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.

Elevated phase amplitude coupling as a depression biomarker in epilepsy.

Depression is prevalent in epilepsy patients and their intracranial brain activity recordings can be used to determine the types of brain activity that are associated with comorbid depression. We performed case-control comparison of spectral power and phase amplitude coupling (PAC) in 34 invasively monitored drug resistant epilepsy patients' brain recordings. The values of spectral power and PAC for one-minute segments out of every hour in a patient's study were correlated with pre-operative assessment of depressive symptoms by Beck Depression Inventory-II (BDI). We identified an elevated PAC signal (theta-alpha-beta phase (5-25 Hz)/gamma frequency (80-100 Hz) band) that is present in high BDI scores but not low BDI scores adult epilepsy patients in brain regions implicated in primary depression, including anterior cingulate cortex, amygdala and orbitofrontal cortex. Our results showed the application of PAC as a network-specific, electrophysiologic biomarker candidate for comorbid depression and its potential as treatment target for neuromodulation.

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.

A Case of Lance-Adams Syndrome with Mixed Cortical and Reticular Reflex Myoclonus.

Background: Lance Adams syndrome is a chronic post-hypoxic myoclonus. Phenomenology Shown: This video abstract illustrates Lance Adams Syndrome with mixed cortical and reticular reflex myoclonus in a 32-year-old woman following respiratory arrest in the setting of an asthma attack, as well as improvement in her exam following pharmacologic management. Educational Value: Lance Adams syndrome can include both cortical and reticular reflex myoclonus features while interdisciplinary intervention and pharmacological treatment can improve symptomatology.

Assessing functional connectivity across 3D tissue engineered axonal tracts using calcium fluorescence imaging.

OBJECTIVE: Micro-tissue engineered neural networks (micro-TENNs) are anatomically-inspired constructs designed to structurally and functionally emulate white matter pathways in the brain. These 3D neural networks feature long axonal tracts spanning discrete neuronal populations contained within a tubular hydrogel, and are being developed to reconstruct damaged axonal pathways in the brain as well as to serve as physiologically-relevant in vitro experimental platforms. The goal of the current study was to characterize the functional properties of these neuronal and axonal networks. APPROACH: Bidirectional micro-TENNs were transduced to express genetically-encoded calcium indicators, and spontaneous fluorescence activity was recorded using real-time microscopy at 20 Hz from specific regions-of-interest in the neuronal populations. Network activity patterns and functional connectivity across the axonal tracts were then assessed using various techniques from statistics and information theory including Pearson cross-correlation, phase synchronization matrices, power spectral analysis, directed transfer function, and transfer entropy. MAIN RESULTS: Pearson cross-correlation, phase synchronization matrices, and power spectral analysis revealed high values of correlation and synchronicity between the spatially segregated neuronal clusters connected by axonal tracts. Specifically, phase synchronization revealed high synchronicity of >0.8 between micro-TENN regions of interest. Normalized directed transfer function and transfer entropy matrices suggested robust information flow between the neuronal populations. Time varying power spectrum analysis revealed the strength of information propagation at various frequencies. Signal power strength was visible at elevated peak levels for dominant delta (1-4 Hz) and theta (4-8 Hz) frequency bands and progressively weakened at higher frequencies. These signal power strength results closely matched normalized directed transfer function analysis where near synchronous information flow was detected between frequencies of 2-5 Hz. SIGNIFICANCE: To our knowledge, this is the first report using directed transfer function and transfer entropy methods based on fluorescent calcium activity to estimate functional connectivity of distinct neuronal populations via long-projecting, 3D axonal tracts in vitro. These functional data will further improve the design and optimization of implantable neural networks that could ultimately be deployed to reconstruct the nervous system to treat neurological disease and injury.