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.

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.

Combined transarterial and percutaneous preoperative embolization of transosseous meningioma.

Meningiomas with transosseous extension provide opportunities for extensive preoperative embolization, through conventional trans-arterial approaches, and also through less commonly used percutaneous methods. This video demonstrates embolization of a 7.6 × 9.5 × 9.9 cm transosseous WHO grade II meningioma.1 Trans-arterial embolization was conducted via the left middle meningeal, occipital, and superficial temporal arteries. Only one superficial temporal artery was embolized to preserve vascular supply to the skin flap. To further devascularize the tumor, concomitant percutaneous embolization was performed. Transosseous extension of the tumor facilitated extensive percutaneous embolization of both the intracranial and extracranial components of the mass. Intraoperative bleeding from the scalp and extracranial component of the tumor was minimal. The intracranial tumor was soft and necrotic and was removed with suction and gentle dissection. Residual tumor was left behind within and adjacent to the superior sagittal sinus. The patient recovered without neurological deficit and was referred for radiation of the residual tumor.

NFIA is a gliogenic switch enabling rapid derivation of functional human astrocytes from pluripotent stem cells.

The mechanistic basis of gliogenesis, which occurs late in human development, is poorly understood. Here we identify nuclear factor IA (NFIA) as a molecular switch inducing human glial competency. Transient expression of NFIA is sufficient to trigger glial competency of human pluripotent stem cell-derived neural stem cells within 5 days and to convert these cells into astrocytes in the presence of glial-promoting factors, as compared to 3-6 months using current protocols. NFIA-induced astrocytes promote synaptogenesis, exhibit neuroprotective properties, display calcium transients in response to appropriate stimuli and engraft in the adult mouse brain. Differentiation involves rapid but reversible chromatin remodeling, glial fibrillary acidic protein (GFAP) promoter demethylation and a striking lengthening of the G1 cell cycle phase. Genetic or pharmacological manipulation of G1 length partially mimics NFIA function. We used the approach to generate astrocytes with region-specific or reactive features. Our study defines key mechanisms of the gliogenic switch and enables the rapid production of human astrocytes for disease modeling and regenerative medicine.

Intraoperative monitoring with visual evoked potentials for brain surgeries.

OBJECTIVE: The goal of this study was to determine the performance of intraoperative visual evoked potentials (VEPs) in detecting visual field changes. METHODS: Assessments of VEPs were performed with simultaneous retinal responses by using white light-emitting diodes protected from scialytic microscope lights. The alarm criterion was a reproducible decrease in amplitude of the VEP P100 wave of 20% or more. Visual fields were assessed preoperatively and 1 month postsurgery (Goldmann perimetry). RESULTS: The VEPs were analyzed for 29 patients undergoing resection of a brain lesion. In 89.7% of patients, steady VEP and retinal responses were obtained for monitoring. The absence of alarm was associated in 94.4% of cases with the absence of postoperative visual changes (specificity). The alarms correctly identified 66.7% of cases with any postoperative changes and 100% of cases with changes more severe than just a discrete quadrantanopia or deterioration of an existing quadrantanopia (sensitivity, new diffuse deterioration < 2 dB). In 11.5% of patients, a transitory VEP decrease with subsequent recovery was observed without postoperative defects. CONCLUSIONS: Intraoperative VEPs were performed with simultaneous recording of electroretinograms, with protection from lights of the operating room and with white light-emitting diodes. Intraoperative VEPs were shown to be reliable in predicting postoperative visual field changes. In this series of intraaxial brain procedures, reliable intraoperative VEP monitoring was achieved, allowing at minimum the detection of new quadrantanopia. The standardization of this technique appears to be a valuable effort in regard to the functional risks of homonymous hemianopia.

Decreased neural precursor cell pool in NADPH oxidase 2-deficiency: From mouse brain to neural differentiation of patient derived iPSC.

There is emerging evidence for the involvement of reactive oxygen species (ROS) in the regulation of stem cells and cellular differentiation. Absence of the ROS-generating NADPH oxidase NOX2 in chronic granulomatous disease (CGD) patients, predominantly manifests as immune deficiency, but has also been associated with decreased cognition. Here, we investigate the role of NOX enzymes in neuronal homeostasis in adult mouse brain and in neural cells derived from human induced pluripotent stem cells (iPSC). High levels of NOX2 were found in mouse adult neurogenic regions. In NOX2-deficient mice, neurogenic regions showed diminished redox modifications, as well as decrease in neuroprecursor numbers and in expression of genes involved in neural differentiation including NES, BDNF and OTX2. iPSC from healthy subjects and patients with CGD were used to study the role of NOX2 in human in vitro neuronal development. Expression of NOX2 was low in undifferentiated iPSC, upregulated upon neural induction, and disappeared during neuronal differentiation. In human neurospheres, NOX2 protein and ROS generation were polarized within the inner cell layer of rosette structures. NOX2 deficiency in CGD-iPSCs resulted in an abnormal neural induction in vitro, as revealed by a reduced expression of neuroprogenitor markers (NES, BDNF, OTX2, NRSF/REST), and a decreased generation of mature neurons. Vector-mediated NOX2 expression in NOX2-deficient iPSCs rescued neurogenesis. Taken together, our study provides novel evidence for a regulatory role of NOX2 during early stages of neurogenesis in mouse and human.

Elimination of proliferating cells from CNS grafts using a Ki67 promoter-driven thymidine kinase.

Pluripotent stem cell (PSC)-based cell therapy is an attractive concept for neurodegenerative diseases, but can lead to tumor formation. This is particularly relevant as proliferating neural precursors rather than postmitotic mature neurons need to be transplanted. Thus, safety mechanisms to eliminate proliferating cells are needed. Here, we propose a suicide gene approach, based on cell cycle-dependent promoter Ki67-driven expression of herpes simplex virus thymidine kinase (HSV-TK). We generated a PSC line expressing this construct and induced neural differentiation. In vitro, proliferating PSC and early neural precursor cells (NPC) were killed by exposure to ganciclovir. In vivo, transplantation of PSC led to tumor formation, which was prevented by early ganciclovir treatment. Transplanted NPC did not lead to tumor formation and their survival and neural maturation were not affected by ganciclovir. In conclusion, the cell cycle promoter-driven suicide gene approach described in this study allows killing of proliferating undifferentiated precursor cells without expression of the suicide gene in mature neurons. This approach could also be of use for other stem cell-based therapies where the final target consists of postmitotic cells.

Clinical outcome in acute small bowel obstruction after surgical or conservative management.

BACKGROUND: Small bowel obstruction (SBO) is characterized by a high rate of recurrence. In the present study, we aimed to compare the outcomes of patients managed either by conservative treatment or surgical operation for an episode of SBO. METHODS: The outcomes of all patients hospitalized at a single center for acute SBO between 2004 and 2007 were assessed. The occurrence of recurrent hospitalization, surgery, SBO symptoms at home, and mortality was determined. RESULTS: Among 221 patients admitted with SBO, 136 underwent a surgical procedure (surgical group) and 85 were managed conservatively (conservative group). Baseline characteristics were similar between treatment groups. The median follow-up time (interquartile range) was 4.7 (3.7-5.8) years. Nineteen patients (14.0 %) of the surgical group were hospitalized for recurrent SBO versus 25 (29.4 %) of the conservative group [hazard ratio (HR), 0.5; 95 % CI, 0.3-0.9]. The need for a surgical management of a new SBO episode was similar between the two groups, ten patients (7.4 %) in the surgical group and six patients (7.1 %) in the conservative group (HR, 1.1; 95 % CI, 0.4-3.1). Five-year mortality from the date of hospital discharge was not significantly different between the two groups (age- and sex-adjusted HR, 1.1; 95 % CI, 0.6-2.1). A follow-up evaluation was obtained for 130 patients. Among them, 24 patients (34.8 %) of the surgical group and 35 patients (57.4 %) of the conservative group had recurrent SBO symptoms (odds ratio, 0.4; 95 % CI, 0.2-0.8). CONCLUSIONS: The recurrence of SBO symptoms and new hospitalizations were significantly lower after surgical management of SBO compared with conservative treatment.