Neurological Complications of Cannabinoids.

Cannabinoid use, particularly for recreational purposes, is increasing exponentially across all age groups, especially in younger populations, due to its perceived low risk and legalization. While cannabinoids may be largely considered as safe, there is mounting evidence of increased risk of systemic and neurological complications through their interaction with the poorly understood endocannabinoid receptor network within the central nervous system and other organ systems. Acute cannabinoid exposure can cause neuropsychiatric symptoms in addition to altering cerebral blood flow, leading to cerebrovascular complications such as ischemic stroke, subarachnoid hemorrhage, and reversible cerebral vasoconstriction syndrome (RCVS). Chronic use, particularly among adolescents, may be associated with increased risk of long-term cognitive deficits, schizophrenia, and other neuropsychiatric effects. Synthetic cannabinoids have increased potency, with reports of causing profound neurological complications including coma, seizures, posterior reversible encephalopathy syndrome, and RCVS. Despite increasing evidence, the quality of literature describing neurologic complications with cannabinoids remains limited to case series and retrospective cohort studies, with significant confounding factors such as concomitant use of other illicit drugs, limiting interpretation. In this review, we summarize the effect of cannabinoids on the neurologic system and associated neurological complications.

Outcome Trajectories after Intracerebral Hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) is the most morbid of all stroke types with a high early mortality and significant early disability burden. Traditionally, outcome assessments after ICH have mirrored those of acute ischemic stroke, with 3 months post-ICH being considered a standard time point in most clinical trials, observational studies, and clinical practice. At this time point, the majority of ICH survivors remain with moderate to severe functional disability. However, emerging data suggest that recovery after ICH occurs over a more protracted course and requires longer periods of follow-up, with more than 40% of ICH survivors with initial severe disability improving to partial or complete functional independence over 1 year. Multiple other domains of recovery impact ICH survivors including cognition, mood, and health-related quality of life, all of which remain under studied in ICH. To further complicate the picture, the most important driver of mortality after ICH is early withdrawal of life-sustaining therapies, before initiation of treatment and evaluating effects of prolonged supportive care, influenced by early pessimistic prognostication based on baseline severity factors and prognostication biases. Thus, our understanding of the true natural history of ICH recovery remains limited. This review summarizes the existing literature on outcome trajectories in functional and nonfunctional domains, describes limitations in current prognostication practices, and highlights areas of uncertainty that warrant further research.

Continuous Monitoring of Cerebral Autoregulation in Adults Supported by Extracorporeal Membrane Oxygenation.

BACKGROUND: Impaired cerebral autoregulation (CA) is one of several proposed mechanisms of acute brain injury in patients supported by extracorporeal membrane oxygenation (ECMO). The primary aim of this study was to determine the feasibility of continuous CA monitoring in adult ECMO patients. Our secondary aims were to describe changes in cerebral oximetry index (COx) and other metrics of CA over time and in relation to functional neurologic outcomes. METHODS: This is a single-center prospective observational study. We measured COx, a surrogate measurement of cerebral blood flow measured by near-infrared spectroscopy, which is an index of CA derived from the moving correlation between mean arterial pressure (MAP) and slow waves of regional cerebral oxygen saturation. A COx value that approaches 1 indicates impaired CA. Using COx, we determined the optimal MAP (MAPOPT) and lower and upper limits of autoregulation for individual patients. These measurements were examined in relation to modified Rankin Scale (mRS) scores. RESULTS: Fifteen patients (median age 57 years [interquartile range 47-69]) with 150 autoregulation measurements were included for analysis. Eleven were on veno-arterial ECMO (VA-ECMO), and four were on veno-venous ECMO (VV-ECMO). Mean COx was higher on postcannulation day 1 than on day 2 (0.2 vs. 0.09, p < 0.01), indicating improved CA over time. COx was higher in VA-ECMO patients than in VV-ECMO patients (0.12 vs. 0.06, p = 0.04). Median MAPOPT for the entire cohort was highly variable, ranging from 55 to 110 mm Hg. Patients with mRS scores 0-3 (good outcome) at 3 and 6 months spent less time outside MAPOPT compared with patients with mRS scores 4-6 (poor outcome) (74% vs. 82%, p = 0.01). The percentage of time when observed MAP was outside the limits of autoregulation was higher on postcannulation day 1 than on day 2 (18.2% vs. 3.3%, p < 0.01). CONCLUSIONS: In ECMO patients, it is feasible to monitor CA continuously at the bedside. CA improved over time, most significantly between postcannulation days 1 and 2. CA was more impaired in VA-ECMO patients than in VV-ECMO patients. Spending less time outside MAPOPT may be associated with achieving a good neurologic outcome.

Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group on Biospecimens and Biomarkers.

BACKGROUND: In patients with disorders of consciousness (DoC), laboratory and molecular biomarkers may help define endotypes, identify therapeutic targets, prognosticate outcomes, and guide patient selection in clinical trials. We performed a systematic review to identify common data elements (CDEs) and key design elements (KDEs) for future coma and DoC research. METHODS: The Curing Coma Campaign Biospecimens and Biomarkers work group, composed of seven invited members, reviewed existing biomarker and biospecimens CDEs and conducted a systematic literature review for laboratory and molecular biomarkers using predetermined search words and standardized methodology. Identified CDEs and KDEs were adjudicated into core, basic, supplemental, or experimental CDEs per National Institutes of Health classification based on level of evidence, reproducibility, and generalizability across different diseases through a consensus process. RESULTS: Among existing National Institutes of Health CDEs, those developed for ischemic stroke, traumatic brain injury, and subarachnoid hemorrhage were most relevant to DoC and included. KDEs were common to all disease states and included biospecimen collection time points, baseline indicator, biological source, anatomical location of collection, collection method, and processing and storage methodology. Additionally, two disease core, nine basic, 24 supplemental, and 59 exploratory biomarker CDEs were identified. Results were summarized and generated into a Laboratory Data and Biospecimens Case Report Form (CRF) and underwent public review. A final CRF version 1.0 is reported here. CONCLUSIONS: Exponential growth in biomarkers development has generated a growing number of potential experimental biomarkers associated with DoC, but few meet the quality, reproducibility, and generalizability criteria to be classified as core and basic biomarker and biospecimen CDEs. Identification and adaptation of KDEs, however, contribute to standardizing methodology to promote harmonization of future biomarker and biospecimens studies in DoC. Development of this CRF serves as a basic building block for future DoC studies.

Continuous Monitoring of Cerebral Autoregulation in Adults Supported by Extracorporeal Membrane Oxygenation.

Background: Impaired cerebral autoregulation (CA) is one of several proposed mechanisms of acute brain injury in patients supported by extracorporeal membrane oxygenation (ECMO). The primary aim of this study was to determine the feasibility of continuous CA monitoring in adult ECMO patients. Our secondary aims were to describe changes in cerebral oximetry index (COx) and other metrics of CA over time and in relation to functional neurologic outcomes. Methods: This is a single-center prospective observational study. We measured Cox, a surrogate measurement of cerebral blood flow, measured by near-infrared spectroscopy, which is an index of CA derived from the moving correlation between mean arterial pressure and slow waves of regional cerebral oxygen saturation. A COx value that approaches 1 indicates impaired CA. Using COx, we determined the optimal MAP (MAPOPT), lower and upper limits of autoregulation for individual patients. These measurements were examined in relation to modified Rankin Scale (mRS) scores. Results: Fifteen patients (median age=57 years [IQR=47-69]) with 150 autoregulation measurements were included for analysis. Eleven were on veno-arterial ECMO and 4 on veno-venous. Mean COx was higher on post-cannulation day 1 than on day 2 (0.2 vs 0.09, p<0.01), indicating improved CA over time. COx was higher in VA-ECMO patients than in VV-ECMO (0.12 vs 0.06, p=0.04). Median MAPOPT for entire cohort was highly variable, ranging 55-110 mmHg. Patients with mRS 0-3 (good outcome) at 3 and 6 months spent less time outside of MAPOPT compared to patients with mRS 4-6 (poor outcome) (74% vs 82%, p=0.01). The percentage of time when observed MAP was outside the limits of autoregulation was higher on post-cannulation day 1 than on day 2 (18.2% vs 3.3%, p<0.01). Conclusions: In ECMO patients, it is feasible to monitor CA continuously at the bedside. CA improved over time, most significantly between post-cannulation days 1 and 2. CA was more impaired in VA-ECMO than VV-ECMO. Spending less time outside of MAPOPT may be associated with achieving a good neurologic outcome.

Therapies for Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) is one of the most important complications of subarachnoid hemorrhage. Despite lack of prospective evidence, medical rescue interventions for DCI include hemodynamic augmentation using vasopressors or inotropes, with limited guidance on specific blood pressure and hemodynamic parameters. For DCI refractory to medical interventions, endovascular rescue therapies (ERTs), including intraarterial (IA) vasodilators and percutaneous transluminal balloon angioplasty, are the cornerstone of management. Although there are no randomized controlled trials assessing the efficacy of ERTs for DCI and their impact on subarachnoid hemorrhage outcomes, survey studies suggest that they are widely used in clinical practice with significant variability worldwide. IA vasodilators are first line ERTs, with better safety profiles and access to distal vasculature. The most commonly used IA vasodilators include calcium channel blockers, with milrinone gaining popularity in more recent publications. Balloon angioplasty achieves better vasodilation compared with IA vasodilators but is associated with higher risk of life-threatening vascular complications and is reserved for proximal severe refractory vasospasm. The existing literature on DCI rescue therapies is limited by small sample sizes, significant variability in patient populations, lack of standardized methodology, variable definitions of DCI, poorly reported outcomes, lack of long-term functional, cognitive, and patient-centered outcomes, and lack of control groups. Therefore, our current ability to interpret clinical results and make reliable recommendations regarding the use of rescue therapies is limited. This review summarizes existing literature on rescue therapies for DCI, provides practical guidance, and identifies future research needs.

Cerebellar restricted diffusion in Wernicke's encephalopathy.

A 50-year-old woman presented to an outside hospital for acute onset bilateral lower limb pain. She was diagnosed with aortoiliac stenosis and underwent stent placement. Post-procedure, she was noted to have altered mental status, truncal ataxia, neck titubation, and incomplete external ophthalmoplegia. She rapidly declined to a stuporous state. She had a history of uterine cancer treated with chemoradiation which was complicated by chronic radiation enteritis. She was also reported to have poor oral intake, recurrent emesis, and weight loss for a month before her presentation. After an extensive work up, she arrived at our facility where an MRI of the brain showed restricted diffusion and T2-FLAIR sequence showed hyperintensities of bilateral cerebellum. T2-FLAIR hyperintensities of bilateral dorsomedial thalami, fornix, and post-contrast-enhancement of mammillary bodies were also noted. The clinical picture with imaging findings was concerning for possible thiamine deficiency. In Wernicke's encephalopathy, restricted diffusion, T2-FLAIR hyperintensities, and contrast enhancement may be seen in mammillary bodies, dorsomedial thalami, tectal plate, periaqueductal grey matter, and rarely in the cerebellum as well. Her thiamine level was 70 nmol/l (reference range: 70-180 nmol/l). Thiamine levels can be falsely elevated in patients who are on enteral feeds, which was the case in our patient. She was started on high dose thiamine replacement. At time of discharge, repeat MRI brain revealed resolution of cerebellar changes with mild atrophy and patient had subtle neurological improvement including consistent eye opening, tracking, and attending to examiner, as well as mumbling words.

Mechanical ventilation in acute brain injury patients with acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is commonly seen in patients with acute brain injury (ABI), with prevalence being as high as 35%. These patients often have additional risk factors for ARDS compared to general critical care patients. Lung injury in ABI occurs secondary to catecholamine surge and neuro-inflammatory processes. ARDS patients benefit from lung protective ventilation using low tidal volumes, permissive hypercapnia, high PEEP, and lower PO2 goals. These strategies can often be detrimental in ABI given the risk of brain hypoxia and elevation of intracranial pressure (ICP). While lung protective ventilation is not contraindicated in ABI, special consideration is warranted to make sure it does not interfere with neurological recovery. Permissive hypercapnia with low lung volumes can be utilized in patients without any ICP issues but those with ICP elevations can benefit from continuous ICP monitoring to personalize PCO2 goals. Hypoxia leads to poor outcomes in ABI, hence the ARDSnet protocol of lower PO2 target (55-80 mmHg) might not be the best practice in patients with concomitant ARDS and ABI. High-normal PO2 levels are reasonable in target in severe ABI with ARDS. Studies have shown that PEEP up to 12 mmHg does not cause significant elevations in ICP and is safe to use in ABI though mean arterial pressure, respiratory system compliance, and cerebral perfusion pressure should be closely monitored. Given most trials investigating therapeutics in ARDS have excluded ABI patients, focused research is needed in the field to advance the care of these patients using evidence-based medicine.

One-Year Outcome Trajectories and Factors Associated with Functional Recovery Among Survivors of Intracerebral and Intraventricular Hemorrhage With Initial Severe Disability.

Importance: Patients who survive severe intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) typically have poor functional outcome in the short term and understanding of future recovery is limited. Objective: To describe 1-year recovery trajectories among ICH and IVH survivors with initial severe disability and assess the association of hospital events with long-term recovery. Design, Setting, and Participants: This post hoc analysis pooled all individual patient data from the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage phase 3 trial (CLEAR-III) and the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation (MISTIE-III) phase 3 trial in multiple centers across the US, Canada, Europe, and Asia. Patients were enrolled from August 1, 2010, to September 30, 2018, with a follow-up duration of 1 year. Of 999 enrolled patients, 724 survived with a day 30 modified Rankin Scale score (mRS) of 4 to 5 after excluding 13 participants with missing day 30 mRS. An additional 9 patients were excluded because of missing 1-year mRS. The final pooled cohort included 715 patients (71.6%) with day 30 mRS 4 to 5. Data were analyzed from July 2019 to January 2022. Exposures: CLEAR-III participants randomized to intraventricular alteplase vs placebo. MISTIE-III participants randomized to stereotactic thrombolysis of hematoma vs standard medical care. Main Outcomes and Measures: Primary outcome was 1-year mRS. Patients were dichotomized into good outcome at 1 year (mRS 0 to 3) vs poor outcome at 1 year (mRS 4 to 6). Multivariable logistic regression models assessed associations between prospectively adjudicated hospital events and 1-year good outcome after adjusting for demographic characteristics, ICH and IVH severity, and trial cohort. Results: Of 715 survivors, 417 (58%) were male, and the overall mean (SD) age was 60.3 (11.7) years. Overall, 174 participants (24.3%) were Black, 491 (68.6%) were White, and 49 (6.9%) were of other races (including Asian, Native American, and Pacific Islander, consolidated owing to small numbers); 98 (13.7%) were of Hispanic ethnicity. By 1 year, 129 participants (18%) had died and 308 (43%) had achieved mRS 0 to 3. In adjusted models for the combined cohort, diabetes (adjusted odds ratio [aOR], 0.50; 95% CI, 0.26-0.96), National Institutes of Health Stroke Scale (aOR, 0.93; 95% CI, 0.90-0.96), severe leukoaraiosis (aOR, 0.30; 95% CI, 0.16-0.54), pineal gland shift (aOR, 0.87; 95% CI, 0.76-0.99]), acute ischemic stroke (aOR, 0.44; 95% CI, 0.21-0.94), gastrostomy (aOR, 0.30; 95% CI, 0.17-0.50), and persistent hydrocephalus by day 30 (aOR, 0.37; 95% CI, 0.14-0.98) were associated with lack of recovery. Resolution of ICH (aOR, 1.82; 95% CI, 1.08-3.04) and IVH (aOR, 2.19; 95% CI, 1.02-4.68) by day 30 were associated with recovery to good outcome. In the CLEAR-III model, cerebral perfusion pressure less than 60 mm Hg (aOR, 0.30; 95% CI, 0.13-0.71), sepsis (aOR, 0.05; 95% CI, 0.00-0.80), and prolonged mechanical ventilation (aOR, 0.96; 95% CI, 0.92-1.00 per day), and in MISTIE-III, need for intracranial pressure monitoring (aOR, 0.35; 95% CI, 0.12-0.98), were additional factors associated with poor outcome. Thirty-day event-based models strongly predicted 1-year outcome (area under the receiver operating characteristic curve [AUC], 0.87; 95% CI, 0.83-0.90), with significantly improved discrimination over models using baseline severity factors alone (AUC, 0.76; 95% CI, 0.71-0.80; P < .001). Conclusions and Relevance: Among survivors of severe ICH and IVH with initial poor functional outcome, more than 40% recovered to good outcome by 1 year. Hospital events were strongly associated with long-term functional recovery and may be potential targets for intervention. Avoiding early pessimistic prognostication and delaying prognostication until after treatment may improve ability to predict future recovery.

Regional Variability in the Care and Outcomes of Subarachnoid Hemorrhage Patients in the United States.

Background and Objectives: Regional variability in subarachnoid hemorrhage (SAH) care is reported in physician surveys. We aimed to describe variability in SAH care using patient-level data and identify factors impacting hospital outcomes and regional variability in outcomes. Methods: A retrospective multi-center cross-sectional cohort study of consecutive non-traumatic SAH patients in the Vizient Clinical Data Base, between January 1st, 2009 and December 30th, 2018 was performed. Participating hospitals were divided into US regions: Northeast, Midwest, South, West. Regional demographics, co-morbidities, severity-of-illness, complications, interventions and discharge outcomes were compared. Multivariable logistic regression was performed to identify factors independently associated with primary outcomes: hospital mortality and poor discharge outcome. Poor discharge outcome was defined by the Nationwide Inpatient Sample-SAH Outcome Measure, an externally-validated outcome measure combining death, discharge disposition, tracheostomy and/or gastrostomy. Regional variability in the associations between care and outcomes were assessed by introducing an interaction term for US region into the models. Results: Of 109,034 patients included, 24.3% were from Northeast, 24.9% Midwest, 34.9% South, 15.9% West. Mean (SD) age was 58.6 (15.6) years and 64,245 (58.9%) were female. In-hospital mortality occurred in 21,991 (20.2%) and 44,159 (40.5%) had poor discharge outcome. There was significant variability in severity-of-illness, co-morbidities, complications and interventions across US regions. Notable findings were higher prevalence of surgical clipping (18.8 vs. 11.6%), delayed cerebral ischemia (4.3 vs. 3.1%), seizures (16.5 vs. 14.8%), infections (18 vs. 14.7%), length of stay (mean [SD] days; 15.7 [19.2] vs. 14.1 [16.7]) and health-care direct costs (mean [SD] USD; 80,379 [98,999]. vs. 58,264 [74,430]) in the West when compared to other regions (all p < 0.0001). Variability in care was also associated with modest variability in hospital mortality and discharge outcome. Aneurysm repair, nimodipine use, later admission-year, endovascular rescue therapies reduced the odds for poor outcome. Age, severity-of-illness, co-morbidities, hospital complications, and vasopressor use increased those odds (c-statistic; mortality: 0.77; discharge outcome: 0.81). Regional interaction effect was significant for admission severity-of-illness, aneurysm-repair and nimodipine-use. Discussion: Multiple hospital-care factors impact SAH outcomes and significant variability in hospital-care and modest variability in discharge-outcomes exists across the US. Variability in SAH-severity, nimodipine-use and aneurysm-repair may drive variability in outcomes.

Spectrum of Hemorrhagic Encephalitis in COVID-19 Patients: A Case Series and Review.

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is an ongoing pandemic that has affected over 400 million people worldwide and caused nearly 6 million deaths. Hemorrhagic encephalitis is an uncommon but serious complication of COVID-19. The etiology of this disease is multifactorial, including secondary to severe hypoxemia, systemic inflammation, direct viral invasion, hypercoagulability, etc. The clinical spectrum of COVID-19-related hemorrhagic encephalitis is also varied, ranging from leukoencephalopathy with microhemorrhage, acute necrotizing hemorrhagic encephalitis (ANHE) involving the cortex, basal ganglia, rarely brain stem and cervical spine, hemorrhagic posterior reversible encephalopathy syndrome (PRES) to superimposed co-infection with other organisms. We report a case series of three young patients with different presentations of hemorrhagic encephalitis after COVID-19 infection and a review of the literature. One patient had self-limiting ANHE in the setting of mild COVID-19 systemic illness. The second patient had self-limiting leukoencephalopathy with microhemorrhages in the setting of severe systemic diseases and ARDS, and clinically improved with the resolution of systemic illness. Both patients were healthy and did not have any premorbid conditions. The third patient with poorly controlled diabetes and hypertension had severe systemic illness with neurological involvement including multiple ischemic strokes, basal meningitis, hemorrhagic encephalitis with pathological evidence of cerebral mucormycosis, and Epstein-Barr virus coinfection, and improved after antifungal therapy.

Continued Underutilization of stroke care during the COVID-19 pandemic.

OBJECTIVE: This study aims to investigate the utilization of acute ischemic stroke (AIS) services during the Corona Virus Disease 2019 (COVID-19) pandemic. Based on early observations among healthcare utilization on stroke and other healthcare services, we hypothesized that there would be a persistent significant decline in AIS patients presenting to hospitals as the pandemic has progressed for over a year. METHOD: TriNetX, a large research network, is used to collect real-time electronic medical data. Data on utilization of acute ischemic stroke service was collected for the years 2018, 2019, and 2020 for variables including overall stroke volume and the number of patients that received intravenous tissue plasminogen activator (tPA) and mechanical thrombectomy (MT). RESULT: We found a 13.2-15.4% decrease in total number of AIS patients in 2020 (n 77231) compared with the years 2018 and 2019 (n 88948 and 91270 respectively, p â€‹< â€‹0.001). In the year 2020 Stroke volume was significantly lower in Q4 comparing to Q1 (Q1 vs Q4, p â€‹< â€‹0.01, while there were no significant differences in stroke volume between Quarters 2, 3, and 4 in 2020 (Q2 vs Q3, p â€‹= â€‹0.39, Q2 vs Q4, p â€‹= â€‹0.61, Q3 vs Q4, p â€‹= â€‹0.18). The Proportion of patients receiving tPA in 2020 was significantly lower compared to prior years (5.4% in 2020 vs 6.4% in 2018 and 6.0% in 2019, p â€‹< â€‹0.01), however, the proportion of patients receiving MT was significantly higher in 2020 than in 2018 (0.024 vs 0.022, p â€‹< â€‹0.01). CONCLUSION: Despite significant alteration in practices to optimize healthcare delivery and mitigate the collateral impact of the pandemic on care for other conditions, a persistent decline in AIS volumes remains. Delayed presentation, fear-of-contagion, reallocation, and poor availability of health care resources are potential contributors. Prospective evaluation and further investigation for these trends is needed.

Critically ill neurologic patients during the COVID-19 pandemic: A short communication.

PURPOSE: We aimed to evaluate utilization of inpatient hospital and critical care services among critically ill neurologic patients during the COVID-19 pandemic. We hypothesized, based on prior observations among ischemic stroke patients, that there would be significant decline in critically ill neurologic patients presenting to hospitals during the pandemic which may impact outcomes. METHODS: We used TriNetX, a large research network, collecting real-time electronic medical records data. We extracted data on utilization of critical care and hospital inpatient services among cohorts of patients with common neurocritical conditions between January-June 2020 and compared it to data from similar time-frames in previous years. We also compared clinical outcomes, comprising need for intubation and 30-day mortality, among these cohorts. RESULTS: We found a 28.1% reduction in intensive care unit (ICU) admissions with critical neurologic illnesses in 2020 when compared to 2019 (8568 vs. 11,917 patients, p â€‹< â€‹0.0001) and a 34.4% reduction compared to 2018 (8568 vs. 13,064 patients, p â€‹< â€‹0.0001). However, there was no statistically significant difference in mortality (2020: 12.2 vs. 2019: 12.4%; p â€‹= â€‹0.7; vs. 2018: 12.6%; p â€‹= â€‹0.62) or intubation rates across the years among patients using critical care services. There was 1% increase in mortality among non-ICU patients with similar diagnoses in 2020 compared to previous years (2020: 3.9% vs. 2019: 2.9% vs. 2018: 3.1%; p â€‹< â€‹0.0001, p â€‹= â€‹0.0001), but no difference in intubation rates. CONCLUSION: There was a significant reduction in hospital and ICU admissions among patients with acute neurologic emergencies in 2020, after onset of COVID-19 pandemic, compared to previous years. While we did not find a significant difference in mortality among patients admitted to the ICU, there was slightly higher mortality among non-ICU patients with same diagnoses in 2020 compared to previous years. Prospective evaluation and further investigation into the reasons for these trends is needed.

Acute encephalopathy is associated with worse outcomes in COVID-19 patients.

BACKGROUND: Acute encephalopathy with COVID-19 has been reported in several studies but its impact on outcomes remains unclear. We hypothesized that hospitalized COVID-19 patients with encephalopathy have worse COVID-19 related outcomes. METHODS: We used TriNetX, with a large COVID-19 database, collecting real-time electronic medical records data. We included hospitalized COVID-19 patients since January 20, 2020 who had encephalopathy based on ICD-10 coding. We examined clinical outcomes comprising need for critical care services, intubation and mortality among these patients and compared it with patients without encephalopathy before and after propensity-score matching. RESULTS: Of 12,601 hospitalized COVID-19 patients, 1092 (8.7%) developed acute encephalopathy. Patients in the acute encephalopathy group were older (67 vs. 61 years) and had higher prevalence of medical co-morbidities including obesity, hypertension, diabetes, heart disease, COPD, chronic kidney and liver disease among others. Before and after propensity score-matching for co-morbidities, patients with acute encephalopathy were more likely to need critical care services (35.6% vs. 16.9%, p â€‹< â€‹0.0001), intubation (19.5% vs. 6.0%, p â€‹< â€‹0.0001) and had higher 30-day mortality (24.3% vs. 17.9%, p 0.0002). CONCLUSION: Among hospitalized COVID-19 patients, acute encephalopathy is common and more likely to occur in patients with medical co-morbidities and are more likely to need critical care, intubation and have higher 30-day mortality even after adjusting for age and underlying medical co-morbidities.

When Telestroke Programs Work, Hospital Size Really Does Not Matter.

Background There are still marked disparities in stroke care between rural and urban communities including difference in stroke-related mortality. We analyzed the efficiency of tissue plasminogen activator (tPA) delivery in the spoke sites in our telestroke network to assess impact of telecare in bridging these disparities. Methods We analyzed critical time targets in our telestroke network. These included door-to-needle (DTN) time, door-to-CT (D2CT) time, door-to-call center, door-to-neurocall, and total consult time. We compared these time targets between the larger and smaller spoke hospitals. Results Across all the 52 spokes sites, a total of 825 stroke consults received intravenous tPA. When compared with larger hospitals (>200 beds), the smaller hospital groups with 0 to 25 and 51 to 100 beds had significantly lower D2CT time ( p -value 0.01 and 0.005, respectively) and the ones with 26 to 50 and 151 to 200 beds had significantly lower consult time ( p -value 0.009 and 0.001, respectively). There was no significant difference in the overall DTN time when all the smaller hospital groups were compared with larger hospitals. Conclusion In our telestroke network, DTN times were not significantly affected by the hospital bed size. This shows that a protocol-driven telestroke network with frequent mock codes can ensure timely administration of tPA even in rural communities regardless of the hospital size and availability of local neurologists.