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Researchers discover new subtype of Multiple sclerosis

Researchers discover new subtype of Multiple sclerosis

Multiple sclerosis (MS) is a disease of the brain’s white matter characterized by the destruction of myelin (demyelination) — the protective covering of nerves. Now, the researchers in a study published in  The Lancet Neurology have identified a new subtype of MS — called myelocortical MS (MCMS) — that features neuronal loss without demyelination of the cerebral white matter.

The findings show that neuron loss and demyelination can occur independently in MS. This highlights the need for more sensitive MRI scans, according to the researchers.

In MCMS, part of the neurons become swollen and appear to be typical MS lesions indicative of white matter myelin loss on MRI, the researchers note. Because it is indistinguishable from traditional MS on an MRI, MCMS was only diagnosed in post-mortem tissues.

Bruce D. Trapp, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, USA, and colleagues conducted the study to determine whether post-mortem brains from patients with MS show pathological evidence of cortical neuronal loss that is independent of cerebral white-matter demyelination.

Also Read: Atrophied brain lesions in MRI indicate progression of Multiple Sclerosis : Study

In this retrospective study, researchers analyzed the brains and spinal cords of 100 MS patients who donated their brains after death. Visual examination of centimeter-thick slices of cerebral hemispheres was done to identify brains without areas of cerebral white-matter discoloration that were indicative of demyelinated lesions (referred to as myelocortical MS) and brains that had cerebral white-matter discolorations or demyelinated lesions (referred to as typical MS).

Neuronal densities in cortical layers III, V, and VI from five cortical regions not directly connected to spinal cord (cingulate gyrus and inferior frontal cortex, superior temporal cortex, and superior insular cortex and inferior insular cortex) were also compared between the two groups and with aged-matched post-mortem brains from individuals without evidence of neurological disease.

Key Results:

  • 12 individuals were identified as having myelocortical MS and were compared with 12 individuals identified as having typical MS.
  • Demyelinated lesions were detected in spinal cord and cerebral cortex, but not in cerebral white matter, of people with myelocortical MS.
  • Cortical demyelinated lesion area was similar between myelocortical and typical multiple sclerosis (median 4·45% [IQR 2·54–10·81] in myelocortical vs 9·74% [1·35–19·50] in typical multiple sclerosis; p=0·5512).
  • Spinal cord demyelinated area was significantly greater in typical than in myelocortical multiple sclerosis (median 3·81% [IQR 1·72–7·42] in myelocortical vs 13·81% [6·51–29·01] in typical multiple sclerosis; p=0·0083).
  • Despite the lack of cerebral white-matter demyelination in myelocortical multiple sclerosis, mean cortical neuronal densities were significantly decreased compared with control brains (349·8 neurons per mm 2 [SD 51·9] in myelocortical multiple sclerosis vs419·0 [43·6] in controls in layer III [p=0·0104]; 355·6 [46·5] vs 454·2 [48·3] in layer V [p=0·0006]; 366·6 [50·9] vs 458·3 [48·4] in layer VI [p=0·0049]).
  •  mean cortical neuronal densities were decreased in typical multiple sclerosis brains compared with those from controls in layer V (392·5 [59·0] vs 454·2 [48·3]; p=0·0182) but not layers III and VI.

While alive, MRI brain scans of those 12 patients were indistinguishable from those with traditional MS, the study authors said. That’s because part of the neurons were swollen in those 12 patients and looked like typical MS lesions caused by white matter myelin loss. Diagnosis of MCMS was only possible after death.

“We propose that myelocortical multiple sclerosis is a subtype of multiple sclerosis that is characterized by demyelination of spinal cord and cerebral cortex but not of cerebral white matter. The cortical neuronal loss is not accompanied by cerebral white-matter demyelination and can be an independent pathological event in myelocortical multiple sclerosis,” conclude the authors.

“Compared with control brains, cortical neuronal loss was greater in myelocortical multiple sclerosis cortex than in typical multiple sclerosis cortex. The molecular mechanisms of primary neuronal degeneration and axonal pathology in myelocortical multiple sclerosis should be investigated in future studies,” they add.

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Source: With inputs from Lancet Neurology

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