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In America, amyotrophic lateral sclerosis (ALS) is often referred to as Lou Gehrig’s disease, after the famous baseball player who in 1939 retired because of the disease.1 ALS is also known as Charcot’s disease (vide infra); but many famous neurologists figure in its history.
“I owe a thousand thanks to my friend Duchenne de Boulogne who freely put at my disposal all his material . . .”
Luys reported in 1860, the underlying anterior horn cell degeneration; and in the same year Duchenne reported progressive bulbar palsy as “glosso-labial-laryngeal paralysis”.4 Not until 1883 did Dejerine connect the disorder with ALS.5
Charcot’s major account in 1865, presented to the Société Médicale des Hôpitaux de Paris, was a woman initially diagnosed as an hysteric who had developed progressive weakness, and increased muscle tone, with contractures of all four limbs. At autopsy, he found no anterior horn cell disease, but he clearly identified lateral column degeneration and sclerosis in the cord6:
“On careful examination of the surface of the spinal cord, on both sides in the lateral areas, there are two brownish-grey streak marks produced by sclerotic changes. These greyish bands begin outside the line of insertion of the posterior roots and their anterior border approaches, but do not include, the entrance area of the anterior roots. They are visible throughout the thoracic region and continue though greatly thinning out, up to the widening point of the cervical cord. Below, they are barely visible in the thoraco-lumbar region. Transverse sections taken at different levels allow one to see that the lateral columns have in their most superficial and posterior regions, a grey, semitransparent appearance, rather gelatinous …. At no point does the diseased tissue penetrate the gray matter which remains unaffected.”
In later cases, he found histological changes in both lateral columns and anterior spinal nerve roots which enabled him to identify both the upper and lower motor neurone motor pathways. He summarised the clinical accompaniments7:
‘’Paresis without anaesthesia, of the upper extremities, accompanied by rapid emaciation of the muscular masses and often preceded by numbness and formication. Spasmodic rigidity seizes, at a given period, on the paralysed and wasted muscles and determines permanent deformations by contracture. The lower extremities are invaded in their turn . . . . A third period . . . the appearance of bulbar symptoms”.
Charcot then demonstrated lesions in the brain stem associated with weakness of the muscles of the face, mouth, and tongue. In 1871–2, his student Albert Gombault (1844–1904) showed symmetrical sclerosis of the lateral columns and of the bulbar pyramids.8 In Charcot’s laboratory, Aleksei Yakovlevich Kozhevnikov (1836–1902) importantly showed that the spinal degeneration could be traced to the motor cortex. Charcot commented that many investigators had previously tried without success to correlate a primary lesion of the grey matter of the medulla with the clinical signs known as glosso-labial-laryngeal paralysis.
The term amyotrophic lateral sclerosis was first used in 1874 in Charcot’s two lectures.7 A year later Erb reported primary lateral sclerosis—that was to cause continuing nosological confusion. It was Gowers who combined PMA, progressive bulbar palsy, and ALS as “Motor Neurone disease” in 1892; in the US, the customary name is “Combined System disease”.
Recent experiments in transgenic mice suggest that in ALS there may be cytoskeletal abnormalities including abnormal inclusions containing neurofilaments and/or peripherin, reduced mRNA levels for the NF light protein, and mutations in the NF heavy gene.9
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