Contributions
Abstract: 1
Type: Hot Topic
Abstract Category: N/A
Background: Demyelination of cerebral white matter is thought to drive neuronal degeneration and permanent neurological disability in individuals with multiple sclerosis (MS). Brain magnetic resonance imaging (MRI) studies, however, support the possibility that demyelination and neuronal degeneration can occur independently. The purpose of this study was to investigate whether post-mortem MS brains show pathological evidence of cortical neuronal loss that is independent of cerebral white-matter demyelination.
Methods: Visual examination of centimeter-thick slices from 97 postmortem MS brains identified 12 without evidence of cerebral white-matter demyelination. Demyelination was quantified histologically in cerebral white matter, cerebral cortex, and spinal cord and compared with demyelination in 12 cases of MS with cerebral white-matter lesions. Atrophy, MRI metrics, cortical neuronal densities, and pathological correlates of MRI abnormalities were compared.
Results: Cases without cerebral macroscopic lesions had demyelination in spinal cord and cortex, but a paucity of histologic cerebral white-matter demyelination. Despite the lack of cerebral white-matter demyelination, cortical neuronal loss, cortical thinning, and cerebral white-matter MRI abnormalities were significantly increased compared to brains from healthy controls and were similar to those in MS brains with cerebral white-matter demyelination. In the 12 brains without cerebral white-matter demyelination, swollen myelinated axons were the pathological correlate of white-matter regions with MRI abnormalities.
Conclusions: A subtype of MS, which we call myelocortical multiple sclerosis (MCMS), is characterized by demyelination of spinal cord and cerebral cortex, but not of cerebral white matter. Cortical neuronal loss is not accompanied by cerebral white-matter demyelination and is therefore an independent pathological event in MCMS.
Disclosure: This work was funded by the National Multiple Sclerosis Society (NMSS) and by the National Institutes of Health (NIH). Dr. Trapp received grants from NIMH/NIH, the State of Ohio, and the ALS Association, grants, personal fees and non-financial support from Sanofi Genzyme, grants and non-financial support from NMSS, personal fees and non-financial support from Genentech, Novartis, Biogen, Disarm Therapeutics, and Renovo Neural Inc., and personal fees from the Lunbeckfonden Foundation outside of the submitted work.
Abstract: 1
Type: Hot Topic
Abstract Category: N/A
Background: Demyelination of cerebral white matter is thought to drive neuronal degeneration and permanent neurological disability in individuals with multiple sclerosis (MS). Brain magnetic resonance imaging (MRI) studies, however, support the possibility that demyelination and neuronal degeneration can occur independently. The purpose of this study was to investigate whether post-mortem MS brains show pathological evidence of cortical neuronal loss that is independent of cerebral white-matter demyelination.
Methods: Visual examination of centimeter-thick slices from 97 postmortem MS brains identified 12 without evidence of cerebral white-matter demyelination. Demyelination was quantified histologically in cerebral white matter, cerebral cortex, and spinal cord and compared with demyelination in 12 cases of MS with cerebral white-matter lesions. Atrophy, MRI metrics, cortical neuronal densities, and pathological correlates of MRI abnormalities were compared.
Results: Cases without cerebral macroscopic lesions had demyelination in spinal cord and cortex, but a paucity of histologic cerebral white-matter demyelination. Despite the lack of cerebral white-matter demyelination, cortical neuronal loss, cortical thinning, and cerebral white-matter MRI abnormalities were significantly increased compared to brains from healthy controls and were similar to those in MS brains with cerebral white-matter demyelination. In the 12 brains without cerebral white-matter demyelination, swollen myelinated axons were the pathological correlate of white-matter regions with MRI abnormalities.
Conclusions: A subtype of MS, which we call myelocortical multiple sclerosis (MCMS), is characterized by demyelination of spinal cord and cerebral cortex, but not of cerebral white matter. Cortical neuronal loss is not accompanied by cerebral white-matter demyelination and is therefore an independent pathological event in MCMS.
Disclosure: This work was funded by the National Multiple Sclerosis Society (NMSS) and by the National Institutes of Health (NIH). Dr. Trapp received grants from NIMH/NIH, the State of Ohio, and the ALS Association, grants, personal fees and non-financial support from Sanofi Genzyme, grants and non-financial support from NMSS, personal fees and non-financial support from Genentech, Novartis, Biogen, Disarm Therapeutics, and Renovo Neural Inc., and personal fees from the Lunbeckfonden Foundation outside of the submitted work.