Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) (sometimes called Lou Gehrig’s Disease) is a neurological disease that primarily affects the nerves of the brainstem, spinal cord and cerebral cortex of the brain. It is a subset of a larger group of diseases called Motor Neuron Disease (MND). The cause of this disease is unknown. ALS affects function most often as upper extremity muscle weakness and wasting. Some individuals will also have the same muscle effects in the lower extremities. Difficulty in controlling speech (dysarthria) and swallowing (dysphagia) occur. As ALS progresses breathing can be affected. Because ALS affects only motor activity, the disease does not impair a person’s mind, personality, intelligence, or memory.

Body Changes in ALS

Information from outside of the body is received by afferent or sensory neurons (feeling nerves) and transmitted to the brain. In response, the brain sends a message to the body by way of motor neurons (moving nerves.) Motor neurons originate in the brainstem, spinal cord and cerebral cortex of the brain, the areas of the central nervous system that are affected by ALS. If you have an itch, pain, or other stimulus in or to your body, the sensory neurons will send a message to the brain. The brain then will send a response to move, scratch or react in some way to the sensation. It is the motor neurons that are delayed, interrupted or destroyed in ALS. Motor function involvement may be different on each side of the body.

Other significant effects of ALS include oral motor (mouth and throat) challenges. Dysarthria is difficulty in controlling muscles for speaking resulting in slow or difficult to understand speech. The muscles for swallowing are affected with increased choking and slowing of the ability to move fluid or food from the mouth to the stomach (dysphagia).

When the brainstem is involved, you might notice fasciculations (involuntary muscle contraction of a single motor neuron, a twitch) in the tongue, hands and arms. Paralysis or muscle paresis (weakness) of muscles controlled by cranial nerves (nerves originating in the brain) can be spastic (unable to relax) or flaccid (unable to contract). See cranial nerve table below for motor function of individual cranial nerves. These are the functions affected by ALS. Cranial nerves particularly affected by ALS are bolded.

Sensory functions of sight, touch, hearing, taste and smell are not affected. Motor functions of eye movement and continence of bladder and bowel function typically remain unchanged until late in the disease. Cognition or thinking ability remains intact throughout the course of the disease.

Cranial Nerve Table

Symptoms of ALS

Symptoms of ALS appear and progress differently in individuals. Some people will notice difficulty with extremities while others will first notice problems with vocal changes. ALS manifests and develops in different ways, depending on which muscles weaken first and how the disease progresses. Symptoms may include:

• Gradual onset, generally painless, general muscle weakness
• Abnormal fatigue of the arms, legs or entire body: dropping things, tripping and falling
• Loss of control in the hands and arms
• Difficulty speaking, chewing, swallowing and/or breathing, slurred or nasal speech
• Muscle cramps (spasms) or twitches (fasciculations) in the shoulders, tongue or legs
• Muscle weakness in arm, leg or diaphragm
• Uncontrollable periods of laughing or crying

ALS is a progressive disease. The first symptoms are usually mild, often even unnoticeable. The first symptoms that might be noticed can be in the hands, voice or legs. In the hands, clumsiness or changes in fine motor function or writing might be a first sign. Changes in the voice, swallowing or handling saliva is called bulbar onset. Changes in the legs noticed by stumbling or walking difficulty is called limb onset.

Types of ALS

ALS has several subtypes, many that relate to a specific genetic mutation. Variations in disease symptoms and progression are based on these subtypes. For example, the physicist, Steven Hawking lived 55 years after diagnosis with ALS. Treatment and research typically do not differentiate by subtype. Care provided is based on individual needs of individuals with any subtype of ALS.

Two development patterns of ALS have been noted.

Sporadic ALS is the most common type. In these cases, ALS develops for no known reason. There is no known family risk or known reason for onset. Inheriting the disease or passing the disease to children is not common. Sporadic ALS accounts for 90% of the diagnosed cases.

Familiar ALS is diagnosed by an abnormality in any of 12 known genes. The most commonly associated genes are C9orf72, SOD1, TARDBP and FUS. The gene: “chromosome 9 open reading frame 72,” or C9ORF72 is one known source of ALS as well as frontal lobe dementia. Individuals with an issue in this gene can have both diseases.

Familiar ALS is inherited from a parent and can be passed to biological children. Genetic irregularity accounts for 5-10% of the cases and on very rare occasions is found in the sporadic ALS population without a known inheritance found.

There are other theories about the development of ALS. These include exposure to toxins, strenuous physical activity and immunological dysfunction. Degeneration of nerves without inflammation is another theory. Demyelination (loss of myelin sheath that covers the nerve) with secondary scaring is an additional theory. However, none of these theories have yet to be definitive for ALS.

ALS Effects on Body Function

Oral Motor Effects

While people with ALS do not overproduce saliva, their swallowing problems can create sialorrhea, or excessive salivation and drooling. It may take trials of several medications until one provides relief without undesirable side effects.

Difficulty with swallowing and chewing food increases over time. Coordination of muscles for effective chewing can increase difficulty in digestion. Weight should be carefully monitored to be sure loss is not too aggressive. Because of diminished oral motor skills, choking problems increase. In later stages of the disease, feeding though a tube placed through the abdominal wall into the stomach may need to be considered.

Communication Effects

The loss of the ability to communicate is not life-threatening or painful but being unable to verbally and physically communicate is a very frustrating aspect of ALS. Assistive devices can help. Much of technology today relies on a simple touch, eye movement or even brain waves to activate devices. Individuals might use self-made communication boards with letters and pictures or mechanical devices that are high-level in sophistication but ease of use.

Obtaining a communication devise early, before it is needed allows time for the individual to record their own voice to be used by the machine. It can be quite satisfying to sound like yourself instead of a mechanical voice.

Numerous communication devices are on the market and can be found in many home health dealers or shopping sites. The ALS Association supports a list of products and vendors. Any body part with the slightest of function can be harnessed to use a communication device.

Respiratory Effects

A problem common to many people with ALS is the inability to cough forcefully enough to clear away even normal amounts of mucus. People are advised to make sure their fluid intake is sufficient to keep the secretions thin. Some take an over-the-counter cough medicine containing the expectorant guaifenesin, a mucus thinner.

A weak cough can be made more effective by assisted coughing, supplying fuller breaths with an ambu-bag to improve the cough, or using a device such as a “cofflator” or “in-exsufflator” (delivers deep breaths through a mask and then quickly reverses to negative pressure to simulate a cough).

Oxygenation levels may decrease at night due to slower night metabolism, lying down and weak musculature. Adding a pulse oximetry clip to your finger will detect if this is happening. If necessary, a nasal pressure device can be added to ensure oxygen levels and carbon dioxide levels in your body are appropriate.

When the muscles that assist in breathing weaken, use of ventilatory assistance (intermittent positive pressure ventilation, IPPV; or bi-level positive airway pressure, BiPAP) may be used to aid breathing during sleep. When muscles are no longer able to maintain oxygen and carbon dioxide levels, these devices may be required full-time. Mechanical ventilation is used when breathing is not effective.

Muscle and Tone (Spasticity) Effects

Tone (spasticity) is present in some people with ALS. It causes a tightening of muscles and a stiffening of the body including the arms, legs, back, abdomen, or neck. Tone can affect the inside of the body as well which might be noticed in bowel and bladder function. Tone (spasms) can be triggered by a simple touch and can be painful especially if it sets off muscle cramps, common in ALS because of muscle fatigue. Cramps become less severe over time due to weakness. In some cases, neuropathic pain (nerve pain) can develop.

Fasciculation (muscle twitching) is common though these are not painful so much as annoying.

Mental Effects

Although thinking remains unaffected in the majority of individuals with ALS, those who have extreme physical issues can develop depression. Being unable to communicate may lead to less options and choices. There is some evidence that dementia can occur due to limited abilities.

Fatigue

Fatigue can be so overwhelming that it affects all activities. Movement is challenged so extra effort must be put forth. As the disease progresses even eating and swallowing can produce fatigue. Increases in tone can tire the body. Depression is also a fatigue factor. Learning energy conservation measures early can help.

Diagnosis of ALS

The symptoms of ALS are rather vague. You might not pay attention to the early symptoms because they mimic other diseases such as cold or flu, fatigue, depression or many others. Testing for ALS is not immediately done until more common diseases are ruled out.

Testing for ALS includes:

Physical examination and history–this is the first step in diagnosis. The examiner will be looking for signs of motor neuron disease. Included will be a general physical examination, a neurological examination which may include a manual muscle test where every part of your body is assessed for function and sensation and a physical assessment of your cranial nerves.

You may have an electromyography (EMG) and nerve conduction studies (NCS). EMG tests the ability of your muscles to conduct movement. NCS evaluates the function of your nerves. These tests will more than likely be performed at the same session.

A magnetic resonance imaging (MRI) of the brain and spinal cord is performed to assess the physiology of your body to rule out any other abnormality that might be causing your symptoms. The MRI of individuals with ALS is typically normal.

Laboratory blood and urine tests will be performed as needed to rule out other possible diagnoses.

Some medical conditions have very similar symptoms as ALS. These can include:

• Polio and post-polio syndrome
• West Nile Virus
• Multiple Sclerosis
• Human immunodeficiency virus (HIV)
• Human T-cell leukemia virus (HTLV)
• Multifocal motor neuropathy
• Spinal and bulbar muscular atrophy
• Fasciculations and muscle cramps also occur in benign conditions

Evaluation of an individual’s function due to ALS is completed by use of the ALS Functional Rating Scale-Revised (ALSFRS-R). This scale measures several domains of function and changes in condition over time. The domains for evaluation include: (1) speech, (2) salivation, (3) swallowing, (4) handwriting, (5) cutting food and handling utensils (with or without gastrostomy), (6) dressing and hygiene, (7) turning in bed and adjusting bed clothes, (8) walking, (9) climbing stairs, (10) breathing. Total rating can range from 0-40 points. The lower the total number scored is indicative of ALS. To maintain consistency in measurement, this scale should be used at each assessment.

Treatment for ALS

Currently, there is no known cure for ALS. However, there some medications and therapies that have greatly enhanced the quality of life of individuals with ALS.

Medications to treat ALS

Two medications have been approved by the FDA to slow the progression of ALS. These drugs do not cure the disease but preserve nerves and thereby may decrease functional decline.

Riluzole (brand names Rilutek-pill, Tiglutik-liquid) was approved by the FDA in 1995. This drug works by stopping the release of glutamate and inactivates voltage-dependent sodium channels. This interferes with transmitter binding at amino acid receptors. In other words, it slows the release of chemicals that might be adversely affecting your muscles. It is a drug that may delay your symptoms of ALS and therefore prolong your life. It cannot reverse damage that has already occurred to nerves. Because the progression is different for everyone with ALS, it is not possible to say how long or how well this drug might work.

Edaravone (brand name Radicava) was approved by the FDA in 2017. It was developed to reduce the death of motor neurons by diminishing the effects of oxidative stress and thereby preserving muscle function. Free radicals produce oxidative stress which destroys muscles. This drug helps removes free radicals. It cannot reverse damage that has already occurred to nerves. It is administered by IV in a complex schedule every 28 days, daily for 14 days followed by two weeks of no drug. Ten days in the next 14 days the drug is received followed by 14 days of no drug. The results of individuals taking this drug were 33% less in symptoms of ALS as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R).

Mexiletine is a drug approved by the FDA to treat irregular heartbeats. It also reduces muscle spasms and cramps in ALS. The thought behind this drug is that is a muscle is not used due to spasm or cramps, becomes weaker and therefore less able to function. This drug allows the muscles to relax and thereby improves function. Spasms and cramps develop because of over production of ions. Mexiletine is a sodium channel blocker that slows the over production of these ions.

Other medications are provided to help control symptoms as needed. These medications do not affect the progression of ALS. An example of symptom-treating medication includes drugs for excessive saliva production, muscle spasms, antibiotics for infection, anxiety medication, bowel and bladder function.

Rehabilitation

Speech therapy is typically provided for individuals to assist in oral motor control. Results are best when therapy is started early to help with strengthening muscles as well as control of speaking and swallowing. As the disease progresses, communication devices can be obtained to facilitate speech. If started early, the individual’s natural voice can be recorded and saved so when assistive speaking devices are needed, the voice will be that of the individual.

Physical therapy and occupational therapy are helpful in providing exercises to improve strength and maintain function. Physical therapists work with gross movement whereas occupational therapist work with fine motor. Overall, both therapies strive to improve activities of daily living either through strengthening without tiring muscles and energy conservation. With therapy, complications of spasms and muscle contractures can be avoided. Specialized equipment to improve mobility and function can be individualized as needed. Home modifications can be determined to improve your function.

Respiratory therapy is provided to assist in making sure that breathing is effective and comfortable. Non-invasive assistive breathing devices might be used at night when breathing is slower and shallower. This equipment can be advanced to full time use. Thoughts about mechanical ventilation use should be discussed with your family and healthcare provider so your wishes are known.

Nutritional support is provided by a dietician who will assess your caloric needs and abilities. Weight loss is a common issue with ALS. Eating can be very tiring when fatigued. Eating smaller, more frequent meals is helpful. Management of food texture and ability to swallow without choking is needed. Thoughts about the use of a feeding tube to avoid aspiration (fluid and food going into the lungs) and pneumonia while maintaining calories should be discussed.

Social workers are valuable assets in locating resources for funding, equipment and caretakers. They know your community well and can connect you with helpful strategies.

A psychologist can assist both you and your family with techniques for your mental health. Adjusting to a chronic disease is challenging. Strategies for coping are beneficial for both you and your family members.

Support Groups are available both in person and online. Hearing about the successes and challenges of others can help you plan for your own care. Be sure to select a support group that is managed by a educated professional in small group work or a moderator to ensure the group is healthy and productive.

Palliative care or hospice might be considered for comfort care if further treatments are declined.

ALS Research

There is an abundance of studies for the treatment and cure of ALS including genetic links, physiologic studies and studies of subtypes. Individual research about complications of ALS, movement, treatments and technology devices are ongoing. Crossover research in neurologic diseases is shared and valued by researchers in all areas.

Drugs, Genetics and Stem Cells

Many medications to treat the physiology of ALS are under investigation. A great list is available in ALS News. You can also check the US government facilitated website. Currently, there are over 450 ALS drug active drug studies.

Some drugs and therapies under investigational study are listed below. The purpose is to alter the process of ALS from progressing.

Discontinued Drug Trials

Lithium Carbonate, a medication that prolongs the life of cells in the body was trialed in individuals with ALS. Although initial studies demonstrated some slowing of ALS progression, larger clinical trials did not and even appear to progress symptoms for some people. Tests of lithium carbonate have been stopped.

Thrombopoietin, a hormone that regulates platelets, was attempted to treat the progression of ALS with some success in individuals, not in study groups. Testing of this drug has stopped and it is no longer being manufactured.

Respiratory Research

Diaphragmatic Pacing are electrodes that are attached to the nerve that causes the diaphragm to pull down to let air into the lungs. When the nerve allows the diaphragm to relax, air is pushed out. With the advent of minimally invasive surgery, this process is being studied as an option for more individuals, like those with ALS, especially for those who would be at high risk for complications from an open surgical procedure.

Movement Research

In experiments using brain waves, people who are locked-in due to ALS have learned to communicate by way of a computer using only their thoughts. For example, trials of the BrainGate System, which implants a sensor in the brain to transmit, have shown that neural signals associated with the intent to move a limb can be “decoded” by a computer in real-time and used to operate external devices, including robot arms. Trials are ongoing.

ALS Facts and Figures

• ALS was first described in 1860 by French neurologist, Jean-Martin Charcot.
• ALS is found worldwide.
• A total average of about 16,000 people have ALS in the United States per year.
• The age of onset is between 40-70 years with 55 years being the average onset age but individuals younger and older are also diagnosed.
• Men are slightly more likely to be affected than women but after menopause, the numbers even.
• ALS appears more frequently in Caucasian and non-Hispanic individuals than in other ethnic groups.
• The military recognizes ALS as a military condition due to the higher number of serving individuals presenting with the diagnosis than in the general population. It is thought that the higher incidence could be due to chemical exposure, but this has not been validated.
• Lifespan of individuals with ALS is approximately 2-5 years from time of diagnosis. Some individuals live much longer. Lifespan may be affected by type of ALS, but this has not been determined.
• Half of the individuals diagnosed with ALS will live three years or longer after diagnosis. This is being lengthened due to the new progression affecting medications.
• Individuals who are diagnosed earlier in life generally survive longer than those diagnosed late in life although there is no research outcome about this topic.
• Individuals whose symptoms begin in the legs have somewhat of a longer lifespan than those whose symptoms develop in the oral motor or throat area.

Source: National Institutes of Neurological Disorders and Stroke

Resources

If you are looking for more information on ALS or have a specific question, our Information Specialists are available business weekdays, Monday through Friday, toll-free at 800-539-7309 from 9:00 am to 8:00 pm ET.

Additionally, the Reeve Foundation maintains an ALS fact sheet with additional resources from trusted sources. Check out our repository of fact sheets on hundreds of topics ranging from state resources to secondary complications of paralysis.

We encourage you to reach out to ALS support groups and organizations, including associations which features news, research support, and resources, national network of support groups, clinics, and specialty hospitals.

Community Resources:

The ALS Association

ALS News Today

Northeast ALS Consortium

Massachusetts General Hospital Neurology Clinical Research Institute

The Muscular Dystrophy Association

The ALS Therapy Development Institute

The National Institute of Neurological Disorders and Stroke

U.S. National Library of Medicine, Clinical Trials

Paralyzed Veterans of America

Resources For Healthcare Professionals: Clinical Guidelines for Best Practice are available by paid subscription:

American Academy of Neurology

BMJ

FURTHER READING

Body Changes in ALS section

Grad LI, Rouleau GA, Ravits J, Cashman NR. Clinical Spectrum of Amyotrophic Lateral Sclerosis (ALS). Cold Spring Harb Perspect Med. 2017 Aug 1;7(8). pii: a024117. doi: 10.1101/cshperspect.a024117.

Crescimanno G. Early non-invasive ventilation in patients affected by amyotrophic lateral sclerosis: revisiting literature in view of new scientific knowledge. Eur J Neurol. 2019 May 6. doi: 10.1111/ene.13918. [Epub ahead of print]

Symptoms of ALS section

Shellikeri S, Karthikeyan V, Martino R, Black SE, Zinman L, Keith J, Yunusova Y. (2017). The neuropathological signature of bulbar-onset ALS: A systematic review. Neurosci Biobehav Rev. 75:378-392. doi: 10.1016/j.neubiorev.2017.01.045. Epub 2017 Feb 2

Fang T, Jozsa F, Al-Chalabi A. Nonmotor Symptoms in Amyotrophic Lateral Sclerosis: A Systematic Review. Int Rev Neurobiol. 2017;134:1409-1441. doi: 10.1016/bs.irn.2017.04.009. Epub 2017 Jun 1.

Types of ALS section

Harlan BA, Pehar M, Killoy KM, Vargas MR. Enhanced SIRT6 activity abrogates the neurotoxic phenotype of astrocytes expressing ALS-linked mutant SOD1. FASEB J. 2019 Mar 6:fj201802752R. doi: 10.1096/fj.201802752R.

ALS Effects on Body Function section

Körner, S., Kollewe, K., Abdulla, S., Zapf, A., Dengler, R. (2015). Interaction of physical function, quality of life and depression in Amy