Methods of Treatment for Amyotrophic Lateral Sclerosis
Patrick Gilbert SPT
Northeastern University
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Abstract
Amyotrophic Lateral Sclerosis is a neurodegenerative disease that affects roughly
1.5/100,000 people worldwide. The mechanisms of this disease are not yet fully understood.
There is currently a large amount of research in progress that should be able to give more insight
as to how the disease acts upon the body and potential methods to halt this progression. At the
present time, there is no cure for the disease, though many treatment options exist. These
treatment options all have varying results, and more research is being done to discover
alternative routes to treatment. The sole FDA approved drug used for treatment of ALS is
riluzole, an anti-glutamate that has been shown to delay the progression of ALS and prolong the
need for a tracheostomy by several months. It has been found that a combination of palliative
therapies is the best way to care for persons with ALS to help make their lives as comfortable as
possible.
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Background
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that affects an
individual’s ability to consciously control skeletal muscle movement. Nerve cells are affected in
the brain as well as the spinal cord. The disease affects both upper and lower motor neurons,
inhibiting actions from being carried out. Information and nutrients are unable to get to the
muscle, which leads to atrophy. Only voluntary movements are involved in this degeneration; the
heart and digestive systems remain unimpaired. While one may think of respiration as an
involuntary reflex crucial to life, it is, in fact a voluntary action.1 In the vast majority of patients
with ALS, respiratory complications are what eventually leads to mortality.
While it is known what ALS can do to the body, the full mechanisms of action of the
disease are not completely understood. Extensive research is being done to find answers to some
of these questions. Once the mechanisms and causes of the disease are better understood, it will
become significantly easier to develop treatment options for this patient population. Without the
knowledge of how the disease acts upon the body, it is unrealistic to have the expectation that a
true treatment or cure is even feasible. Hopefully more can be learned to make this dream a
reality in the not-so-distant future. This paper will examine the current methods of treatment,
ranging from physical activity to medication to surgical intervention. Treatment options that are
currently being researched will also be included.
Existing Treatment Methods
While there is no “effective treatment” for ALS currently, there are still many methods
health care providers use to combat the effects and alleviate the symptoms of the disease. Some
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of the major methods include: physical and occupational therapy, the drug riluzole, and both
non-invasive and invasive ventilation techniques.
Physical and Occupational Therapy
PT and OT have been crucial components of treating ALS for quite some time. An
integral part of PT and OT is improving quality of life in patients with ALS. The main goals of
these therapies are to maintain functionality and allow patients to continue with their activities of
daily living. Assessment for the necessity of assistive equipment, patient education, exercise
prescription and preventing or alleviating pain all fall under secondary goals of PT and OT.2
Work capacity becomes significantly decreased in the ALS population. Therefore, steps
need to be taken to minimize energy expenditure throughout the day. Assistive devices can and
should be used to help minimize the energy needed to complete functional activities in patients
with ALS. Assistive devices can include a rolling walker, shower aides, self-feeding equipment,
and more. Increasing the handle length of objects can decrease amount of necessary bending,
which will decrease energy expenditure. This is due to the fact that the muscles in the lower
extremity will not need to be utilized as much. In addition, increasing the diameter of grip on
items used to perform manual tasks can also decrease energy expenditure. Tasks that require fine
motor skills become increasingly difficult in this population. By increasing the diameter of
objects, patients do not need to grip as tightly and will expend less energy. Through minimizing
work output, devices such as these can help to prolong the time it will take until another
individual is needed to help the patient with their daily life.2 In addition to utilizing assistive
devices to minimize work, it is also extremely helpful to “bundle” tasks. This means completing
similar tasks in the same setting, or floor of a building to minimize the necessary movement
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between activities. Ascending stairs is quite a taxing activity, so the less patients need to do this,
the more energy they will have to complete other activities throughout the rest of the day. People
may also complete tasks in a seated position, as opposed to standing. This requires less energy,
as leg muscles are able to relax when seated, whereas they would be supporting body weight in
standing.
Another component of physical and occupational therapy intervention in patients with
ALS is exercise. Exercise has been a controversial subject within the ALS population. Numerous
studies have been done to evaluate the effectiveness of various exercise regiments. It is important
to remember that strength cannot be regained in patients with ALS. This makes it difficult to see
improvements with resistive exercise. This type of exercise has generally been found to be
ineffective, and sometimes even detrimental to these patients.3 The type of exercise that has been
shown to be most beneficial is aquatic therapy, as well as general swimming. However, the one
drawback to this type of exercise is that there must be adequate supervision at all times due to the
increased risk of drowning. The patient may also require assistance in the water along with this
supervision.2 A slightly less effective, yet safer type of exercise is on a stationary bike. This
allows for ROM to be maintained, and it also does not produce ground reaction forces on joints
of the lower extremity. It seems to be most advantageous to prescribe a variety of these exercises
to a patient with ALS in order to reap the benefits of all that these activities have to offer.
In addition to aerobic and resisted exercise, physical and occupational therapists can
decrease spasticity and pain through stretching and ROM exercises. It is recommended that
stretches be held for a minimum of 30 seconds per static muscle stretch.2 Maintaining a stretch
for this period of time while in the “plastic” range allows the muscle to truly lengthen its fibers.
The “plastic” range refers to the force of the stretch placed on a muscle. A weaker stretch will be
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ineffective at lengthening the muscle sufficiently. Likewise, a stretch held for less than the
recommended 30 seconds will be ineffective at lengthening the muscle.
A combination of ROM, stretching, assistive devices and simple, lightly resisted aerobic
activity have proven to be the best treatment strategies that physical and occupational therapists
have at their disposal when treating a patient with ALS. In addition to these techniques,
medicinal intervention has also proven effective.
Riluzole
Riluzole is the sole FDA approved drug that is used during the treatment of ALS. It has
been observed that an excess release of glutamate can cause neurodegeneration. This becomes a
large issue in ALS, as the neurons are already degenerated. The action of riluzole is to block the
release of glutamate into the synapse.4 This delays some of the degeneration associated with
ALS. While riluzole is unable to reverse the effects of ALS, it has been shown to delay the need
for a tracheostomy by anywhere from 2-4 months.4 There is also evidence showing a slight
increase in limb function. Though function was improved, there was no effect on the muscle
strength.5 Riluzole has also been shown to have a greater effect in a slightly younger population
whose disease has not progressed as far as those of a greater age. The drug is generally
administered at a dose of 100 mg/day, with minimal side effects. Some of the more serious
effects include fatigue, dizziness and nausea, and diarrhea. An increase in liver enzymes is also a
fairly frequent occurrence, but does not elevate them to a level that would be considered
clinically significant.4
With very limited side effects seen as a result of taking this drug, it seems that most
patients with ALS should be prescribed this medication in addition to their physical and
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occupational therapy treatments. There are not many things that can be done for this population
that will definitely bring about a change. However, this medication is one thing that can help
delay the disease, even by a few months. By extending life by a couple months, the patient as
well as their family will have more time to enjoy each other. That time may be the greatest result
of therapeutic intervention for patients with ALS.
There are also various surgical interventions that have been shown to aid this population
with respiration.
Ventilation
Ventilation is another important aspect of care for patients with ALS. This category can
be broken up into invasive and non-invasive ventilation. These forms of treatment are extremely
important because, as mentioned earlier, respiratory failure or dysfunction is almost always the
cause of death in these patients. Frequent respiratory system testing needs to be completed in
order to evaluate the necessity for further tests. Accurately diagnosing weakness of respiratory
muscles can be the difference between prescribing the most effective treatment option and letting
the patient suffer. Forced vital capacity (FVC) is used to detect respiratory insufficiency.
Typically, at any level below 50% of the predicted FVC, respiratory failure seems inevitable.
This is when ventilation starts to be considered as a treatment option.6
The most preferred method of non-invasive ventilation is known as non-invasive positive
pressure ventilation (NIPPV). This method has been shown to slow the decline of FVC more
effectively than other methods of non-invasive ventilation, and has significant benefits over not
utilizing ventilation. NIPPV can be used to prolong survival and maintain quality of life in
patients with ALS.7 Quite possibly the most exciting news is that NIPPV has the potential to
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delay the atrophy of respiratory muscles, which could prove extremely useful in future treatment
options. While it can prevent atrophy, there is still no way to increase strength. For this reason, it
has also been shown that beginning NIPPV treatment in the earlier stages of ALS can be more
beneficial than waiting until the FVC has declined further. This allows the respiratory muscles to
maintain the higher level of strength, before that strength is lost to atrophy. However, there is no
set value or timetable for when to begin this type of therapy. For this reason, careful monitoring
needs to take place between the patient, the family, and the health care provider. Some clinically
accepted levels of respiratory function used to begin NIPPV are the observance of hypercapnia, a
FVC below 50% predicted, and hypoventilation during the nighttime.6 If these symptoms are
observed, they will always lead to respiratory complications, which will eventually lead to a
decrease in quality of life. Beginning this treatment before this stage has been reached is crucial
to extending the patient’s life and preserving their quality of life.
The other form of ventilation is a tracheostomy, or mechanical ventilation. This method
is an invasive form of ventilation. It is the sole way that the respiratory system can be supported
interminably in patients with ALS. While it can be used indefinitely, mechanical ventilation is
not without complications or issues. It is extremely expensive, and requires more work for
caregivers. For these reasons, a vast majority of patients would rather undergo NIPPV than opt
for the tracheostomy. In addition, mechanical ventilation can also be truncated at the patients’
wishes. This will inevitably lead to the death of the patient, which is something to be aware of
when treating a patient with mechanical ventilation.6 While this treatment can help the patient to
a certain extent, it also presents a large burden on their life. This burden is also placed upon their
caregiver. In the majority of situations this caregiver is a spouse or some other member of the
family. In addition, health care professionals will be utilized to come into the home to aid with
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treatment. Placing extra strain on all these individuals may not provide for the most pleasant
environment, so sometimes this is a significant enough reason to opt out of the tracheostomy.
Due to the fact that their life will inevitably be cut short, it is important to these patients to live as
comfortable and happy a life as possible.
Potential Future Treatment Methods
While multiple current treatment strategies have been detailed, there is also a great deal
of research being done to discover new treatment options for ALS. One of the most promising
methods is stem cell transportation. A ketogenic diet has also been studied for use in patients
with ALS.
Stem Cell Transportation
In theory, stem cell transportation into patients with ALS should be able to improve some
aspects of motor performance. In stem cells from bone marrow, both hematopoietic and
mesenchymal aspects are present. Mesenchymal stem cells can become astrocytes or neurons. If
this occurs, some of the neurodegenerative effects may have the potential for reversal, or at least
improvement. It can also decrease inflammation of the neurons caused by the disease.8
This method of treatment has been shown to be a safe and reasonable procedure. In
addition, positive results have been reported from follow-up measurements in patients
undergoing trials for this treatment. The disease has seemed to remain constant, rather than
progress, and there do not seem to be any serious side effects.8
While this method shows extreme promise, it is still very much in the experimental
phase. More research and access to larger scale trials and subjects are needed before any
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definitive conclusions can be drawn from this treatment.9 It is extremely important for studies
such as this to be expanded upon in order to gain the most benefit from potentially
groundbreaking ideas such as this.
Other methods, such as a dietary intervention have been explored to discover their link to
helping treat patients with ALS.
Ketogenic Diet
A ketogenic diet is simply one that is high in ketones. The diet consists of high fats, low
carbohydrates as well as a reasonable amount of protein. This forces the body to burn the high
amounts of fat rather than carbohydrates. Burning these fats will convert them to fatty acids and
ketones. These ketones increase the energy manufacturing of mitochondria, and play a role in
steadying their membrane. The mitochondria can create more ATP, which is used to fuel the
body for movement and action. It is possible for this motor function to be increased. This
increased presence of ATP can delay the degeneration of muscles as well as form a protective
barrier for motor neurons, saving them from further deterioration. This ATP synthesis is able to
occur because a portion of the mitochondrial formation is skipped on the way to making ATP,
improving production and decreasing time spent producing said ATP. The third aspect of the
ketogenic diet that was researched was the potential impact it has on body weight. Another
aspect of ALS is a drop in body weight due to atrophy and an increasing inability to consume
foods normally. While the study did not confirm that this diet had a positive effect on body
weight, there was strong evidence to suggest that it may be able to increase body weight more
effectively than a typical diet.10
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Like stem cell transportation, more research is needed to confirm the efficacy of this
treatment. Though this may seem like a simple treatment option, it is also a fairly easy one to
follow. If something can be done to aid the patient simply by ingesting certain foods, it seems
that this course should absolutely be taken. This is especially pertinent given the fact that little to
no side effects were observed during this treatment plan.
Conclusions
Many areas and methods have been examined in the treatment of ALS. While no true
“cure” exists, it is important to be aware of and familiar with these options. These will allow
health care professionals to put their patients in the best position to deal with this disease. It is
recommended to apply a combination of the current treatment methods in order to provide the
best environment for control of symptoms.
In the future, as knowledge about the disease and its mechanisms of action grows, there
becomes an increasing potential to find even more effective treatments, and possibly even a cure.
However, much more research is needed on the topic before that thought has much substance to
it. The existing knowledge as well as the research being carried out currently provides an
excellent framework for the future research that will be done regarding this topic.
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