Also referred to as motor neurone disease (by the British), amyotrophic lateral sclerosis (ALS) is a progressive and ultimately fatal disorder characterized by degeneration of the upper and lower motor neurons of the brain and spinal cord. ALS occurs worldwide with a prevalence of approximately 10 cases per 100,000. Age specific rates in sporadic ALS peak between 50 and 70 years, and the course of the disease ranges from 4 to 6 years. More men than women develop sporadic ALS (M:F = 1.5:1). Between 5 and 10% of cases demonstrate an autosomal dominant pattern of inheritance. 20% of familial (and 5% of apparently sporadic) ALS patients posses mutations in the gene encoding superoxide dismutase 1 (SOD 1).

ALS has a characteristic pattern of selective vulnerability involving somatic motor neurons of the cerebral cortex, brainstem and spinal cord, with relative sparing of the oculomotor nuclei and Onufs (preganglionic parasympathetic) nucleus in the sacral cord. However, if "early" death from respiratory failure is prevented more widespread neuronal degeneration may ensue. The characteristic cytopathologic hallmark of ALS is the Bunina body, a very small (1 to 4 micrometer) eosinophilic cytoplasmic body. Although difficult to appreciate due to their small size, Bunina bodies may be found in surviving anterior horn neurons in about three-quarters of ALS patients. Larger, dense bodies similar to Lewy bodies can be seen in the anterior horn cells of approximately 20% of cases. Utilizing antibodies to ubiquitin (a stress or "heat shock" protein which binds to abnormal cytoplasmic proteins in order to facilitate their proteolysis) and TAR-DNA binding protein 43 (TDP-43), anterior horn cell inclusions can be identified in virtually all patients with ALS.

Degeneration of upper motor neurons (with consequent corticospinal tract degeneration “lateral sclerosis”) results in spasticity and hyperactive reflexes (including the Babinski sign) . With degeneration of lower motor neurons patients show flaccidity, fasciculations, and severe atrophy of denervated muscles (“amyotrophy”). Due to the relative sparing of oculomotor nuclei and Onufs nucleus, eye movements and bowel and bladder function tend to be preserved, at least early in the disease.

Further Reading

Wijesekera LC, Leigh PN. Amyotrophic lateral sclerosis. Orphanet J Rare Dis. 2009 Feb 3;4:3.

Rothstein, Jeffrey D. Current hypotheses for the underlying biology of amyotrophic lateral sclerosis. Annals of Neurology, Volume 65, issue S1 – Updates on Amyotrophic Lateral Sclerosis: Improving Patient Care (January 2009), p. S3 - S9

Geser F, Martinez-Lage M, Robinson J, et al. Clinical and pathological continuum of multisystem TDP-43 proteinopathies. Arch Neurol. 2009 Feb;66(2):180-9.