Predictors of clinical outcomes in space-occupying cerebellar infarction undergoing suboccipital decompressive craniectomy.

Introduction: Despite current clinical guidelines recommending suboccipital decompressive craniectomy (SDC) in cerebellar infarction when patients present with neurological deterioration, the precise definition of neurological deterioration remains unclear and accurate timing of SDC can be challenging. The current study aimed at characterizing whether clinical outcomes can be predicted by the GCS score immediately prior to SDC and whether higher GCS scores are associated with better clinical outcomes. Methods: In a single-center, retrospective analysis of 51 patients treated with SDC for space-occupying cerebellar infarction, clinical and imaging data were evaluated at the time points of symptom onset, hospital admission, and preoperatively. Clinical outcomes were measured by the mRS. Preoperative GCS scores were stratified into three groups (GCS, 3-8, 9-11, and 12-15). Univariate and multivariate Cox regression analyses were performed using clinical and radiological parameters as predictors of clinical outcomes. Results: In cox regression analysis GCS scores of 12-15 at surgery were significant predictors of positive clinical outcomes (mRS, 1-2). For GCS scores of 3-8 and 9-11, no significant increase in proportional hazard ratios was observed. Negative clinical outcomes (mRS, 3-6) were associated with infarct volume above 6.0 cm3, tonsillar herniation, brainstem compression, and a preoperative GCS score of 3-8 [HR, 2.386 (CI, 1.160-4.906); p = 0.018]. Conclusion: Our preliminary findings suggest that SDC should be considered in patients with infarct volumes above 6.0 cm3 and with GCS between 12 and 15, as these patients may show better long-term outcomes than those in whom surgery is delayed until a GCS score below 11.

Brain-specific biomarkers in urine as a non-invasive approach to monitor neuronal and glial damage.

BACKGROUND AND PURPOSE: This study evaluates the quantitative measurability of glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and total tau (t-tau) in urine of patients with acute cerebral damage. METHODS: Serum and urine samples were prospectively collected from patients with an acute ischemic stroke or intracerebral hemorrhage (target group) and compared to healthy subjects (control group); samples were measured using ultrasensitive single-molecule arrays (Simoa®). Glomerular barrier function was assessed based on albumin-creatinine ratio (ACR); biomarker-creatinine ratios were calculated for correction of urine dilution. RESULTS: Ninety-three urine-serum pairs in the target group and 10 urine-serum pairs in the control group were measured. The mean absolute concentration ± standard deviation in urine of the target and control groups were 184.7 ± 362.4 pg/ml and 27.3 ± 24.1 pg/ml for GFAP (r = 0.3 [Wilcoxon effect size], p = 0.007), 17.5 ± 38.6 pg/ml and 0.9 ± 0.3 pg/ml for NfL (r = 0.4, p < 0.005), 320.2 ± 443.3 pg/ml and 109.6 ± 116.8 pg/ml for UCH-L1 (r = 0.26, p = 0.014), and 219.5 ± 255.8 pg/ml and 21.1 ± 27.1 pg/ml for t-tau (r = 0.37, p < 0.005), respectively, whereas biomarker-creatinine ratio was significantly different only for NfL (r = 0.29, p = 0.015) and t-tau (r = 0.32, p < 0.01). In patients with intact glomerular barrier (ACR < 30 mg/g), only NfL in urine was significantly different between the target and control group and showed a significant correlation with the respective serum concentrations (r = 0.58 [Pearson's correlation-coefficient], p < 0.005). CONCLUSION: All four investigated biomarkers could be measured in urine, with NfL and t-tau showing the strongest effect size after correction for urine dilution. NfL revealed the most accurate relation between serum and urine concentrations in patients with intact kidney function.

Reduction of Ischemic Stroke Associated Disability in the Population: A State-Wide Stroke Registry Analysis over a Decade.

(Background): Effective prevention strategies and acute therapies have been established and distributed in recent years to reduce the global burden of stroke. However, beyond randomized clinical trials, limited data exist on the real-world impact of these measures. Our goal was to analyze whether the stroke-associated disability in the population decreased over time based on a state-wide stroke registry analysis. (Methods): Consecutive data from a state-wide inpatient stroke registry covering the entire federal state of Hesse, Germany, were obtained. The clinical data of 141,287 patients with ischemic stroke (ICD-10: I63) admitted between 2010 and 2019 were included. The primary outcome was the odds ratio for a change of modified Ranking Scale (mRS) at discharge over time, estimated by ordinary logistic regression and adjusted for age and sex. The secondary outcome was the odds ratio for a lower National Institutes of Health Stroke Scale (NIHSS) score at hospital admission. (Results): The absolute number of severely disabled (mRS 4−5) stroke patients at discharge decreased over time (2010: 3223 (equivalent to 53/100,000 population); 2019: 2429 [39/100,000 population]). The odds at hospital admission for a higher mRS at discharge decreased significantly by 3.7% per year (OR 0.963 (95% CI 0.960−0.966), p < 0.001). The absolute number of severely affected stroke patients (NIHSS > 15) at admission declined over time (2010: 1589 [26/100,000]; 2019: 1185 [19/100,000]; p < 0.001). The odds for a higher NIHSS score at admission to hospital decreased by 3.8% per year (OR 0.962 (95% CI 0.959−0.965), p < 0.001). Trends were most prominent for patients aged 80 years and older and for patients with atrial fibrillation but absent in patients <60 years. (Conclusions): Stroke-associated disability in the population steadily decreased between 2010 and 2019. The improved prevention of severe strokes in elderly patients may be a major driver of this observation.

Dysphagia assessment in ischemic stroke after mechanical thrombectomy: When and how?

Background: Dysphagia is a frequent symptom in acute ischemic stroke (AIS). Endovascular treatment (EVT) has become the standard of care for acute stroke secondary to large vessel occlusion. Although standardized guidelines for poststroke dysphagia (PSD) management exist, they do not account for this setting in which patients receive EVT under general anesthesia. Therefore, the aim of this study was to evaluate PSD prevalence and severity, as well as an appropriate time point for the PSD evaluation, in patients undergoing EVT under general anesthesia (GA). Methods: We prospectively included 54 AIS patients undergoing EVT under GA. Fiberoptic Endoscopic Evaluation of Swallowing (FEES) was performed within 24 h post-extubation in all patients. Patients presenting significant PSD received a second FEES-assessment to determine the course of dysphagia deficits over time. Dysphagia severity was rated according the Fiberoptic Dysphagia Severity Scale (FEDSS). Results: At first FEES (FEES 1) assessment, performed in the median 13 h (IQR 5-17) post-extubation, 49/54 patients (90.7%) with dysphagia were observed with a median FEDSS of 4 (IQR 3-6). Severe dysphagia requiring tube feeding was identified in 28/54 (51.9%) subjects, whereas in 21 (38.9%) patients early oral diet with certain food restrictions could be initiated. In the follow up FEES examination conducted in the median 72 h (IQR 70-97 h) after initial FEES 34/49 (69.4%) patients still presented PSD. Age (p = 0.030) and ventilation time (p = 0.035) were significantly associated with the presence of PSD at the second FEES evaluation. Significant improvement of dysphagia frequency (p = 0.006) and dysphagia severity (p = 0.001) could be detected between the first and second dysphagia assessment. Conclusions: PSD is a frequent finding both immediately within 24 h after extubation, as well as in the short-term course. In contrast to common clinical practice, to delay evaluation of swallowing for at least 24 h post-extubation, we recommend a timely assessment of swallowing function after extubation, as 50% of patients were safe to begin oral intake. Given the high amount of severe dysphagic symptoms, we strongly recommend application of instrumental swallowing diagnostics due to its higher sensitivity, when compared to clinical swallowing examination. Furthermore, advanced age, as well as prolonged intubation, were identified as significant predictors for delayed recovery of swallowing function.

Endovascular treatment for ischemic stroke with the drip-and-ship model-Insights from the German Stroke Registry.

Background: Endovascular therapy (EVT) in acute ischemic stroke has been widely established. Globally, stroke patients are transferred either directly to a thrombectomy center (DC) or a peripheral stroke unit with a "drip-and-ship" (DS) model. We aimed to determine differences between the DS and DC paradigms after EVT of acute stroke patients with large-vessel-occlusion (LVO) in the database of the German Stroke Registry (GSR). Methods: We performed a retrospective analysis of GSR patients between June 2015 and December 2019 in 23 German centers. Primary outcome was an ordinal shift analysis of modified Rankin Scale (mRS) 90 days after index event. Secondary endpoints included time from symptom onset to recanalization and complications. Tertiary endpoint was the association of imaging strategies in DS admissions with outcome. Results: 2,813 patients were included in the DS and 3,819 in the DC group. After propensity score matching mRS after 90 days was higher in DS than DC admissions (OR 1.26; 95%-CI 1.13-1.40). Time from symptom-onset to flow-restoration was shorter in DC than DS (median 199.0 vs. 298.0 min; p < 0.001). DS patients undergoing magnetic resonance imaging (MRI; n=183) before EVT had a lower 90-day mRS than without (n = 944) (OR 0.63; 95%-CI 0.45-0.88). ASPECTS assessed on MRI correlated with 90-day mRS (ρ = -0.326; p < 0.001). Conclusions: Clinical outcome was worse for EVT-eligible patients in the DS setting, even though patients were in a better state of health prior to stroke. A potentially mutable factor was the time delay of 99 min from symptom-onset to successful recanalization. Performing MRI before thrombectomy was associated with good outcome and MRI-ASPECTS was negatively correlated with mRS after 90 days.

Sudden vision loss and neurological deficits after facial hyaluronic acid filler injection.

BACKGROUND: The ongoing expansion of the cosmetic armamentarium of facial rejuvenation fails to uncover the inherent risks of cosmetic interventions. Informed consent to all risks of cosmetic filler injections and potential sequelae, including ocular and neurological complications, should be carefully ensured. We present two cases of complications following facial hyaluronic acid filler injections. CASE PRESENTATIONS: Case 1: A 43-year-old woman presented with monocular vision loss of the left eye, associated ptosis, ophthalmoplegia, periocular pain and nausea, cutaneous changes of the glabella region and forehead, and sensory impairment in the left maxillary branch dermatome (V2) after receiving a hyaluronic acid (HA) filler injection into the left glabellar area. On ophthalmological examination, an ophthalmic artery occlusion (OAO) was diagnosed upon identification of a "cherry-red spot". Magnetic resonance imaging (MRI) revealed a left ischemic optic neuropathy. Supportive therapy and hyaluronidase injections were initiated. A follow-up MRI of the head performed two months after presentation corresponded to stable MRI findings. The patient had irreversible and complete vision loss of the left eye, however, the ptosis resolved. Case 2: A 29-year-old woman was admitted to hospital a few hours after a rhinoplasty and cheek augmentation with hyaluronic acid, presenting with acute monocular vision loss in the right eye, retrobulbar pain, fatigue and vomiting. In addition, the patient presented a harbinger of impending skin necrosis and a complete oculomotor nerve palsy on the right side, choroidal ischemia and vision impairment. Supportive treatment and hyaluronidase injections into the ischemic tissue were initiated. A small scar at the tip of the nose, vision impairment and an irregular pupillary margin on the right side persisted at follow-up. CONCLUSION: These two case reports and the literature review emphasize the pathophysiological mechanisms leading to potentially devastating complications. In order to reduce the risk of vision loss secondary to cosmetic filler injections, practitioners should possess a thorough knowledge of anatomy and preventive strategies.

Exploring Contraindications for Thrombolysis: Risk of Hemorrhagic Transformation and Neurological Deterioration after Thrombolysis in Mice with Recent Ischemic Stroke and Hyperglycemia.

(1) Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke is limited because of several contraindications. In routine clinical practice, patients with a recent stroke are typically not treated with rt-PA in case of a recurrent ischemic event. The same applies to its use in the context of pulmonary artery embolism and myocardial infarction with a recent stroke. In this translational study, we evaluated whether rt-PA treatment after experimental ischemic stroke with or without additional hyperglycemia increases the risk for hemorrhagic transformation (HT) and worsens functional outcome regarding the old infarct area. (2) In total, 72 male C57BL/6N mice were used. Ischemic stroke (index stroke) was induced by transient middle cerebral artery occlusion (tMCAO). Mice received either rt-PA or saline 24 h or 14 days after index stroke to determine whether a recent ischemic stroke predisposes to HT. In addition to otherwise healthy mice, hyperglycemic mice were analyzed to evaluate diabetes as a second risk factor for HT. Mice designated to develop hyperglycemia were pre-treated with streptozotocin. (3) The neurological outcome in rt-PA and saline-treated normoglycemic mice did not differ significantly, either at 24 h or at 14 days. In contrast, hyperglycemic mice treated with rt-PA had a significantly worse neurological outcome (at 24 h, p = 0.02; at 14 days, p = 0.03). At 24 h after rt-PA or saline treatment, HT scores differed significantly (p = 0.02) with the highest scores within hyperglycemic mice treated with rt-PA, where notably only small petechial hemorrhages could be detected. (4) Thrombolysis after recent ischemic stroke does not increase the risk for HT or worsen the functional outcome in otherwise healthy mice. However, hyperglycemia as a second risk factor leads to neurological deterioration after rt-PA treatment, which cannot be explained by an increase of HT alone. Direct neurotoxic effects of rt-PA may play a role.

Predictive Factors of Acute Symptomatic Seizures in Patients With Ischemic Stroke Due to Large Vessel Occlusion.

Introduction: Acute symptomatic seizures (ASz) after ischemic stroke are associated with increased mortality; therefore, identifying predictors of ASz is important. The purpose of this study was to analyze predictors of ASz in a population of patients with ischemic stroke due to large arterial vessel occlusion (LVO). Materials and Methods: This retrospective study examined patients with acute ischemic stroke caused by LVO between 2016 and 2020. Identification of predictive factors was performed using univariate and subsequent multiple logistic regression analysis. In addition, subgroup analysis regarding seizure semiology and time of seizure occurrence (≤ 24 h and > 24 h after stroke) was performed. Results: The frequency of ASz among 979 patients was 3.9 % (n = 38). Univariate logistic regression analysis revealed an increased risk of ASz in patients with higher National Institutes of Health Stroke Scale (NIHSS) score at admission or 24 h after admission, hypernatremia at admission ≥ 145 mmol/L, and pneumonia. Further multiple logistic regression analysis revealed that NIHSS 24 h after admission was the strongest predictor of ASz, particularly relating to ASz occurring later than 24 h after stroke. Patients who experienced a seizure within the first 24 h after stroke were more likely to have a generalized tonic-clonic (GTCS) and focal motor seizure; beyond 24 h, seizures with impaired awareness and non-convulsive status epilepticus were more frequent. Conclusion: NIHSS score 24 h after admission is a strong predictive factor for the occurrence of ASz in patients with ischemic stroke caused by LVO. The semiology of ASz varied over time, with GTCS occurring more frequently in the first 24 h after stroke.

Analysis of CSF D-Dimer to Identify Intrathecal Fibrin-Driven Autoimmunity in Patients With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Proteins of the coagulation system contribute to autoimmune inflammation in patients with multiple sclerosis (MS). On blood-brain barrier (BBB) disruption, fibrinogen enters the CNS and is rapidly converted to fibrin, unfolding pleiotropic autoimmune mechanisms. Fibrin accumulation leads to subsequent proteolytic degradation that results in D-dimer generation. The primary objective of this study was to determine intrathecal levels of D-dimer in CSF as a measure of intrathecal coagulation cascade activation and to evaluate its diagnostic utility in patients with MS in contrast to healthy subjects. Key secondary objectives included analysis of CSF D-dimer in differential diagnoses of MS and its relation to routine clinical markers of disease activity. METHODS: Patients admitted for the assessment of suspected MS were prospectively recruited from October 2017 to December 2020. Blood plasma and citrated CSF samples were analyzed using a highly sensitive luminescent oxygen channeling immunoassay. Intrathecal generation of D-dimer was analyzed by adjusting for CSF/serum albumin (Qalb) and CSF/plasma D-dimer quotients (QD-dimer), and corresponding CSF fibrinogen levels were determined. Final diagnoses after full evaluation and clinical data were recorded. RESULTS: Of 187 patients, 113 patients received a diagnosis of MS or clinically/radiologically isolated syndrome. We found increased intrathecal CSF D-dimer generation levels (QD-dimer/Qalb-index) for patients with relapsing-remitting MS (RRMS; n = 71, median 4.7, interquartile range [IQR] 2.5-8.0) when compared with those for disease controls (n = 22, median 2.6, IQR 2.1-4.8, p = 0.031). Absolute CSF D-dimer values correlated with CSF fibrinogen levels (r = 0.463; p < 0 .001) and CSF leukocytes (r = 0.273; p = 0.003) and were elevated in MS patients with contrast enhancement (CE) compared with MS patients without CE on MRI (n = 48, median 6 ng/mL, and IQR 3-15.25 vs n = 41, median 4 ng/mL, and IQR 2-7; p = 0.026). Exploratory subgroup analyses indicated a correlation of intrathecal inflammatory activity and CSF D-dimer levels. DISCUSSION: D-dimer in CSF can be reliably determined and correlates with markers of CNS inflammation and CSF fibrinogen levels. Adjusted for BBB dysfunction, CSF D-dimer may allow the identification of intrathecal coagulation cascade activation in patients with MS. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that CSF D-dimer levels are elevated in patients with RRMS.

Mechanical thrombectomy does not increase the risk of acute symptomatic seizures in patients with an ischaemic stroke: a propensity score matching study.

BACKGROUND: Mechanical thrombectomy and systemic thrombolysis are important therapies for stroke patients. However, there is disagreement about the accompanying risk of acute symptomatic seizures. METHODS: A retrospective analysis of patients with an acute ischaemic stroke caused by large vessel occlusion was performed. The patients were divided into four groups based on whether they received either mechanical thrombectomy (MT) or systemic thrombolysis (ST; group 1: MT+/ST-; group 2: MT+/ST+; group 3: MT-/ST+; group 4: MT-/ST-). Propensity score matching was conducted for each group combination (1:3, 1:4, 2:3, 2:4, 1:2, 3:4) using the covariates "NIHSS at admission", "mRS prior to event" and "age". The primary endpoint was defined as the occurrence of acute symptomatic seizures. RESULTS: A total of 987 patients met the inclusion criteria, of whom 208, 264, 169 and 346 belonged to groups 1, 2, 3 and 4, respectively. Propensity score matched groups consisted of 160:160, 143:143, 156:156, 144:144, 204:204 and 165:165 patients for the comparisons 1:3, 1:4, 2:3, 2:4, 1:2 and 3:4, respectively. Based on chi-squared tests, there was no significant difference in the frequency of acute symptomatic seizures between the groups. Subgroups varied in their frequency of acute symptomatic seizures, ranging from 2.8 to 3.8%, 2.8-4.4%, 3.6-3.8% and 4.9-6.3% in groups 1, 2, 3 and 4, respectively. CONCLUSION: There was no association between MT or ST and an increased risk of acute symptomatic seizures in patients with an acute ischaemic stroke caused by large vessel occlusion who were treated at a primary stroke centre.

Spinal dural leaks in patients with infratentorial superficial siderosis of the central nervous system-Refinement of a diagnostic algorithm.

BACKGROUND AND PURPOSE: Superficial siderosis of the central nervous system is a sporadic finding in magnetic resonance imaging, resulting from recurrent bleedings into the subarachnoid space. This study aimed to determine the frequency of spinal dural cerebrospinal fluid (CSF) leaks amongst patients with a symmetric infratentorial siderosis pattern. METHODS: In all, 97,733 magnetic resonance images performed between 2007 and 2018 in our neurocenter were screened by a keyword search for "hemosiderosis" and "superficial siderosis." Siderosis patterns on brain imaging were classified according to a previously published algorithm. Potential causative intracranial bleeding events were also assessed. Patients with a symmetric infratentorial siderosis pattern but without causative intracranial bleeding events in history were prospectively evaluated for spinal pathologies. RESULTS: Forty-two patients with isolated supratentorial siderosis, 30 with symmetric infratentorial siderosis and 21 with limited (non-symmetric) infratentorial siderosis were identified. Amyloid angiopathy and subarachnoid hemorrhage were causes for isolated supratentorial siderosis. In all four patients with a symmetric infratentorial siderosis pattern but without a causative intracranial bleeding event in history, spinal dural abnormalities were detected. Dural leaks were searched for in patients with symmetric infratentorial siderosis and a history of intracranial bleeding event without known bleeding etiology, considering that spinal dural CSF leaks themselves may also cause intracranial hemorrhage, for example by inducing venous thrombosis due to low CSF pressure. Thereby, one additional spinal dural leak was detected. CONCLUSIONS: Persisting spinal dural CSF leaks can frequently be identified in patients with a symmetric infratentorial siderosis pattern. Diagnostic workup in these cases should include magnetic resonance imaging of the whole spine.

Simulation-based training improves process times in acute stroke care (STREAM).

BACKGROUND: The objective of the STREAM Trial was to evaluate the effect of simulation training on process times in acute stroke care. METHODS: The multicenter prospective interventional STREAM Trial was conducted between 10/2017 and 04/2019 at seven tertiary care neurocenters in Germany with a pre- and post-interventional observation phase. We recorded patient characteristics, acute stroke care process times, stroke team composition and simulation experience for consecutive direct-to-center patients receiving intravenous thrombolysis (IVT) and/or endovascular therapy (EVT). The intervention consisted of a composite intervention centered around stroke-specific in situ simulation training. Primary outcome measure was the 'door-to-needle' time (DTN) for IVT. Secondary outcome measures included process times of EVT and measures taken to streamline the pre-existing treatment algorithm. RESULTS: The effect of the STREAM intervention on the process times of all acute stroke operations was neutral. However, secondary analyses showed a DTN reduction of 5 min from 38 min pre-intervention (interquartile range [IQR] 25-43 min) to 33 min (IQR 23-39 min, p = 0.03) post-intervention achieved by simulation-experienced stroke teams. Concerning EVT, we found significantly shorter door-to-groin times in patients who were treated by teams with simulation experience as compared to simulation-naive teams in the post-interventional phase (-21 min, simulation-naive: 95 min, IQR 69-111 vs. simulation-experienced: 74 min, IQR 51-92, p = 0.04). CONCLUSION: An intervention combining workflow refinement and simulation-based stroke team training has the potential to improve process times in acute stroke care.

Measuring Patient Safety Climate in Acute Stroke Therapy.

Background: Treatment of acute stroke is highly time-dependent and performed by a multiprofessional, interdisciplinary team. Interface problems are expectable and issues relevant to patient safety are omnipresent. The Safety Attitudes Questionnaire (SAQ) is a validated and widely used instrument to measure patient safety climate. The objective of this study was to evaluate the SAQ for the first time in the context of acute stroke care. Methods: A survey was carried out during the STREAM trial (NCT00032282) at seven university hospitals in Germany from October 2017 to October 2018. The anonymous survey included 33 questions (5-point Likert scale, 1 = disagree to 5 = agree) and addressed the entire multiprofessional stroke team. Statistical analyses were used to examine psychometric properties as well as descriptive findings. Results: 164 questionnaires were completed yielding a response rate of 66.4%. 67.7% of respondents were physicians and 25.0% were nurses. Confirmatory Factor Analysis revealed that the original 6-factor structure fits the data adequately. The SAQ for acute stroke care showed strong internal consistency (α = 0.88). Exploratory analysis revealed differences in scores on the SAQ dimensions when comparing physicians to nurses and when comparing physicians according to their duration of professional experience. Conclusion: The SAQ is a helpful and well-applicable tool to measure patient safety in acute stroke care. In comparison to other high-risk fields in medicine, patient safety climate in acute stroke care seems to be on a similar level with the potential for further improvements. Trial registration: www.ClinicalTrials.gov Identifier: NCT032282.

Multicenter Prospective Analysis of Hypertrophic Olivary Degeneration Following Infratentorial Stroke (HOD-IS): Evaluation of Disease Epidemiology, Clinical Presentation, and MR-Imaging Aspects.

Introduction: Ischemic and hemorrhagic strokes in the brainstem and cerebellum with injury to the functional loop of the Guillain-Mollaret triangle (GMT) can trigger a series of events that result in secondary trans-synaptic neurodegeneration of the inferior olivary nucleus. In an unknown percentage of patients, this leads to a condition called hypertrophic olivary degeneration (HOD). Characteristic clinical symptoms of HOD progress slowly over months and consist of a rhythmic palatal tremor, vertical pendular nystagmus, and Holmes tremor of the upper limbs. Diffusion Tensor Imaging (DTI) with tractography is a promising method to identify functional pathway lesions along the cerebello-thalamo-cortical connectivity and to generate a deeper understanding of the HOD pathophysiology. The incidence of HOD development following stroke and the timeline of clinical symptoms have not yet been determined in prospective studies-a prerequisite for the surveillance of patients at risk. Methods and Analysis: Patients with ischemic and hemorrhagic strokes in the brainstem and cerebellum with a topo-anatomical relation to the GMT are recruited within certified stroke units of the Interdisciplinary Neurovascular Network of the Rhine-Main. Matching lesions are identified using a predefined MRI template. Eligible patients are prospectively followed up and present at 4 and 8 months after the index event. During study visits, a clinical neurological examination and brain MRI, including high-resolution T2-, proton-density-weighted imaging, and DTI tractography, are performed. Fiberoptic endoscopic evaluation of swallowing is optional if palatal tremor is encountered. Study Outcomes: The primary endpoint of this prospective clinical multicenter study is to determine the frequency of radiological HOD development in patients with a posterior fossa stroke affecting the GMT at 8 months after the index event. Secondary endpoints are identification of (1) the timeline and relevance of clinical symptoms, (2) lesion localizations more prone to HOD occurrence, and (3) the best MR-imaging regimen for HOD identification. Additionally, (4) DTI tractography data are used to analyze individual pathway lesions. The aim is to contribute to the epidemiological and pathophysiological understanding of HOD and hereby facilitate future research on therapeutic and prophylactic measures. Clinical Trial Registration: HOD-IS is a registered trial at https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00020549.

COVID-19 Vaccine-Associated Cerebral Venous Thrombosis in Germany.

OBJECTIVE: We aimed to estimate the incidence of cerebral sinus and venous thrombosis (CVT) within 1 month from first dose administration and the frequency of vaccine-induced immune thrombotic thrombocytopenia (VITT) as the underlying mechanism after vaccination with BNT162b2, ChAdOx1, and mRNA-1273, in Germany. METHODS: A web-based questionnaire was e-mailed to all departments of neurology. We requested a report of cases of CVT occurring within 1 month of a COVID-19 vaccination. Other cerebral events could also be reported. Incidence rates of CVT were calculated by using official statistics of 9 German states. RESULTS: A total of 45 CVT cases were reported. In addition, 9 primary ischemic strokes, 4 primary intracerebral hemorrhages, and 4 other neurological events were recorded. Of the CVT patients, 35 (77.8%) were female, and 36 (80.0%) were younger than 60 years. Fifty-three events were observed after vaccination with ChAdOx1 (85.5%), 9 after BNT162b2 (14.5%) vaccination, and none after mRNA-1273 vaccination. After 7,126,434 first vaccine doses, the incidence rate of CVT within 1 month from first dose administration was 0.55 (95% confidence interval [CI] = 0.38-0.78) per 100,000 person-months (which corresponds to a risk of CVT within the first 31 days of 0.55 per 100,000 individuals) for all vaccines and 1.52 (95% CI = 1.00-2.21) for ChAdOx1 (after 2,320,535 ChAdOx1 first doses). The adjusted incidence rate ratio was 9.68 (95% CI = 3.46-34.98) for ChAdOx1 compared to mRNA-based vaccines and 3.14 (95% CI = 1.22-10.65) for females compared to non-females. In 26 of 45 patients with CVT (57.8%), VITT was graded highly probable. INTERPRETATION: Given an incidence of 0.02 to 0.15 per 100,000 person-months for CVT in the general population, these findings point toward a higher risk for CVT after ChAdOx1 vaccination, especially for women. ANN NEUROL 2021;90:627-639.

Simulation-based training improves patient safety climate in acute stroke care (STREAM).

BACKGROUND: Treatment of acute stroke performed by a multiprofessional, interdisciplinary team is highly time dependent. Interface problems are preprogrammed and pitfalls relevant to patient safety are omnipresent. The Safety Attitudes Questionnaire (SAQ) is a validated and widely used instrument to measure patient safety. The objective of this study was to evaluate the influence of Simulation-based Training of the Rapid Evaluation and Management of Acute Stroke (STREAM) on patient safety measured by SAQ in the context of acute stroke care. METHODS: During the STREAM trial at seven university hospitals in Germany from October 2017 to October 2018, an anonymous survey was conducted before and after the STREAM intervention centering around interdisciplinary simulation training. The questionnaire, based on the SAQ, included 33 items (5-point Likert scale, 1 = disagree to 5 = agree) and was addressed at the whole multiprofessional stroke team. Statistical analyses were used to examine psychometric properties as well as descriptive findings. RESULTS: In total 167 questionnaires were completed representing an overall response rate of 55.2%, including especially physicians (65.2%) and nurses (26.3%). Safety climate was significantly improved (pre-interventional: 3.34 ± .63 vs. post-interventional: 3.56 ± .69, p = .028). The same applies for teamwork climate among stroke teams (pre-interventional: 3.76 ± .59 vs. post-interventional: 3.84 ± .57, p = .001). The perceived benefit was most relevant among nurses. CONCLUSIONS: The STREAM intervention centering around interdisciplinary simulation training increases perceived patient safety climate assessed by the SAQ in acute stroke therapy. These results have the potential to be a basis for future quality improvement programs.

Evaluation of Endovascular Treatment for Acute Basilar Occlusion in a State-Wide Prospective Stroke Registry.

Context: Despite overwhelming evidence for endovascular therapy in anterior circulation ischemic stroke due to large-vessel occlusion, data regarding the treatment of acute basilar artery occlusion (BAO) are still equivocal. The BASICS trial failed to show an advantage of endovascular therapy (EVT) over best medical treatment (BMT). In contrast, data from the recently published BASILAR registry showed a better outcome in patients receiving EVT. Objective: The aim of the study was to investigate the safety and efficacy of EVT plus BMT vs. BMT alone in acute BAO. Methods: We analyzed the clinical course and short-term outcomes of patients with radiologically confirmed BAO dichotomized by BMT plus EVT or BMT only as documented in a state-wide prospective registry of consecutive patients hospitalized due to acute stroke. The primary endpoint was a favorable functional outcome (mRS 0-3) at hospital discharge assessed as common odds ratio using binary logistic regression. Secondary subgroup analyses and propensity score matching were added. Safety outcomes included mortality, the rate of intracerebral hemorrhages, and complications during hospitalization. Results: We included 403 patients with acute BAO (2017-2019). A total of 270 patients (67%) were treated with BMT plus EVT and 133 patients (33%) were treated with BMT only. A favorable outcome (mRS 0-3) was observed in 33.8% of the BMT and 26.7% of the BMT plus EVT group [OR.770, CI (0.50-1.2)]. Subgroup analyses for patients with a NIHSS score > 10 at admission to the hospital revealed a benefit from EVT [OR 3.05, CI (1.03-9.01)]. Conclusions: In this prospective, quasi population-based registry of patients hospitalized with acute BAO, BMT plus EVT was not superior to BMT alone. Nevertheless, our results suggest that severely affected BAO patients are more likely to benefit from EVT.

Lessons in clinical reasoning - pitfalls, myths, and pearls: the contribution of faulty data gathering and synthesis to diagnostic error.

OBJECTIVES: Errors in clinical reasoning are a major factor for delayed or flawed diagnoses and put patient safety at risk. The diagnostic process is highly dependent on dynamic team factors, local hospital organization structure and culture, and cognitive factors. In everyday decision-making, physicians engage that challenge partly by relying on heuristics - subconscious mental short-cuts that are based on intuition and experience. Without structural corrective mechanisms, clinical judgement under time pressure creates space for harms resulting from systems and cognitive errors. Based on a case-example, we outline different pitfalls and provide strategies aimed at reducing diagnostic errors in health care. CASE PRESENTATION: A 67-year-old male patient was referred to the neurology department by his primary-care physician with the diagnosis of exacerbation of known myasthenia gravis. He reported shortness of breath and generalized weakness, but no other symptoms. Diagnosis of respiratory distress due to a myasthenic crisis was made and immunosuppressive therapy and pyridostigmine were given and plasmapheresis was performed without clinical improvement. Two weeks into the hospital stay, the patient's dyspnea worsened. A CT scan revealed extensive segmental and subsegmental pulmonary emboli. CONCLUSIONS: Faulty data gathering and flawed data synthesis are major drivers of diagnostic errors. While there is limited evidence for individual debiasing strategies, improving team factors and structural conditions can have substantial impact on the extent of diagnostic errors. Healthcare organizations should provide the structural supports to address errors and promote a constructive culture of patient safety.