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.


CONCLUSIONS
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.
UK Multiple Sclerosis Tissue Bank, Wolfson Neuroscience Laboratories, Imperial College London Faculty of Medicine, Hammersmith Hospital Campus, UK r.nicholas@imperial.ac.uk.
Richard
R
Nicholas
UK Multiple Sclerosis Tissue Bank, Wolfson Neuroscience Laboratories, Imperial College London Faculty of Medicine, Hammersmith Hospital Campus, UK/Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
Roberta
R
Magliozzi
Centre for Neuroregeneration, University of Edinburgh, UK.
Graham
G
Campbell
Centre for Neuroregeneration, University of Edinburgh, UK/Centre for Clinical Brain Sciences, University of Edinburgh, UK.
Don
D
Mahad
UK Multiple Sclerosis Tissue Bank, Wolfson Neuroscience Laboratories, Imperial College London Faculty of Medicine, Hammersmith Hospital Campus, UK.
Richard
R
Reynolds
D000328:Adult; D000368:Aged; D002540:Cerebral Cortex / Q000473:pathology*; D005260:Female; D059330:GABAergic Neurons / Q000473:pathology*; D006801:Humans; D007395:Interneurons / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000453:epidemiology / Q000473:pathology*; D012640:Seizures / Q000453:epidemiology / Q000209:etiology / Q000473:pathology*; D013702:Temporal Lobe / Q000473:pathology*; D014015:Tissue Banks; D006113:United Kingdom / Q000453:epidemiology
Multiple sclerosis; epilepsy; neuropathology; seizure; temporal lobe