Novel MS subtype suggests neurodegeneration and demyelination occur independently
medwireNews: Researchers have discovered a new subtype of multiple sclerosis (MS) that features neuronal loss but not demyelination of the brain’s white matter.
“Our findings provide pathological evidence that cerebral white-matter demyelination and neurodegeneration can be independent events in multiple sclerosis”, say Bruce Trapp (Cleveland Clinic, Ohio, USA) and fellow researchers in The Lancet Neurology.
The researchers analysed the post-mortem brains and spinal cords of 100 patients with MS. The new subtype – myelocortical MS (MCMS) – could not be distinguished from traditional MS on magnetic resonance imaging (MRI) scans, but comparison of white-matter discolouration in hemispheric brain slices showed that 12 of the patients had significantly fewer cerebral white-matter lesions per hemisphere and significantly smaller individual lesions, on average, than the remaining patients.
When these 12 patients, who were classified as having MCMS as a result of absent white-matter demyelination, were matched with 12 of the remaining patients with traditional MS for age, sex, MRI protocol, disease duration, and Expanded Disability Status Scale score, the median number of lesions per hemisphere was 0.5 in the MCMS patients versus 10.0 in the traditional MS patients and the lesion area per hemisphere was 0.40 versus 14.14 cm2, respectively.
Despite the absence of demyelinated cerebral white-matter lesions, the MCMS patients still had demyelinated lesions in the spinal cord and cerebral cortex, and significant cortical neurodegeneration.
This finding highlights “the non-specific nature of the MRI abnormalities that are traditionally assessed in patients with multiple sclerosis and their lack of specificity for demyelination”, say the researchers.
“Inclusion of patients with myelocortical multiple sclerosis in immunomodulatory clinical trials could explain the variable responses of individuals to treatment as monitored with MRI.”
The MCMS patients’ cortical demyelinated lesion area was similar to that of the patients with traditional MS, at a median 4.45% versus 9.74% per patient, while their spinal cord lesion areas were significantly smaller, at a median 3.81% versus 13.81% per patient.
Mean cortical neuronal density was significantly reduced in the MCMS patients compared with that of age-matched controls without neurological disease, at layer III (49.8 vs 419.0 neurons/mm2), V (355.6 vs 454.2 neurons/mm2) and VI (366.6 vs 458.3 neurons/mm2), whereas a significant difference versus controls was only seen in layer V for patients with traditional MS (392.5 vs 454.2 neurons/mm2). Cortical thickness was significantly reduced in both MCMS and traditional MS patients compared with controls, at an average of 2.97 and 2.70 versus 3.75 mm.
“Cerebral white-matter demyelination and cortical neuronal loss therefore seem to be independent events in myelocortical multiple sclerosis”, say the researchers “Spinal cord demyelination is the likely cause of the severe physical disability in people with myelocortical multiple sclerosis”.
They therefore suggest that “cortical neuronal degeneration and swollen myelinated axons are attractive targets for neuroprotective therapies.”
By Lucy Piper
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