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Electron microscopic studies of cerebrospinal fluid sediment in demyelinating disease
Abstract:
Cerebrospinal fluid specimens from 31 patients with multiple sclerosis (MS) and 2 with progressive multifocal leukoencephalopathy (PML) were subjected to ultracentrifugation, and the resulting pellets were examined in an electron microscope. Cell types seen in the pellets included lymphocytes, occasional plasma cells, polymorphonuclear leukocytes, monocytes, eosinophils, lipid-laden macrophages, and fibroblasts. The most interesting noncellular elements were extracellular myelin fragments, recognizable by their characteristic alternation of major dense lines and intraperiod lines. Myelin fragments were seen in the CSF from 7 of 9 patients with MS in exacerbation involving areas other than the optic nerve. These fragments were not observed in 4 specimens from patients with acute attacks manifested by optic neuritis. Myelin fragments were present in 1 of the 2 patients with PML. These observations indicate that a portion of the myelin destruction seen in MS and PML occurs extracellularly, with release of myelin fragments and degradation products into the CSF.
Insights
Extracellular myelin fragments were found in cerebrospinal fluid of patients with multiple sclerosis (MS) and progressive multifocal leukoencephalopathy (PML), indicating extracellular myelin destruction in these neurological diseases.
Area of Science:
- Neuroscience
- Neuropathology
- Cell Biology
Background:
- Multiple sclerosis (MS) and progressive multifocal leukoencephalopathy (PML) are demyelinating diseases of the central nervous system.
- The precise mechanisms and locations of myelin breakdown in MS and PML are not fully understood.
Purpose of the Study:
- To investigate the presence and origin of noncellular elements in the cerebrospinal fluid (CSF) of patients with MS and PML.
- To determine if myelin destruction occurs extracellularly in these conditions.
Main Methods:
- Cerebrospinal fluid (CSF) specimens from 31 patients with MS and 2 with PML were analyzed.
- Ultracentrifugation was used to concentrate cellular and noncellular elements from CSF.
- Pellets were examined using electron microscopy to identify cell types and extracellular structures.
Main Results:
- Lymphocytes, plasma cells, various leukocytes, macrophages, and fibroblasts were identified in CSF pellets.
- Extracellular myelin fragments, characterized by their distinct ultrastructure, were observed in 7 of 9 MS patients during exacerbation (excluding optic neuritis).
- Myelin fragments were also found in one PML patient and absent in MS patients with optic neuritis.
Conclusions:
- These findings demonstrate that myelin destruction occurs extracellularly in multiple sclerosis and progressive multifocal leukoencephalopathy.
- Extracellular myelin fragments are released into the cerebrospinal fluid during active demyelination in MS and PML.
- The presence of myelin fragments in CSF provides direct evidence of myelin breakdown and release into the extracellular space.