Temporal lobe cortical pathology and inhibitory GABA interneuron cell loss are associated with seizures in multiple sclerosis

BACKGROUND: Seizures are recognised in multiple sclerosis (MS), but their true incidence and the mechanism by which they are associated with MS is unclear. OBJECTIVE: The objective of this paper is to determine the lifetime frequency of seizures in the United Kingdom MS Tissue Bank (UKMSTB) population and any pathological features associated with seizures. METHODS: We evaluated 255 individuals from the UKMSTB. A subset underwent analysis of cortical thickness, grey matter lesion (GML) (type and number) and cortical neuronal numbers (total and GABAergic). RESULTS: A total of 37/255 patients had seizures (14.5% lifetime incidence); in 47% they were associated with concurrent infection. In those with seizures, death and wheelchair use occurred earlier and in 59% seizures developed after 15 years of disease. Seizures were associated with Type 1 GMLs and reduced cortical thickness in the middle temporal gyrus. Localised selective GABAergic interneuron loss in layers IV and VI was related to GMLs but was not explained by the presence of inflammation or by mitochondrial dysfunction within Type I GMLs. CONCLUSION: We confirm that seizure frequency rises in MS. Type I GMLs in the temporal lobe underlie a loss of inhibitory interneurons in cortical layers IV and VI and these changes could together with concurrent infection enhance susceptibility to seizures.