Clinical Neuroscience

[The problem of the pathogenesis of amyotrophic lateral sclerosis]

GEORGIEV Iván1

APRIL 01, 1967

Clinical Neuroscience - 1967;20(04)

[The author bases his hypothesis on the pathogenesis of amyotrophic lateral sclerosis (ALS) on the following factors: 1. The fact that the disease process involves certain systems of the nervous system and is dystrophic in nature; 2. Analogies with the anatomic-clinical syndrome of tri-ortho-cresyl phosphate (TOCP) poisoning. 3. Certain biochemical data observed in both processes. Experimental subacute and chronic TOCP poisoning has been established in mice, rabbits and dogs. Histological, histochemical and biochemical studies were performed in brain tissue and serum. Changes in serum protein composition were also studied by electrophoresis. The results suggested that, in addition to irreversible inhibition of cholinesterase activity, several different, poorly studied factors are involved in the pathogenesis of TOCP intoxication. The pathophysio-clinical picture of TOCP intoxication represents an experimental model of neurological systemic lacrosis, the analogy of which with amyotrophic lateral sclerosis is undoubted. This analogy is not based on an exogenous toxic factor, i.e. ALS is not simply TOCP neurotoxicosis. We must assume a similar pathogenesis of the two processes. In the pathogenetic view of ALS, we can attribute a role to certain congenital enzyme biochemical abnormalities. Among these, perhaps those of cholinesterase nature or enzymes related to the biochemistry of acetyl-choline cholinesterase are of greatest importance. The decrease in cholinesterase activity observed in the serum of patients is in favour of the cholinesterase activity hypothesis. In analogy to the pathogenesis of TOCP poisoning, the pathogenesis of ALS is likely to involve a more complex perturbation of several enzyme chains, the most important of which are enzymopathic nature of the disease process.]

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  1. Szófiai Neurológiai Klinika

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Clinical Neuroscience

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