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.

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.

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.

Stroke due to Left Atrial Appendage Thrombus after Pulmonary Vein Isolation despite Novel Oral Anticoagulant: A Case Report.

In patients with atrial fibrillation, catheter ablation is suggested to reduce the mortality rate and is thus frequently performed. However, peri- and postprocedural thromboembolic complications as well as high recurrence rates of atrial fibrillation limit its advantages and require concomitant anticoagulation. With the advent of novel oral anticoagulants (NOACs), fixed dosing without routine laboratory monitoring became feasible. Nevertheless, several factors are associated with either an overdose or an insufficient drug activity of NOACs. We report on a patient with atrial fibrillation undergoing catheter ablation and cardioversion suffering from ischemic stroke despite being under oral anticoagulation. It turned out that the drug activity of the NOACs used was repeatedly insufficient in spite of regular intake and adequate dosing. In sum, drug activity controls should be taken into consideration in patients with thrombotic events despite oral anticoagulation with NOACs.

Evaluating Magnetic Resonance Spectroscopy as a Tool for Monitoring Therapeutic Response of Whole Brain Radiotherapy in a Mouse Model for Breast-to-Brain Metastasis.

Brain metastases are the most common intracranial tumor in adults and are associated with poor patient prognosis and median survival of only a few months. Treatment options for brain metastasis patients remain limited and largely depend on surgical resection, radio- and/or chemotherapy. The development and pre-clinical testing of novel therapeutic strategies require reliable experimental models and diagnostic tools that closely mimic technologies that are used in the clinic and reflect histopathological and biochemical changes that distinguish tumor progression from therapeutic response. In this study, we sought to test the applicability of magnetic resonance (MR) spectroscopy in combination with MR imaging to closely monitor therapeutic efficacy in a breast-to-brain metastasis model. Given the importance of radiotherapy as the standard of care for the majority of brain metastases patients, we chose to monitor the post-irradiation response by magnetic resonance spectroscopy (MRS) in combination with MR imaging (MRI) using a 7 Tesla small animal scanner. Radiation was applied as whole brain radiotherapy (WBRT) using the image-guided Small Animal Radiation Research Platform (SARRP). Here we describe alterations in different metabolites, including creatine and N-acetylaspartate, that are characteristic for brain metastases progression and lactate, which indicates hypoxia, while choline levels remained stable. Radiotherapy resulted in normalization of metabolite levels indicating tumor stasis or regression in response to treatment. Our data indicate that the use of MR spectroscopy in addition to MRI represents a valuable tool to closely monitor not only volumetrical but also metabolic changes during tumor progression and to evaluate therapeutic efficacy of intervention strategies. Adapting the analytical technology in brain metastasis models to those used in clinical settings will increase the translational significance of experimental evaluation and thus contribute to the advancement of pre-clinical assessment of novel therapeutic strategies to improve treatment options for brain metastases patients.

Generation of an Atxn2-CAG100 knock-in mouse reveals N-acetylaspartate production deficit due to early Nat8l dysregulation.

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disorder caused by CAG-expansion mutations in the ATXN2 gene, mainly affecting motor neurons in the spinal cord and Purkinje neurons in the cerebellum. While the large expansions were shown to cause SCA2, the intermediate length expansions lead to increased risk for several atrophic processes including amyotrophic lateral sclerosis and Parkinson variants, e.g. progressive supranuclear palsy. Intense efforts to pioneer a neuroprotective therapy for SCA2 require longitudinal monitoring of patients and identification of crucial molecular pathways. The ataxin-2 (ATXN2) protein is mainly involved in RNA translation control and regulation of nutrient metabolism during stress periods. The preferential mRNA targets of ATXN2 are yet to be determined. In order to understand the molecular disease mechanism throughout different prognostic stages, we generated an Atxn2-CAG100-knock-in (KIN) mouse model of SCA2 with intact murine ATXN2 expression regulation. Its characterization revealed somatic mosaicism of the expansion, with shortened lifespan, a progressive spatio-temporal pattern of pathology with subsequent phenotypes, and anomalies of brain metabolites such as N-acetylaspartate (NAA), all of which mirror faithfully the findings in SCA2 patients. Novel molecular analyses from stages before the onset of motor deficits revealed a strong selective effect of ATXN2 on Nat8l mRNA which encodes the enzyme responsible for NAA synthesis. This metabolite is a prominent energy store of the brain and a well-established marker for neuronal health. Overall, we present a novel authentic rodent model of SCA2, where in vivo magnetic resonance imaging was feasible to monitor progression and where the definition of earliest transcriptional abnormalities was possible. We believe that this model will not only reveal crucial insights regarding the pathomechanism of SCA2 and other ATXN2-associated disorders, but will also aid in developing gene-targeted therapies and disease prevention.