Ischemic Stroke Occurs Less Frequently in Patients With COVID-19: A Multicenter Cross-Sectional Study.

BACKGROUND AND PURPOSE: The impact of coronavirus disease 2019 (COVID-19) on the occurrence of ischemic stroke has been the subject of increased speculation but has not been confirmed in large observational studies. We investigated the association between COVID-19 and stroke. METHODS: We performed a cross-sectional study involving patients discharged from a healthcare system in New York State, from January to April 2020. A mixed-effects logistic regression analysis and a propensity score-weighted analysis were used to control for confounders and investigate the association of COVID-19 with ischemic stroke. Similar techniques were used to detect the impact of concurrent COVID-19 infection on unfavorable outcomes for patients with stroke. RESULTS: Among 24 808 discharges, 2513 (10.1%) were diagnosed with COVID-19, and 566 (0.2%) presented with acute ischemic stroke. Patients diagnosed with COVID-19 were at one-quarter the odds of stroke compared with other patients (odds ratio, 0.25 [95% CI, 0.16-0.40]). This association was consistent in all age groups. Our results were robust in sensitivity analyses, including propensity score-weighted regression models. In patients presenting with stroke, concurrent infection with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was associated with higher case-fatality (odds ratio, 10.50 [95% CI, 3.54-31.18]) and a trend towards increased occurrence of discharge to rehabilitation (odds ratio, 2.45 [95% CI, 0.81-1.25]). CONCLUSIONS: Using a comprehensive cross-section of patients from a large NY-based healthcare system, we did not identify a positive association between ischemic stroke and COVID-19. However, patients with stroke with COVID-19 had worse outcomes compared with those without, with over a 9-fold increase in mortality. Although no definitive conclusions can be reached from our observational study, our data do not support the concerns for an epidemic of stroke in young adults with COVID-19.

Neurologic manifestations in hospitalized patients with COVID-19: The ALBACOVID registry.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) has spread worldwide since December 2019. Neurologic symptoms have been reported as part of the clinical spectrum of the disease. We aimed to determine whether neurologic manifestations are common in hospitalized patients with COVID-19 and to describe their main characteristics. METHODS: We systematically reviewed all patients diagnosed with COVID-19 admitted to the hospital in a Spanish population during March 2020. Demographic characteristics, systemic and neurologic clinical manifestations, and complementary tests were analyzed. RESULTS: Of 841 patients hospitalized with COVID-19 (mean age 66.4 years, 56.2% men), 57.4% developed some form of neurologic symptom. Nonspecific symptoms such as myalgias (17.2%), headache (14.1%), and dizziness (6.1%) were present mostly in the early stages of infection. Anosmia (4.9%) and dysgeusia (6.2%) tended to occur early (60% as the first clinical manifestation) and were more frequent in less severe cases. Disorders of consciousness occurred commonly (19.6%), mostly in older patients and in severe and advanced COVID-19 stages. Myopathy (3.1%), dysautonomia (2.5%), cerebrovascular diseases (1.7%), seizures (0.7%), movement disorders (0.7%), encephalitis (n = 1), Guillain-Barré syndrome (n = 1), and optic neuritis (n = 1) were also reported, but less frequent. Neurologic complications were the main cause of death in 4.1% of all deceased study participants. CONCLUSIONS: Neurologic manifestations are common in hospitalized patients with COVID-19. In our series, more than half of patients presented some form of neurologic symptom. Clinicians need to maintain close neurologic surveillance for prompt recognition of these complications. The mechanisms and consequences of severe acute respiratory syndrome coronavirus type 2 neurologic involvement require further studies.

The EMCOOLs surface cooling system for fever control in neurocritical care patients: A pilot study.

OBJECTIVES: Fever occurs in up to 50% of critically-ill patients with acute neurological injury. Small temperature elevations have been correlated with increased morbidity and mortality in this patient population. We sought to evaluate a novel single-use surface cooling system for the treatment of fever in patients with acute brain injury. PATIENTS AND METHODS: We conducted a retrospective analysis of a prospective product evaluation using the EMCOOLS Flex.Pad™ system for acute fever (≥38.3 °C) in our 16-bed neuro-ICU. Four refrigerated pads (-18 °C) were applied to the chest, back, and anterior thighs. Core temperature (bladder) was continuously recorded over 4 h, and the highest Bedside Shivering Assessment Scale (BSAS) score was recorded hourly. RESULTS: Twelve subjects were included in the analysis. Mean age was 55 ±â€¯9 years, 9 patients were men, and mean weight was 85 ±â€¯12 kg. The most common primary diagnoses were subarachnoid (N = 5) and intracerebral (N = 4) hemorrhage. Application of the EMCOOLS system resulted in a linear 1.3 ±â€¯0.6 °C drop (T0avg = 38.9 °C, T90avg = 37.6 °C, P = 0.0032) in mean temperature over 90 min, followed by a plateau with only one subject rebounding to >38 °C within 4 h. Normothermia (<38.0 °C) was achieved in all but one patient (92%) in an average of 65 min. Comatose patients displayed a non-significantly higher degree of cooling at 90 min than did awake subjects (ΔTcoma = 1.74 °C vs ΔTawake = 0.74 °C hr-1, P = 0.067). There was no observed skin irritation upon removal of the device for any patients. CONCLUSION: The EMCOOLs system is a well-tolerated, safe and effective short-term intervention for control of fever in neurological patients. Future studies are needed to compare efficacy of the EMCOOLs to other devices and interventions.

Anti-n-Methyl-d-Aspartate-Receptor (NMDAR) Encephalitis in Association with Ovarian Teratoma.

Anti-N-methyl-D-aspartate-Receptor (NMDAR) encephalitis is an autoimmune disorder with a multifaceted presentation that involves memory deficits, psychiatric symptoms, and autonomic instability. This case report describes the classic presentation of Anti-NMDAR encephalitis and highlights its association with ovarian teratomas. We present a 26 -year-old female who came in with new onset seizures and altered mentation who subsequently developed automatism. Electroencephalograms (EEG) showed left frontal spikes and right temporal delta activity. Magnetic resonance imaging (MRI) revealed right temporal hyper-intensity. The diagnosis was established with positive anti-NMDAR antibodies in the cerebrospinal fluid (CSF). The patient was initially treated with steroids and valproic acid, however, her condition progressively worsened. A five-day course of intravenous immunoglobulins (IVIG) was started followed by rituximab. The clinical course was complicated with the patient developing neutropenic fever and cerebrospinal fluid cultures (CSF) growing methicillin-sensitive Staphylococcus aureus (MSSA). She underwent pelvic imaging which showed a right ovarian teratoma. Evidence suggests that removal of ovarian tumor leads to better clinical and mortality outcomes in patients with Anti-NMDAR encephalitis. It is important for the internist to consider paraneoplastic syndromes in patients with Anti-NMDAR encephalitis.

Systematic Review and Pooled Analyses of Recent Neurointerventional Randomized Controlled Trials: Setting a New Standard of Care for Acute Ischemic Stroke Treatment after 20 Years.

BACKGROUND: Recent advances in the treatment of ischemic stroke have focused on revascularization and led to better clinical and functional outcomes. A systematic review and pooled analyses of 6 recent multicentered prospective randomized controlled trials (MPRCT) were performed to compare intravenous tissue plasminogen activator (IV tPA) and endovascular therapy (intervention) with IV tPA alone (control) for anterior circulation ischemic stroke (AIS) secondary to large vessel occlusion (LVO). OBJECTIVES: Six MPRCTs (MR CLEAN, ESCAPE, EXTEND IA, SWIFT PRIME, REVASCAT and THERAPY) incorporating image-based LVO AIS were selected for assessing the following: (1) prespecified primary clinical outcomes of AIS patients in intervention and control arms: good outcomes were defined by a modified Rankin Scale score of 0-2 at 90 days; (2) secondary clinical outcomes were: (a) revascularization rates [favorable outcomes defined as modified Thrombolysis in Cerebral Infarction scale (mTICI) score of 2b/3]; (b) symptomatic intracranial hemorrhage (sICH) rates and mortality; (c) derivation of number needed to harm (NNH), number needed to treat (NNT), and relative percent difference (RPD) between intervention and control groups, and (d) random effects model to determine overall significance (forest and funnel plots). RESULTS: A total of 1,386 patients were included. Good outcomes at 90 days were seen in 46% of patients in the intervention (p < 0.00001) and in 27% of patients in the control groups (p < 0.00002). An mTICI score of 2b/3 was achieved in 70.2% of patients in the intervention arm. The sICH and mortality in the intervention arm compared with the control arm were 4.7 and 14.3% versus 7.9 and 17.8%, respectively. The NNT and NNH in the intervention and control groups were 5.3 and 9.1, respectively. Patients in the intervention arm had a 50.1% (RPD) better chance of achieving a good 90-day outcome as compared to controls. CONCLUSIONS: Endovascular therapy combined with IV tPA (in appropriately selected patients) for LVO-related AIS is superior to IV tPA alone. These results support establishing an endovascular therapy in addition to IV tPA as the standard of care for AIS secondary to LVO.

Prediction of repeat-dose occupancy from single-dose data: characterisation of the relationship between plasma pharmacokinetics and brain target occupancy.

Positron emission tomography (PET) is used in drug development to assist dose selection and to establish the relationship between blood and tissue pharmacokinetics (PKs). We present a new biomathematical approach that allows prediction of repeat-dose (RD) brain target occupancy (TO) using occupancy data obtained after administration of a single dose (SD). A PET study incorporating a sequential adaptive design was conducted in 10 healthy male adults who underwent 4 PET scans with [(11)C]DASB ([(11)C]N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine): 1 at baseline, 2 after 20 mg SD of the 5-hydroxytryptamine transporter (5-HTT) inhibitor duloxetine, and 1 after 4 days daily administration of 20 mg duloxetine. An adaptive design was used to select optimal times after SD for measurement of occupancy. Both direct and indirect PK/TO models were fitted to the SD data to characterise the model parameters and then applied to a predicted RD duloxetine plasma time course to predict the 5-HTT occupancy after RD. Repeat-dose prediction from the indirect model (OC(50)=2.62±0.93 ng/mL) was significantly better (P<0.05) than that from the direct model (OC(50)=2.29±1.11 ng/mL). This approach increases the value of SD occupancy studies that are performed as part of first time in human drug development programmes by providing an estimate of the dose required to achieve the desired TO at RD.