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.

Background: Chorea as a symptom of late-onset post-infectious autoimmune encephalitis has been reported with HSV-1 but not HSV-2 encephalitis. Extrapyramidal symptoms are typically associated with the presence of anti-NMDA receptor antibodies but may also exist in antibody-negative individuals.Case: This case highlights a patient who presented with mental status changes and chorea as the initial manifestation of HSV-2 encephalitis. The choreiform movements failed to respond to antiviral medications but were rapidly responsive to plasmapheresis, which, together with abnormal intrathecal immunoglobulin synthesis, suggests a potential contribution of parainfectious immune-mediated process. The patient made a full recovery and a complete resolution of the chorea.Discussion: This is the first case associating HSV-2 encephalitis presentation with chorea. The neurological complications, including chorea, are largely related to active CNS HSV-2 infection, possibly together with triggered CNS autoimmunity despite undetectable CSF neuronal autoantibodies and normal neuroimaging. Early diagnosis and treatment with antiviral agent and immune therapies might be pivotal to optimize the clinical outcome.

BackgroundThe globus pallidus is a highly mitochondria-rich metabolic structure that is particularly sensitive to metabolic disturbances and hypoxia. Symmetric lesions of globus pallidus and delayed diffuse leukoencephalopathy were documented in toxic–metabolic disorders, hypoxia, a neurodegenerative disorder, and mitochondrial encephalopathies. Similar changes are also reported in individuals with active COVID-19 infections with associated hypoxia or critical illness.Case informationWe describe a patient with post–COVID-19 infection who presented with rapid cognitive and neurological decline associated with similar neuroimaging structural changes but without toxic–metabolic changes or hypoxia. Despite multiple non-inflammatory cerebrospinal fluid studies, mechanisms involving post–COVID-19 inflammation and immune dysregulation are suspected, given the unexplained continued decline in the neurological status, lack of concurrent hypoxia or antecedent respiratory difficulties, and after a reasonable exclusion of alternative etiologies. Hypermetabolism of both anteromedial temporal structures and diffuse hypometabolism predominantly in the frontal region on PET scan provided indirect support for possible inflammatory mechanisms after reasonable exclusion of alternative etiologies, such as direct CNS infection, among others. The patient's neurological impairment improved substantially after treatment with pulse steroids, plasmapheresis, and rituximab.ConclusionTo the best of our knowledge, this is the first report of post–COVID-19 with bilateral symmetric contrast-enhancing necrotic lesions of globus pallidus with delayed diffuse supratentorial leukoencephalopathy with microhemorrhages without concurrent hypoxia or reported preceding symptoms suggestive of hypoxia. We suspect that these inflammatory mechanisms might be triggered by prior COVID-19 exposure/infection. Furthermore, the role of the cross-talk between inflammation and clinically mild or silent hypoxia linked to prior COVID-19 infection cannot be excluded. Awareness of these post–COVID-19 neurological sequelae and their potential pathophysiology among those with no known antecedent significant hypoxia are important for early recognition and treatment.

Introduction Vagus nerve stimulation (VNS) treatment for patients with intractable epilepsy has been shown to effectively lower seizure frequency and improve quality of life. However, due to stimulation of the vagus nerve, alterations in both central regulation of breathing and laryngeal muscle stimulation can precipitate obstructive sleep apnea (OSA). While there have been case reports describing OSA following VNS implantation, there has yet to be a detailed evaluation of this complication in a large cohort of VNS patients. The objective of this meta-analysis was to determine OSA rates in patients following VNS implantation. Methods English full-text articles were searched for on Pubmed, Scopus, and Embase databases. Articles had to follow patients before and after VNS implantation; report apnea-hypopnea index (AHI), respiratory disturbance index (RDI), or OSA rates following VNS implantation; be from a clinical trial, cohort, or case-control study. Two reviewers reviewed articles and a third settled disagreements. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies were used. Following Freeman-Tukey transformation, the generic inverse variance method with random effects model was used for meta-analysis. Results Ten studies, seven retrospective and three prospective, representing a cohort of 306 patients were included in this study. Pooled OSA rates following VNS implantation were 27.3%, 95% CI: 15.1 - 41.5%. Subgroup analysis found no difference in rates between studies of pediatric populations (22.1%, 95% CI: 8.2 - 40.5%) and adult populations (31.9%, 95% CI: 18.9 - 47.5%) following VNS implantation (P = 0.39). There was significant heterogeneity in pooled analysis (P < 0.00001, I2 = 100%), but no inter-subgroup heterogeneity (I2 = 0%). Conclusion Obstructive sleep apnea is a common adverse effect following VNS treatment and patients should be monitored following implantation. There are no differences in OSA rates between pediatric and adult populations. Routine screening for OSA following VNS implantation may be a reasonable choice. Support (if any) No institutional or NIH funding was received for this project