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The lack of ideal measurement of treatment efficacy is a well acknowledged problem in the epilepsy community, both in clinical care and clinical trials. Whilst still the current gold-standard, self-reported seizure frequency significantly underestimates the true number of seizures and does not account for any other at least equally important outcome parameters, such as neurodevelopment and cognition. With the rise of disease modifying treatments, the need for more reliable endpoints in practice and clinical trials becomes more pressing. In this paper we assembled an expert panel to discuss the nature of these needs, current limitations, and obstacles based on a survey amongst these experts who were queried about the most important issues regarding the use of electroencephalography (EEG) parameters as endpoints in clinical drug and device development.A structured survey was sent to a group of experts in the design and conduct of epilepsy trials in adults and children. This was followed by a virtual in-person meeting discussing the results of the trial and identifying a list of most important issues.Six clinical trialists and 5 individuals from pharmaceutical companies returned the survey containing 14 questions, and 8 clinical trialists and 10 pharma-representatives attended the meeting. Three main issues were identified (1) lack of accuracy of seizure diaries due to nocturnal seizures, subtle motor seizures, impairment of consciousness and lack of awareness of the seizure by the patient (2) inter-rater variability of EEG assessment (3) lack of standardization regarding definition(s) of seizures (clinical and electrographic), EEG recording methods and EEG data management. Recommended solutions included (1) validation of EEG parameters as biomarkers and use of wearables (2) development of a manual that describes EEG rating criteria, protocol for validation by 1 central reader and use of a resolution of disagreements reporting template (3) standardization of EEG recording, data management and reporting.Current developments in research and technology seem promising to advance the use of EEG parameters as potential endpoints and offer partial solutions to the current needs. However, continuous, focused and collaborative efforts of all stakeholders (academia, industry and regulatory agencies) are needed to formulate guidelines, validate emerging technologies and approve them for use in trials. It is the intent of this opinion "position paper" to stimulate those efforts.

Clinicians who manage patients with epilepsy are expected to assess the relevance of clinical trial results to their practice, integrate new treatments into the care algorithm, and implement epilepsy quality measures, with the overall goal of improving patient outcomes. A disease-based clinical framework that helps with choice and combinations of interventions facilitates provision of efficient, cost-effective, and high-quality care. This article addresses the current conceptual framework that informs clinical evaluation of epilepsy, explores gaps between development of treatment options, quality measures and clinical goals, and proposes an outcome-centered approach that bridges these gaps with the aim of improving patient and population-level clinical outcomes in epilepsy.

This is a critical time in neurotherapeutics. The prevalence of neurological disease, such as dementia, stroke, and peripheral neuropathy, is large and growing consequent to the aging population. The personal and societal impact of these disorders is enormous, and the number of novel therapies in the pipeline for these disorders has been contracting. Support for the development of neurotherapies must continue from the bench to their ultimate place at the bedside. Academic medicine must continue to play a critical role, in league with industry and government, in the development of novel neurotherapies desperately needed by an ever-expanding population. Critical steps include the identification and adoption of reliable, valid, and reproducible biomarkers to serve as primary endpoints in clinical trials of neurological disease.

To the Editor. —Plasmapheresis combined with immunosuppressive drug therapy is of proven benefit in both acute and chronic progressive multiple sclerosis.1,2We present our experience with plasmapheresis alone in a pregnant patient with multiple sclerosis with high-risk obstetric profile and severely progressive multiple sclerosis. Report of a Case. —A 28-year-old patient with a clinically definite diagnosis of multiple sclerosis had a 2-month history of progressive neurological deterioration. She was 9 weeks pregnant, confined to a wheel-chair, and unable to stand or transfer independently; unable to feed herself because of weakness; incontinent of bowel and bladder; and experienced diplopia when tired. The previous two pregnancies had resulted in stillbirths. Immunosuppressive drug therapy for her multiple sclerosis was considered to be a relative contraindication because of its adverse effect on the fetus and also given her high-risk obstetric history. Therefore, intensive plasmapheresis (five treatments in 10 days) was begun with significant