Jan Hendrik Schaefer

Background: The timing of ischemic stroke and intracerebral hemorrhage (ICH) onsets follow distinct daily patterns, but it remains unclear whether these patterns influence ICH outcomes. Methods: Consecutive data were obtained from the prospective stroke inpatient quality assurance registry of Hesse, Germany from 2015 to 2023. Patients with ICH were grouped according to the time of symptom onset: morning (5:00 AM to 10:59 AM), midday (11:00 AM to 4:59 PM), evening (5:00 PM to 10:59 PM), and night (11:00 PM to 4:59 AM). The primary outcome was global disability at discharge, analyzed using ordinal logistic regression. Secondary outcomes included mortality and complications during hospitalization. To account for potential confounding, the analysis incorporated both inverse probability weighting (IPW) and propensity score matching (PSM) based on baseline characteristics. Results: After exclusions, 5665 patients underwent final analysis. Peak ICH incidences occurred around 8:30 AM and 5:00 PM with a minimum at approximately midnight. Patients experiencing ICH during the evening and particularly at night had higher discharge disability, compared to those with symptom onset in the morning or midday. Unadjusted analyses found daily variations in mortality and in‐hospital complications that were no longer significant after adjustment by PSM or IPW. Conclusion: Our study confirms the daily pattern previously observed in ICH onset, with peak onset during daytime. Functional outcomes were worse in evening and night onset ICH patients. These findings underscore the potential for chronobiologically informed prevention and treatment strategies and the need for further research into time‐dependent pathophysiology and care delivery.

Background/Objectives: After the negative results of the SAMMPRIS trial, the indication for endovascular treatment of atherosclerotic intracranial artery stenosis (ICAS) was widely restricted. It was the aim of our study to report whether intracranial arterial percutaneous transluminal angioplasty and stenting (PTAS) as ultima ratio therapy is still effective and safe enough. Methods: Between February 2011 and June 2019, 63 consecutive patients with and without emergent large vessel occlusion (ELVO) who received PTAS for symptomatic ICAS in the anterior or vertebrobasilar circulation were included in our study. Results: A total of 32 patients had ELVO. In the remaining 31 patients, a known ICAS was treated with PTAS either because of recurrent stroke despite aggressive medical therapy with dual antiplatelet inhibition (n = 24) or due to progressive hemodynamic ischemia (n = 7). Stenting was successful in all 63 cases. Successful reperfusion was achieved in 94% of ELVO patients. Complications with new neurologic deficits, including dissection, subarachnoid hemorrhage, intracerebral hemorrhage (PH2), and stent thrombosis, were seen in five ELVO patients (16%). At discharge, neurological status improved in 16 patients (50%) and deteriorated in 7 patients (22%). In-hospital mortality happened in 5 of 32 ELVO cases (16%), and all of them had lesions in the vertebrobasilar circulation. Regarding non-ELVO cases, two patients (6%) developed new neurologic deficits due to perforator strokes. There was no in-hospital mortality in this group. Conclusions: Even in unfavorable situations with acute atherothrombotic occlusions or recurrent strokes under aggressive medical therapy of known ICAS, PTAS remains a treatment option with reasonable effectiveness. This should be balanced against other treatment options, taking into account the complication rate, which is not negligible.

Background: The drip-and-ship model is a common practice for patients with ischemic stroke due to large-vessel occlusion (LVO), providing initial diagnostics and thrombolysis in transition to endovascular treatment (EVT). However, hospital transfer results in treatment delays for patients requiring EVT, potentially affecting outcomes. We sought to explore the association between distance from residence and time intervals to admission with clinical outcomes after EVT. Methods: In this monocentric retrospective cohort study, patients with acute ischemic stroke due to LVO who underwent EVT at Frankfurt University Hospital between 2017 and 2023 were analyzed. Patients were grouped according to direct-to-center (DC) or drip-and-ship (DS) admission. Clinical outcome parameters included patient global disability after 90 days as measured by the modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS) score improvements analyzed in relation to geographical distance and time metrics. A subgroup analysis based on the distance from residence in 10 km intervals was added. Results: A total of 334 patients were included. Of these, 41.9% were DC admissions and 58.1% DS were admissions. Distances from home to center were shorter for DC patients (11.1 km vs. 36.4 km, p < 0.001), resulting in significantly shorter times from symptom onset to admission (−114 min; 71 min vs. 185 min; p < 0.001) and to flow restoration (−88 min; 213 min vs. 301 min; p < 0.001). After 90 days, no significant differences in clinical outcomes between DC and DS were observed. However, DC patients living closer than 10 km to the center were more likely to achieve an mRS score p = 0.012). Conclusion: Proximity of residence to a thrombectomy center may be advantageous for stroke patients, most likely in association with direct pre-hospital transfers. Distances above 30 km more frequently led to drip-and-ship, which may facilitate care through early diagnostics as, signified by a reduction in the relative time delay to flow restoration.

Background/ Objectives; After negative results of the SAMMPRIS-trial the indication for endovascular treatment of atherosclerotic intracranial artery stenosis (ICAS) was widely restricted. It was the aim of our study to report whether intracranial arterial percutaneous transluminal angioplasty and stenting (PTAS) as ultima ratio therapy is still effective and safe enough. Methods: Between February 2011 and June 2019, 63 consecutive patients with and without emergent large vessel occlusion (ELVO) who received PTAS for symptomatic ICAS in the anterior or vertebrobasilar circulation were in-cluded in our study. Results: 32 patients had ELVO. In the remaining 31 patients, a known ICAS was treated with PTAS either because of recurrent stroke despite aggressive medical therapy with dual antiplatelet inhibition (n=24) or due to progressive hemodynamic ischemia (n=7). Stenting was successful in all 63 cases. Successful reperfusion was achieved in 94% of ELVO patients. Complications with new neurologic deficits, including dissection, subarachnoid hemorrhage, in-tracerebral hemorrhage (PH2), and stent-thrombosis, were seen in 5 ELVO patients (16%). At discharge, neuro-logical status improved in 16 patients (50%) and deteriorated in 7 patients (22%). In-hospital mortality happened in 5 of 32 ELVO cases (16%), all of them had lesions in the vertebrobasilar circulation. Regarding non-ELVO cases, two patients (6%) developed new neurologic deficits due to perforator strokes. There was no in-hospital mortality in this group. Conclusion: Even in unfavorable situations with acute atherothrombotic occlusions or recurrent strokes under ag-gressive medical therapy of known ICAS, PTAS remains a treatment option with reasonable efficacy and tolerable complication rates.

Impaired renal function can influence biomarker levels through mechanisms involving blood–brain barrier integrity and clearance pathways; however, the impact of variations within normal renal function remains unclear. The main aim of this study was to determine whether adjustment for the specific level of renal function is necessary when renal function remains within physiological levels. We studied n = 183 patients (NID n = 122; other neurological diseases n = 39; somatoform controls n = 22) who underwent lumbar puncture at University Hospital Frankfurt. Serum and cerebrospinal fluid (CSF) levels of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total tau protein (tTAU), and ubiquitin C-terminal hydrolase-L1 (UCHL1) were measured using the single molecule array (SIMOA) technique. Estimated glomerular filtration rate (eGFR) correlated negatively with CSF GFAP (r = −0.217, p = 0.004) and serum NfL (r = −0.164, p = 0.032). Patients with impaired renal function exhibited higher CSF NfL (p = 0.036) and CSF GFAP (p = 0.026) levels. However, these findings did not remain significant after adjusting for BMI and age. Importantly, in patients with normal renal function, no significant correlations with eGFR and biomarker levels were observed after adjustment. Our findings indicate that serum and CSF concentrations of NfL, GFAP, tTAU, and UCHL1 are not significantly affected by fluctuations in physiological kidney function but emphasize the importance of considering comorbidities in impaired renal function when interpreting biomarker levels.

Background and purpose: Swallowing is a complex task, moderated by a sophisticated bilateral network including multiple supratentorial regions, the brainstem and the cerebellum. To date, conflicting data exist about whether focal lesions to the cerebellum are associated with dysphagia. Therefore, the aim of the study was to evaluate dysphagia prevalence, recovery and dysphagia pattern in patients with ischaemic cerebellar stroke.Methods: A retrospective analysis of patients consecutively admitted to an academic stroke centre with ischaemic stroke found only in the cerebellum was performed. The presence of dysphagia was the primary end‐point and was assessed by a speech‐language pathologist, according to defined criteria. Dysphagia pattern was evaluated by analysing the videos of the flexible endoscopic evaluation of swallowing. Brain imaging was used to identify lesion size and location associated with dysphagia.Results: Between January 2016 and December 2021, 102 patients (35.3% female) with a mean age of 52.8 ± 17.3 years were included. Thirteen (12.7%) patients presented with dysphagia. The most frequently observed flexible endoscopic evaluation of swallowing phenotype was premature spillage (n = 7; 58.3%), whilst significant residues or aspiration did not occur. One patient died (7.7%); the other patients showed improvement of dysphagia and one patient (7.7%) was discharged with dietary restrictions.Conclusions: Although the involvement of the cerebellum in deglutition has become increasingly evident, isolated lesions to the cerebellum are less likely to cause clinically relevant and persisting dysphagia compared to other brain regions. The observed dysphagia pattern shows a lack of coordination and control, resulting in premature spillage or fragmented bolus transfer in some patients.

Background: The clinical course of ischemic and hemorrhagic strokes can be influenced by the coagulation status of individual patients. The prior use of antiplatelet therapy (APT) such as acetylsalicylic acid (ASA) or P2Y12-antagonists has been inconsistently described as possibly increasing the risk of hemorrhagic transformation or expansion. Since clinical studies describing prior use of antiplatelet medication are overwhelmingly lacking specific functional tests, we aimed to implement testing in routine stroke care.Methods: We used fluorescence-activated cell sorting (FACS) with antibodies against CD61 for thrombocyte identification and CD62p or platelet activation complex-1 (PAC-1) to determine platelet activation. Aggregometry and automated platelet functioning analyzer (PFA-200) were employed to test thrombocyte reactivity. FACS and aggregometry samples were stimulated in vitro with arachidonic acid (AA) and adenosine diphosphate (ADP) to measure increase in CD62p-/PAC-1-expression or aggregation, respectively.Results: Between February and July 2023, 20 blood samples (n = 11 ischemic strokes; n = 7 hemorrhagic strokes; n = 2 controls) were acquired and analyzed within 24 h of symptom onset. N = 11 patients had taken ASA, n = 8 patients no APT and n = 1 ASA+clopidogrel. ASA intake compared to no APT was associated with lower CD62p expression after stimulation with AA on FACS analysis (median 15.8% [interquartile range {IQR} 12.6–37.2%] vs. 40.1% [IQR 20.3–56.3%]; p = 0.020), lower platelet aggregation (9.0% [IQR 7.0–12.0%] vs. 88.5% [IQR 11.8–92.0%]; p = 0.015) and longer time to plug formation with PFA-200 (248.0 s [IQR 157.0–297] vs. 121.5 s [IQR 99.8–174.3]; p = 0.027). Significant correlations were noted between AA-induced CD62p expression and aggregometry analysis (n = 18; ρ = 0.714; p < 0.001) as well as a negative correlation between CD62p increase and PFA clot formation time (n = 18; ρ = −0.613; p = 0.007). Sensitivity for ASA intake was highest for PFA (81.8% for values ≥155.5 s). The combination of ASA + clopidogrel also affected ADP-induced CD62p and PAC-1 expression.Conclusion: In the clinical setting it is feasible to use differentiated platelet analytics to determine alterations caused by antiplatelet therapy. Among the tests under investigation, PFA-200 showed the highest sensitivity for the intake of ASA in stroke patients. FACS analysis on the other hand might be able to provide a more nuanced approach to altered platelet reactivity.

BACKGROUND: Several individual predictors for outcomes in patients with cerebellar stroke (CS) have been previously identified. There is, however, no established clinical score for CS. Therefore, the aim of this study was to develop simple and accurate grading scales for patients with CS in an effort to better estimate mortality and outcomes. METHODS: This multicentric retrospective study included 531 patients with ischemic CS presenting to 5 different academic neurosurgical and neurological departments throughout Germany between 2008 and 2021. Logistic regression analysis was performed to determine independent predictors related to 30-day mortality and unfavorable outcome (modified Rankin Scale score of 4–6). By weighing each parameter via calculation of regression coefficients, an ischemic CS-score and CS-grading scale (CS-GS) were developed and internally validated. RESULTS: Independent predictors for 30-day mortality were aged ≥70 years (odds ratio, 5.2), Glasgow Coma Scale score 3 to 4 at admission (odds ratio, 2.6), stroke volume ≥25 cm ³ (odds ratio, 2.7), and involvement of the brain stem (odds ratio, 3.9). When integrating each parameter into the CS-score, age≥70 years and brain stem stroke were assigned 2 points, Glasgow Coma Scale score 3 to 4, and stroke volume≥25 cm ³ 1 point resulting in a score ranging from 0 to 6. CS-score of 0, 1, 2, 3, 4, 5, and 6 points resulted in 30-day mortality of 1%, 6%, 6%, 17%, 21%, 55%, and 67%, respectively. Independent predictors for 30-day unfavorable outcomes consisted of all components of the CS-score with an additional variable focused on comorbidities (CS-GS). Except for Glasgow Coma Scale score 3 to 4 at admission, which was assigned 3 points, all other parameters were assigned 1 point resulting in an overall score ranging from 0 to 7. CS-GS of 0, 1, 2, 3, 4, 5, 6, and 7 points resulted in 30-day unfavorable outcome of 1%, 17%, 33%, 40%, 50%, 80%, 77%, and 100%, respectively. Both 30-day mortality and unfavorable outcomes increased with increasing CS-score and CS-GS ( P <0.001). CONCLUSIONS: The CS-score and CS-GS are simple and accurate grading scales for the prediction of 30-day mortality and unfavorable outcome in patients with CS. While the score systems proposed here may not directly impact treatment decisions, it may help discuss mortality and outcome with patients and caregivers.

Background: The presence of contrast enhancement (CE) on magnetic resonance imaging (MRI) is one of the principal criteria for diagnosis and disease activity of multiple sclerosis (MS). Therefore, MS patients are frequently exposed to contrast agents, which may cause deposition in the brain, restricting its use in repeat examinations. Thus, serum biomarkers may be valuable as surrogate parameters to evaluate MS activity.Methods: REDUCE‐GAD was a prospective, multicentric, biobanking study to determine whether established serum markers (neurofilament light chain [NfL], glial fibrillary acidic protein [GFAP], tau protein, ubiquitin‐carboxyl‐terminal‐hydrolase (UCH‐L1), S100B and matrix‐metalloproteinase 9 [MMP9]) are predictive of CE‐positive MRI lesions. Blood samples were obtained from patients undergoing MRI 5 days before or after collection.Results: Patients (N = 102) from four different centers with confirmed MS or related disorders were included; n = 57 (55.9%) showed CE on MRI versus n = 45 (44.1%) without CE. Only higher NfL values indicated CE (odds ratio [OR] 1.05; 95% CI 1.0–1.09) and were correlated with number (ρ = 0.47; p < 0.001) and diameter of CE lesions (ρ = 0.58; p < 0.001). Nfl Z‐scores improved diagnostic accuracy (OR 1.52; 95% CI 1.06–2.18). Receiver operator characteristic analysis revealed a reasonable cut‐off value for NfL at 14.1 pg/mL (sensitivity 49.1%; specificity 82.2%; positive predictive value 77.8%; negative predictive value 56.0%). NfL ≥59.2 pg/mL was exclusively observed in patients with CE.Conclusions: Evaluation of several possible serum biomarkers for CE in MS patients provided the most robust results for NfL, particularly as Z‐scores. Following further evaluation, biomarkers may help stratify the application of contrast agents for brain imaging in MS patients.

Background: The incidence of ischemic stroke was previously expected to rise among countries with an aging population. Lately, several studies from developed countries have reported a decline in certain cohorts. Whether this applies to all sexes, however, is uncertain, with limited data on the temporal development in incidence, treatment, and recovery. Methods and Results: We analyzed a prospective stroke inpatient quality‐assurance registry of the federal state of Hesse, Germany. Recruitment of all patients with a final diagnosis of ischemic stroke at hospital discharge ( International Classification of Diseases , Tenth Revision [ ICD‐10 ]: I63) is mandatory by law. Incidence rates were calculated based on census data of all inhabitants and stratified according to age. Between 2010 and 2019, there were 141 277 patients included, 73 770 (52.2%) male patients and 67 507 (47.8%) female patients. Overall, the incidence of ischemic stroke was 228 per 100 000 in 2010 and 226 per 100 000 in 2019 (−0.8%; odds ratio [OR], 0.99 [95% CI, 0.96–1.02]; P =0.50). For male patients, the incidence increased continuously from 236 per 100 000 to 245 per 100 000 (+3.8%); in female patients it decreased from 220 per 100 000 to 208 per 100 000 (−5.6%). After adjusting for age, the OR for ischemic stroke between male and female patients was 1.40 in 2010 (95% CI, 1.35–1.44; P P <0.001). This development was most pronounced in male patients aged 45 to 59 years with an increase from 151 per 100 000 to 176 per 100 000. In this age group, male patients showed increasing rates of prior strokes and atrial fibrillation, surpassing the prevalence in female patients over time. After multivariable regression analysis, male patients had a lower modified Rankin Scale at discharge compared with female patients, but this difference has decreased since 2015 (common OR in 2010, 0.83 [95% CI, 0.78–0.88]; common OR in 2019, 0.90 [95% CI, 0.84–0.95]), which coincided with rising rates of endovascular treatment. Conclusions: Over the past decade in the federal state of Hesse, the overall incidence of ischemic stroke has declined predominantly in the female population. In contrast, for male patients, the incidence has risen by about 4%, with a steeper increase of 16% in male patients aged 45 to 59 years, which might be related to increasing rates of recurrent strokes and atrial fibrillation in this cohort. This finding provides a cautionary tale for effective secondary prevention. Female patients were generally less likely to achieve a favorable outcome, but since the introduction of endovascular treatment, the outcome gap is decreasing.