certain metals, chemicals, intense exertion, or a viral infection contracted while abroad in Iraq or Iran.
• The neurologist ordered an electromyogram, nerve conduction study, muscle biopsy, blood and urine test and an MRI. The MRI showed an axial FLAIR which demonstrates increased T2 signal within the posterior part of the internal capsule, consistent with the clinical diagnosis of ALS.
• When the neurologist asked if there were others in his family who had been diagnosed with ALS the answer was negative.

Brandon and his family were devastated. He was determined to survive and saw a physical therapist, occupational therapist, and speech therapist. Everyone was doing research on the internet and consulted with organizations dedicated to overcoming this disease. He believed no one had the right to tell him he had only three to five years to live. He decided to strengthen his positive mental attitude and started visualizing himself at his next family holiday using all of his senses.

Individuals and their significant others diagnosed with ALS need help coping with this devastating disease. Other treatments for ALS are designed to relieve symptoms and improve the quality of life for individuals with ALS. This supportive care is provided by multidisciplinary teams of health care professionals such as physicians, pharmacists, physical, occupational, and speech therapists, nutritionists, social workers, and home care, and hospice nurses. Working with patients and caregivers, these health care teams can design an individualized plan of medical and physical therapy and provide special equipment aimed at keeping patients as mobile and comfortable as possible. Support the Grieving Process. It is important for the healthcare team to help in the grieving process and to help individuals with ALS and their families to be hopeful. Some people with ALS live much longer than the three to five years typically associated with this condition. Some live 10 years or more. Maintaining a positive mental attitude and an optimistic outlook can help improve quality of life for people with ALS. It is important for those with ALS to think beyond the physical changes. Many people with amyotrophic lateral sclerosis lead rich, rewarding lives despite physical limitations. ALS is only one part of an individual's life and is not one's entire identity.

Be hopeful and join a Support Group. Those with ALS and their significant others, and family should join a support group. There is comfort in sharing concerns in a support group with others who have ALS. Family members and friends helping with caring for others with ALS may benefit from a support group of others who care for people with ALS. Support groups can be found on the internet, at teaching hospitals, from physicians and by contacting the ALS Association.

Work as a Team. Social workers and healthcare providers can help individuals with ALS make decisions about future medical care. Planning for the future in its early stages allows those with ALS to be in control of decisions about their life and care. With the help of their doctor, hospice nurse or social worker, they can decide whether they want certain life-extending procedures. Where an individual with ALS wants to spend their final days can be determined in the early stages of ALS. Some individuals with ALS plan their own funeral. This can help loved ones put to rest certain anxieties about the future.

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 care nurses are available not only to provide medical care but also to teach caregivers about tasks such as maintaining respirators, giving tube 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 and answer questions that may arise during this emotional process.

This year progress was made by Feinberg School scientists when they discovered a protein, Ubiquilin 2 whose critical job is to recycle damaged or misfolded proteins in motor and cortical neurons. When Ubiquilin2 malfunctions it is not able to shuttle the damaged and misfolded proteins to be reprocessed.

Consequently, the damaged proteins and ubiquilin2 loiter accumulate in the motor neurons located in the spinal cord and cortical and hippocampal neurons in the brain. The damaged proteins pile up in the cells and eventually block normal transmission of brain signals in the spinal cord and brain, leading to paralysis. This accumulated protein resembles twisted skeins of yarn and causes degeneration of the neurons. Researchers found ubiquilin2 in these skeins of yarn, characteristic of ALS in the spinal cords of ALS cases and ALS /dementia, whether or not they had the gene mutation. The scientific assumption was that a defect in the protein degradation pathway causes neurodegenerative disease (Han-Xiang Deng, M.D.; Wenjie Chen, 2011).

About 90 percent of ALS is sporadic, without any known cause, until this study. The remaining 10 percent is familial. To date, mutations in about 10 genes, several of which were discovered at Northwestern, including SOD1 and in ALS, account for about 30 percent of classic familial ALS, noted Faisal Fecto, M.D., study co-author and a graduate student in neuroscience at Feinberg.

The discovery of the breakdown in protein recycling may also have a wider role in other neurodegenerative diseases, specifically the dementias. These include Alzheimer's disease and frontotemporal dementia as well as Parkinson's disease, all of which are characterized by aggregations of proteins, (Siddique, 2011). The removal of damaged or misfolded proteins is critical for optimal cell functioning. This breakdown occurs in all three forms of ALS: hereditary, which is called familial; ALS that is not hereditary, called sporadic; and ALS that targets the brain, ALS/dementia (Nature, 2011).

Once we understand at the cellular level what is going wrong we can begin to design drugs to meet the needs that our body requires (Gublitz, A., National Institute of Neurological Disorders and Stroke, 2011).

The discovery by Northwestern University Feinberg School of Medicine researchers, published in the journal Nature, provides a common target for drug therapy and shows that all types of ALS are, indeed, tributaries, pouring into a common river of cellular incompetence (Nature, 2011).

The discovery of the breakdown in protein recycling may also have a wider role in other neurodegenerative diseases, specifically dementias. These include Alzheimer's disease, and frontotemporal dementia as well as Parkinson's disease which are also characteristic by aggregations of proteins. Thus the removal of damaged or misfolded proteins is critical for optimal cell functioning (Siddifque, 2011).

Healthcare providers at all levels working together can become "earth angels" helping those with ALS successfully live richer and fuller lives while overcoming the challenges this devastating disease incurs. Scientists and health care professionals all become educators striving to prevent, identify, and treat the signs and symptoms of ALS, never giving up hope and maintaining a positive mental attitude.
Resources Available: You can call these sites for more information and they can connect you to your state resources. This internet site can locate what is available in your community ALSA.org.

Resources Available in Florida.
ALS Multispecialty Clinic
UF & Shands Jacksonville
580 West 8th Street
Tower 1, 9th floor
Jacksonville, FL 32209
Medical Director - Michael T. Pulley, MD, PhD
Phone: 904-244-9922

University of South Florida ALS Clinic
Morsani Advanced Health Center
13330 Laurel Dr.
Tampa, FL 33612
Medical Director - Tuan Vu, MD & Lara Katzin, MD
Phone: 813-905-9820

Lee Memorial Health System ALS Clinic
Outpatient Center at Plantation
13601 Plantation Road
Fort Myers, FL 33912
Medical Director - Nima Mowzoon, MD & Adam L. Heller, MD
Phone: 239-343-0776
Website

Suncoast ALS Clinic
Suncoast Medical Group
2201 Central Ave
St. Petersburg, FL 33713
Medical Director - Alberto B. Vasquez, MD / Adam S. Didio, MD
Phone: 727-824-7132

Mayo Clinic Jacksonville
4500 San Pablo Road South
Department of Neurology
Jacksonville, FL 32224
Medical Director - Kevin Boylan, MD
Phone: 904-953-2000
Website

Manasota Area
1st Saturday of the month
Lakewood Ranch Medical Center
Bradenton, FL 34202
Phone: (888) 257-1717
Website

Weston Area
2nd Tuesday of the month
Broward Health Weston
Weston, FL 33326
Phone: (888) 257-1717
Website

Gainesville Area
3rd Wednesday of the month
CAREtenders
Gainesville, FL 32606
Phone: (888) 257-1717

Ft. Myers Area
4th Sunday of the month
Lee Memorial Plantation Center
13601 Plantation Rd.
Ft. Myers, FL 33912
Phone: (888) 257-1717
Website

Highlands Area
3rd Thursday of the month
Sebring Chamber of Commerce
Sebring, FL 33870
Phone: (888) 257-1717
Website

Mayo Clinic Jacksonville
An ALS Association Certified Center of Excellence
4500 San Pablo Road S.
Department of Neurology
Jacksonville, FL 32224
Medical Director - Kevin Boylan, MD
Phone: 904-953-6915
Website

Ormond Beach/Daytona
2nd Wednesday of the month
Easter Seals
1219 Dunn Ave, Room 98A
Daytona Beach, FL 32114
Phone: (888) 257-1717
Website

Ocala Area
2nd Thursday of the month
Paddock Park South Community Clubhouse
Ocala, FL 34476
Phone: (888) 257-1717

Tampa Area
3rd Saturday of the month
Morsani Center for Health Care
Tampa, FL 33613
Phone: (888) 257-1717

Brevard Area
3rd Tuesday of the month
Sea Pines Health South
101 East Florida Ave.
Melbourne, FL 32901
Phone: (888) 257-1717
Website

Boynton Beach
3rd Tuesday of each month
United Way Palm Beach
2600 Quantum Blvd
Boynton Beach, FL 33426
Phone: 888-257-1717
Website

Florida Chapter
3242 Parkside Center Circle
Tampa, FL 33619-0907
Phone 1: 813-637-9000
Phone 2: 888-257-1717
Fax: 813-637-9010
office@als-florida.org
Website

Jacksonville Area
2nd Saturday of the month
South Mandarin Library
Jacksonville, FL 32223
Phone: (888) 257-1717
Website

Pensacola
West Florida Rehab. Center
Pensacola, FL 32514
Phone: (888) 257-1717
Website

Orlando Area
1st Thursday of the month
Center for Independent Living
720 Denning Dr. N
Winter Park, FL 32789
Phone: 888-257-1717
Website
 

1. ALS Division of MDA. Retrieved August 24, 2011.

2. ALS Association Research Program. Retrieved August 24, 2011.

3. Amyotrophic lateral sclerosis. Genetics Home Reference (GHR).(2007) Retrieved on August 25, 2011.

4. The CDC Bruijn, L., ALS Association Research Program., Retrieved on August 25, 2011.

5. NCBI Donkervoort S, Siddique T. Amyotrophic Lateral Sclerosis. Gene Reviews.(2009). Retrieved August 25, 2011.

6. Feldman EL. Amyotrophic lateral sclerosis and other motor neuron diseases. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap. 435.

7. Nature.com Han-Xiang Deng, Wenjie Chen, Teepu Siddique et al. Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. Nature, 2011; DOI: 10.1038/nature10353. Retrieved on August 25, 2011.

8. Mateen FJ, Carone M, Sorenson EJ (October 2010). "Patients who survive 5 years or more with ALS in Olmsted County, 1925-2004.". J Neurol Neurosurg Psychiatry 81 (10): 1144-6. PMID 20627966.

9. Northwestern University (2011, August 22). Common cause of all forms of amyotrophic lateral sclerosis (ALS) discovered.

10. O'Sullivan, Susan B.; Thomas J. Schmitz (2007). Physical Rehabilitation (Fifth Edition ed.). Philadelphia: Davis Company. pp. 835836.

11. NIH US National Library of Medicine. ALS Retrieved on August 25, 2011.

12. Wicks P, Abrahams S, Masi D, Hejda-Forde S, Leigh PN & Goldstein LH (2005) The Prevalence of Depression and Anxiety in MND, Amyotrophic Lateral Sclerosis and other Motor Neuron Disorders, Volume 6, Supplement 1, p. 147