Prospective neuroimaging and neuropsychological evaluation in adults with newly diagnosed focal epilepsy

Objective: There are few prospective longitudinal studies in patients with newly diagnosed epilepsy (NDE) despite that this is a key time point to understand the underlying biology of epilepsy and to identify potential interventions and biomarkers for seizure and cognitive outcomes. Here we have performed a prospective combined neuroimaging and neuropsychological study in a cohort of patients with focal NDE and healthy controls. Methods: We recruited 104 patients with NDE and 45 healthy controls for research-grade 3 Tesla MRI (diagnostic and structural imaging, diffusional kurtosis imaging, resting-state functional MRI, task-based functional MRI), EEG, comprehensive neuropsychological, and blood biomarker investigations. We report here on the baseline clinical, neuroradiological, MRI morphometric, and neuropsychological findings in this cohort. Results: 38% of patients had unremarkable MRI features, 12% had lesions of known significance in epilepsy, 49% with abnormalities of unknown significance in epilepsy, and 23% with incidental findings. In comparison, 56% of controls had unremarkable MRI features, 7% had lesions of known significance in epilepsy, 33% with abnormalities of unknown significance in epilepsy, and 16% had incidental findings. Patients had a higher incidence of white matter hyperintensities compared to controls. Reduced bihemispheric frontal lobe cortical thickness and thalamic volumes were observed in patients with moderate effect sizes. Patients scored significantly lower on tasks of executive function, processing speed, and visual, delayed, and immediate memory, and significantly higher on depression and anxiety assessments compared to controls. Patient neuropsychological performance was related to various brain morphometric features. Significance: People with adult focal NDE have a greater proportion of MRI-positive findings than previously reported. Subtle white matter lesions may represent an important diagnostic criterion and have a pathophysiological basis in focal epilepsy. Morphometric and neuropsychological alterations are present at the point of diagnosis of epilepsy, which suggests that brain and cognitive changes are not exclusively due to the deleterious impact of chronic epilepsy. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was funded by a UK Medical Research Council (MRC) research grant (MR/S00355X/1). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Northwest Liverpool East Research Ethics Committee (19/NW/0384) through the Integrated Research Application System (Project ID 260623). The research is sponsored by the University of Liverpool (UoL001449) and UK Health Research Authority approval was provided on 22nd August 2019. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors