Amyotrophic Lateral Sclerosis
Amyotrophic Lateral SclerosisAmyotrophic Lateral Sclerosis (ALS), sometimes referred to as "Lou Gehrig's Disease," is a progressive fatal neuromuscular disease that attacks nerve cells and pathways in the brain and spinal cord. Motor neurons, among the largest of all nerve cells, reach from the brain to the spinal cord and from the spinal cord to muscles throughout the body with connections to the brain. When they die, the ability of the brain to start and control muscle movement dies with them. With all voluntary muscle action affected, ALS patients in the later stages are totally paralyzed; through it all, however, their minds remain unaffected.
Amyotrophic comes from the Greek language. "A" means no or negative. "Myo" refers to muscle, and "Trophic" means nourishment--"No muscle nourishment." When a muscle has no nourishment, it "Atrophies" or wastes away. "Lateral" identifies the areas in a person's spinal cord where portions of the nerve cells that nourish the muscles are located. As this area degenerates it leads to scarring or hardening ("Sclerosis") in the region.
Over 5,000 Americans are diagnosed with ALS each year. There is great variation in the course of the disease. Symptoms usually appear in individuals between the ages of 40-70, though the disease has been reported in both younger and older persons. Survival after the confirming diagnosis is, on average, two to five years. Progression of ALS varies with each individual; therefore, some will live longer--up to 10 years, and about five percent will exceed 12 years. In some cases, the disease seems to plateau. Many patients are able to live productive and satisfying lives especially with the use of assistive devices for daily living, and later in the disease, augmentative communication equipment.
Men and women are affected in almost equal numbers. Also, up to 10 percent of ALS cases are familial occurring more than once in a family lineage; but 90 percent of ALS cases show no hereditary pattern.
Approximately one-third of patients become aware of the onset of the disease when their hands become clumsy, causing difficulty in the performance of fine tasks. Another one-third experience
weakness in the legs and may trip because of mild foot drop. The
remaining one-third notice slowing of speech or difficulty in
swallowing. ALS may be present for some time before any
symptoms are noticed. This lack of noticeable symptoms occurs
because the lost or damaged nerve cells are compensated for by
nerve cells that remain functioning. One early symptom is
generalized fatigue. As muscle cells deteriorate, patients may
experience stiffness or occasional jerking of the arms or legs
resulting from spasticity (muscle tenseness). Often symptoms begin
in the hands and feet, then travel inward toward the center of the
body. One side is usually more affected. Paralysis eventually may
be virtually complete, except for the muscles of the eyes. Anal and
bladder muscles and function are not usually affected.
There is no specific clinical test that can identify ALS. Diagnosis is
made by a neurologist through a physical examination, a thorough
patient medical history, and neurological testing. Diagnostic testing
often includes the electromyogram (EMG) to test muscle activity,
CT Scan, MRI (Magnetic Resonance Imaging), muscle and/or
nerve biopsy, and extensive blood work.
While it is true that there is no cure for ALS, much can be done to
help the patient live with the disease. Treatment aimed at relieving
symptoms can be very effective. Generally, patients should
continue usual daily activities, stopping before they become
fatigued. Patients should be encouraged to set their own limits of
exertion, and to plan how they will use their energy and strength.
The physician will probably suggest exercises, including breathing
exercises, to strengthen unaffected or less-affected muscles. These
exercises are not vigorous or tiring, but are intended to help
maintain mobility and prevent joint stiffness and muscle
contracture.
Various devices such as foot-drop braces, hand splints, limb
supports or wheelchairs enable the patient to remain as
independent as possible. Good skin care, massage and knowledge
of proper body positioning can prevent sores for those who are
confined to bed for lengthy periods of time. If bowel and bladder
function are affected by immobility, increasing daily fluid intake
should improve the situation or the doctor may prescribe stool
softeners, bulk formers or laxatives.
A palate lift may help if there are speech problems, and soft
foods are indicated if the patient has difficulty in swallowing.
Because ALS selectively destroys the motor neurons in the
nervous system, several hypotheses have been put forth as to the
cause or causes of ALS. Researchers are exploring such areas as
genetic factors, susceptibility genes, excitotoxicity, and premature
cell death.
In 1991, a team of ALSA-funded researchers linked familial
ALS to chromosone 21. In 1993 the research team identified a
defective SOD1 gene on Chromo-sone 21 as responsible for
many cases of familial ALS. Further study indicated structural
defects in the SOD (super oxide dismutase) enzyme which
reduces the enzyme's ability to protect against free radical damage
to motor neurons.
In January 1996, a team of researchers reported that their
studies suggest that the SOD1 gene mutations may enhance the
ability of the SOD enzyme to act as a "peroxidase," that is,
oxidizing and thereby damaging cell components. These studies
open up possibilities for possible therapies or strategies to
effectively mediate the effects of ALS. But much more research on
the SOD enzyme is needed.
Clinical trials of selected neurotrophic and growth factors are
continuing as biotechnology companies search for possible
therapies for ALS.
After 127 plus years, there is a first-ever treatment for ALS. It is
Rilutekr, manufactured by Rhone-Poulenc Rorer. The drug, an
antiglutamate, extends survival in ALS patients by an average three
months. The drug was approved by the FDA in December 1995
and became available by prescription in January 1996.
In addition, two other potential treatments could be approved
for marketing by 1997, pending outcome of clinical data and FDA
review. These are Myotrophin, a development from Cepalon, Inc.,
and BDNF (brain derived neurotrophic factor) being tested by
Amgen-Regeneron Partners. Both BDNF and Myotrophin appear
to slow progression of the disease in distinct areas according to
clinical trial data thus far. BDNF effects are shown in a slowing of
the deterioration of breathing capacity; Myotrophin appears to
slow the progression of muscle deterioration. Therefore, both have
demonstrated the capacity to extend quality of life in the ALS
patient.
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder, characterized
by progressive degeneration of motor cells in the spinal cord and brain.
When the motor neuron cell can no longer send the impulses to the muscles there is
increased muscle weakness, especially in the arms and legs, speech, swallowing,
breathing. When muscles no longer receive the messages they require to function,
they begin to atrophy (waste away). ALS is very often referred to as "Lou Gehrig's
disease." Neither its cause or cure is known. Three known classifications of ALS
have been described:
Sporadic - the most common form of ALS in the United States
Familial - suggest genetic dominant inheritance and accounts for a very
small number of cases in the United States. Familial ALS requires further
investigation before the significance of the hereditary factor can be firmly
established.
Guamanian - an extremely high incidence of ALS has been observed in
Guam and the Trust Territories of the Pacific.
At the onset of ALS the symptoms may be so slight that they are frequently
overlooked. With regard to the progression of the illness, and the appearance of
symptoms, the course of the disease may include the following:
twitching and cramping of muscles, especially those in the hands and feet
impairment of the use of the arms and legs
"thick speech" and difficulty in projecting the voice
in more advanced stages, shortness of breath, difficulty in breathing and
swallowing
ALS is individual in each person -- in the area of the body affected as well as in the
rate of progression.
It is important to stress that ALS does not affect the intellectual functioning. Nor
does it interfere with the ability to taste, see, smell, hear or recognize touch.
Symptoms of the disease
What is ALS?
Amyotrophic lateral sclerosis (ALS), often referred to as "Lou Gehrig's disease," is
a progressive fatal neuromuscular disease that attacks nerve cells and pathways in
the brain to the spinal cord. Motor neurons, among the largest of all nerve cells,
reach from the brain to the spinal cord and from the spinal cord to the muscles
throughout the body with connections to the brain. When they die, as with ALS, the
ability of the brain to start and control muscle movement dies with them. With all
voluntary muscle action affected, patients in the later stages are totally paralyzed;
yet, through it all, their minds remain unaffected.
A-myo-trophic comes from the Greek language. "A" means no or negative.
"Myo" refers to muscle, and "Trophic" means nourishment---"No muscle
nourishment." When a muscle has no nourishment, it "atrophies" or wastes away.
"Lateral" identifies the areas in a person's spinal cord where portions of the nerve
cells that nourish the muscles are located. As this area degenerates it leads to
scarring or hardening ("sclerosis") in the region.
Incidence of ALS
ALS is one of the most devastating of disorders which affect the function of nerves
and muscles. Once thought rare, it is now fairly common. According to the United
States National Institutes of Health, nearly 5,000 people in the U.S. are newly
diagnosed with ALS each year. (That's about 13 new cases a day!) It is estimated
that as many as 30,000 Americans have the disease at any given time. And that
some 300,000 men and women who are alive and apparently well in the country
today will die with ALS unless a cure or prevention is found.
Most who develop ALS are between the ages of 40 and 70. There are, however,
cases of the disease attacking persons in their twenties and thirties. Generally,
though, ALS occurs in greater percentages as men and women grow older. It was
once believed that men developed ALS more frequently than women. That no
longer appears to be the case, and today both sexes are affected in nearly equal
numbers.
With recent advances in research and improved medical care, many ALS patients
are living longer and more productive lives. Half of all affected live at least three or
more years after diagnosis. Twenty percent live five years or more; up to ten
percent will survive more than ten years.
Forms of ALS
The most common form of ALS in the United States is known as "sporadic" ALS.
It may affect anyone, anywhere.
"Familial" ALS suggests the disease is inherited, although no heredity pattern exists
in the majority of ALS cases. Only about five to ten percent of all ALS patients
appear to have some kind of genetic or inherited component. In those families,
there is a 50 percent chance the offspring will have the disease.
Other terms which have been used to categorize variants of the classical form of
ALS include spinal muscular atrophy, progressive bulbar palsy and lateral sclerosis.
Other variants of ALS whose prognosis is better and whose relationship to ALS is
not yet determined include primary lateral sclerosis, juvenile muscular atrophy and
benign facial amyotrophy.
Symptoms of ALS
Early symptoms vary with each individual, but usually include tripping, dropping
things, abnormal fatigue of the arms and/or legs, slurred speech, muscle cramps and
twitches and uncontrollable periods of laughing or crying.
The hands and feet may be affected first, causing difficulty in walking or using the
hands for the activities of daily living such as dressing, washing and buttoning
clothes.
As the weakening and paralysis continue to spread to the muscles of the trunk of
the body the disease eventually affects swallowing, chewing and breathing. When
the breathing muscles are attacked, the patient faces permanent ventilatory support
in order to survive.
Since ALS attacks only motor neurons, the sense of sight, touch, hearing, taste and
smell and muscles of the eyes and bladder are generally not affected.
The mind, though, is not impaired and remains sharp despite the progressive
degenerating condition of the body.
Diagnosis of ALS
ALS is a very difficult disease to diagnose. There is no one test or procedure to
ultimately establish the diagnosis of ALS. It is through a clinical examination and
series of diagnostic tests, often ruling out other diseases that mimic ALS, that a
diagnosis can be established. A comprehensive diagnostic workup includes most, if
not all, of the following procedures: electrodiagnostic tests including
electomyography (EMG) and nerve conduction velocity (NCV), blood and urine
studies including high resolution serum protein electrophoresis, thyroid and
parathyroid hormone levels, 24 hour urine collection for heavy metals, spinal tap
and x-rays, including magnetic resonance imaging (MRI) and/or myelogram of
cervical spine, and muscle and/or nerve biopsy. These tests are done at the
discretion of the physician, usually based on the results of other diagnostic tests.
There are many diseases that have some of the same symptoms as ALS; some of
them are treatable. It is for this reason that The ALS Association recommends that
a person diagnosed with ALS seek a second opinion from an ALS "expert",
someone who sees many ALS patients. The Association maintains a list of
recognized experts in the field of ALS. This is not meant to imply that other
neurologists cannot make a diagnosis, only that physicians referred by ALSA see
many ALS patients.
ALS, a motor neuron disease, was first identified in 1869 by the noted French
neurologist Jean-Martin Charcot. However, the cause, cure or means of control of
ALS are presently unknown.
The onset of ALS is insidious with muscle weakness or stiffness as early symptoms.
Inevitable progression of wasting and paralysis of the muscles of the limbs and
trunk as well as those that control vital functions such as speech, swallowing and
respiration follows.
Mental faculties are not affected. Also, ALS is not contagious.
It is estimated that ALS is responsible for nearly two deaths per hundred thousand
population annually. More people die every year of ALS than of Huntington's
disease or multiple sclerosis. (1)
Nearly 5,000 people in the U.S. are newly diagnosed with ALS each year. The
incidence of ALS (two per 100,000 people) is five times higher than Huntington's
disease and about equal to multiple sclerosis. The prevalence of ALS is six to eight
per 100,000.
The life expectancy of an ALS patient averages about two to five years from the
time of diagnosis. But with recent advances in research and improved medical care,
many patients are living longer, more productive lives. Half of all affected live at
least three years after diagnosis.
About twenty percent live five years or more and up to ten percent will survive
more than ten years.
ALS is not a rare disease and occurs throughout the world with no racial, ethnic or
socioeconomic boundaries.
(1) Kurtzke, J.F. & Kurland, L.T. "The Epidemiology of Neurologic Disease,"
Clinical Neurology, 1989.
ALS can strike anyone, and it is projected that of the U.S. population living today,
in excess of 300,000 Americans will die from ALS unless a cure or prevention is
found.
ALS selectively destroys the motor neurons in the nervous system. Therefore,
consideration as to its cause has been given to agents with selective properties such
as toxic agents and genetic factors. Approximately five to ten percent of ALS is
familial, occurring more than once in a family lineage.
In 1991 a team of ALSA-funded researchers linked familial ALS to chromosome
21. In 1993 the research team identified a defective SOD1 gene on chromosome
21 as responsible for many cases of familial ALS. Further study indicated structural
defects in the SOD (superoxide dismutase) enzyme which reduces the enzyme's
ability to protect against free radical damage to motor neurons. These studies open
possibilities for possible therapies or strategies to effectively mediate ALS. But
much more research on the SOD enzyme is needed. Also, researchers have not
ruled out other gene involvement (perhaps on other chromosomes) in ALS.
Present treatment of ALS is aimed at symptomatic relief, prevention of
complications and maintenance of maximum optimal function and optimal quality of
life. Most of this, in the later stages, requires nursing management of a patient who
is alert but functionally quadriplegic with intact sensory function, bedridden and
aware he or she is going to die.
The financial cost to families of persons with ALS is exceedingly high. In the
advanced stages care can cost up to $200,000 a year. Entire savings of relatives of
patients are quickly depleted because of the extraordinary cost involved in the care
of ALS patients.
Rilutek�, the first ever treatment to alter the course of ALS, was approved by the
FDA in late 1995. This antiglutamate appears to prolong the life of persons with
ALS by at least a few months. Rilutek is manufactured by Rh�ne-Poulenc Rorer.
Amyotrophic Lateral Sclerosis, (also known as ALS, Lou Gehrig's Disease, Motor
Neuron Disease, Charcot's Disease), is a neurological disease affecting the nerves
that supply all voluntary muscles. ALS was first identified in 1874 by a French
doctor named Charcot. It is one of the most devastating diagnoses to receive.
There is no known cure and, until this year, no medical treatment that could alter
the course of this disease. Fortunately, we now have one drug shown to extend
the survival of some ALS patients, Riluzole (Rilutek), as well as several other
drugs being investigated.
ALS affects the muscles of arms, legs, posture, face, tongue, speech, swallowing,
and eventually, breathing. It may also affect emotion, resulting in periods of
inappropriate or exaggerated emotional responses. What it does not affect is
thinking or intelligence, sensation/sense of touch, taste, smell, hearing, sight,
eye movement, involuntary muscles of the heart, bowel, bladder, or sexual
function.
The two currently identified forms of ALS are "Sporadic" and "Familial." The most
common type is "Sporadic ALS," accounting for over 90% of the cases of ALS. Here
the cause is unknown and may affect anyone at random. "Familial ALS" accounts
for the remaining cases (less than 10%) and is caused by inheriting a dominant
gene from one parent. In this case, there would be a family history of ALS among
blood relatives and also a 50/50 chance of the affected person passing it onto
their children. If neither parent or other blood relatives have ALS, you'd expect to
have the Sporadic form and, therefore, not expect to pass it onto your children.
Presently there is no blood or genetic screening test to detect "the ALS gene" for
all familial forms of ALS, but, there is a test for the chromosome 21 defect.
However, only approximately 20% of the people who have familial ALS have this
defect. These studies are designed for research, & aren't yet available for general
testing. It takes months to get results & there can be problems with the tests,
(ie. unreadable.) For information call ALSA at (800)-782-4747 or the Les Turner
Center (708)-679-3311.
ALS is a very uncommon disease, affecting about 1 per 100,000 each year. It more
often affects people over age 40, men slightly more than women. The usual cause
of death is through respiratory complications. Survival time, as well as the course
of the disease (the order in which symptoms develop) varies widely. Historically,
from textbooks, ALS has an average survival time of 3 to 5 years, with about 20%
of those affected living past 5 years. The classic "Progressive Bulbar Palsy"
variant has a survival time of 1 to 3 years. Let me state clearly that there are a
lot of reasons not to get caught up with numbers on survival time. First, those
numbers are averages based on thousands of people and that doesn't tell us, as
individuals, how we'll do. Every individual's course is different. Second, there are
documented cases of spontaneous remission and long term ALS survivors. Third,
with the availability of gastrostomy feeding tubes, home ventilators, etc, not only
length of survival, but quality of life can be extended. Finally, it's far too early to
tell what impact these new research drugs, (and others to follow), will have with
early and long term treatment. Also, I firmly believe that state of mind has a
significant influence over survival time. I'll comment more on that under "My
Personal Philosophy" at the end of "Practical Tips."
Regarding the disease process, there are 2 types of motor nerves that supply
voluntary muscles; both are affected in ALS. One type are called Upper Motor
Neurons (UMN's). These begin in the brain and extend into the spinal cord. When
these nerves are affected, the result is spasticity, weakness and over-reactive
reflexes. The second type are called Lower Motor Neurons (LMN's). These begin
where UMN's end (in the Anterior Horn Cell region of the spinal cord), and each
travels to a specific muscle. When these are affected, the result is marked
weakness leading to paralysis, muscle wasting and diminished to lost reflexes. As
these nerves become dysfunctional you may see muscle fasciculations. When
symptoms begin in the arms or legs it may be referred to as "Limb Onset ALS."
To make matters a little more complicated, there is a special subset of nerves
that come directly from the brainstem and control specialized functions like
speech and swallowing. When symptoms arise from these nerves they may be
referred to as "Bulbar" symptoms. Bulbar is a traditional term for brainstem.