Treatment of acute ischemic stroke in patients with active malignancy: insight from a comprehensive stroke center.

Background: Despite the high incidence of acute ischemic stroke (AIS) in cancer patients, there is still no consensus about the safety of recanalization therapies in this cohort. Objectives: In this observational study, our aim was to investigate the bleeding risk after acute recanalization therapy in AIS patients with active malignancy. Methods and Study Design: We retrospectively analyzed observational data of 1016 AIS patients who received intravenous thrombolysis with rtPA (IVT) and/or endovascular therapy (EVT) between January 2017 and December 2020 with a focus on patients with active malignancy. The primary safety endpoint was the occurrence of stroke treatment-related major bleeding events, that is, symptomatic intracranial hemorrhage (SICH) and/or relevant systemic bleeding. The primary efficacy endpoint was neurological improvement during hospital stay (NI). Results: None of the 79 AIS patients with active malignancy suffered from stroke treatment-related systemic bleeding. The increased rate (7.6% versus 4.7%) of SICH after therapy compared to the control group was explained by confounding factors. A total of nine patients with cerebral tumor manifestation received acute stroke therapy, two of them suffered from stroke treatment-related intracranial hemorrhage remote from the tumor, both asymptomatic. The group of patients with active malignancy and the control group showed comparable rates of NI. Conclusion: Recanalization therapy in AIS patients with active malignancy was not associated with a higher risk for stroke treatment-related systemic or intracranial bleeding. IVT and/or EVT can be regarded as a safe therapy option for AIS patients with active malignancy.

Frequency and Characteristics of Non-Neurological and Neurological Stroke Mimics in the Emergency Department.

BACKGROUND: Stroke mimics are common in the emergency department (ED) and early detection is important to initiate appropriate treatment and withhold unnecessary procedures. We aimed to compare the frequency, clinical characteristics and predictors of non-neurological and neurological stroke mimics transferred to our ED for suspected stroke. METHODS: This was a cross-sectional study of consecutive patients with suspected stroke transported to the ED of the University Hospital Essen between January 2017 and December 2021 by the city's Emergency Medical Service. We investigated patient characteristics, preclinical data, symptoms and final diagnoses in patients with non-neurological and neurological stroke mimics. Multinominal logistic regression analysis was performed to assess predictors of both etiologic groups. RESULTS: Of 2167 patients with suspected stroke, 762 (35.2%) were diagnosed with a stroke mimic. Etiology was non-neurological in 369 (48.4%) and neurological in 393 (51.6%) cases. The most common diagnoses were seizures (23.2%) and infections (14.7%). Patients with non-neurological mimics were older (78.0 vs. 72.0 y, p < 0.001) and more likely to have chronic kidney disease (17.3% vs. 9.2%, p < 0.001) or heart failure (12.5% vs. 7.1%, p = 0.014). Prevalence of malignancy (8.7% vs. 13.7%, p = 0.031) and focal symptoms (38.8 vs. 57.3%, p < 0.001) was lower in this group. More than two-fifths required hospitalization (39.3 vs. 47.1%, p = 0.034). Adjusted multinominal logistic regression revealed chronic kidney and liver disease as independent positive predictors of stroke mimics regardless of etiology, while atrial fibrillation and hypertension were negative predictors in both groups. Prehospital vital signs were independently associated with non-neurological stroke mimics only, while age was exclusively associated with neurological mimics. CONCLUSIONS: Up to half of stroke mimics in the neurological ED are of non-neurological origin. Preclinical identification is challenging and a high proportion requires hospitalization. Awareness of underlying etiologies and differences in clinical characteristics is important to provide optimal care.

Validation of a German-language modified Rankin Scale structured telephone interview at 3 months in a real-life stroke cohort.

BACKGROUND: The modified Rankin scale (mRS) at 3 months is established as the primary outcome measure in clinical stroke trials. Traditionally, the mRS is assessed through an unstructured face-to-face interview. This approach can be labor-intensive and lead to suboptimal inter-rater reliability. Recently, the Covid-19 pandemic made face-to-face contact even more challenging. To address these issues, we developed and validated a structured German-language questionnaire for mRS testing by telephone. METHODS: In this prospective cohort study, we compared the mRS testing results of the standard face-to-face interview with those obtained in a structured interview by telephone using Cohen's Kappa. RESULTS: At our tertiary care stroke center, we included 108 patients who underwent both assessments. In 80.6% of cases (87/108) face-to-face and telephone interview reached identical scores. Linear weighted Kappa was 0.82 (p < 0.001). Unweighted Kappa for dichotomized mRS between fair (0-2) and poor (3-6) functional outcome was κ = 0.97 (p < 0.001). CONCLUSIONS: Our study validates the use of the German-language structured telephone interview as a reliable instrument for the use in clinical trials. We encourage others to utilize the questionnaire. It is available as an Appendix (Additional file 1) to this publication.

Predictors of Early Neurological Improvement in Patients with Anterior Large Vessel Occlusion and Successful Reperfusion Following Endovascular Thrombectomy-Does CT Perfusion Imaging Matter?

PURPOSE: We aimed to investigate treatment effect of endovascular thrombectomy (EVT) on the change of National Institutes of Health Stroke Scale (NIHSS) scores in acute ischemic stroke (AIS) patients with anterior large vessel occlusion (LVO). Predictors of early neurological improvement (ENI) were assessed in those with successful reperfusion. METHODS: Data on stroke patients from January 2018 to December 2020 were retrospectively analyzed. Anterior LVO was defined as occlusion of internal carotid artery and/or M1/M2 branch of middle cerebral artery. A reduction of at least 8 NIHSS points at 24 h after EVT or NIHSS score ≤ 1 at discharge was defined as ENI. In patients with successful reperfusion (TICI score of 2b/3) and available CT perfusion (CTP) imaging, 20 variables were tested in a smoothed ridge regression for their association with ENI. RESULTS: One hundred seventy two out of 211 patients had successful perfusion with 54 patients achieving ENI. Impact of successful EVT on reducing NIHSS score grew continuously on a daily basis up to the date of discharge. 105 out of 172 patients were included in final regression model. Short time from onset to admission and from groin-puncture to reperfusion, young age, low prestroke disability, high baseline CTP ASPECTS and high follow-up non-contrast CT (NCCT) ASPECTS were significantly associated with ENI. Neither baseline NCCT ASPECTS nor the volume of penumbra or ischemic core measured on CTP were associated with ENI. CONCLUSION: CTP ASPECTS might better predict ENI than non-contrast CT at baseline in patients with successful reperfusion following EVT.

Reclassifications of ischemic stroke patterns due to variants of the Circle of Willis.

BACKGROUND: Variants of the Circle of Willis (vCoW) may impede correct identification of ischemic lesion patterns and stroke etiology. We assessed reclassifications of ischemic lesion patterns due to vCoW. METHODS: We analyzed vCoW in patients with acute ischemic stroke from the 1000+ study using time-of-flight magnetic resonance angiography (TOF MRA) of intracranial arteries. We assessed A1 segment agenesis or hypoplasia in the anterior circulation and fetal posterior cerebral artery in the posterior circulation. Stroke patterns were classified as one or more-than-one territory stroke pattern. We examined associations between vCoW and stroke patterns and the frequency of reclassifications of stroke patterns due to vCoW. RESULTS: Of 1000 patients, 991 had evaluable magnetic resonance angiography. At least one vCoW was present in 37.1%. VCoW were more common in the posterior than in the anterior circulation (33.3% vs. 6.7%). Of 238 patients initially thought to have a more-than-one territory stroke pattern, 20 (8.4%) had to be reclassified to a one territory stroke pattern after considering vCoW. All these patients had fetal posterior cerebral artery and six (30%) additionally had carotid artery disease. Of 753 patients initially presumed to have a one-territory stroke pattern, four (0.5%) were reclassified as having more-than-one territory pattern. CONCLUSIONS: VCoW are present in about one in three stroke patients and more common in the posterior circulation. Reclassifications of stroke lesion patterns due to vCoW occurred predominantly in the posterior circulation with fetal posterior cerebral artery mimicking multiple territory stroke pattern. Considering vCoW in these cases may uncover symptomatic carotid disease.

Primary Angiitis of the CNS: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: To facilitate and improve the diagnostic and therapeutic process by systematically reviewing studies on patients with primary angiitis of the CNS (PACNS). METHODS: We searched PubMed, looking at the period between 1988 and February 2020. Studies with adult patients with PACNS were included. We extracted and pooled proportions using fixed-effects models. Main outcomes were proportions of patients with certain clinical, imaging, and laboratory characteristics and neurologic outcomes. RESULTS: We identified 46 cohort studies including a total of 911 patients (41% biopsy confirmed, 43% angiogram confirmed, and 16% without clear assignment to the diagnostic procedure). The most frequent onset symptoms were focal neurologic signs (63%), headache (51%), and cognitive impairment (41%). Biopsy- compared with angiogram-confirmed cases had higher occurrences of cognitive impairment (55% vs 39%) and seizures (36% vs 16%), whereas focal neurologic signs occurred less often (56% vs 95%). CSF abnormalities were present in 75% vs 65% and MRI abnormalities in 97% vs 98% of patients. Digital subtraction angiography was positive in 33% of biopsy confirmed, and biopsy was positive in 8% of angiogram-confirmed cases. In 2 large cohorts, mortality was 23% and 8%, and the relapse rate was 30% and 34%, during a median follow-up of 19 and 57 months, respectively. There are no randomized trials on the treatment of PACNS. The initial treatment usually includes glucocorticoids and cyclophosphamide. DISCUSSION: PACNS is associated with disabling symptoms, frequent relapses, and significant mortality. Differences in symptoms and neuroimaging results and low overlap between biopsy and angiogram suggest that biopsy- and angiogram-confirmed cases represent different histopathologic types of PACNS. The optimal treatment is unknown.

Student engagement in medical education: A mixed-method study on medical students as module co-directors in curriculum development.

Introduction: Beyond participation in evaluation of teaching, there is sparse research available on more active roles of medical students in curriculum development. We report on a model of student engagement where medical students function as module co-directors, and how this is experienced by faculty and student module directors. Methods: Student engage in co-development of their curriculum with a high level of autonomy in organizing their activities. We conducted a mixed-methods, convergent design study based on surveys with faculty and student module co-directors and a student co-director focus group. Quantitative data were analyzed descriptively. Qualitative analysis was performed inductively. Results: Quantitatively, the majority of both faculty and student module directors report that the curriculum benefits from the students' work (95 and 94%). Both groups see each other as equal partners (80 and 87%). Qualitatively, this is related to students' competencies such as "bringing in broad and unique knowledge of the curriculum", "giving the students' perspective a voice," and "contributing ideas for improvement". Key strategies and challenges of the student co-module directors are illuminated. Conclusions: Student module co-directors represent a well-accepted practice model for curriculum development. This report may stimulate other faculties to engage their students more actively in medical education.

Biomarkers in Vasculitides of the Nervous System.

Besides being affected by the rare and severe primary angiitis of the central nervous system (PACNS) the nervous system is also affected by primary systemic vasculitides (PSV). In contrast to PACNS, PSV affect not only the central but also the peripheral nervous system, resulting in a large array of potential symptoms. Given the high burden of disease, difficulties in distinguishing between differential diagnoses, and incomplete pathophysiological insights, there is an urgent need for additional precise diagnostic tools to enable an earlier diagnosis and initiation of effective treatments. Methods available to date, such as inflammatory markers, antibodies, cerebrospinal fluid (CSF) analysis, imaging, and biopsy, turn out to be insufficient to meet all current challenges. We highlight the use of biomarkers as an approach to extend current knowledge and, ultimately, improve patient management. Biomarkers are considered to be useful for disease diagnosis and monitoring, for predicting response to treatment, and for prognosis in clinical practice, as well as for establishing outcome parameters in clinical trials. In this article, we review the recent literature on biomarkers which have been applied in the context of different types of nervous system vasculitides including PACNS, giant-cell arteritis, Takayasu's arteritis, polyarteritis nodosa, ANCA (anti-neutrophil cytoplasm antibody)-associated vasculitides, cryoglobulinemic vasculitis, IgA vasculitis, and Behçet's disease. Overall, the majority of biomarkers is not specific for vasculitides of the nervous system.

Clinical significance of acute and chronic ischaemic lesions in multiple cerebral vascular territories.

OBJECTIVES: To investigate the association between acute and chronic ischaemic lesions in a multiple territory lesion pattern (MTLP) detected by 3-Tesla MRI and stroke aetiology, specifically atrial fibrillation-associated stroke. METHODS: We analysed data from the 1000+ study - a prospective, observational 3-Tesla MRI cohort study of consecutively included acute stroke patients. Acute and chronic lesions were detected by DWI and fluid-attenuated inversion recovery, respectively. Observers blinded to clinical data allocated lesions to the right anterior, left anterior or posterior circulation. Lesion pattern was categorised as MTLPa/c when more than one territory was affected by either acute or chronic lesions or as MTLPa when more than one territory was affected by acute lesions alone. RESULTS: Of the 1,000 included patients, an MTLPa/c was found in 43% and MTLPa in 24%. Advanced age (aOR=1.21 per 10 years, 95% CI 1.06-1.39), atrial fibrillation (aOR=1.44, 95% CI 1.06-1.94), aortic arch atherosclerosis (aOR=2.52, 95% CI 1.10-5.77), malignant disease (aOR=1.99, 95% CI 1.25-3.16) and lower estimated glomerular filtration rate (eGFR) (aOR=0.90 per 10 ml, 95% CI 0.84-0.97) were associated with MTLPa/c. Only malignant disease (aOR=2.03, 95% CI 1.27-3.23) and lower eGFR (aOR=0.91 per 10 ml, 95% CI 0.85-0.97) were associated with MTLPa. CONCLUSIONS: An MRI-detected multiple territory lesion pattern of acute and chronic ischaemic lesions is frequent and more often present in older patients and patients with atrial fibrillation, aortic arch atherosclerosis, malignant disease and lower eGFR. Considering not only acute but also chronic ischaemic lesions may facilitate identifying atrial fibrillation-associated or aorto-embolic stroke. KEY POINTS: • Brain imaging with MRI may help to determine the aetiology of stroke. • Of 1,000 stroke patients undergoing 3-Tesla MRI, 43% had acute and chronic ischaemic lesions in multiple cerebral vascular territories. • Atrial fibrillation, aortic arch atherosclerosis and malignant disease were associated with a multiple territory lesion pattern.