Amyotrophic lateral sclerosis
Summary
Amyotrophic lateral sclerosis (ALS), also referred to as “Lou Gehrig’s disease,” is a progressive motor neuron disease which leads to problems with muscle control and movement.[1][2] There are various types of ALS that are distinguished by symptoms and, in some cases, genetic cause.[2] Early symptoms may include muscle twitching, cramping, stiffness, or weakness, slurred speech, and/or difficulty chewing or swallowing. As the disease progresses, people become weaker and are eventually wheelchair-dependent. Death often results from respiratory failure within 2 to 10 years after the symptoms begin.[2][3]
Most people with ALS have a sporadic (not inherited) form of ALS. It is believed that these cases are caused by an interaction between genetic and environmental factors. This means that a person may have inherited genetic changes (variants) that increase their risk to develop ALS, but the person will only develop ALS if exposed to certain environmental triggers. About 10% of the people with ALS have at least one relative with the disease and are said to have have a familial (inherited) form of the disease (FALS). Familial ALS may be caused by changes (pathogenic variants, also known as mutations) in any one of several genes and the pattern of inheritance varies depending on the gene involved. The distinction between sporadic and familial cases is not always clear.[2][3] The average age at which symptoms begin is 56 years old in the sporadic cases and 46 years old in the familial cases.[1]
Diagnosis of ALS is based on symptoms and a variety of tests to rule out other possible medical diseases that can cause similar symptoms.[1][4] The goal of treatment is to improve the quality of life for people with ALS, by assisting with breathing, nutrition, mobility, and communication.[3][5] Medications specifically approved for the treatment of ALS in the United States include riluzole and edaravone.[6][7]
Last updated: 9/27/2018
Inheritance
About 90-95% percent of cases of ALS are not inherited and occur in individuals with no history of the disease in their family. The remaining 5-10% of cases are familial, and are thought to be caused by mutations in any one of several genes. The inheritance pattern associated with familial ALS varies depending on the disease-causing gene involved.
Most familial cases are inherited in an autosomal dominant manner. This means that only one altered (mutated) copy of the disease-causing gene in each cell is sufficient to cause the condition. In most of these cases, an affected individual has one parent with the condition. When an individual with an autosomal dominant form of ALS has children, each child has a 50% (1 in 2) risk to inherited the mutated copy of the gene and be affected.
Less frequently, ALS is inherited in an autosomal recessive manner. In autosomal recessive inheritance, both copies of the disease-causing gene (typically one copy inherited from each parent) must have a mutation for the individual to be affected. The parents of an individual with an autosomal recessive condition, who presumably each carry one mutated copy of the gene, are referred to as carriers. Carriers typically do not have any signs or symptoms of the condition. When two carriers for the same condition are having children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each parent, and a 25% risk to not have the condition and not be a carrier. Autosomal recessive forms of ALS may be mistaken for non-inherited (sporadic) forms due to having a negative family history of the condition.
In rare cases, ALS is inherited in an X-linked dominant manner. This occurs when the disease-causing gene is located on the X chromosome (a sex chromosome). Although females have 2 X chromosomes, having a mutation in one X chromosome is still sufficient to cause the condition. Males who have a mutation (and only one X chromosome) will have the condition. Usually, males with an X-linked dominant form of ALS experience more severe symptoms than females with the same form.
Some individuals who do inherit a mutation known to cause ALS never develop signs and symptoms of ALS, although the reason for this is unclear. This phenomenon is referred to as reduced penetrance.[2]
Last updated: 5/9/2017
Diagnosis
Diagnosis of amyotrophic lateral sclerosis (ALS) may be suspected due to symptoms and the history of the way the symptoms progressed. ALS is usually strongly considered if the symptoms suggest both upper and lower motor neurons are affected. Basically, upper motor neurons (UPN) are found in the brain, whereas lower motor neurons are found in the spinal cord (LMN). UMN problems that can be found in a physical exam include tight and stiff muscles (spasticity), quicker than normal reflexes, and the Babinski reflex, which is when stroking the bottom of the foot causes the big toe to move upward and is not normally present after the age of 2 years. LMN problems that can be found in a physical exam include loss of muscle mass (muscle atrophy), muscle weakness, and muscle twitching (fasciculations). These signs can occur in any muscle group, including the arms, legs, chest, abdomen, and back, as well as the muscles involved in breathing, speaking, and swallowing. Even if symptoms of UMN and LMN problems are found, further testing must rule out other possible causes.[1][4]
Tests to rule out other possible diseases and medical causes include electromyography (EMG), nerve conduction study (NCS), magnetic resonance imaging (MRI) of brain and spinal cord, and urine and blood tests. After ALS is diagnosed, genetic testing may also be considered depending on family history, age the symptoms began, and the person’s wishes.[1][4]
Last updated: 9/27/2018
Treatment
Riluzole and endaravone are the two therapies approved by the United States Food and Drug Administration (FDA) specifically for the treatment of amyotrophic lateral scelerosis (ALS). Riluzole has been available in tablet form for over twenty years. It is believed to reduce damage to motor neurons. Riluzole may increase survival by several months and also extend the time before mechanical breathing support (ventilation) is needed. Riluzole does not reverse damage already done to motor neurons. The tablet form is available in generic versions and has been approved by the drug regulating agencies of most countries.[6][7] As of 2018, a liquid form, Tiglutik, has been approved by the FDA, which allows those who have a hard time swallowing a tablet to continue treatment.[8]
Edaravone (Radicava) has been available in the United States since 2017. It is an antioxidant and may slow the decline of physical function in some people with ALS. Physical function is measured by ALS Functional Rating Scale-Revised (ALSDRS-R). This scale measures problems with speech, swallowing, and breathing, as well as daily functioning such as walking, holding items like a pen or fork, dressing, and general care of oneself, like bathing. Edaravone does not improve function that has already been lost. The clinical trials took place in Japan and were six months long. As of 2018, long term effects of treatment with edaravone on physical function, survival, and quality of life are not known. It can be used along with riluzole. Edaravone is delivered by IV infusion on usually a two week on, two week off cycle. The IV infusion takes about one hour and is initially given in a hospital or clinic setting, but many have been able to transition to having the IV infusions at home.[6][7] Edaravone is also approved by regulating agencies in Japan and South Korea, and is waiting for approval in Canada, Switzerland, and the European Union as of 2018.
Other treatments for ALS are designed to relieve symptoms and improve the quality of life for patients. This type of care is known as palliative care, supportive care that is typically provided by multidisciplinary teams of health care professionals such as physicians, pharmacists, physical therapists, occupational therapists, speech therapists, nutritionists, social workers, and home care and hospice nurses. These teams along with the patients and caregivers can design an individualized plan of medical and physical therapy and provide special equipment aimed at keeping patients as mobile and comfortable as possible.[4]
- Physicians: 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, and constipation.
- Pharmacists: Can give advice on the proper use of medications and monitor a patient’s prescriptions to avoid risks of drug interactions.
- Physical therapist: Can provide physical therapy and recommend special equipment to help the patient be independent and safe during the course of their ALS.
- Occupational therapists: Can suggest devices such as ramps, braces, walkers, and wheelchairs that help patients conserve energy and remain mobile.
- Speech therapists: Can provide speech therapy to those people with ALS who have difficulty speaking.
- Nutritionists: Can help teach people with ALS and their caregivers 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.
- 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.
- Respiratory therapists: Can help caregivers with tasks such as operating and maintaining respirators.
- Home care nurses: Are available not only to provide medical care but also to teach caregivers about 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.
Last updated: 9/27/2018
Source:
https://rarediseases.info.nih.gov/diseases/5786/amyotrophic-lateral-scle…
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