Amyotrophic Lateral Sclerosis

(ALS) and Other Motor Neuron

Diseases (MNDs)
Motor neuron diseases are characterized by progressive deterioration of the nerve cells
that initiate muscle movement. As a result, the muscles stimulated by these nerves
deteriorate, become weak, and no longer function normally.

 Amyotrophic lateral sclerosis (Lou Gehrig disease) is the most common form of motor
neuron disease.
 Typically, muscles are weak and waste away, and movements become stiff, clumsy, and
progressively more difficult to execute.

Motor neuron diseases may involve the central nervous system (brain and spinal cord) as well as
the peripheral nervous system (nerves outside the brain and spinal cord).

For normal muscle function, muscle tissue and nerve connections between the brain and muscle
must be normal.

Muscle movement is initiated by nerve cells (neurons) that are located in the spinal cord and in the
front part of the brain (called the motor cortex).

Nerve cells in the motor cortex connect with the nerve cells in the spinal cord that stimulate
muscles to move (called motor nerves).

In motor neuron diseases, these nerve cells progressively wither away and the peripheral nerves
that connect them to the muscle deteriorate.

As a result, muscles weaken, waste away (atrophy), and can become completely paralyzed even
though the muscles themselves are not the cause of the problem.
A person consciously decides to move a muscle—for example, to pick up a book.

For example, special nerve endings in the skin (sensory receptors) enable people to sense
pain or a change in temperature. This sensory information is sent to the brain, and the brain
may send a message to the muscle about how to respond. This type of exchange involves
two complex nerve pathways:

 The sensory nerve pathway to the brain

 The motor nerve pathway to the muscle

1. If sensory receptors in the skin

detect pain or a change in
temperature, they transmit an
impulse (signal), which
ultimately reaches the brain.
2. The impulse travels along a
sensory nerve to the spinal
cord.
3. The impulse crosses a
synapse (the junction between
two nerve cells) between the
sensory nerve and a nerve cell
in the spinal cord.
4. The impulse crosses from the
nerve cell in the spinal cord to
the opposite side of the spinal
cord.
5. The impulse is sent up the
spinal cord and through the
brain stem to the thalamus,
which is a processing center
for sensory information,
located deep in the brain.
6. The impulse crosses a
synapse in the thalamus to
nerve fibers that carry the
impulse to the sensory cortex
of the cerebrum (the area that
receives and interprets
information from sensory
receptors).
7. The sensory cortex perceives
the impulse. A person may
then decide to initiate
movement, which triggers the
motor cortex (the area that
plans, controls, and executes
voluntary movements) to
Motor neuron diseases have various forms, such as the following:

 Amyotrophic lateral sclerosis (the most common)

 Primary lateral sclerosis
 Progressive pseudobulbar palsy
 Progressive muscular atrophy
 Progressive bulbar palsy

Motor neuron diseases are more common among men and usually develop in people who are in
their 50s to 70s. The cause is usually unknown. About 5 to 7% of people who have a motor neuron
disease have a hereditary type and thus have family members who also have the disease.

Different parts of the nervous system may be affected first. For example, some forms of motor
neuron disease affect the mouth and throat first. Others affect a hand or foot first or affect them
most severely.

Long-lasting paralysis can lead to permanent shortening of muscles (contractures).

Symptoms

Muscle strength is affected, but people do not have pain or any changes in sensation. Depression
is common.

Amyotrophic lateral sclerosis (Lou Gehrig disease)

This progressive form begins with weakness, often in the hands and less frequently in the feet or
mouth and throat.

Weakness may progress more on one side of the body than on the other and usually proceeds up
the arm or leg.

Muscles, usually those in the hands and feet, start to waste away (atrophy). Muscle cramps are
also common and may occur before the weakness, but no changes in sensation occur.

People lose weight and feel unusually tired.

Over time, weakness increases.

When amyotrophic lateral sclerosis affects motor nerves in the brain, muscle tone typically
increases, and muscles tend to become stiff and tight, leading spasticity. Movements are stiff and
clumsy.

When motor nerves in the spinal cord are affected, muscle tone decreases, making the limbs
seem loose and floppy. When the connection between motor nerves and muscles is lost, the
muscles twitch spontaneously (called fasciculations).

Controlling facial expressions may become difficult.

Weakening of muscles in the throat may lead to slurred speech and difficulty swallowing
(dysphagia). Because swallowing is difficult, people sometimes drool and are more likely to choke
on liquids.
Food or saliva can be inhaled (aspirated) into the lungs, increasing the risk of pneumonia
(called aspiration pneumonia). The voice usually sounds nasal but may be hoarse.
As symptoms progress, people may be unable to control emotional responses and may laugh or
cry inappropriately.

Eventually, the muscles involved in breathing weaken, leading to breathing problems. Some
people need a ventilator to breathe. VIDEO

Primary lateral sclerosis and progressive pseudobulbar palsy

These motor neuron diseases are rare, slowly progressive variants of amyotrophic lateral
sclerosis:

 Primary lateral sclerosis affects mainly the arms and legs.

 Progressive pseudobulbar palsy affects mainly the muscles of the face, jaw, and
throat.

Muscle weakness and spasticity, but muscle twitching (called fasciculations) and wasting do not
occur.

Inappropriate emotional outbursts (for example, sudden laughter or crying) are common.

Symptoms usually progress for several years before total disability results.

Progressive muscular atrophy

It progresses more slowly, spasticity does not occur, but muscles weaken, become limp (flaccid),
and waste away. Involuntary contractions or twitching of muscle fibers (fasciculations) may be the
earliest symptoms.

The hands are usually affected first, followed by the arms, shoulders, and legs. Eventually, the
whole body is affected.

Many people with this form survive 25 years or longer.

Progressive bulbar palsy

In progressive bulbar palsy, the nerves controlling the muscles of chewing, swallowing, and talking
are affected, making these functions increasingly difficult. The voice may have a nasal tone. In
some people, emotions are changeable.

Because swallowing is difficult, food or saliva is often inhaled into the lungs, causing choking or
gagging and increasing the risk of aspiration pneumonia.

Death, which is often due to pneumonia, usually occurs 1 to 3 years after symptoms appear.
Diagnosis

 A doctor's evaluation
 Tests such as magnetic
resonance imaging,
electromyography, and nerve
conduction studies
 Blood, and sometimes urine
tests and a spinal tap

Muscle weakness can have many

causes. Diagnostic tests, such as the
following, are done to help narrow the
possibilities:
 Electromyography, which
involves recording electrical
activity in the muscles, can
help determine whether the
problem is in nerves,
neuromuscular junction, or
muscles.
 Nerve conduction studies ,
which measure how fast
nerves transmit impulses, may
also be done. The speed of
impulses is not affected until
late in motor neuron disease,
so if impulses are
unexpectedly slow, the cause
of symptoms may be another
disorder.
 Magnetic resonance imaging
(MRI) of the brain and
sometimes the spinal cord is
done to check for abnormalities
that may cause similar
symptoms.
  Blood tests to check for infections and metabolic disorders
 Urine tests to check for heavy metals (such as lead or mercury) if people have been
exposed to them
 A spinal tap (lumbar puncture) to check for signs of inflammation in the fluid that surrounds
the brain and spinal cord (cerebrospinal fluid)

 Genetic tests to check for hereditary disorders such as hereditary neuropathies

Treatment

 Physical therapy
 Drugs to relieve symptoms

Physical therapy helps people maintain muscle strength and keep joints flexible and thus helps
prevent contractures.
Nurses or other caregivers must feed people with swallowing difficulties carefully to prevent
choking.
Some people must be fed through a tube inserted through the abdominal wall into the stomach
(gastrostomy tube).
Certain drugs can help relieve symptoms:

 Baclofen may help make muscles less spastic.

 Phenytoin or quinine may help decrease cramps.
 Drugs with anticholinergic effects , such as amitriptyline (an antidepressant), may be used
to reduce drooling because one anticholinergic effect is to reduce saliva formation.
 Amitriptyline or fluvoxamine (also an antidepressant) may help people who have
changeable emotions or depression.
 A drug that combines dextromethorphan (a cough suppressant) with quinidine may help
control changeable emotions.

Amyotrophic lateral sclerosis, riluzole, a drug that protects nerve cells and Edaravone, a new
drug, may slow the decline in function to some degree in people with amyotrophic lateral sclerosis.

If pain develops as the disease progresses (for example, if pain occurs when a person has to sit in
one position too long), benzodiazepines, which are mild sedatives, may be used.

Surgery to improve swallowing helps only a few people with progressive bulbar palsy.