MELD Project: Atlas of lesion locations and postsurgical seizure freedom in focal cortical dysplasia
Authors: Wagstyl Konrad , Whitaker Kirstie , Raznahan Armin , Seidlitz Jakob , Vértes Petra E , Foldes Stephen , Humphreys Zachary , Hu Wenhan , Mo Jiajie , Likeman Marcus , Davies Shirin , Lenge Matteo , Cohen Nathan T , Tang Yingying , Wang Shan , Ripart Mathilde , Chari Aswin , Tisdall Martin , Bargallo Nuria , Conde-Blanco Estefanía , Pariente Jose Carlos , Pascual-Diaz Saül , Delgado-Martínez Ignacio , Pérez-Enríquez Carmen , Lagorio Ilaria , Abela Eugenio , Mullatti Nandini , O’Muircheartaigh Jonathan , Vecchiato Katy , Liu Yawu , Caligiuri Maria , Sinclair Ben , Vivash Lucy , Willard Anna , Kandasamy Jothy , McLellan Ailsa , Sokol Drahoslav , Semmelroch Mira , Kloster Ane , Opheim Giske , Yasuda Clarissa , Zhang Kai , Hamandi Khalid , Barba Carmen , Guerrini Renzo , Gaillard William Davis , You Xiaozhen , Wang Irene , González-Ortiz Sofía , Severino Mariasavina , Striano Pasquale , Tortora Domenico , Kalviainen Reetta , Gambardella Antonio , Labate Angelo , Desmond Patricia , Lui Elaine , O’Brien Terry , Shetty Jay , Jackson Graeme , Duncan John S , Winston Gavin P , Pinborg Lars , Cendes Fernando , Cross J Helen , Baldeweg Torsten , Adler Sophie 
Published: February 2021

Drug-resistant focal epilepsy is often caused by focal cortical dysplasias (FCDs). The distribution of these lesions across the cerebral cortex and the impact of lesion location on clinical presentation and surgical outcome are largely unknown. We created a neuroimaging cohort of patients with individually mapped FCDs to determine factors associated with lesion location and predictors of postsurgical outcome.

The Multi-centre Epilepsy Lesion Detection (MELD) project collated a retrospective cohort of 580 patients with epilepsy attributed to FCD from 20 epilepsy centres worldwide. MRI-based maps of individual FCDs with accompanying demographic, clinical and surgical information were collected. We mapped the distribution of FCDs, examined for associations between clinical factors and lesion location, and developed a predictive model of postsurgical seizure freedom.

FCDs were non-uniformly distributed, concentrating in the superior frontal sulcus, frontal pole and temporal pole. Epilepsy onset was typically before age 10. Earlier epilepsy onset was associated with lesions in primary sensory areas while later epilepsy onset was associated with lesions in association cortices. Lesions in temporal and occipital lobes tended to be larger than frontal lobe lesions. Seizure freedom rates varied with FCD location, from around 30% in visual, motor and premotor areas to 75% in superior temporal and frontal gyri. The predictive model of postsurgical seizure freedom had a positive predictive value of 70% and negative predictive value of 61%.

FCD location is an important determinant of its size, the age of epilepsy onset and the likelihood of seizure freedom post-surgery. Our atlas of lesion locations can be used to guide the radiological search for subtle lesions in individual patients. Our atlas of regional seizure freedom rates and associated predictive model can be used to estimate individual likelihoods of postsurgical seizure freedom. Data-driven atlases and predictive models are essential for evidence-based, precision medicine and risk counselling in neurology.