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In a small but well-designed study, Schutzer et al used high-resolution mass spectrometry to compare CSF proteins in patients with clinically isolated syndrome (CIS) who eventually developed multiple sclerosis (MS), patients with established relapsing-remitting MS, and controls with no obvious neurologic disease. CSF proteins from patients with CIS were differentially enriched for gray matter components (eg, axons, neurons, and synapses), compared with other groups.
The prominence of gray matter CSF proteins early in MS evolution is not surprising. Sophisticated MRI techniques have allowed investigators to describe gray matter lesions as an early phenomenon in MS, and these lesions may even be more prominent than white matter lesions. Cerebral gray matter is active metabolically; it has greater blood flow, oxygen consumption, and tissue volume than white matter. Axonal pathology is an early and common finding in MS, even in apparently normal white matter, possibly because of immune-mediated inflammatory damage and associated Wallerian degeneration. In addition, gray matter MS pathology can be seen adjacent to meningeal inflammation, and oligodendrocytes and myelinated axons are present in gray matter. These findings are consistent with diffusion of CSF-reactive lymphocytes or their products into cerebral gray matter, and a similar mechanism may occur in white matter across the blood–brain barrier.
However, the concept that CSF gray matter proteins are more enriched in patients with CIS than in those with established MS comes as somewhat of a surprise. While patients with CIS have had only one clinically documented event, there are usually multiple brain lesions that are clinically silent but detected on MRI. These can be considered subclinical relapses because the lesions occur in less eloquent areas or are less destructive. Thus, one does not usually know with certainty when MS actually starts. In this regard, it would be interesting to obtain information on gray matter proteins after a second spinal tap in patients with CIS who later develop definite MS.
Lastly, although gray matter may be affected early in MS, there is insufficient evidence as to whether or not a gray matter protein is an autoimmune trigger in MS.
—Stuart D. Cook, MD
Ruth Dunietz Kushner and Michael Jay Serwitz Professor
of Neurology and Neurosciences
Rutgers, The State University of New Jersey, Newark
In a small but well-designed study, Schutzer et al used high-resolution mass spectrometry to compare CSF proteins in patients with clinically isolated syndrome (CIS) who eventually developed multiple sclerosis (MS), patients with established relapsing-remitting MS, and controls with no obvious neurologic disease. CSF proteins from patients with CIS were differentially enriched for gray matter components (eg, axons, neurons, and synapses), compared with other groups.
The prominence of gray matter CSF proteins early in MS evolution is not surprising. Sophisticated MRI techniques have allowed investigators to describe gray matter lesions as an early phenomenon in MS, and these lesions may even be more prominent than white matter lesions. Cerebral gray matter is active metabolically; it has greater blood flow, oxygen consumption, and tissue volume than white matter. Axonal pathology is an early and common finding in MS, even in apparently normal white matter, possibly because of immune-mediated inflammatory damage and associated Wallerian degeneration. In addition, gray matter MS pathology can be seen adjacent to meningeal inflammation, and oligodendrocytes and myelinated axons are present in gray matter. These findings are consistent with diffusion of CSF-reactive lymphocytes or their products into cerebral gray matter, and a similar mechanism may occur in white matter across the blood–brain barrier.
However, the concept that CSF gray matter proteins are more enriched in patients with CIS than in those with established MS comes as somewhat of a surprise. While patients with CIS have had only one clinically documented event, there are usually multiple brain lesions that are clinically silent but detected on MRI. These can be considered subclinical relapses because the lesions occur in less eloquent areas or are less destructive. Thus, one does not usually know with certainty when MS actually starts. In this regard, it would be interesting to obtain information on gray matter proteins after a second spinal tap in patients with CIS who later develop definite MS.
Lastly, although gray matter may be affected early in MS, there is insufficient evidence as to whether or not a gray matter protein is an autoimmune trigger in MS.
—Stuart D. Cook, MD
Ruth Dunietz Kushner and Michael Jay Serwitz Professor
of Neurology and Neurosciences
Rutgers, The State University of New Jersey, Newark
In a small but well-designed study, Schutzer et al used high-resolution mass spectrometry to compare CSF proteins in patients with clinically isolated syndrome (CIS) who eventually developed multiple sclerosis (MS), patients with established relapsing-remitting MS, and controls with no obvious neurologic disease. CSF proteins from patients with CIS were differentially enriched for gray matter components (eg, axons, neurons, and synapses), compared with other groups.
The prominence of gray matter CSF proteins early in MS evolution is not surprising. Sophisticated MRI techniques have allowed investigators to describe gray matter lesions as an early phenomenon in MS, and these lesions may even be more prominent than white matter lesions. Cerebral gray matter is active metabolically; it has greater blood flow, oxygen consumption, and tissue volume than white matter. Axonal pathology is an early and common finding in MS, even in apparently normal white matter, possibly because of immune-mediated inflammatory damage and associated Wallerian degeneration. In addition, gray matter MS pathology can be seen adjacent to meningeal inflammation, and oligodendrocytes and myelinated axons are present in gray matter. These findings are consistent with diffusion of CSF-reactive lymphocytes or their products into cerebral gray matter, and a similar mechanism may occur in white matter across the blood–brain barrier.
However, the concept that CSF gray matter proteins are more enriched in patients with CIS than in those with established MS comes as somewhat of a surprise. While patients with CIS have had only one clinically documented event, there are usually multiple brain lesions that are clinically silent but detected on MRI. These can be considered subclinical relapses because the lesions occur in less eloquent areas or are less destructive. Thus, one does not usually know with certainty when MS actually starts. In this regard, it would be interesting to obtain information on gray matter proteins after a second spinal tap in patients with CIS who later develop definite MS.
Lastly, although gray matter may be affected early in MS, there is insufficient evidence as to whether or not a gray matter protein is an autoimmune trigger in MS.
—Stuart D. Cook, MD
Ruth Dunietz Kushner and Michael Jay Serwitz Professor
of Neurology and Neurosciences
Rutgers, The State University of New Jersey, Newark