Neuropsychiatric complications of coronavirus disease 2019: Mount Sinai Health System cohort study.

OBJECTIVE: To describe the frequency of neuropsychiatric complications among hospitalized patients with coronavirus disease 2019 (COVID-19) and their association with pre-existing comorbidities and clinical outcomes. METHODS: We retrospectively identified all patients hospitalized with COVID-19 within a large multicenter New York City health system between March 15, 2020 and May 17, 2021 and randomly selected a representative cohort for detailed chart review. Clinical data, including the occurrence of neuropsychiatric complications (categorized as either altered mental status [AMS] or other neuropsychiatric complications) and in-hospital mortality, were extracted using an electronic medical record database and individual chart review. Associations between neuropsychiatric complications, comorbidities, laboratory findings, and in-hospital mortality were assessed using multivariate logistic regression. RESULTS: Our study cohort consisted of 974 patients, the majority were admitted during the first wave of the pandemic. Patients were treated with anticoagulation (88.4%), glucocorticoids (24.8%), and remdesivir (10.5%); 18.6% experienced severe COVID-19 pneumonia (evidenced by ventilator requirement). Neuropsychiatric complications occurred in 58.8% of patients; 39.8% experienced AMS; and 19.0% experienced at least one other complication (seizures in 1.4%, ischemic stroke in 1.6%, hemorrhagic stroke in 1.0%) or symptom (headache in 11.4%, anxiety in 6.8%, ataxia in 6.3%). Higher odds of mortality, which occurred in 22.0%, were associated with AMS, ventilator support, increasing age, and higher serum inflammatory marker levels. Anticoagulant therapy was associated with lower odds of mortality and AMS. CONCLUSION: Neuropsychiatric complications of COVID-19, especially AMS, were common, varied, and associated with in-hospital mortality in a diverse multicenter cohort at an epicenter of the COVID-19 pandemic.

Initiation of Antiseizure Medications by US Board-Certified Neurologists After a First Unprovoked Seizure Based on EEG Findings.

Background and Objectives: To investigate neurologists' practice variability in antiseizure medication (ASM) initiation after a first unprovoked seizure based on reported EEG interpretations. Methods: We developed a 15-question multiple-choice survey incorporating a standardized clinical case scenario of a patient with a first unprovoked seizure for whom different EEG reports were provided. The survey was distributed among board-certified neurologists practicing in the United States. Associations between categorical variables were evaluated using the Fisher Exact test. Multivariate analysis was performed using logistic regression. Results: A total of 106 neurologists responded to the survey. Most responders (75%-95%) would start ASM for definite epileptiform features on EEG, with similar rates between subgroups differing in years of practice, presence of subspecialty EEG training, and self-reported confidence in EEG interpretation. There was greater variability in practice for nonspecific EEG abnormalities, with sharply contoured activity, sharp transients, and focal delta slowing associated with the highest variability and uncertainty. Neurologists with >5 years of practice experience (21% vs 44%, OR 0.35 [95% CI 0.13-0.89], p = 0.021), subspecialty EEG training (15% vs 50%, OR = 0.17 [95% CI 0.06-0.48], p < 0.001), and greater confidence in EEG interpretation (21% vs 52%, OR 0.24 [95% CI 0.09-0.62], p = 0.001) were less likely to start ASM for ≥2 nonspecific EEG abnormalities and reported greater uncertainty. In multivariate analysis, seniority (p = 0.039) and subspecialty EEG training (p = 0.032) were associated with decreased ASM initiation for nonspecific EEG features. Discussion: There was substantial variability in ASM initiation practices between board-certified neurologists after a first unprovoked seizure with nonspecific EEG abnormalities. These findings clarify specific areas where EEG reporting may be optimized and reinforces the importance of implementing evidence-based practice guidelines.

Interictal epileptiform discharges in Alzheimer's disease: prevalence, relevance, and controversies.

Alzheimer's disease (AD) is the most common type of dementia and remains an incurable, progressive disease with limited disease-modifying interventions available. In patients with AD, interictal epileptiform discharges (IEDs) have been identified in up to 54% of combined cohorts of mild cognitive impairment (MCI) or mild dementia and are a marker of a more aggressive disease course. Studies assessing the role of IEDs in AD are limited by the lack of standardization in the definition of IEDs or the different neurophysiologic techniques used to capture them. IEDs are an appealing treatment target given the availability of EEG and anti-seizure medications. There remains uncertainty regarding when to treat IEDs, the optimal drug and dose for treatment, and the impact of treatment on disease course. This review covers the state of knowledge of the field of IEDs in AD, and the steps needed to move the field forward.

In-hospital outcomes in patients with and without epilepsy diagnosed with COVID-19-A cohort study.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is associated with mortality in persons with comorbidities. The aim of this study was to evaluate in-hospital outcomes in patients with COVID-19 with and without epilepsy. METHODS: We conducted a retrospective study of patients with COVID-19 admitted to a multicenter health system between March 15, 2020, and May 17, 2021. Patients with epilepsy were identified using a validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)/ICD-10-CM case definition. Logistic regression models and Kaplan-Meier analyses were conducted for mortality and non-routine discharges (i.e., not discharged home). An ordinary least-squares regression model was fitted for length of stay (LOS). RESULTS: We identified 9833 people with COVID-19 including 334 with epilepsy. On univariate analysis, people with epilepsy had significantly higher ventilator use (37.70% vs 14.30%, p < .001), intensive care unit (ICU) admissions (39.20% vs 17.70%, p < .001) mortality rate (29.60% vs 19.90%, p < .001), and longer LOS (12 days vs 7 days, p < .001). and fewer were discharged home (29.64% vs 57.37%, p < .001). On multivariate analysis, only non-routine discharge (adjusted odds ratio [aOR] 2.70, 95% confidence interval [CI] 2.00-3.70; p < .001) and LOS (32.50% longer, 95% CI 22.20%-43.60%; p < .001) were significantly different. Factors associated with higher odds of mortality in epilepsy were older age (aOR 1.05, 95% CI 1.03-1.08; p < .001), ventilator support (aOR 7.18, 95% CI 3.12-16.48; p < .001), and higher Charlson comorbidity index (CCI) (aOR 1.18, 95% CI 1.04-1.34; p = .010). In epilepsy, admissions between August and December 2020 or January and May 2021 were associated with a lower odds of non-routine discharge and decreased LOS compared to admissions between March and July 2020, but this difference was not statistically significant. SIGNIFICANCE: People with COVID-19 who had epilepsy had a higher odds of non-routine discharge and longer LOS but not higher mortality. Older age (≥65), ventilator use, and higher CCI were associated with COVID-19 mortality in epilepsy. This suggests that older adults with epilepsy and multimorbidity are more vulnerable than those without and should be monitored closely in the setting of COVID-19.

Evaluation of epilepsy surgery scope and training in Latin America.

INTRODUCTION: To describe the variety of surgical epilepsy procedures offered in Latin America and characterize the training in surgical management for epilepsy and neurophysiology fellows. MATERIALS & METHODS: A 15-question survey was sent to Spanish-speaking epilepsy specialists in Latin America (members of the International Consortium in Epilepsy Surgery Education) to characterize their epilepsy surgery practices and formal training programs when present, including fellowship program characteristics, trainee involvement, and assessment of trainee performance. Epilepsy surgery procedures included resective/ablative interventions and neuromodulation therapies approved for drug-resistant epilepsy. Associations between categorical variables were evaluated using the Fisher Exact test. RESULTS: There were 42 responses from a total of 57 survey recipients (73% response rate). Most surgical programs performed either 1 to 10 procedures (36%) or 11 to 30 procedures (31%) per year. Most centers (88%) performed resective procedures, while none of the surveyed institutions performed laser ablations. Most of the centers performing intracranial EEG (88%) and advanced neuromodulation (93%) were in South America. Centers with formal fellowship training programs were more likely to perform intracranial EEG procedures compared to centers without fellows (92% vs 48%, respectively, OR = 12.2 [95% CI 1.45-583], p = 0.007). DISCUSSION: There is significant variability in surgical procedures performed across epilepsy centers in a Latin American educational consortium. Advanced surgical diagnostic procedures and interventions are performed in a fair number of surveyed institutions. Strategies to enhance access to epilepsy surgery procedures and facilitate formal training in surgical management are necessary.

Epilepsy care in nursing facilities: Knowledge gaps and opportunities.

Epilepsy in the elderly is a complex disease, often underdiagnosed, and inadequately treated. It requires a multi-disciplinary approach and care coordination especially if the patient resides in a nursing facility. Episodes of loss of consciousness falls, or amnestic events in those living in a nursing facility require a detailed description and an urgent assessment to rule out an epileptic seizure. Prompt recognition of seizures and the implementation of treatment protocols in those with recurrent seizures are needed to prevent unnecessary emergency visits. Although there is a myriad of antiseizure medications (ASM) to treat seizures, clinicians should be aware of common interactions, side effects, and changes in pharmacodynamics with age. There is a limited number of ASMs that have been properly studied in clinical trials to assess tolerability and efficacy in the elderly, and an over-reliance on enzyme-inducing ASMs. Strategies to improve the knowledge of health care providers include electronic resources, treatment protocols, and improving awareness of the efficacy, drug-drug interaction, and short-term and long-term monitoring of ASM side effects.

Analysis of Electrocorticography in Epileptic Patients With Responsive Neurostimulation Undergoing Scalp Electroencephalography Monitoring.

PURPOSE: To describe the relationship of electrocorticography events detected by a brain-responsive neurostimulation system (RNS) and their association with ictal and interictal activity detected on simultaneous scalp EEG. METHODS: We retrospectively identified patients with drug-resistant epilepsy implanted with RNS who subsequently underwent long-term scalp EEG monitoring. RNS detections were correlated to simultaneous activity recorded on scalp EEG to determine the characteristics of electrocorticography-stored long episodes associated with seizures or other findings on scalp EEG. RESULTS: Eleven patients were included with an average of 3.6 days of monitoring. Most RNS detections were of very brief duration (<10 seconds, 92.9%) and received one stimulation therapy (80.8%). A high proportion of long episodes (67.1%) were not identified as electrographic seizures on scalp EEG. Of those ictal-appearing (71.2%) long episodes, 68.2% had seizure correlates. Long episodes associated with seizures on scalp EEG had a longer median duration compared with those without (39.7 vs. 16.8 seconds, P < 0.002) and had broader spread pattern and were of higher amplitude on electrocorticography. Brief potentially ictal rhythmic discharges were the most common EEG findings associated with long episodes that did not have scalp EEG seizure correlates (100% for ictal- and 50% for non-ictal-appearing long episodes). CONCLUSIONS: Longer, broader spread and higher amplitude intracranial RNS detections are more likely to manifest as electrographic seizures on scalp EEG. Brief potentially ictal rhythmic discharges may serve as a scalp EEG biomarker of ictal intracranial episodes that are detected as long episodes by the RNS but not identified as electrographic seizures on scalp EEG.

Refractory Seizures Secondary to Vitamin B6 Deficiency in Parkinson Disease: The Role of Carbidopa-Levodopa.

Carbidopa-levodopa has been used for more than 50 years in the treatment of Parkinson disease (PD) and other movement disorders. Pyridoxal 5'-phosphate (PLP), an active form of vitamin B6 (pyridoxine), is involved in the decarboxylation of levodopa to dopamine; carbidopa, which is combined with levodopa to reduce peripheral levodopa conversion and minimize peripheral dopamine side effects, binds irreversibly with PLP. As a result, carbidopa-levodopa may cause vitamin B6 deficiency and associated sequelae, including seizures, especially in high doses. A 78-year-old gentleman with a 6-year history of PD on carbidopa-levodopa therapy and recent weight loss presented with new-onset myoclonus and focal to bilateral tonic-clonic seizures. Workup for vascular, infectious, malignant, metabolic, and autoimmune causes of seizure was unrevealing. The folate level was critically low at <2.20 ng/dL. Video EEG studies showed moderate cerebral dysfunction and seizures with diffuse onsets. Several anti-seizure medications (ASMs) were unsuccessfully tried, so empiric treatment with high-dose steroids was initiated eventually alongside intravenous vitamin B6 therapy. Following introduction of these interventions, the patient had no further epileptic events. The vitamin B6 level came back as undetectable at <1 µg/dL. The patient was discharged to a rehabilitation center for improved strength and function. At the time of writing, he remained on two ASMs as well as IV B6 supplementation. Vitamin B6 is a required cofactor in the decarboxylation of levodopa to dopamine, and high levodopa dosages may cause B6 deficiency; in addition, carbidopa binds B6 irreversibly. We recommend screening of vitamin B6 levels in PD patients, especially those requiring high or increasing doses of carbidopa-levodopa and those with poor nutrition.

Acute Cerebellitis and Myeloradiculitis Associated With SARS-CoV-2 Infection in Common Variable Immunodeficiency-A Case Report.

The role of the adaptive immune system in mediating COVID-19 is largely unknown. Therefore, it is difficult to predict the clinical course in patients with common variable immunodeficiency (CVID), a disease characterized by dysfunctional lymphocytes and impaired antibody production. We report a case of SARS-CoV-2 infection presenting as isolated neurological symptoms in a patient with CVID. The patient subsequently improved following steroids, intravenous immunoglobulin, and convalescent plasma (CP). The latter has been shown to be safe and efficacious in treating COVID-19 in patients with primary immunodeficiency. Recent data suggest that the mechanism of CNS injury in COVID-19 may be due to immunological dysregulation rather than direct viral-mediated injury. This case exemplifies the complex interaction between the brain, the immune system, and the SARS-CoV-2 virus.

Ictal head roll: a seizure semiology from the anterior prefrontal lobe.

Longstanding epilepsy can lead to modulation of cortical networks over time and unexpected seizure onset zones. Frontal lobe seizures, in particular, can have diverse semiologies and evolution patterns. We present a male patient with drug-resistant epilepsy secondary to severe traumatic brain injury who underwent bilateral stereo electroencephalography (SEEG) for surgical planning. SEEG localized an ictal circular head roll to the right anterior prefrontal region. This was followed by spread to the left orbitofrontal region and later the left amygdala and hippocampus, at which point a different semiology with behavioral arrest, lip smacking and oral automatisms began. This case, in which an ictal circular head roll was localized to the anterior prefrontal region, demonstrates the complexity of broad seizure networks that develop over time, leading to remote seizure spread.

Readmission for cardiac and non-cardiac causes among adults with epilepsy or multiple sclerosis - A nationwide analysis.

PURPOSE: The aim of this study was to determine proportions of 30-day cardiac readmissions in adults with epilepsy compared to multiple sclerosis (MS) or those with neither condition. Predictors and causes of readmissions were also examined. METHODS: We used the 2014 Nationwide Readmissions Database and ICD-9-CM codes to identify people with epilepsy, MS, and without epilepsy or MS. Multinomial logistic regressions were fitted to: (1) examine association between 30-day readmissions and epilepsy, MS or neither, and (2) to describe causes and predictors of 30-day readmission for cardiac readmissions in epilepsy. RESULTS: Out of 6,870,508 adults admitted in 2014, 202,938 (2.98%) had epilepsy and 29,556 (0.45%) had MS. The proportion of 30-day readmission for epilepsy and MS were, respectively: (1) due to cardiac causes (0.17% vs. 0.13%); (2) due to other causes (13.89% vs. 10.61%). The odds of 30-day cardiac readmission in those with epilepsy and MS were lower compared to those without either condition (OR = 0.64, 95% CI 0.57-0.73, p < 0.0001; OR = 0.60, 95% CI 0.43-0.84, p = 0.003). Among those with epilepsy, increasing age (OR = 1.03, 95% CI 1.02-1.04, p < 0.0001) and a Charlson comorbidity index ≥1 (OR = 1.79, 95% CI 1.24-2.60, p = 0.002) were associated with higher odds of 30-day cardiac readmission. A higher proportion of those with epilepsy readmitted within 30-days due to cardiac causes died in hospital (10.09%) compared to those with MS (not reportable due to cell frequency <10) or without epilepsy or MS (5.61%). CONCLUSION: Those admitted to a hospital and living with epilepsy had a higher proportion of cardiac readmissions and death in hospital when compared to those living with MS, and the determinants are likely multifactorial. These findings are important and need to be further explored to identify strategies to prevent readmissions due to any cause and treatments that could reduce mortality.

Psychiatric comorbidities, sexual health and neurodevelopmental outcomes of offspring in men with epilepsy.

BACKGROUND: There is a paucity of data in the literature specific to men with epilepsy on anti-seizure medication (ASM). The current study investigated the time to conception as well as the gestational and the neurodevelopmental outcomes of offspring of men with epilepsy on ASM compared to controls. Additionally, the prevalence of psychiatric comorbidities, and measures of sexual performance in males with and without epilepsy were analyzed. METHODS: A total of 450 male patients with and without epilepsy at one hospital were provided questionnaires to determine demographic characteristics, epilepsy history, type of ASM at the time of conception, comorbidities and sexual health. Time to conception, fertility methods and offspring birth and developmental history born to males with and without epilepsy was recorded. Survey data was evaluated using Student's t-test for continuous variables and Fisher's exact test for categorical variables. Odds ratio (OR) were calculated to determine associations between the measured data. RESULTS: After matching for age, we analyzed a total of 110 males with epilepsy and 110 without epilepsy. In the epilepsy group there was a higher rate of psychiatric comorbidities such as major depressive disorder, general anxiety disorder, bipolar disorder, and suicidal ideation when compared to the control group (N = 110; OR 3.39; 95% IC: 1.87-6.13, p < 0.001). Males with epilepsy also had a higher frequency of low erection scores when compared to males without epilepsy (N = 70 with epilepsy, N = 76 without epilepsy; OR 3.67; 95% IC: 1.44-9.39, p = 0.005). Of the 110 men with a diagnosis of epilepsy, 17 conceived children while using ASMs (38 total children). A total of 18.42% of children born to fathers on ASMs experienced developmental delays compared to 2.63% of controls, however this result was not statistically significant (p = 0.056). In addition, we did not find that offspring had significantly different birth weights or gestational ages in men on ASM compared to controls (p > 0.05). CONCLUSIONS: The present study suggests that men with epilepsy have an increased incidence of psychiatric comorbidities, and altered sexual performance, specifically erectile dysfunction, when compared with men without epilepsy. There was no statistically significant difference in the rates of developmental disorders and birth characteristics among those men with epilepsy on ASM at the time of conception and controls.

Fructosuria and recurrent hypoglycemia in a patient with a novel c.1693T>A variant in the 3' untranslated region of the aldolase B gene.

Hereditary fructose intolerance, caused by mutations in the ALDOB gene, is an unusual cause of hypoglycemia. ALDOB encodes the enzyme aldolase B, responsible for the hydrolysis of fructose 1-phosphate in the liver. Here, we report the case of a 33-year-old female patient who consulted due to repetitive episodes of weakness, dizziness and headache after food ingestion. An ambulatory 72-h continuous glucose monitoring revealed multiple short hypoglycemic episodes over the day. After biochemical exclusion of other endocrine causes of hypoglycemia, hereditary fructose intolerance seemed a plausible diagnosis. Repeated measurements of urinary fructose revealed pathologic fructosuria, but genetic testing for the three most common mutations in ALDOB resulted negative. We decided to perform complete Sanger sequencing of the ALDOB gene and encountered a variant consisting of a T>A substitution in position 1963 of the ALDOB transcript (c.1693T>A). This position is located within the 3' untranslated region of exon 9, 515 nucleotides downstream the stop codon. After complete withdrawal of dietary fructose and sucrose, the patient presented no new hypoglycemic episodes.

An Assay that Predicts In Vivo Efficacy for DNA Aptamers that Stimulate Remyelination in a Mouse Model of Multiple Sclerosis.

Multiple sclerosis (MS) is a debilitating disease for which regenerative therapies are sought. We have previously described human antibodies and DNA aptamer-streptavidin conjugates that promote remyelination after systemic injection into mice infected by Theiler's murine encephalomyelitis virus. Here, we report an in vitro assay of myelin binding with results that correlate with remyelination outcome in vivo, as shown for data from a set of DNA aptamer complexes of different size and formulation. This in vitro assay will be valuable for future screening of MS regenerative therapies targeting remyelination.

Multiple Sclerosis: Mechanisms of Disease and Strategies for Myelin and Axonal Repair.

Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system with a variety of presentations and unclear pathogenesis. Multiple sclerosis has been associated with the term autoimmunity as a surrogate for pathogenesis. Multiple sclerosis is an organ-specific disease with immune-mediated myelin destruction. Understanding the complex etiology of multiple sclerosis and the importance of axon integrity is critical for clinicians who treat the disease. This review discusses the immune and autoimmune aspects of multiple sclerosis based on the current published data and novel evidence of strategies that promote remyelination and protect axons.

Treatment with a recombinant human IgM that recognizes PSA-NCAM preserves brain pathology in MOG-induced experimental autoimmune encephalomyelitis.

A single peripheral dose of CNS-binding IgMs promote remyelination and preserve axons in a number of animal models of neurologic disease. A myelin-binding recombinant human IgM (rHIgM22) is presently in a safety trial in MS patients following an acute MS exacerbation. rHIgM22 (directed against oligodendrocytes) or rHIgM12 (directed against neurons) were administered to mice with MOG-induced experimental autoimmune encephalomyelitis (EAE) with study endpoints: clinical deficits and brain and spinal cord pathology. IgMs were administered at a therapeutic dose of 100 µ g intra peritoneal at the time of immunization (day -1, 0, +$1), disease onset (15 days) or peak of the disease (28 days). Disease course was not worsened by either human IgM regardless of the time of treatment. Of note, the human IgM that recognizes a carbohydrate epitope on gangliosides and NCAM, rHIgM12, reduced brain pathology when given at time of immunization or at onset of disease, but did not reduce clinical deficits or spinal cord disease burden. Hence, treatment with rHIgM12 resulted in marked reduction in meningeal inflammation. Data consistent with the hypothesis that in the EAE model this molecule has an immune-modulatory effect. Treatment with an anti-CD4 blocking IgG prevented both clinical course and CNS pathology. This pre-clinical study further supports the safety of therapeutic CNS-binding human IgMs in the presence of autoimmunity and clearly differentiates them from IgGs directed against MOG or aquaporin-4 that worsen neurologic disease.

Gastric Antral Vascular Ectasia in Systemic Sclerosis: Current Concepts.

Introduction. Gastric antral vascular ectasia (GAVE) is a rare entity with unique endoscopic appearance described as "watermelon stomach." It has been associated with systemic sclerosis but the pathophysiological changes leading to GAVE have not been explained and still remain uncertain. Methods. Databases Medline, Scopus, Embase, PubMed, and Cochrane were searched for relevant papers. The main search words were "Gastric antral vascular ectasia," "Watermelon Stomach," "GAVE," "Scleroderma," and "Systemic Sclerosis." Fifty-four papers were considered for this review. Results. GAVE is a rare entity in the spectrum of manifestations of systemic sclerosis with unknown pathogenesis. Most patients with systemic sclerosis and GAVE present with asymptomatic anemia, iron deficiency anemia, or heavy acute gastrointestinal bleeding. Symptomatic therapy and endoscopic ablation are the first-line of treatment. Surgical approach may be recommended for patients who do not respond to medical or endoscopic therapies. Conclusion. GAVE can be properly diagnosed and treated. Early diagnosis is key in the management of GAVE because it makes symptomatic therapies and endoscopic approaches feasible. A high index of suspicion is critical. Future studies and a critical review of the current findings about GAVE are needed to understand the role of this condition in systemic sclerosis.