Submission ID 93581

Poster Code HR-P-24
Title of Abstract Surgical Management of Familial Focal Epilepsy with Variable Foci: Contribution of Genetics to Unveil Focal Cortical Dysplasia
Abstract Submission Rationale Familial focal epilepsy with variable foci (FFEVF) and focal cortical dysplasia are increasingly recognized as caused by mTOR pathway dysregulation. Despite its safety and efficacy, surgery is often considered late or denied in cases of drug-resistant focal epilepsy. Recent experience from our epilepsy program suggests that genetics may be an additional criterion to pursue surgical candidacy. Methods We describe three related subjects with drug resistant FFEVF. All were underwent standard of care pre-surgical evaluations including genetic investigation, MRI, FDG-PET, SPECT and video-EEG monitoring. All underwent research-based MEG and EEG-fMRI. Careful review was performed when initial interpretation of MRI data failed to reveal a lesion. Research-based MRI post-processing was performed for one subject whose MRI did not reveal an anomaly. All underwent surgical excision of the lesion using standard surgical techniques supplemented by intra-operative neuronavigation. Specimen were submitted to neuropathology for clinical diagnosis. Results The proband had a clearly visible FCD on MRI with corresponding PET hypometabolism. Next-generation sequencing revealed pathogenic mutations in NPRL3 and MT-TK. Proband's sibling and cousin had long standing focal epilepsy but no diagnosed lesion. Genetic investigations confirmed the mutation in NRPL3 in both. Review of available MRIs revealed a transmantle dysplasia in the sibling, with congruent hypometabolism on PET. Post-processing revealed a small transmantle dysplasia, supported by MEG results, that was previously overlooked on MRI. All had EEG anomalies and semiology compatible with their respective lesions. Pathology found FCD IIa in all cases. Subjects had been seizure and medication free for over 1.5 years at the time of submission. Conclusions: Genetics investigation should be considered in cases of unexplained drug-resistant epilepsy. The discovery of an mTOR pathway mutation should increase the suspicion of an occult dysplasia and drive supplementary investigations to assess surgical candidacy.
Please indicate who nominated you Kevin Whittingstall
What Canadian Institutes of Health Research (CIHR) institute is your research most closely aligned? Genetics
Neurosciences, Mental Health and Addiction
What Canadian Institutes of Health Research (CIHR) pillar of health research does your research fall under? Clinical
PDF of abstract No file
Presenter and Author(s) David Dufresne
Benoit Caldairou
Neda Bernasconi
Andrea Bernasconi
Roy Dudley
Cécile Cieuta-Walti
Steffen Albrecht
Marc-André Levasseur
Masataka Tanaka
Jean Gotman
David Dufresne

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