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Seizures are an infrequent and serious neurological complication of SARS-CoV-2 infection, with limited data describing the etiology and the clinical context in which these occur or the associated electrographic and imaging findings. This series details four cases of seizures occurring in patients with COVID-19 with distinct time points, underlying pathology, and proposed physiological mechanisms. An enhanced understanding of seizure manifestations in COVID-19 and their clinical course may allow for earlier detection and improved patient management.

BackgroundSince 2020, over 250 million doses of mRNA-based SARS-CoV-2 vaccines have been administered in the United States and hundreds of millions worldwide between the Pfizer-BioNTech and Moderna SARS-CoV-2 vaccines. To date, there have been rare reports associating mRNA-based SARS-CoV-2 vaccines with episodes of inflammatory and autoimmune CNS disorders. We report a case series of five patients with new-onset neurological disorders of inflammatory or immunological origin temporally associated with these vaccines.MethodsA case-series of five patients within a single 23-hospital health system who developed new-onset CNS inflammatory disease within 2 weeks of receiving a dose of an mRNA-based SARS-CoV-2 vaccine.ResultsFive cases of post-vaccination CNS disorders of immune origin (fatal ADEM; n = 1, new-onset NMOSD; n = 2, new-clinical onset MS-like syndrome but with preexisting clinically silent mild demyelination; n = 1, meningoencephalitis; n = 1) observed within 2 weeks of inoculation with either the first or second dose of mRNA-based SARS-CoV-2 vaccines (Moderna = 3, Pfizer = 2).DiscussionTo our knowledge, these are among the emerging cases of CNS adverse events of immunological or inflammatory origin. These findings should be interpreted with great caution as they neither prove a mechanistic link nor imply a potential long-term increased risk in post-vaccination CNS autoimmunity. Larger prospective studies assessing the potential association between mRNA-based vaccination and the development of neurological adverse events of suspected immune origin, particularly among those with underlying CNS or systemic autoimmune disorders, are needed. The use of mRNA-based SARS-CoV-2 vaccines should continue to be strongly encouraged given their high efficacy in overcoming this pandemic.

Recurrent stroke risk secondary to intracranial atherosclerotic disease remains high despite aggressive medical treatment. This risk is further amplified in subgroups possessing biomarkers of hemodynamic insufficiency and potential for embolization, which have been shown to be independently and synergistically predictive of recurrent stroke. Luminal stenosis was predominantly used as entry criteria in major treatment trials, discounting the potential role of hemodynamics from primary analyses, limiting the strength of evidence and conclusions of these biomarkers to post-hoc analyses and other natural history studies. Future treatment trials should consider stratifying patients using a combination of these high-risk biomarkers. In the absence of trials, risk stratifying patients based on the presence of these markers may lend to more individualized clinical decisions. We aimed to summarize the studies that have investigated the relationship between biomarkers and their role in predicting recurrent stroke risk in intracranial atherosclerotic disease.