Amyotrophic lateral sclerosis: current understanding.

Abstract

Amyotrophic lateral sclerosis (ALS), or motor neuron disease (MND) as it is usually termed in the United Kingdom, is a fatal degenerative disease resulting in progressive weakness and wasting of voluntary muscles. The disease is caused by degeneration of upper motor neurons in the motor cortex and of lower motor neurons in the brainstem and spinal cord. This combined loss of function causes spastic paralysis, flaccid muscle weakness, wasting, and fasciculations. The disease process spares the sensory, autonomic, and oculomotor neurons. ALS is the most common of the MND syndromes in adults. Although the cause of ALS is unknown, there is evidence that the excitatory neurotransmitter glutamate plays an important role in neuronal cell death in the disease. Several risk factors, such as exposure to welding and soldering, inhalation of lead vapor, exposure to chemicals, and electrical trauma are postulated as contributing to the pathogenesis of ALS. About 90% of all ALS patients have the sporadic form. Approximately 20% of all familial ALS cases are associated with mutations of the copper/zinc superoxide dismutase-1 gene. What is not clear is what factors contribute to the causation of the more common sporadic cases. The drug riluzole has neuroprotective effects in ALS and is the only disease-specific treatment available to date. Riluzole has been approved by the National Institute for Clinical Excellence for use in the National Health Service of the United Kingdom. Other treatments are aimed at managing the devastating symptoms of ALS.