Motor Neuron Disease

05 November 2004

What is ALS?

Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig's disease as it is commonly known in the United States, was first described in the late 1880's by Charcot, a French neurologist. The disease causes progressive weakness and wasting of muscles. Virtually all muscles may be affected, resulting in impaired ability to use the arms and legs, speak, swallow, and breathe. The extent and degree of impairment vary from patient to patient.

The primary targets of the disease are the motor nerve cells in the motor cortex, brainstem, and spinal cord. The reason for the greatly accelerated loss of motor nerve cells had eluded us to date, although recent research has revealed intriguing clues. These include the identification of mutations in certain genes in some of the familial cases of ALS; evidence for toxic injury resulting from an excess of glutamate, the major excitatory chemical transmitter in the central nervous system; the suggestion that motor nerve cells are unable to properly rid themselves of highly toxic oxidizing compounds; and the finding of abnormalities in certain proteins essential to the cytoskeleton of motor neurons. Each of these factors, or some combination of them, may play a role in the premature death of the motor nerve cells in ALS.

ALS is uncommon, affecting about 1 per 100,000 persons each year. It usually begins after 40 years of age and affects men a little more often than women. Although the average survival time is reported as 3 to 5 years, about one in five patients live past 5 years, and there are even some reported instances of spontaneous remissions. Indeed, some survival times are for much longer periods. In this day and age, new drugs are being introduced which clearly slow the progression of the disease and the quality of life can be enhanced by a variety of interventions.

Types of Nerve Cells

There are two types of motor nerve cells which control our muscles and both are affected in ALS. The Upper Motor Neuron (UMN) resides in the cortex of the brain and helps to direct lower motor nerve cells in the brainstem and spinal cord. When the upper motor neurons are affected, weakness, over-reactive tendon reflexes and stiffness often develop. The second type of neuron is called the Lower Motor Neuron (LMN). These cells are found in the brainstem and spinal cord, and directly supply specific muscles. When these cells are affected, wasting as well as weakness develop and fasciculations (twitching) may be seen. When symptoms begin in the arms or legs it may be referred to as "Limb Onset ALS".

There is a special subset of motor neurons in the brainstem which control speech and swallowing. Weakness in these muscles may therefore produce difficulties speaking and swallowing. When symptoms arise from the loss of brainstem motor neurons, the symptoms are often referred to as "Bulbar" symptoms.

Diagnosis

The diagnosis of ALS is a clinical diagnosis. There is no single test which can prove the diagnosis. Instead, it requires a thorough exam and many tests, sometimes over a period of weeks, all of which need to be interpreted by an experienced neurologist in order to confirm or reject a diagnosis. The diagnosis of ALS is primarily based on the history and clinical findings. There are no specific laboratory tests to make the diagnosis. However, some tests, including electromyography, magnetic resonance imaging (MRI) and other studies can greatly enhance the ability to make an accurate diagnosis and differentiate ALS from other sometimes quite treatable disorders.

The vigour and quality of present day research in ALS hold forth the promise that a cure for ALS will soon be found. Treatment with riluzole, a glutamate inhibitor, is already available. Other drugs, such as growth factors, have been shown in experimental studies to enhance nerve cell survival, and may slow the progression of the disease. There is real reason for hope in ALS.