Motor Neuron Diseases - An Overview

Types of Motor Neuron Diseases Including ALS and More

Young man hand behind neck, rear view, close-up
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If most people think of anything when they hear the words “motor neuron disease,” they think of amyotrophic lateral sclerosis (ALS). There are, however, several other types of motor neuron disease as well. Fortunately, all motor neuron diseases are uncommon.

Overview

When we move, electrical signals are sent from the brain to the spinal cord along upper motor neurons. The nerve cells synapse in the anterior horn of the spinal cord and then are sent out along lower motor neurons in peripheral nerves.

Electrical signals traveling along these neurons signal for a muscle to contract, resulting in movement. Depending on certain physical exam findings, neurologists can determine where the problem is in the nervous system, and based off that, a potential diagnosis.

Conditions which affect this normal signaling are referred to as motor neuron diseases.  The posterior horn of the spinal cord carries information that pertains to sensation, whereas the anterior horn carries information which pertains to movement. Motor neurons diseases, for this reason, primarily affect movement.

General Signs and Symptoms

Motor neuron diseases may be separated into two main categories, depending on whether they affect upper motor neuron or lower motor neurons. Some motor neuron diseases affect only the upper motor neurons, whereas others affect primarily the lower motor neurons. Some, like ALS, affect both.

Symptoms of upper motor neuron disease include:

  • Spasticity - A combination of muscle stiffness, tightness, rigidity, and inflexibility. With severe spasticity, your muscles may feel "stuck." With mild spasticity, you may be able to move your muscles, but they respond in an unexpected or jerky way.
  • Rigidity - An involuntary "stiffness" of the muscles.
  • Increased deep tendon reflexes - For example, your knee jerk may be more pronounced than usual.

Symptoms of lower motor neuron disease include:

  • Atrophy - The loss of strength and mass of muscles.
  • Fasciculations - A spontaneous and involuntary contraction of muscles which may be visible as twitching under the skin.

Types of Motor Neuron Diseases

There are several different motor neuron diseases which differ with respect to whether they affect upper or lower motor neurons, the initial symptoms, the age group they affect, and prognosis. Some of these include:

Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a progressive motor neuron disease which affects roughly 6,000 people each year in the United States. It begins with muscle weakness, usually on only one side of the body. The condition begins in the hands more often than the feet. Early on, the primary sign may be fasciculations, but eventually, progresses with both upper and motor neuron signs and symptoms. When the diaphragm is affected, mechanical ventilation may be needed. The disease usually does not usually affect cognition, and most people are alert (without any dementia) even when the disease is very advanced.

The average life expectancy with ALS is roughly two to five years but can vary widely, with five percent of people alive after 20 years. Thankfully, people such as scientist Stephen Hawking are helping to raise awareness both for ALS and other motor neuron diseases.

Primary Lateral Sclerosis

Primary lateral sclerosis (PLS) is a disease of upper motor neurons, disrupting signals from the brain to the spinal cord. The cells in the cerebral cortex responsible for movement slowly die away. The result is a slowly progressive weakness associated with upper motor neuron signs, such as spasticity, rigidity, and increased deep tendon reflexes.

Unlike amyotrophic lateral sclerosis, lower motor neuron findings, such as atrophy and fasciculations, are not as prominent. It is not certain just how common PLS is, but we believe it is less common than ALS.

Early in the course of the disease, primary lateral sclerosis may be confused with ALS. Since ALS can begin with just upper motor neuron signs, it may be years before a diagnosis of PLS becomes apparent. Even at that time, it may be difficult to tell which of the conditions is causing the symptoms, since some people with supposed PLS will develop lower motor neuron findings, proving the disease is actually ALS. All of that is a rather confusing way to say that it may be impossible to know if a condition is really ALS or PLS for several years after the onset of symptoms.

Other conditions, such as hereditary spastic paraparesis, will also need to be ruled out. PLS tends to progress more slowly than ALS, with patients commonly living up to 20 years with their symptoms.

Progressive Muscular Atrophy

In some ways, progressive muscular atrophy (PMA) is the opposite of primary lateral sclerosis. In PMA, only the lower motor neurons are affected, whereas, in PLS, only the upper motor neurons are injured. Since lower motor neurons are affected, progressive weakness is a common symptom. Since upper motor neurons are not affected, upper motor neuron signs such as rigidity do not occur. Progressive muscular atrophy is less common than ALS but has a better prognosis.

It can be a painstaking process to make the diagnosis of progressive muscular atrophy since the symptoms are similar to other conditions. In particular, diseases such as ALS, multifocal motor neuropathy (a form of peripheral neuropathy) and spinal muscular atrophy need to first be ruled out first before a conclusive diagnosis can be made.

Progressive Bulbar Palsy

Progressive bulbar palsy involves a slow degeneration of the brainstem, which contains the nerves (cranial nerves) which control the face, tongue, and throat. As a result, someone with progressive bulbar palsy will start having difficulty speaking, swallowing and chewing. Limb weakness may also become more evident as the disease progresses, with both upper and lower motor neuron signs. People with progressive bulbar palsy may also have uncontrollable and sometimes inappropriate outbursts of laughing or crying. It is not uncommon for people with progressive bulbar palsy to go on to develop ALS. Myasthenia gravis is an autoimmune neuromuscular disorder that may also present in a similar fashion.

Post-Polio Syndrome

Polio is a virus that attacks motor neurons in the anterior horn of the spinal cord, resulting in paralysis. Thankfully, due to aggressive vaccinations, this virus has largely been eradicated. Some of those who have had the disease, however, may complain of a weakness known as post-polio syndrome. This may be due to aging or injury causing the relatively few surviving motor neurons controlling the movement of a previously affected limb to die. The disorder only affects older people who have had polio in the past. It is usually not life-threatening.

Kennedy’s Disease

Kennedy's disease is due to an X-linked genetic mutation that affects the androgen receptor. The disorder causes slowly progressive weakness and pain of the muscles closest to the torso. The face, jaw, and tongue are also involved. Because it is X-linked, Kennedy’s disease generally affects men. Women with the genetic mutation are carriers, with a 50 percent chance of passing the gene on to their children. Women with the mutation may also suffer from minor symptoms, such as finger cramps, instead of more profound weakness.

Because the disease affects the androgen receptor (the receptor to which estrogen and testosterone attach), men with the disorder may also suffer from symptoms such as gynecomastia (breast enlargement), testicular atrophy, and erectile dysfunction. The lifespan of people with Kennedy’s disease is usually normal, though as their weakness progresses they may require a wheelchair.

Spinal Muscular Atrophy

Spinal muscular atrophy is an inherited disease that predominantly affects children. It is caused by defects in the SMN1 gene and is inherited in an autosomal recessive pattern. Due to this defective gene, not enough SMN protein is made, and this leads to degeneration of lower motor neurons. This leads to weakness and muscle wasting.

There are three main types of SMA, each involving children at a different age.

  • SMA type 1, also called Werdnig-Hoffman disease, becomes obvious by the time a child is six months old. The child will have hypotonia (floppy muscles) and will not often move spontaneously. They will not be able to sit up on their own at the expected time. Due to difficulty with the airway and maintaining strength enough to breathe, most of these children die by the age of two.
  • SMA type II starts a little later, becoming apparent between the ages of 6 to 18 months. These children will not be able to stand or walk without assistance, and will also have difficulties with respiration. However, children with SMA type II typically live longer than those with Werdnig-Hoffman, sometimes living into young adulthood.
  • SMA type IIII also called Kugelberg-Welander disease, becomes apparent between the ages of 2 and 17 years. Children with this disorder may have some difficulty running or climbing steps. They may also have back problems, such as scoliosis. However, children with this disorder may have a normal lifespan.

Diagnosis and Treatment

There is no very effective treatment for any of the motor neuron diseases. Medical therapy focuses on controlling symptoms of the disease as best as possible. However, in order to know what symptoms to anticipate, as well as rule out other more treatable diseases, it is important to get the right diagnosis.

Using their physical exam and other techniques such as electromyography, nerve conduction studies, and genetic testing when appropriate, neurologists can help define the correct diagnosis. Having the right diagnosis allows your neurologist to manage your symptoms as much as possible and to anticipate and prepare for any expected complications.

Coping

In the beginning, we commented that "fortunately" motor neuron diseases are uncommon. This may be good unless you or a loved one develop one of these conditions. Then, in addition to suffering the symptoms of these diseases, you may find that there are less research and less support than you would hope. While these diseases are uncommon, measures such as the Orphan Drug Act are directing more attention towards these less common but no less important conditions.

You may feel alone if you've been diagnosed with a motor neuron disease. Unlike the large groups of "breast cancer advocates" out there, we do not see huge groups of, for example, progressive bulbar palsy advocates. Yet awareness is rising, and at least for ALS, support.

People with motor neuron diseases need support just as those with more common conditions. While you may not have a support group in your community, there are support communities online where people with specific motor neuron conditions can "meet" and communicate with others who are facing some of the same challenges. Though we don't have a "pill" or a surgery to treat the disease, there is much that can be done to help people live well ​with the disease, and current research offers hope that advances will be made in the not so far off future.

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