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Introduction and purposeBasilar artery occlusion (BAO) is still one of the most devastating neurological conditions associated with high morbidity and mortality. In the present study, we aimed to assess the role of posterior circulation collaterals as predictors of outcome in the BASICS trial and to compare two grading systems (BATMAN score and PC-CS) in terms of prognostic value.MethodsWe performed a sub-analysis of the BASICS trial. Baseline clinical and imaging variables were analyzed. For the imaging analysis, baseline CT and CTA were analyzed by a central core lab. Only those patients with good or moderate quality of baseline CTA and with confirmed BAO were included. Multivariable binary logistic regression analysis was used to test the independent association of clinical and imaging characteristics with a favorable outcome at 3 months (defined as a modified Rankin Score of ≤3). ROC curve analysis was used to assess and compare accuracy between the two collateral grading systems.ResultsThe mean age was 67.0 (±12.5) years, 196 (65.3%) patients were males and the median NIHSS was 21.5 (IQR 11–35). Median NCCT pc-ASPECTS was 10 (IQR10-10) and median collateral scores for BATMAN and PC-CS were 8 (IQR 7–9) and 7 (IQR 6–8) respectively. Collateral scores were associated with favorable outcome at 3 months for both BATMAN and PC-CS but only with a modest accuracy on ROC curve analysis (AUC 0.62, 95% CI [0.55–0.69] and 0.67, 95% CI [0.60–0.74] respectively). Age (OR 0.97, 95% CI [0.95–1.00]), NIHSS (OR 0.91, 95% CI [0.89–0.94]) and collateral score (PC-CS – OR 1.2495% CI [1.02–1.51]) were independently associated with clinical outcome.ConclusionThe two collateral grading systems presented modest prognostic accuracy. Only the PC-CS was independently associated with a favorable outcome at 3 months.

Background We studied the association of bridging intravenous thrombolysis (IVT) before thrombectomy for anterior circulation large‐vessel occlusion and functional outcome and scrutinized its dependence on grade of reperfusion and distal thrombus migration. Methods and Results We included consecutive patients with anterior circulation large‐vessel occlusion from our prospective registry of thrombectomy‐eligible patients treated from January 1, 2017 to January 1, 2023 at a tertiary stroke center in Germany in this retrospective cohort study. To evaluate the association of bridging IVT and functional outcome quantified via modified Rankin Scale score at 90 days we used multivariable logistic and lasso regression including interaction terms with grade of reperfusion quantified via modified Thrombolysis in Cerebral Infarction (mTICI) scale and distal thrombus migration adjusted for demographic and cardiovascular risk profiles, clinical and imaging stroke characteristics, onset‐to‐recanalization time and distal thrombus migration. We performed sensitivity analysis using propensity score matching. In our study population of 1000 thrombectomy‐eligible patients (513 women; median age, 77 years [interquartile range, 67–84]), IVT emerged as a predictor of favorable functional outcome (modified Rankin Scale score, 0–2) independent of modified mTICI score (adjusted odds ratio, 0.49 [95% CI, 0.32–0.75]; P=0.001). In those who underwent thrombectomy (n=812), the association of IVT and favorable functional outcome was reproduced (adjusted odds ratio, 0.49 [95% CI, 0.31–0.74]; P=0.001) and was further confirmed on propensity score analysis, where IVT led to a 0.35‐point decrease in 90‐day modified Rankin Scale score (ß=–0.35 [95 CI%, −0.68 to 0.01]; P=0.04). The additive benefit of IVT remained independent of modified mTICI score (ß=–1.79 [95% CI, −3.43 to –0.15]; P=0.03) and distal thrombus migration (ß=–0.41 [95% CI, −0.69 to –0.13]; P=0.004) on interaction analysis. Consequently, IVT showed an additive association with functional outcome in the subpopulation of patients undergoing thrombectomy who achieved successful reperfusion (mTICI ≥2b; ß=–0.46 [95% CI, −0.74 to –0.17]; P=0.002) and remained beneficial in those with unsuccessful reperfusion (mTICI ≤2a; ß=–0.47 [95% CI, −0.96 to 0.01]; P=0.05). Conclusions In thrombectomy‐eligible patients with anterior circulation large‐vessel occlusion, IVT improves functional outcome independent of grade of reperfusion and distal thrombus migration.

BackgroundThe impact of COVID-19 on clinical outcomes in acute ischemic stroke patients receiving reperfusion therapy remains unclear. We therefore aimed to synthesize the available evidence to investigate the safety and short-term efficacy of reperfusion therapy in this patient population.MethodsWe searched the electronic databases MEDLINE, Embase and Cochrane Library Reviews for randomized controlled trials and observational studies that investigated the use of intravenous thrombolysis, endovascular therapy, or a combination of both in acute ischemic stroke patients with laboratory-confirmed COVID-19, compared to controls. Our primary safety outcomes included any intracerebral hemorrhage (ICH), symptomatic ICH and all-cause in-hospital mortality. Short-term favorable functional outcomes were assessed at discharge and at 3 months. We calculated pooled risk ratios (RR) and 95% confidence intervals (CI) using DerSimonian and Laird random-effects model. Heterogeneity was evaluated using Cochran’s Q test and I2 statistics.ResultsWe included 11 studies with a total of 477 COVID-19 positive and 8,092 COVID-19 negative ischemic stroke patients who underwent reperfusion therapy. COVID-19 positive patients exhibited a significantly higher risk of experiencing any ICH (RR 1.54, 95% CI 1.16–2.05, p

Abstract Background Neurologic manifestations are increasingly reported in patients with coronavirus disease 2019 (COVID-19). Yet, data on prevalence, predictors and relevance for outcome of neurological manifestations in patients requiring intensive care are scarce. We aimed to characterize prevalence, risk factors and impact on outcome of neurologic manifestations in critically ill COVID-19 patients. Methods In the prospective, multicenter, observational registry study PANDEMIC (Pooled Analysis of Neurologic DisordErs Manifesting in Intensive care of COVID-19), we enrolled COVID-19 patients with neurologic manifestations admitted to 19 German intensive care units (ICU) between April 2020 and September 2021. We performed descriptive and explorative statistical analyses. Multivariable models were used to investigate factors associated with disorder categories and their underlying diagnoses as well as to identify predictors of outcome. Results Of the 392 patients included in the analysis, 70.7% (277/392) were male and the mean age was 65.3 (SD ± 3.1) years. During the study period, a total of 2681 patients with COVID-19 were treated at the ICUs of 15 participating centers. New neurologic disorders were identified in 350 patients, reported by these centers, suggesting a prevalence of COVID-19-associated neurologic disorders of 12.7% among COVID-19 ICU patients. Encephalopathy (46.2%; 181/392), cerebrovascular (41.0%; 161/392) and neuromuscular disorders (20.4%; 80/392) were the most frequent categories identified. Out of 35 cerebrospinal fluid analyses with reverse transcriptase PCR for SARS-COV-2, only 3 were positive. In-hospital mortality was 36.0% (140/389), and functional outcome (mRS 3 to 5) of surviving patients was poor at hospital discharge in 70.9% (161/227). Intracerebral hemorrhage (OR 6.2, 95% CI 2.5–14.9, p

Cardiac damage has been attributed to SARS-CoV-2-related pathology contributing to increased risk of vascular events. Heart rate variability (HRV) is a parameter of functional neurocardiac integrity with low HRV constituting an independent predictor of cardiovascular mortality. Whether structural cardiac damage translates into neurocardiac dysfunction in patients infected with SARS-CoV-2 remains poorly understood. Hypothesized mechanisms of possible neurocardiac dysfunction in COVID-19 comprise direct systemic neuroinvasion of autonomic control centers, ascending virus propagation along cranial nerves and cardiac autonomic neuropathy. While the relationship between the autonomic nervous system and the cytokine cascade in general has been studied extensively, the interplay between the inflammatory response caused by SARS-CoV-2 and autonomic cardiovascular regulation remains largely unclear. We reviewed the current literature on the potential diagnostic and prognostic value of autonomic neurocardiac function assessment via analysis of HRV including time domain and spectral analysis techniques in patients with COVID-19. Furthermore, we discuss potential therapeutic targets of modulating neurocardiac function in this high-risk population including HRV biofeedback and the impact of long COVID on HRV as well as the approaches of clinical management. These topics might be of particular interest with respect to multimodal pandemic preparedness concepts.

Abstract Background Hepatitis E infection affects over 20 million people worldwide. Reports of neurological manifestations are largely limited to the peripheral nervous system. We report a middle-aged genotype 3c male patient with acute hepatitis E virus (HEV) infection and severe neurological deficits with evidence of multiple disseminated inflammatory lesions of the central nervous system. Case presentation A 42-year-old male patient presented to our emergency department with musculoskeletal weakness, bladder and bowel retention, blurred vision and ascending hypoesthesia up to the level of T8. Serology showed elevated liver enzymes and positive IgM-titers of hepatitis E. Analysis of cerebrospinal fluid (CSF) showed mild pleocytosis and normal levels of glucose, lactate and protein. HEV-RNA-copies were detected in the CSF and stool. Within 3 days after admission the patient became paraplegic, had complete visual loss and absent pupillary reflexes. MRI showed inflammatory demyelination of the optic nerve sheaths, multiple subcortical brain regions and the spinal cord. Electrophysiology revealed axonal damage of the peroneal nerve on both sides with absent F-waves. Treatment was performed with methylprednisolone, two cycles of plasma exchange (PLEX), one cycle of intravenous immunoglobulins (IVIG) and ribavirin which was used off-label. Liver enzymes normalized after 1 week and serology was negative for HEV-RNA after 3 weeks. Follow-up MRI showed progressive demyelination and new leptomeningeal enhancement at the thoracic spine and cauda equina 4 weeks after admission. Four months later, after rehabilitation was completed, repeated MRI showed gliotic transformation of the spinal cord without signs of an active inflammation. Treatment with rituximab was initiated. The patient remained paraplegic and hypoesthesia had ascended up to T5. Nevertheless, he regained full vision. Conclusions Our case indicates a possible association of acute HEV infection with widespread disseminated central nervous system inflammation. Up to now, no specific drugs have been approved for the treatment of acute HEV infection. We treated our patient off-label with ribavirin and escalated immunomodulatory therapy considering clinical progression and the possibility of an autoimmune response targeting nerve cell structures. While response to treatment was rather limited in our case, detection of HEV in patients with acute neurological deficits might help optimize individual treatment strategies.

Background: The clinical benefit from endovascular therapy (EVT) for patients with acute ischemic stroke is time-dependent. We tested the hypothesis that team prenotification results in faster procedure times prior to initiation of EVT.Methods: We analyzed data from our prospective database (01/2016–02/2018) including all patients with acute ischemic stroke who were evaluated for EVT at our comprehensive stroke center. We established a standardized algorithm (EVT-Call) in 06/2017 to prenotify team members (interventional neuroradiologist, neurologist, anesthesiologist, CT and angiography technicians) about patient transfer from remote hospitals for evaluation of EVT, and team members were present in the emergency department at the expected patient arrival time. We calculated door-to-image, image-to-groin and door-to-groin times for patients who were transferred to our center for evaluation of EVT, and analyzed changes before (–EVT-Call) and after (+EVT-Call) implementation of the EVT-Call.Results: Among 494 patients in our database, 328 patients were transferred from remote hospitals for evaluation of EVT (208 -EVT-Call and 120 +EVT-Call, median [IQR] age 75 years [65–81], NIHSS score 17 [12–22], 49.1% female). Of these, 177 patients (54%) underwent EVT after repeated imaging at our center (111/208 [53%) -EVT-Call, 66/120 [55%] +EVT-Call). Median (IQR) door-to-image time (18 min [14–22] vs. 10 min [7–13]; p < 0.001), image-to-groin time (54 min [43.5–69.25] vs. 47 min [38.3–58.75]; p = 0.042) and door-to-groin time (74 min [58–86.5] vs. 60 min [49.3–71]; p < 0.001) were reduced after implementation of the EVT-Call.Conclusions: Team prenotification results in faster patient assessment and initiation of EVT in patients with acute ischemic stroke. Its impact on functional outcome needs to be determined.

Objective: To determine the diagnostic agreement of CT angiography (CTA) manual multiplanar reformatting (MPR) stenosis diameter measurement and semiautomated perpendicular stenosis area minimal caliber computation of extracranial internal carotid artery (ICA) stenosis.Methods: We analyzed acute cerebral ischemia CTA at our tertiary stroke center in a 12-month period. Prospective NASCET-type stenosis grading for each ICA was independently performed using (1) MPR to manually determine diameters and (2) perpendicular stenosis area with minimal caliber semiautomated computation to grade luminal constriction. Corresponding to clinically relevant NASCET strata, results were grouped into severity ranges: normal, 1–49%, 50–69%, and 70–99%, and occlusion.Results: We included 647 ICA pairs from 330 patients (median age of 74 [66–80, IQR]; 38–92 years; 58% men; median NIHSS 4 [1–9, IQR]). MPR diameter and semiautomated caliber measurements resulted in stenosis grades of 0–49% in 143 vs. 93, 50–69% in 29 vs. 27, 70–99% in 6 vs. 14, and occlusion in 34 vs. 34 ICAs (p = 0.003), respectively. We found excellent reliability between repeated manual CTA assessments of one expert reader (ICC = 0.997; 95% CI, 0.993–0.999) and assessments of two expert readers (ICC = 0.972; 95% CI, 0.936–0.988). For the semiautomated vessel analysis software, both intrarater reliability and interrater reliability were similarly strong (ICC = 0.981; 95% CI, 0.952–0.992 and ICC = 0.745; 95% CI, 0.486–0.883, respectively). However, Bland–Altman analysis revealed a mean difference of 1.6% between the methods within disease range with wide 95% limits of agreement (−16.7–19.8%). This interval even increased with exclusively considered vessel pairs of stenosis ≥1% (mean 5.3%; −24.1–34.7%) or symptomatic stenosis ≥50% (mean 0.1%; −25.7–26.0%).Conclusion: Our findings suggest that MPR-based diameter measurement and the semiautomated perpendicular area minimal caliber computation methods cannot be used interchangeably for the quantification of ICA steno-occlusive disease.

Background: The constantly increasing incidence of stroke in younger individuals substantiates an urgent need for research to elucidate underlying risk factors and etiologies. Heretofore, the vast majority of studies on stroke in the young have been carried out in European and North American regions. We aimed to characterize cerebrovascular risk profiles in a Saudi Arabic cohort of consecutive young stroke patients.Methods: We retrospectively analyzed data from consecutive ischemic stroke patients aged 15 to 49 years who underwent detailed cardiocerebrovascular evaluation at a tertiary stroke care center in Makkah, Saudi Arabia. Distributions of risk factors and stroke etiologies were assessed in the entire cohort and in two strata of very young (15–40 years) and young to middle-aged patients (41–49) to account for variability in suggested age cutoffs.Results: In the entire cohort [n = 63, ages 44 (34–47) median, interquartile range], dyslipidemia (71.4%) and small vessel occlusion (31.7%) displayed highest prevalence followed by diabetes (52.4%) and cardioembolism (19%). In very young patients, cardioembolism was the most prevalent etiology (27.3%). Risk profiles were similar between both age strata except for a higher prevalence of diabetes among the older cohort (31.8 vs. 63.4%, p = 0.01). Logistic regression identified diabetes as strongest predictor for association to the older strata (odds ratio = 4.2, 95% confidence interval = 1.2–14.1, p = 0.02).Conclusion: Cerebrovascular risk profiles and stroke etiologies in our cohort of young stroke patients differ from those of previous cohorts, suggesting the need for tailored prevention strategies that take into account local epidemiological data on cerebrovascular health.

Background: While intravenous thrombolysis (IVT) in ischemic stroke can be safely applied in telestroke networks within 3 h from symptom onset, there is a lack of evidence for safety in the expanded 3- to 4. 5-h time window. We assessed the safety and short-term efficacy of IVT in acute ischemic stroke (AIS) in the expanded time window delivered through a hub-and-spoke telestroke network.Methods: Observational study of patients with AIS who received IVT at the Stroke Eastern Saxony Telemedical Network between 01/2014 and 12/2015. We compared safety data including symptomatic intracerebral hemorrhage (sICH; according to European Cooperative Acute Stroke Study II definition) and any intracerebral hemorrhage (ICH) between patients admitted to telestroke spoke sites and patients directly admitted to a tertiary stroke center representing the hub of the network. We also assessed short-term efficacy data including favorable functional outcome (i.e., modified Rankin Scale ≤ 2) and National Institutes of Health Stroke Scale (NIHSS) at discharge, hospital discharge disposition, and in-hospital mortality.Results: In total, 152 patients with AIS were treated with IVT in the expanded time window [spoke sites, n = 104 (26.9%); hub site, n = 48 (25.9%)]. Patients treated at spoke sites had less frequently a large vessel occlusion [8/104 (7.7) vs. 20/48 (41.7%); p < 0.0001], a determined stroke etiology (p < 0.0001) and had slightly shorter onset-to-treatment times [210 (45) vs. 228 (58) min; p = 0.02] than patients who presented to the hub site. Both cohorts did not display any further differences in demographics, vascular risk factors, median baseline NIHSS scores, or median baseline Alberta stroke program early CT score (p > 0.05). There was no difference in the frequency of sICH (4.9 vs. 6.3%; p = 0.71) or any ICH (8.7 vs. 16.7%; p = 0.15). Neither there was a difference regarding favorable functional outcome (44.1 vs. 39.6%; p = 0.6) nor median NIHSS [3 (5.5) vs. 2.5 (5.75); p = 0.92] at discharge, hospital discharge disposition (p = 0.28), or in-hospital mortality (9.6 vs. 8.3%; p = 1.0). Multivariable modeling did not reveal an association between telestroke and sICH or favorable functional outcome (p > 0.05).Conclusions: Delivery of IVT in the expanded 3- to 4.5-h time window through a telestroke network appears to be safe with equivalent short-term functional outcomes for spoke-and-hub center admissions.

Background: Neuroprotective and neurorestorative effects have been postulated for selective serotonin-reuptake inhibitors (SSRI). We hypothesized that sertraline, which is characterized by less severe adverse effects and more stable pharmacokinetics than classic SSRI, is associated with improved functional recovery in acute ischemic stroke patients with motor deficits.Methods: Prospective observational study of consecutive acute ischemic stroke patients who received sertraline for clinically suspected post-stroke depression (PSD) or at high risk for PSD. Eligibility comprised acute motor deficit caused by ischemic stroke (≥2 points on NIHSS motor items) and functional independence pre-stroke (mRS ≤1). Decision to initiate treatment with SSRI during hospital stay was at the discretion of the treating stroke physician. Patients not receiving sertraline served as control group. Favorable functional recovery defined as mRS ≤2 was prospectively assessed at 3 months. Multivariable logistic regression analysis was used to explore the effects of sertraline on 3-months functional recovery. Secondary outcomes were frequency of any and incident PSD (defined by BDI ≥10) at 3 months.Results: During the study period (03/2017–12/2018), 114 patients were assigned to sertraline (n = 72, 62.6%) or control group (n = 42, 37.4%). At study entry, patients in sertraline group were more severely neurologically affected than patients in the control group (NIHSS: 8 [IQR, 5–11] vs. 5 [IQR, 4–7]; p = 0.002). Also, motor NIHSS scores were more pronounced in sertraline than in control group (4 [IQR 2–7] vs. 2 [IQR 2–4], p = 0.001). After adjusting for age and baseline NIHSS, multivariable regression analysis revealed a significant association between sertraline intake and favorable functional outcome at 3 months (OR 3.10, 95% CI 1.02–9.41; p = 0.045). There was no difference between both groups regarding the frequency of any depression at 3 months (26/53 [49.1%] vs. 14/28 [50.0%] patients, p = 0.643, BDI ≥10). However, fewer incident depressions were observed in sertraline group patients compared to patients in control group (0/53 [0%] vs. 5/28 [17.9%] patients, p = 0.004).Conclusions: In this non-randomized comparison, early treatment with sertraline tended to favor functional recovery in patients with acute ischemic stroke. While exploratory in nature, this hypothesis needs further investigation in a clinical trial.

Background: Neurocardiac dysfunction worsens clinical outcome and increases mortality in stroke survivors. We hypothesized that heart rate variability (HRV) biofeedback improves neurocardiac function by modulating autonomic nervous system activity after acute ischaemic stroke (AIS).Methods: We randomly allocated (1:1) 48 acute ischaemic stroke patients to receive nine sessions of HRV- or sham biofeedback over 3 days in addition to comprehensive stroke unit care. Before and after the intervention patients were evaluated for HRV via standard deviation of normal-to-normal intervals (SDNN, primary outcome), root mean square of successive differences between normal heartbeats (RMSSD), a predominantly parasympathetic measure, and for sympathetic vasomotor and sudomotor function. Severity of autonomic symptoms was assessed via survey of autonomic symptom scale total impact score (TIS) at baseline and after 3 months.Results: We included 48 patients with acute ischaemic stroke [19 females, ages 65 (4.4), median (interquartile range)]. Treatment with HRV biofeedback increased HRV post intervention [SDNN: 43.5 (79.0) ms vs. 34.1 (45.0) ms baseline, p = 0.015; RMSSD: 46.0 (140.6) ms vs. 29.1 (52.2) ms baseline, p = 0.015] and alleviated autonomic symptoms after 3 months [TIS 3.5 (8.0) vs. 7.5 (7.0) baseline, p = 0.029], which was not seen after sham biofeedback (SDNN: p = 0.63, RMSSD: p = 0.65, TIS: 0.06). There were no changes in sympathetic vasomotor and sudomotor function (p = ns).Conclusions: Adding HRV biofeedback to standard stroke unit care led to improved neurocardiac function and sustained alleviation of autonomic symptoms after acute ischaemic stroke, which was likely mediated by a predominantly parasympathetic mechanism.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03865225.

Background: We hypothesized that autotitrating bilevel positive airway pressure (auto-BPAP) favorably affects short-term clinical outcomes in hyperacute ischemic stroke.Methods: In a multicenter, randomized, controlled trial patients with large vessel steno-occlusive stroke and clinically suspected sleep apnea were allocated to auto-BPAP or standard stroke care alone. Auto-BPAP was initiated within 24 h from stroke onset and performed over 48 h during diurnal and nocturnal sleep. Sleep apnea was assessed using cardiorespiratory polygraphy. Primary endpoint was early neurological improvement on National Institutes of Health Stroke Scale (NIHSS) score at 72 h. Safety and tolerability of BPAP, functional independence [modified Rankin Scale (mRS) 0–2], stroke recurrence, and mortality at 90 days were assessed.Results: Due to low recruitment, the trial was prematurely stopped after 24 patients had been randomized (auto-BPAP, n = 14; control, n = 10): median baseline NIHSS 13 (5.5–18), 88% large vessel occlusion, and 12% large vessel stenosis. Polygraphy confirmed sleep apnea in 64% of auto-BPAP and 88% of control patients (p = 0.34). Adherence to auto-BPAP was achieved by 9 of the 14 (64%) patients. Between auto-BPAP and control patients, no differences were observed in early neurological improvement (median NIHSS change: −2.0, IQR = 7 points vs. −0.5, IQR = 3 points), 90 days functional independence (21 vs. 30%, p = 0.67), stroke recurrence (0 vs. 20%, p = 0.16), and death (14 vs. 20%, p = 1.0). No safety concerns were identified.Conclusions: In this prematurely terminated trial, auto-BPAP was safe but did not show an effect on short-term clinical outcomes in selected ischemic stroke patients. Its tolerability, however, may be limited in hyperacute stroke care and needs to be improved before larger trials are conducted.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT01812993.

With the onset of the COVID-19 pandemic, it became apparent that, in addition to pulmonary infection, extrapulmonary manifestations such as cardiac injury and acute cerebrovascular events are frequent in patients infected with SARS-CoV-2, worsening clinical outcome. We reviewed the current literature on the pathophysiology of cardiac injury and its association with acute ischaemic stroke. Several hypotheses on heart and brain axis pathology in the context of stroke related to COVID-19 were identified. Taken together, a combination of disease-related coagulopathy and systemic inflammation might cause endothelial damage and microvascular thrombosis, which in turn leads to structural myocardial damage. Cardiac complications of this damage such as tachyarrhythmia, myocardial infarction or cardiomyopathy, together with changes in hemodynamics and the coagulation system, may play a causal role in the increased stroke risk observed in COVID-19 patients. These hypotheses are supported by a growing body of evidence, but further research is necessary to fully understand the underlying pathophysiology and allow for the design of cardioprotective and neuroprotective strategies in this at risk population.

We aimed to assess how evidence-based stroke care changed over the two waves of the COVID-19 pandemic. We analyzed acute stroke patients admitted to a tertiary care hospital in Germany during the first (2 March 2020–9 June 2020) and second (23 September 2020–31 December 2020, 100 days each) infection waves. Stroke care performance indicators were compared among waves. A 25.2% decline of acute stroke admissions was noted during the second (n = 249) compared with the first (n = 333) wave of the pandemic. Patients were more frequently tested SARS-CoV-2 positive during the second than the first wave (11 (4.4%) vs. 0; p < 0.001). There were no differences in rates of reperfusion therapies (37% vs. 36.5%; p = 1.0) or treatment process times (p > 0.05). However, stroke unit access was more frequently delayed (17 (6.8%) vs. 5 (1.5%); p = 0.001), and hospitalization until inpatient rehabilitation was longer (20 (1, 27) vs. 12 (8, 17) days; p < 0.0001) during the second compared with the first pandemic wave. Clinical severity, stroke etiology, appropriate secondary prevention medication, and discharge disposition were comparable among both waves. Infection control measures may adversely affect access to stroke unit care and extend hospitalization, while performance indicators of hyperacute stroke care seem to be untainted.

Abstract Background A randomized controlled study (RCT) recently showed that short-term heart rate variability (HRV) biofeedback in addition to standard rehabilitation care for alcohol dependence can reduce craving, anxiety and improve cardiovascular autonomic function. In this one-year follow-up study we aimed to explore whether completion of 2-week HRV-Biofeedback training is associated with long-term abstinence. Furthermore, we sought to identify potential predictors of post-treatment abstinence. Methods We conducted a survey on abstinence in patients with alcohol dependence 1 year after completion of an RCT comparing HRV-biofeedback in addition to inpatient rehabilitation treatment alone (controls). Abstinence rates were compared and analysed for association with demographic data as well as psychometric and autonomic cardiac assessment before and after completion of the biofeedback training using bivariate and multivariate regression analyses. Results Out of 48 patients who participated in the RCT, 27 patients (9 females, ages 42.9 ± 8.6, mean ± SD) completed our one-year follow-up. When including in the analysis only patients who completed follow-up, the rate of abstinence tended to be higher in patients who underwent HRV-biofeedback 1 year earlier compared to those who received rehabilitative treatment alone (66.7% vs 50%, p = ns). This non-significant trend was also observed in the intention-to-treat analysis where patients who did not participate in the follow-up were assumed to have relapsed (46,7% biofeedback vs. 33.3% controls, p = ns). Neither cardiac autonomic function nor psychometric variables were associated with abstinence 1 year after HRV-biofeedback. Conclusion Our follow-up study provide a first indication of possible increase in long-term abstinence after HRV-biofeedback for alcohol dependence in addition to rehabilitation. Trial registration The original randomized controlled trial was registered in the German Clinical Trials Register ( DRKS00004618 ). This one-year follow-up survey has not been registered.

Background: The optimal sedative regimen with general anesthesia (GA) or conscious sedation for patients undergoing endovascular therapy (EVT) remains controversial. Apart from sedative regimen, the duration of anesthetic exposure may affect clinical outcomes. We aimed to determine whether there is an association between anesthetic exposure time and clinical outcomes in mechanically ventilated stroke patients undergoing EVT for large vessel occlusion.Methods: This was an observational study of consecutive ischemic stroke patients who underwent EVT for anterior circulation large vessel occlusion under GA from January 2016 to March 2018. To minimize confounding by indication, we restricted our analysis to patients whose anesthetic exposure lasted

Ischemic stroke is one of the leading causes for death and disability worldwide. In patients with large space-occupying infarction, the subsequent edema complicated by transtentorial herniation poses a lethal threat. Especially in patients with malignant middle cerebral artery infarction, brain swelling secondary to the vessel occlusion is associated with high mortality. By decompressive craniectomy, a significant proportion of the skull is surgically removed, allowing the ischemic tissue to shift through the surgical defect rather than to the unaffected regions of the brain, thus avoiding secondary damage due to increased intracranial pressure. Several studies have shown that decompressive craniectomy reduces the mortality rate in patients with malignant cerebral artery infarction. However, this is done for the cost of a higher proportion of patients who survive with severe disability. In this review, we will describe the clinical and radiological features of malignant middle cerebral artery infarction and the role of decompressive craniectomy and additional therapies in this condition. We will also discuss large cerebellar stroke and the possibilities of suboccipital craniectomy.

Background In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation (HT). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT, (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT. Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3–8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0–6.0) of those without HT; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT. On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24–2.35). Conclusions In patients with HT, anticoagulation was initiated about 12 days later than patients without HT. This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability.

Background: The diagnostic value of cerebrospinal fluid (CSF) analysis in juvenile stroke, i.e., stroke in young adult patients, is not well studied. We sought to determine the therapeutic impact of routine CSF-analysis in young adults with acute ischemic stroke or transient ischemic attack (TIA).Methods: We abstracted data from patients with acute cerebral ischemia aged 18–45 years who were consecutively admitted to our stroke center between 01/2008 and 12/2015. We routinely performed CSF-analysis in patients with hitherto unknown stroke etiology after complete diagnostic work up. We assessed the frequency and underlying causes of abnormal CSF-findings and their impact on secondary stroke prevention therapy.Results: Among 379 patients (median [IQR:IQR3-IQR1] age 39 [10:43-33] years, 48% female) with acute ischemic stroke (n = 306) or TIA (n = 73), CSF analysis was performed in 201 patients (53%). Of these, 25 patients (12.4 %) had CSF pleocytosis (leucocyte cell count ≥ 5 Mpt/L), that was rated as non-specific (e.g., traumatic lumbar puncture, reactive pleocytosis) in 22 patients. Only 3 patients (1.5% of all patients who underwent CSF-analysis) with CSF-pleocytosis had specific CSF-findings that were related to stroke etiology and affected secondary stroke prevention therapy. Imaging findings had already suggested cerebral vasculitis in two of these patients.Conclusions: The diagnostic yield of routine CSF-analysis in juvenile stroke was remarkably low in our study. Our data suggest that CSF-analysis should only be performed if further findings raise the suspicion of cerebral vasculitis.

The vasomotor axon reflex can be evoked in peripheral epidermal nociceptive C-fibers to induce local vasodilation. This neurogenic flare response is a measure of C-fiber functional integrity and therefore shows impairment in patients with small fiber neuropathy. Laser Doppler flowmetry (LDF) and laser Doppler imaging (LDI) are both techniques to analyze vasomotor small fiber function by quantifying the integrity of the vasomotor-mediated axon reflex. While LDF assesses the flare response following acetylcholine iontophoresis with temporal resolution at a single defined skin point, LDI records flare responses with spatial and temporal resolution, generating a two-dimensional map of superficial blood flow. LDF is characterized by a high intra- and interindividual measurement variability, which is smaller in LDI due to its spatial resolution. Nevertheless, LDI still lacks standardized methods for image analysis. Consequently, use of the technique currently remains on an experimental level. Here, we sought to review the current literature on laser Doppler assessment of vasomotor function and discuss potential future applications of established techniques as well as those that are still experimental.

BackgroundAntidepressants are widely used in the treatment of chronic pain. Applied doses are lower than those needed to unfold an antidepressive effect. While efficacy of antidepressants for chronic pain has been reported in large randomized-controlled trials (RCT), there is inconsistent data on adverse effects and tolerability. We aimed at synthesizing data from RCT to explore adverse effect profiles and tolerability of antidepressants for treatment of chronic pain.MethodsSystematic literature research and meta-analyses were performed regarding side effects and safety of different antidepressants in the treatment of chronic pain according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The National Center for Biotechnology Information library and MEDLINE were searched. Randomized placebo-controlled trials were included in quantitative data synthesis.ResultsOut of 1,975 screened articles, 33 papers published between 1995 and 2015 were included in our review and 23 studies were included in the meta-analyses. A higher risk for adverse effects compared to placebo was observed in all antidepressants included in our analyses, except nortriptyline. The most prevalent adverse effects were dry mouth, dizziness, nausea, headache, and constipation. Amitriptyline, mirtazapine, desipramine, venlafaxine, fluoxetine, and nortriptyline showed the highest placebo effect-adjusted risk of adverse effects. Risk for withdrawal due to adverse effects was highest in desipramine (risk ratio: 4.09, 95%-confidence interval [1.31; 12.82]) followed by milnacipran, venlafaxine, and duloxetine. The most common adverse effects under treatment with antidepressants were dry mouth, dizziness, nausea, headache, and constipation followed by palpitations, sweating, and drowsiness. However, overall tolerability was high. Each antidepressant showed distinct risk profiles of adverse effects.ConclusionOur synthesized data analysis confirmed overall tolerability of low-dose antidepressants for the treatment of chronic pain and revealed drug specific risk profiles. This encompassing characterization of adverse effect profiles might be useful in defining multimodal treatment regimens for chronic pain which also consider patients’ comorbidities and co-medication.

BackgroundIn Parkinson’s disease (PD), alpha-synuclein accumulation in cutaneous autonomic pilomotor and sudomotor nerve fibers has been linked to autonomic nervous system disturbances even in the early stages of the disease. This study aims to assess the association between alpha-synuclein-mediated structural autonomic nerve fiber damage and function in PD, elucidate the role of neuropathy progression during the early disease stages, and test reproducibility and external validity of pilomotor function assessment using quantitative pilomotor axon-reflex test and sudomotor function via quantitative direct and indirect test of sudomotor function.Methods/designA prospective controlled study will be conducted at four study sites in Europe and the USA. Fifty-two male and female patients with idiopathic PD (Hoehn and Yahr 1–2) and 52 age- and sex-matched healthy controls will be recruited. Axon-reflex-mediated pilomotor erection will be induced by iontophoresis of phenylephrine on the dorsal forearm. Silicone impressions of the response will be obtained, scanned, and quantified for pilomotor muscle impressions by number, impression size, and area of axon-reflex spread. Axon-reflex-mediated sweating following acetylcholine iontophoresis will be quantified for number and size of droplets and axon-reflex spread. Sympathetic skin responses, autonomic and motor symptoms will be evaluated. Tests will be performed at baseline, after 2 weeks, 1, 2, and 3 years. Skin biopsies will be obtained at baseline and after 3 years and will be analyzed for nerve fiber density and alpha-synuclein accumulation.DiscussionWe anticipate that progression of autonomic nerve dysfunction assessed via pilomotor and sudomotor axon-reflex tests is related to progression of autonomic symptom severity and alpha-synuclein deposition. Potential applications of the techniques include interventional studies evaluating disease-modifying approaches and clinical assessment of autonomic dysfunction in patients with PD.Clinical trail registrationTRN NCT03043768.

Background and PurposeSickle cell disease (SCD) is strongly linked to stroke across all haplotypes in the pediatric population. Transcranial Doppler (TCD) ultrasound is known to identify the highest risk group in African-Americans who need to receive and stay on blood transfusions, but it is unclear if the same flow velocity cut-offs can be applied to the Iranian population. We aimed to evaluate baseline TCD findings in Iranian children with SCD and no prior strokes.MethodsChildren with genetically confirmed SCD (Arabian haplotype, homozygote) and without SCD (controls) were prospectively recruited from pediatric outpatient clinic over a period of 9 months. We performed TCD in both groups to determine flow velocities in the middle cerebral (MCA) and terminal internal carotid arteries (TICA).ResultsOf 74 screened children, 60 met the inclusion/exclusion criteria (62% female; mean age 10±4 years). Baseline characteristics did not differ between the cases and controls, except hemoglobin (Hb) which was significantly lower in the SCD group (P

Background. Obstructive sleep apnea (OSA) is a common condition in patients with acute ischemic stroke and associated with early clinical deterioration and poor functional outcome. However, noninvasive ventilatory correction is hardly considered as a complementary treatment option during the treatment phase of acute ischemic stroke. Summary of Case. A 55-year-old woman with an acute middle cerebral artery (MCA) occlusion received intravenous tissue plasminogen activator (tPA) and enrolled into a thrombolytic research study. During tPA infusion, she became drowsy, developed apnea episodes, desaturated and neurologically deteriorated without recanalization, re-occlusion or intracerebral hemorrhage. Urgent noninvasive ventilatory correction with biphasic positive airway pressure (BiPAP) reversed neurological fluctuation. Her MCA completely recanalized 24 hours later. Conclusions. Noninvasive ventilatory correction should be considered more aggressively as a complementary treatment option in selected acute stroke patients. Early initiation of BiPAP can stabilize cerebral hemodynamics and may unmask the true potential of other therapies.

With majority of ischemic strokes attributable to atherothrombosis and many being predictable after transient ischemic attacks (TIA), the role of early secondary prevention with antiplatelet agents is under renewed investigation. Prior major clinical trials of various secondary stroke prevention regimens pointed to a greater efficacy of dual antiplatelet agents if initiated early from symptom onset. This paper examines data and rationale behind dual antiplatelet regimens across the completed clinical trials. The safety of dual antiplatelets approach is of concern, but it could be outweighed, at least in early management, by a greater reduction in recurrence of ischemic events since this risk is “front loaded” after minor stroke or TIA. Aspirin monotherapy, though considered standard of care, is compared to aspirin-extended release dipiridamole and its combination with clopidogrel in early-phase completed and efficacy-phase ongoing clinical trials.

BackgroundThere is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19.MethodsThis multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes.ResultsA total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054).ConclusionIV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.