Amyotrophic Lateral Sclerosis (ALS)

*The information on this website is not intended to diagnose, treat, cure or prevent any disease.

What is Amyotrophic Lateral Sclerosis (ALS)?

Amyotrophic lateral sclerosis, also simply called ALS or Lou Gehrig’s Disease, a disease of the nervous system which results in progressive loss of muscle control. Although the muscles themselves are not directly affected by the disease, the neurons which control muscles, called motor neurons, begin to die. It is a, irreversible, progressive condition, although the rate of deterioration varies from person to person. Eventually, the disease becomes debilitating, and affected individuals lose the ability to use their arms and legs, speak, eat, swallow, or cough. Some individuals may also develop a specific type of dementia called frontotemporal dementia, which results in impaired memory and decision-making abilities.

The name amyotrophic lateral sclerosis comes from the postmortem findings of lesions affecting the outer regions of the spinal cord (where motor neurons are located). Microscopically, clumps of abnormal proteins (inclusion bodies) accumulate within the bodies of the neurons, eventually leading to the death of the cell. This may start in one region of the spinal cord, and then spread to other regions over time.

There are different variations of ALS, and the progression can vary considerably depending on the specific variation. The disease usually arises around 50-60 years of age; however, it can arise at any age. Survival times after diagnosis are usually only around 2-4 years, with eventual death from respiratory failure. This is not the case for everyone, however. The renowned physicist Stephen Hawking famously lived for 55 years following his diagnosis of ALS in 1963, living to the age of 76. Although he was severely debilitated for most of this time, he was able to live a remarkable full live and continued to make profound intellectual contributions to science until his death in 2018.

Common Symptoms

Although the advanced signs of ALS are often completely debilitating, the early signs may be subtle and attributed to ageing or other motor neuron diseases. Early symptoms include:

Clumsiness/poor coordination/poor dexterity
Weakness in hands
Slurred speech
Stumbling, tripping, or falling while walking
“Dropped foot” which drags on the ground
Cramping and twitching in arms, shoulders, and tongue
Loss of muscle mass
Difficulty maintaining erect posture
Difficulty holding head level
Difficulty breathing (rarely part of the initial signs)
Exaggerated reflexes

Later symptoms of ALS include:

Extreme difficulty chewing and swallowing
- May result in pneumonia from accidental inhalation of food and/or saliva
Difficult breathing
Loss of use of arms and legs
Dementia in some cases

Diagnosis

There is not a single test used to diagnose ALS. Diagnosis is mostly based on assessment of physical symptoms and a neurologic examination. Diagnostic tests are most useful for excluding other conditions which can present with similar signs. Tests which can help support a diagnosis of ALS or rule out other conditions include:

- Electromyography (EMG):
  This test measures the electrical impulses within the muscles. This can help rule out other neuromuscular disorders.
- Nerve Conduction Velocity (NCV):
  This test measures the rate at which electrical transmission occurs down nerve fibers. NCV should be normal in patients with ALS. If it is delayed, a diagnosis of a peripheral neuropathy may be made instead.

MRI:
This can help rule out other structural diseases which may cause similar signs to ALS (such as multiple sclerosis, herniated disks, or other spinal cord diseases. In the early stages of the disease, an MRI typically appears normal

Muscle Biopsies:
This can be performed to exclude muscle diseases (myopathies).

Infectious disease testing:
There is some thought that ALS may be another manifestation of Lyme disease in some people. Testing for Lyme may be indicated in people who are considered at risk of Lyme based on risk factors such as geography or life-style. Other infectious agents such as herpesvirus-6 and
Chlamydia pneumoniae
have also been proposed as potential agents linked to ALS.

Routine Bloodwork:
This can be performed to ensure that other markers of systemic health are not abnormal, and help exclude other causes of ALS.

Treatment Options

There is currently no known cure for ALS, however there are approaches which may slow progression of the disease or make the condition more manageable/bearable for the individual patient.

Pharmaceuticals and Medical Procedures:

Specific Medications for ALS

Riluzole (Rilutek):
This is an oral medication which can slow down the advanced stages of ALS, although the effect is rather moderate. On average, it prolongs survival times by about 2-3 months. It has effects at multiple sites on damaged neurons. It is a rather expensive medication, and can become cost-prohibitive. Additionally, it has a range of side effects, most commonly nausea, weakness, and impaired lung function.
Edaravone (Radicava):
This is an IV medication which may be helpful in a small subset of people with ALS, slightly slowing the decline of motor function. It must be administered daily for 10 days, followed by 2 weeks off, and then daily again. It can also be cost-prohibitive. There are specific criteria to determine if a person is a candidate for this drug. The mechanism is unknown, but is thought to be protective through its anti-oxidant properties. The small benefits from the medication may not outweigh the burden of daily hospital visits and infusions for some people.

Medications to Manage Other Aspects of ALS:

Non-steroidal Anti-inflammatories:
These drugs are primarily prescribed for pain which may accompany ALS. Over the counter options include ibuprofen (Advil) or naproxen (Aleve). Prescription options may include meloxicam or diclofenac.

Muscle relaxants:
Muscle spasms can frequently accompany ALS. As such, drugs with muscle relaxing properties like baclofen and diazepam (Valium) may be prescribed.

Drugs to control saliva production:
As ALS progresses, people often develop difficulty swallowing, and normal saliva production can become difficult to manage, or even increase risk of inhaling and causing pneumonia. To control saliva production, some drugs are used “off-label” due to their side-effects of causing dry-mouth. Examples include trihexyphenidyl (an anti-Parkinson drug), amitriptyline (an anti-depressant), or glycopyrrolate, a medication often used around the time of anesthesia to reduce airway secretions and increase heart rate.

Drugs for muscle cramps:
Various drugs may be recommended for cramping, however most lack scientific support. An exception is mexiletine, an anti-arrhythmic medication, which does appear to be safe and effective.

Antibiotics:
Antibiotics/antimicrobials may have an important role in ALS. If a suspected link to Lyme disease is determined, treatment may be warranted. As ALS advances pneumonia is a common consequence, and antibiotic treatment is absolutely required in these cases.

Respiratory Support:

Non-invasive ventilation:
This perhaps the most important and effective treatment for people in the advanced stages of ALS. A face mask is attached connected to a ventilator which generates intermittent positive pressure (pressure which drives air into the lungs). This may be required at night for many people suffering from ALS. Some people find this therapy difficult to endure, and it does not necessarily improve survival times for all variants of ALS.
Invasive Ventilation:
This form of ventilation is usually reserved for the later stages of ALS. A tracheostomy is performed, and a tube is inserted into the trachea which is then connected to a ventilator. Many people with ALS find that this significantly decreases their quality of life, but others tolerate it well.

Nutritional Support:

Feeding Tubes:
As the ability to swallow and chew food is lost, feeding tubes may be placed in order to provide nutrition. There are different forms of feeding tubes, but for long-term use, a gastrostomy tube is usually better-tolerated with fewer complications. This type of feeding tube usually connects into the stomach through the skin from the outside of the abdomen.

Experimental Treatments

T-cell Therapy:
An experimental therapy which has been performed on three patients so far. A special type of white blood cell called a T-regulatory cell was injected into ALS patients, and it appeared to slow progression of ASL signs. Not widely available yet, but the results are promising.

Non-pharmaceutical options:

There are many non-pharmaceutical therapies for ALS which may be beneficial in some people.

Physical Therapy:
Physical therapy can help slow down loss of muscle mass and loss of function. The activity and socialization which often goes along with physical therapy can also be helpful in fighting depression. Many ALS sufferers find that physical therapy is also helpful in managing pain and decreasing muscle cramps/spasms. Perhaps the biggest benefit of physical therapy is maintaining the ability to be functionally independent for as long as possible.

Speech Therapy:
Speech therapy, like physical therapy, can help individuals maintain a quality of life. Working with the muscles involved in speech can help slow down loss of muscle control. For those who are more advanced in the disease process, speech therapists can help build non-verbal communication strategies, or train people in the use of devices which amplify voice or generate speech based on other inputs.

Water Aerobics:
This is a form of exercise which is often performed in physical therapy routines, however a physical therapist is not necessarily required, although they can recommend specific exercises to maintain muscle strength. Water aerobics provides natural resistance to movements, while eliminating the risk of falling. It is also often a group activity, which helps maintain socialization.

Yoga:
Yoga may be helpful even for those who have lost full control of arms and legs. Many yoga poses focus on posture, and seated yoga techniques can be quite beneficial. Maintaining core strength will help maintain respiratory ability.

Stem Cell Therapy:
This is promising area of research; however, it is in its early stages. Stem cell therapy for ALS is not available in the United States, however it may be available in some parts of the world. If you are interested in pursuing this therapy, extreme care should be taken in selection of doctors and clinics, and keep in mind that benefits are uncertain.

Mind Body Techniques:

Mindfulness/Meditation:
Being diagnosed and living with ALS is psychologically challenging, life-altering, and brings physical pain and impairments. Meditation can be helpful in coping with the stresses of ALS, help maintain mood and perspective, and may also be helpful in the management of chronic pain.

Acupuncture:
The application of needles to the skin is frequently helpful in relieving pain and muscle tension. This may be useful in people with ALS who suffer from muscle discomfort, and may serve as an alternative to medications.

Massage Therapy:
Therapeutic massage can help relieve muscle pain, particularly from spasms or from cramping. It also relieves stress and can improve mood in those with ALS.

Hypnotherapy:
Hypnotherapy has been clinically evaluated and been found to improve depression, anxiety, and quality of life while reducing pain and muscle twitching in people diagnosed with ALS. Hypnotherapy works best on people who are open to the idea. Self-hypnosis techniques can be taught as well, removing the need for a specific hypnotherapist.

Chiropractic Therapy:
Spinal adjustments may be helpful in ALS sufferers who have chronic pain and posture issues.

Supplements:

Vitamin B12:
Supplementation may help slow muscle wasting and help reduce oxidative damage to neurons. Low levels of vitamin B12 are also associated with other degenerative neurologic disease.

Vitamin E:
Vitamin E is an important antioxidant which may be protective of neurons and help slow down degeneration.

- - Vitamins D:
    Another important anti-oxidant and essential nutrient. Vitamin D supplementation may also help slow down progression in some ALS patients.
  - Co-enzyme Q10:
    Clinical trials of CoQ10 are being conducted. It is a potent anti-oxidant and may help regenerate free radical-scavenging systems in the body. Oxidative stress is highly associated with progression of ALS.
  - Vinpocetine
    : This is an extract from the periwinkle plant which may help improve blood flow to the brain and protect neurons from injury. It is sometimes used to treat Parkinson’s, but have benefits in ALS as well.
  - Melatonin:
    Melatonin can help improve sleep quality in those with ALS – important for maintaining health, but also has anti-oxidant properties and helps prevent cell death.
  - Alpha-lipoic Acid:
    This serves to restore glutathione, an important part of the free-radical scavenging systems in the body. Supplementing with alpha-lipoic acid can help decrease oxidative stress.

Creatine:
Creatine supplementation may have beneficial effects in the central nervous system as well as the muscles. Creatinine may help protect and stabilize cell membranes, improve metabolic function, and decrease levels of glutamate (an excitatory neurotransmitter which can be toxic). It may also help maintain muscle strength to some extent. Human studies have shown mixed results, although animal studies have been promising. Creatine levels in the blood are also predictive of outcomes in people with ALS, but this is probably due to low levels being reflective of decreased muscle mass, rather than a causative effect.

Acetyl-L-carnitine:
This amino acid may help neurons repair and recover from damage, and protect against excessive glutamate. In mouse models of ALS, acetyl-L-carnitine improves survival, and a small, placebo-controlled study in people was promising.

- - Glutathione/N-Acetyl-cysteine:
    Supplementing with glutathione and N-acetyl-cysteine can help restore the body’s natural anti-oxidant systems, slowing down progression of ALS.
  - Ginkgo biloba:
    Ginkgo biloba may slow down ALS in some animal models and increase expression of the natural anti-oxidant systems in the body.

Pycnogenol:
An extract from the bark of a specific type of pine tree. Pycnogenol is a potent antioxidant, and like the others listed here, may help slow down progression of ALS.

Resveratrol:
A potent anti-oxidant compound found in grapes. In cell culture models, resveratrol reduces cell death in response to oxidative stress and may have a role to play in ALS.

Gamisoyo-San (GSS):
This is an herbal remedy used a variety of issues in many Asian countries. In an animal model of ALS, GSS appeared to be a potent anti-inflammatory in the central nervous system. Results are very preliminary and it has not been evaluated in humans with ALS.

Zinc:
Some cases of ALS may be due to a genetic mutation which alters certain enzymatic affinities to zinc. Supplementing with zinc may be helpful in in these cases, however care should be taken, as large doses of zinc can impede the absorption of copper.

- The Deanna Protocol:
  This is a treatment regimen developed by a surgeon for his daughter, Deanna, who was diagnosed with ALS. This treatment plan combines multiple supplements which have been shown to be beneficial for ALS sufferers.
- Dietary Modifications:

Chelation therapy:
There may be a link between heavy metal toxicities and ALS. Chelation therapy with Succimer or EDTA can help remove metals such as mercury and lead from the body.

Prevention

There is no definitive way to prevent ALS, however there seem to be certain factors which may increase or decrease the risk of ALS. For prevention, one of the most important factors appears to be
a diet rich in vegetables containing carotene and lutein
. People who consume large amounts of these vegetables seen to have a decreased risk of ALS over the course of their entire lives. Polyunsaturated fatty acids, such as those found in fish oil, may also be protective.

Reducing known risk factors is another strategy that can be taken to reduce the risk of ALS. Smoking is the number one risk factor which is within an individual’s control. Post-menopausal women who smoke seem to be at the greatest risk. It is not known whether quitting smoking will reduce the risk of ALS over a lifetime, however given the other negative health effects, quitting smoking is a generally wise idea.

A more recent risk factor which is still being evaluated is chronic exposure to low-frequency
electromagnetic fields
. Certain occupations have high levels of exposure to electromagnetic fields, and there appears to be a slight increase in ALS people with these types of jobs. Avoiding excessive exposure is recommended, however, for someone in one of these occupations, may not always be practical.

For non-specific approaches, maintaining a healthy lifestyle and being aware of water and food sources. Avoid consuming food and water which may have risk of heavy metal contamination. When possible, test water sources and use special filtration devices if lead levels exceed acceptable limits.

Causes

There is no known definitive cause for ALS, which makes it an intriguing disease. It is possible there are multiple triggers which result in a common disease process. In some cases of ALS, genetics appear to play a role. Two genes have been identified with very strong correlations to ALS. One of these is a mutation affecting an enzyme called superoxide dismutase (SOD). SOD is an important enzyme which converts harmful free radicals into less harmless substances. The mutation does not appear to disable the enzyme, but rather makes it toxic and leads to accumulation of the abnormal enzyme within the cell body, eventually killing the neuron. The second gene is called C9ORF72. Like the SOD mutation, this may lead to an abnormal protein which accumulates in toxic quantities within the neuron.

Smoking is the strongest life-style risk factor for ALS known at this time. For unknown reasons, post-menopausal women who smoke are at the highest risk of developing ALS. Among men, smoking has not been definitively shown to be a risk factor. It is not understood why this is the case or what the relationship between smoking and ALS actually is.

Most people seem to have non-genetic causes of ALS. Chronic traumatic encephalopathy (CTE), which has recently gained public awareness due to its link to concussions in professional athletes, is also suspected to be a risk factor in ALS. Professional athletes seem to be at a higher risk of ALS compared to non-professional athletes, possibly reflecting the increased demands placed on the body at higher levels of competition.

As previously mentioned, high levels of electromagnetic field exposure may also be a risk factor for ALS. How this could trigger the degenerative changes seen in the nervous system is unclear, and the association is far from proven. Occupations which have at various times been identified as being at increased risk include power plant workers, airline pilots, military service members, laboratory technicians, electrical workers, and a plethora of others, which do not necessarily have high exposure to electromagnetic fields.

Heavy metal exposure is also a possible cause for some people. Elevated lead levels in blood and /or bone have been associated with ALS. Manganese is another metal which may be linked to ALS. Occupational welders often have high exposures to manganese throughout their lives and often exhibit neurologic impairments similar to those seen in ALS. Even metals which make up parts of our diet like iron have been possibly linked to ALS. Increases areas of iron concentrations are found in the spinal cord and parts of the brain which appear to be most affected be ALS. Other metals also have some evidence linking them to ALS as well, including selenium, copper, aluminum, arsenic, zinc, cadmium, and uranium.

Non-metal toxins like pesticides have also been speculated to be linked to ALS. Interestingly, males appear to be affected by pesticide exposure than females.

Certain metabolic conditions may also play a role in ALS. Type II diabetes seems to carry an increased risk of ALS (although type I diabetes has a decreased risk of ALS). It is unclear whether the disease itself may be responsible for the increased risk of ALS, or the different treatment strategies and medications used which increase or decrease the risk, respectively.

Inappropriate immune regulation and neuroinflammation may also be involved. As discussed under the “Treatments” section, dysfunctional T-regulatory cells seem to be present in some ALS sufferers. These cells normally function to quiet and regulate the immune system. Runaway inflammation may be responsible for some of the neurologic degeneration seen in ALS, and restoring the balance with T-regulatory cells may be a promising avenue. Why this immune dysregulation occurs in the first place, however, is a mystery, but is perhaps due to the other possible causes described in this section.

Finally, infectious diseases may also play a role.
Borrelia burgdorferi
, the causative agent of Lyme disease, seems to be behind many different syndromes, and it may play a role in ALS as well. Lyme disease sometimes present as a neurologic form, which manifests in similar ways to ALS. It is possible that some cases of ALS are atypical forms of Lyme disease. Other infectious agents include viruses such as human herpesvirus-6 (HHV-6) and human herpesvirus-8 (HHV-8). Previous infection with these viruses was associated with a three and eightfold risk of ALS, respectively. It is also known that retroviruses like HIV can cause motor neuron disease, and similar viruses may be responsible for ALS which have yet to be identified.

Clinics for Management of ALS

ALS can be challenging condition to manage, particularly in the later stages. Establishing a long-term health care whom you trust to carry out your wishes is of utmost importance.

Standard Clinics

Johns Hopkins ALS Clinic

The Mayo Clinic

Providence ALS Center

Colorado Springs Neurological Associates

UCSF ALS Center

Alternative Clinics

Northwest Natural Health

Richmond Natural Medicine

The Redwood Clinic

Marin Natural Medicine Clinic

Seattle Integrative Medicine