Amyotrophic Lateral Sclerosis

[EDDIEKIRK]

Amyotrophic Lateral Sclerosis (ALS)<div><div><div>
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a fatal neurodegenerative disorder that is characterized by the selective loss of motor neurons in the spinal cord, brain stem, and motor cortex. An estimated 30,000 Americans are living with ALS, which often arises spontaneously and afflicts otherwise healthy adults. More than half of ALS patients die within 2.5 years following the onset of symptoms.

A review of the scientific literature reveals an absence of clinical trials investigating the use of cannabinoids for ALS treatment. However, recent preclinical findings indicate that cannabinoids can delay ALS progression, lending support to anecdotal reports by patients that cannabinoids may be efficacious in moderating the diseases development and in alleviating certain ALS-related symptoms such as pain, appetite loss, depression and drooling.[1]

Writing in the March 2004 issue of the journal Amyotrophic Lateral Sclerosis & Other Motor Neuron Disorders, investigators at the California Pacific Medical Center in San Francisco reported that the administration of THC both before and after the onset of ALS symptoms staved disease progression and prolonged survival in animals compared to untreated controls.[2]

Additional trials in animal models of ALS have shown that the administration of other naturally occurring and synthetic cannabinoids can also moderate ALS progression but not necessarily impact survival.[3-4] One recent study demonstrated that blocking the CB1 cannabinoid receptor did extend life span in an ALS mouse model, suggesting that cannabinoids' beneficial effects on ALS may be mediated by non-CB1 receptor mechanisms.[5]

As a result, experts are calling for clinical trials to assess cannabinoids for the treatment of ALS. Writing in the American Journal of Hospice & Palliative Medicine in 2010, a team of investigators reported, "Based on the currently available scientific data, it is reasonable to think that cannabis might significantly slow the progression of ALS, potentially extending life expectancy and substantially reducing the overall burden of the disease." They concluded, "There is an overwhelming amount of preclinical and clinical evidence to warrant initiating a multicenter randomized, double-blind, placebo-controlled trial of cannabis as a disease-modifying compound in ALS."[6]

REFERENCES

[1] Amtmann et al. 2004. Survey of cannabis use in patients with amyotrophic lateral sclerosis. The American Journal of Hospice and Palliative Care 21: 95-104.

[2] Raman et al. 2004. Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid. Amyotrophic Lateral Sclerosis & Other Motor Neuron Disorders 5: 33-39.

[3] Weydt et al. 2005. Cannabinol delays symptom onset in SOD1 transgenic mice without affecting survival. Amyotrophic Lateral Sclerosis & Other Motor Neuron Disorders 6: 182-184.

[4] Bilsland et al. 2006. Increasing cannabinoid levels by pharmacological and genetic manipulation delay disease progression in SOD1 mice. The FASEB Journal 20: 1003-1005.

[5] Ibid.

[6] Carter et al. 2010. Cannabis and amyotrophic lateral sclerosis: hypothetical and practical applications, and a call for clinical trials. American Journal of Hospice & Palliative Medicine 27: 347-356.



Tests and diagnosis By Mayo Clinic staffAmyotrophic lateral sclerosis is difficult to diagnose early because it may appear similar to several other neurological diseases. Tests to rule out other conditions may include:

• Electromyogram. This test measures the tiny electrical discharges produced in muscles. A fine wire electrode is inserted into the muscles that your doctor wants to study. An instrument records the electrical activity in your muscle as you rest and contract the muscle. Generally, this test is mildly uncomfortable.
  
• Nerve conduction study. For this test, electrodes are attached to your 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. Using radio waves and a powerful magnetic field, MRI can produce detailed images of your brain and spinal cord. It involves lying on a movable bed that slides into a tube-shaped machine that makes loud thumping and banging noises during operation. Some people feel uncomfortable in the confined space.
  
• Blood and urine tests. Analyzing samples of your blood and urine in the laboratory may help your doctor eliminate other possible causes of your signs and symptoms.
  
• Muscle biopsy. If your doctor believes you may have a muscle disease rather than ALS, you may undergo a muscle biopsy. In this procedure, a small portion of muscle is removed while you're under local anesthesia and is sent to a lab for analysis.
  

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</div> How is ALS treated?



No cure has yet been found for ALS. However, the Food and Drug Administration (FDA) has approved the first drug treatment for the diseaseriluzole (Rilutek). Riluzole is believed to reduce damage to motor neurons by decreasing the release of glutamate. Clinical trials with ALS patients showed that riluzole prolongs survival by several months, mainly in those with difficulty swallowing. The drug also extends the time before a patient needs ventilation support. Riluzole does not reverse the damage already done to motor neurons, and patients taking the drug must be monitored for liver damage and other possible side effects. However, this first disease-specific therapy offers hope that the progression of ALS may one day be slowed by new medications or combinations of drugs.

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 such as physicians; pharmacists; physical, occupational, and speech therapists; nutritionists; social workers; and home care and hospice nurses. Working with patients and caregivers, these 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.

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 therapy and special equipment can enhance patients' independence and safety throughout the course of ALS. Gentle, low-impact aerobic exercise such as 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 therapists can recommend exercises that provide these benefits without overworking muscles. Occupational therapists can suggest devices such as ramps, braces, walkers, and wheelchairs that help patients conserve energy and remain mobile.

ALS patients who have difficulty speaking may benefit from working with a speech therapist. These health professionals can teach patients adaptive strategies such as techniques to help them speak louder and more clearly. As ALS progresses, speech therapists can help patients develop ways for responding to yes-or-no questions with their eyes or by other nonverbal means and can recommend aids such as speech synthesizers and computer-based communication systems. These methods and devices help patients communicate when they can no longer speak or produce vocal sounds.

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. Patients may begin using 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.

When the muscles that assist in breathing weaken, use of nocturnal ventilatory assistance (intermittent positive pressure ventilation [iPPV] or bilevel positive airway pressure [bIPAP]) may be used to aid breathing during sleep. 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.

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.

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. Respiratory therapists can help caregivers with tasks such as operating and maintaining respirators, and 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. The home hospice team can also counsel patients and caregivers about end-of-life issues.

What research is being done?



The National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, is the Federal Government's leading supporter of biomedical research on ALS. The goals of this research are to find the cause or causes of ALS, understand the mechanisms involved in the progression of the disease, and develop effective treatment.

Scientists are seeking to understand the mechanisms that trigger selective motor neurons to degenerate in ALS and to find effective approaches to halt the processes leading to cell death. This work includes studies in animals to identify the means by which SOD1 mutations lead to the destruction of neurons. The excessive accumulation of free radicals, which has been implicated in a number of neurodegenerative diseases including ALS, is also being closely studied. In addition, researchers are examining how the loss of neurotrophic factors may be involved in ALS. Neurotrophic factors are chemicals found in the brain and spinal cord that play a vital role in the development, specification, maintenance, and protection of neurons. Studying how these factors may be lost and how such a loss may contribute to motor neuron degeneration may lead to a greater understanding of ALS and the development of neuroprotective strategies. By exploring these and other possible factors, researchers hope to find the cause or causes of motor neuron degeneration in ALS and develop therapies to slow the progression of the disease.

Researchers are also conducting investigations to increase their understanding of the role of programmed cell death or apoptosis in ALS. In normal physiological processes, apoptosis acts as a means to rid the body of cells that are no longer needed by prompting the cells to commit "cell suicide." The critical balance between necessary cell death and the maintenance of essential cells is thought to be controlled by trophic factors. In addition to ALS, apoptosis is pervasive in other chronic neurodegenerative conditions such as Parkinson's disease and Alzheimer's disease and is thought to be a major cause of the secondary brain damage seen after stroke and trauma. Discovering what triggers apoptosis may eventually lead to therapeutic interventions for ALS and other neurological diseases.

Scientists have not yet identified a reliable biological marker for ALSa biochemical abnormality shared by all patients with the disease. Once such a biomarker is discovered and tests are developed to detect the marker in patients, allowing early detection and diagnosis of ALS, physicians will have a valuable tool to help them follow the effects of new therapies and monitor disease progression.

NINDS-supported researchers are studying families with ALS who lack the SOD1 mutation to locate additional genes that cause the disease. Identification of additional ALS genes will allow genetic testing useful for diagnostic confirmation of ALS and prenatal screening for the disease. This work with familial ALS could lead to a greater understanding of sporadic ALS as well. Because familial ALS is virtually indistinguishable from sporadic ALS clinically, some researchers believe that familial ALS genes may also be involved in the manifestations of the more common sporadic form of ALS. Scientists also hope to identify genetic risk factors that predispose people to sporadic ALS.

Potential therapies for ALS are being investigated in animal models. Some of this work involves experimental treatments with normal SOD1 and other antioxidants. In addition, neurotrophic factors are being studied for their potential to protect motor neurons from pathological degeneration. Investigators are optimistic that these and other basic research studies will eventually lead to treatments for ALS.