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Introduction: Epilepsy is a common neurological disorder characterised by recurrent seizures. Almost half of patients who have an unprovoked first seizure (UFS) have additional seizures and develop epilepsy. No current predictive models exist to determine who has a higher risk of recurrence to guide treatment. Emerging evidence suggests alterations in cognition, mood and brain connectivity exist in the population with UFS. Baseline evaluations of these factors following a UFS will enable the development of the first multimodal biomarker-based predictive model of seizure recurrence in adults with UFS., Methods and Analysis: 200 patients and 75 matched healthy controls (aged 18-65) from the Kingston and Halifax First Seizure Clinics will undergo neuropsychological assessments, structural and functional MRI, and electroencephalography. Seizure recurrence will be assessed prospectively. Regular follow-ups will occur at 3, 6, 9 and 12 months to monitor recurrence. Comparisons will be made between patients with UFS and healthy control groups, as well as between patients with and without seizure recurrence at follow-up. A multimodal machine-learning model will be trained to predict seizure recurrence at 12 months., Ethics and Dissemination: This study was approved by the Health Sciences and Affiliated Teaching Hospitals Research Ethics Board at Queen's University (DMED-2681-22) and the Nova Scotia Research Ethics Board (1028519). It is supported by the Canadian Institutes of Health Research (PJT-183906). Findings will be presented at national and international conferences, published in peer-reviewed journals and presented to the public via patient support organisation newsletters and talks., Trial Registration Number: NCT05724719., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/objective: Identifying a patient's dominant language hemisphere is an important evaluation performed prior to epilepsy surgery and is commonly assessed using functional magnetic resonance imaging (fMRI). However, the lack of standardization and resultant heterogeneity of fMRI paradigms used in clinical practice limits the ability of cross-center comparisons to be made regarding language laterality results., Methods: Through surveying Canadian Epilepsy Centres in combination with reviewing supporting literature, current fMRI language lateralization practices for the clinical evaluation of patients with epilepsy were assessed. To encourage standardization of this practice, we outlined a two-part paradigm series that demonstrates widespread acceptance, reliability and accessibility in lateralizing various aspects of language functioning in individuals with average or near-average IQ and normal literacy skills., Results: The collected data confirm a lack of standardization in fMRI laterality assessments leading to clinical heterogeneity in stimulation and control tasks, paradigm design and timing, laterality index calculations, thresholding values and analysis software and technique. We suggest a Sentence Completion (SC) and Word Generation (WG) paradigm series as it was most commonly employed across Canada, demonstrated reliability in lateralizing both receptive and expressive language areas in supporting literature, and could be readily intelligible to an inclusive population., Conclusion: Through providing recommendations for a two-part paradigm series, we hope to contribute to the standardization of this practice across Canada to reduce clinical heterogeneity, encourage communicability between institutions, and enhance methodologies for the surgical treatment of epilepsy for the benefit of all individuals living with epilepsy in Canada.