Myelin composition in acute and chronic multiple sclerosis in relation to cerebral lysosomal activity

doi:10.1016/0022-510X(76)90181-7

Journal of the Neurological Sciences

Volume 29, Issues 2–4, October 1976, Pages 323-334

https://doi.org/10.1016/0022-510X(76)90181-7 Get rights and content

Abstract

The neuropathology of 3 cases of acute multiple sclerosis was correlated with biochemical analyses. Astrocytosis was a characteristic feature of the diffuse demyelinating lesions in one case and lymphocytic cuffing characterized the well-defined plaques present in the white matter of the other two cases. No abnormalities were found in the protein or lipid composition of isolated myelin, despite a wide range of recovery. Nevertheless, the gel electrophoretic protein pattern of white matter adjacent to plaque areas showed selective loss of myelin basic protein. Lysosomal acid proteinase and β-glucuronidase levels were very significantly increased in all white matter samples in which astrocytosis was a major neuropathological feature. Levels were less markedly raised in samples containing discrete active plaques. Enzyme changes were also found in the apparently normal white matter of 2 of the cases. Acid proteinase activity was in the normal range but the activities of β-glucuronidase and acetylcholine esterase were elevated. The significance of these results in relation to glial cell activity in the early stages of demyelination is discussed.

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The change in activity of lysosomal hydrolases in the brain tissue of patients with demyelinating disease has been suggested to reflect the demyelination process. In this study we measured neutral proteinase (NP), acid proteinase (AP), and β-glucuronidase (BG) activities in CSF of 32 patients with multiple sclerosis (MS) (remitting, remitting and relapsing, or chronic progressive course of the disease), 62 controls, and 4 patients with chronic inflammatory disease of central nervous system (ID). Samples from MS patients were taken at different clinical conditions of the disease during the 22-month follow-up. Elevated NP activity was found in patients with relapsing course of MS and also in patients with ID (P < 0.05). NP activity correlated with the number of leucocytes in CSF of both MS (P < 0.005, r = 0.50) and control (P < 0.05, r = 0.21) patients. AP activity decreased in the MS group, especially in patients with remitting or remitting and relapsing courses of the disease (P < 0.05), but even more in patients with ID (P < 0.01). During the follow-up the increase in NP activity seemed to be associated with the clinical relapses of MS patients. Other enzymes did not fluctuate with the disease. This study suggests that the change in activity of lysosomal hydrolases is not specific for MS. The increase in NP activity in CSF is associated with clinical relapse of individual MS patients during the follow-up and may indicate immunological activation of the demyelination process in the brain. The large intra- and interindividual variation in enzyme activities in the CSF, however, makes the use of these enzymes difficult for diagnosis of MS and follow-up of MS activity.
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Myelin composition in acute and chronic multiple sclerosis in relation to cerebral lysosomal activity

Abstract

J. neurol. Sci.

Brain Res.

J. neurol. Sci.

J. Lipid Res.

Partial characterization of a new myelin protein component

J. Neurochem.

Studies on the pathogenesis of multiple sclerosis

Europ. Neurol.

Biochemical studies on degenerative neurological disorders, Part 1 (Acute experimental encephalitis)

J. Neurochem.

Biochemical and morphological indices of brain degeneration — Computer-established inter-relationships in a memory disorder