A molecular genetic approach to amyotrophic lateral sclerosis.
Disorders of the motor neurons may affect both the upper and lower neurons, primarily the lower motor neurons as in the spinal muscular atrophies are primarily the upper motor neurons as in the familial spastic paraplegias. Amyotrophic lateral sclerosis is a degenerative disorder of the motor neuron that results in paralysis and wasting of voluntary muscles. Large motor neurons in the cerebral cortex, brain stem and spinal cord degenerate or are lost. Hyaline inclusions may be seen in the cytoplasm of surviving motor neurons. Acute axonal degeneration of peripheral motor fibers occurs at all levels, including the distal axon. Subclinical involvement of the spinecerebellar tracts, posterior column and Clarke's column as well as loss of large neurons in the dorsal root ganglia and neurons of oculomotor nuclei has been reported. The average duration of life onset of symptoms of amyotrophic lateral sclerosis is three years and ninety per cent of patients died within 5 years. The basic mechanism of disease in amyotrophic lateral sclerosis remains unknown. There is no known treatment that will prevent, reverse or otherwise alter the course of the disease. Autosomal dominant and autosomal recessive forms of amyotrophic lateral sclerosis are genetic models of amyotrophic lateral sclerosis which may provide insight into the disease mechanism of sporadic amyotrophic lateral sclerosis, five to ten percent of adult cases of amyotrophic lateral sclerosis with early onset of symptoms and a more benign course. It is conceivable that both genetic and sporadic forms of amyotrophic lateral sclerosis result from failure of the same or similar neuronal mechanism triggered by defective genes and by an environment agent in sporadic amyotrophic lateral sclerosis.
Siddique
T
T
Department of Neurology, Northwestern University Medical School Chicago, 300 E. Superior Street, Tarry 13-715, Chicago, IL 60611, USA.
Hu
P
P
Hentati
A
A
Deng
G
G
Hung
W Y
WY
McInnis
M G
MG
Warren
A C
AC
Rimmler
J
J
Antonarakis
S
S
Pericak-Vance
M A
MA
D000690:Amyotrophic Lateral Sclerosis / Q000145:classification / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans