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Background and Purpose: Acute ischemic stroke due to basilar artery occlusion (BAO) causes the most severe strokes and has a poor prognosis. Data regarding efficacy of endovascular thrombectomy in BAO are sparse. Therefore, in this study, we performed an analysis of the therapy of patients with BAO in routine clinical practice., Methods: Patients enrolled between June 2015 and December 2019 in the German Stroke Registry-Endovascular Treatment (GSR-ET) were analyzed. Primary outcomes were successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] score of 2b-3), substantial neurological improvement (≥8-point National Institute of Health Stroke Scale [NIHSS] score reduction from admission to discharge or NIHSS score at discharge ≤1), and good functional outcome at 3 months (modified Rankin Scale [mRS] score of 0-2)., Results: Out of 6635 GSR-ET patients, 640 (9.6%) patients (age 72.2 ± 13.3, 43.3% female) experienced BAO (median [interquartile range] NIHSS score 17 [8, 27]). Successful reperfusion was achieved in 88.4%. Substantial neurological improvement at discharge was reached by 45.5%. At 3-month follow-up, good clinical outcome was observed in 31.1% of patients and the mortality rate was 39.2%. Analysis of mTICI3 versus mTICI2b groups showed considerable better outcome in those with mTICI3 (38.9% vs. 24.4%; p = 0.005). The strongest predictors of good functional outcome were intravenous thrombolysis (IVT) treatment (odds ratio [OR] 3.04, 95% confidence interval [CI] 1.76-5.23) and successful reperfusion (OR 4.92, 95% CI 1.15-21.11), while the effect of time between symptom onset and reperfusion seemed to be small., Conclusions: Acute reperfusion strategies in BAO are common in daily practice and can achieve good rates of successful reperfusion, neurological improvement and good functional outcome. Our data suggest that, in addition to IVT treatment, successful and, in particular, complete reperfusion (mTICI3) strongly predicts good outcome, while time from symptom onset seemed to have a lower impact., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: Approximately 20% of strokes are embolic strokes of undetermined source (ESUS). Undetected atrial fibrillation (AF) remains an important cause. Yet, oral anticoagulation in unselected ESUS patients failed in secondary stroke prevention. Guidance on effective AF detection is lacking. Here, we introduce a novel, non-invasive AF risk assessment after ESUS., Methods: Catch-Up ESUS is an investigator-initiated, observational cohort study conducted between 2018 and 2019 at the Munich University Hospital. Besides clinical characteristics, patients received ≥72 h digital electrocardiogram recordings to generate the rhythm irregularity burden. Uni- and multivariable regression models predicted the primary endpoint of incident AF, ascertained by standardized follow-up including implantable cardiac monitors. Predictors included the novel rhythm irregularity burden constructed from digital electrocardiogram recordings. We independently validated our model in ESUS patients from the University Hospital Tübingen, Germany., Results: A total of 297 ESUS patients were followed for 15.6 ± 7.6 months. Incident AF (46 patients, 15.4%) occurred after a median of 105 days (25th to 75th percentile 31-33 days). Secondary outcomes were recurrent stroke in 7.7% and death in 6.1%. Multivariable-adjusted analyses identified the rhythm irregularity burden as the strongest AF-predictor (hazard ratio 3.12, 95% confidence interval 1.62-5.80, p < 0001) while accounting for the known risk factors age, CHA 2 DS 2 -VASc-Score, and NT-proBNP. Independent validation confirmed the rhythm irregularity burden as the most significant AF-predictor (hazard ratio 2.20, 95% confidence interval 1.45-3.33, p < 0001)., Interpretation: The novel, non-invasive, electrocardiogram-based rhythm irregularity burden may help adjudicating AF risk after ESUS, and subsequently guide AF-detection after ESUS. Clinical trials need to clarify if high-AF risk patients benefit from tailored secondary stroke prevention. ANN NEUROL 2023;93:479-488., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Although of high individual and socioeconomic relevance, a reliable prediction model for the prognosis of juvenile stroke (18-55 years) is missing. Therefore, the study presented in this protocol aims to prospectively validate the discriminatory power of a prediction score for the 3 months functional outcome after juvenile stroke or transient ischemic attack (TIA) that has been derived from an independent retrospective study using standard clinical workup data., Methods: PREDICT-Juvenile-Stroke is a multi-centre (n = 4) prospective observational cohort study collecting standard clinical workup data and data on treatment success at 3 months after acute ischemic stroke or TIA that aims to validate a new prediction score for juvenile stroke. The prediction score has been developed upon single center retrospective analysis of 340 juvenile stroke patients. The score determines the patient's individual probability for treatment success defined by a modified Rankin Scale (mRS) 0-2 or return to pre-stroke baseline mRS 3 months after stroke or TIA. This probability will be compared to the observed clinical outcome at 3 months using the area under the receiver operating characteristic curve. The primary endpoint is to validate the clinical potential of the new prediction score for a favourable outcome 3 months after juvenile stroke or TIA. Secondary outcomes are to determine to what extent predictive factors in juvenile stroke or TIA patients differ from those in older patients and to determine the predictive accuracy of the juvenile stroke prediction score on other clinical and paraclinical endpoints. A minimum of 430 juvenile patients (< 55 years) with acute ischemic stroke or TIA, and the same number of older patients will be enrolled for the prospective validation study., Discussion: The juvenile stroke prediction score has the potential to enable personalisation of counselling, provision of appropriate information regarding the prognosis and identification of patients who benefit from specific treatments., Trial Registration: The study has been registered at https://drks.de on March 31, 2022 ( DRKS00024407 )., (© 2023. The Author(s).)

Establishment of the Chair of Neurology at the University of Munich in 1971 as well as the opening of the Neurology Department at the newly built Großhadern campus (1974) provide an occasion to review the 50 years that have passed since. Further, the early history of Munich neurology is described, with its slow pace of separation (in comparison to e.g. Heidelberg, Frankfurt and Hamburg) from the parent disciplines, psychiatry and internal medicine. In Munich, they were long shaped by psychiatrists such as Bernhard von Gudden, Emil Kraepelin, Kurt Kolle and Hanns Hippius and by Friedrich von Müller and, in particular, by Gustav Bodechtel in internal medicine.Once independent, further development of neurology in Munich was characterized by fast-paced, almost revolutionary changes in neuroimaging, electrophysiology, sonography, and engineering as well as in basic neuroscience, neurogenetics included. The new department thrived under the leadership of Adolf Schrader (from 1971), Thomas Brandt (from 1984) and Marianne Dieterich (from 2008) who enjoyed the support of an ever-increasing specialised clinical-scientific staff.Evidence-based treatment of neurological disorders became the overarching and internationally visible focus of Munich neurology, with respect to both practical implementation and to research. The exemplary diseases and syndromes of multiple sclerosis, epilepsy, stroke, movement disorders, dizziness and disorders of balance and gait as well as diseases of the musculature and peripheral nerves are cared for not only within the inpatient and outpatient sections of the Neurology Department but also by units such as the Friedrich Baur Institute (FBI), the German Dizziness and Balance Centre (DSGZ), the Institutes for Stroke and Dementia Research (ISD) and for Clinical Neuroimmunology as well as in the interdisciplinary Department of Palliative Care., (© 2022. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background and Purpose: Reperfusion treatment in patients presenting with large vessel occlusion (LVO) and minor neurological deficits is still a matter of debate. We aimed to compare minor stroke patients treated with endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) or IVT alone., Methods: Patients enrolled in the German Stroke Registry-Endovascular Treatment (GSR-ET) and the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Registry (SITS-ISTR) between June 2015 and December 2019 were analyzed. Minor stroke was defined as National Institutes of Health Stroke Scale (NIHSS) score ≤5, and LVO as occlusion of the internal carotid, carotid-T, middle cerebral, basilar, vertebral or posterior cerebral arteries. GSR-ET and SITS-ISTR IVT-treated patients were matched in a 1:1 ratio using propensity-score (PS) matching. The primary outcome was good functional outcome at 3 months (modified Rankin Scale score 0-2)., Results: A total of 272 GSR-ET patients treated with EVT and IVT (age 68.6 ± 14.0 years, 43.4% female, NIHSS score 4 [interquartile range 2-5]) were compared to 272 IVT-treated SITS-ISTR patients (age 69.4 ± 13.7, 43.4% female, NIHSS score 4 [2-5]). Good functional outcome was seen in 77.0% versus 82.9% (p = 0.119), mortality in 5.9% versus 7.9% (p = 0.413), and intracranial hemorrhage in 8.8% versus 12.5% (p = 0.308) of patients in the GSR-ET versus the SITS-ISTR IVT group, respectively. In a second PS-matched analysis, 624 GSR-ET patients (IVT rate 56.7%) and 624 SITS-ISTR patients (IVT rate 100%), good outcome was more often observed in the SITS-ISTR patients (68.2% vs. 80.9%; p < 0.001), and IVT independently predicted good outcome (odds ratio 2.16, 95% confidence interval 1.43-3.28)., Conclusions: Our study suggests similar effectiveness of IVT alone compared to EVT with or without IVT in minor stroke patients. There is an urgent need for randomized controlled trials on this topic., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: A sensitive and frequent clinical sign of a vestibular tone imbalance is the tilt of the perceived subjective visual vertical (SVV). There are no data yet focusing on lesion location at the cortical level as a factor for predicting compensation from the tilt of the SVV., Methods: With modern voxelwise lesion behavior mapping analysis, the present study determines whether lesion location in 23 right-hemispheric cortical stroke patients with an otolith dysfunction could predict the compensation of a vestibular tone imbalance in the chronic stage., Results: Our statistical anatomical lesion analysis revealed that lesions of the posterior insular cortex are involved in vestibular otolith compensation., Conclusion: The insular cortex appears to be a critical anatomical region for predicting a tilt of the SVV as a chronic disorder in stroke patients., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: To provide real-world data on outcome and procedural factors of late thrombectomy patients., Methods: We retrospectively analyzed patients from the multicenter German Stroke Registry. The primary endpoint was clinical outcome on the modified Rankin scale (mRS) at 3 months. Trial-eligible patients and the subgroups were compared to the ineligible group. Secondary analyses included multivariate logistic regression to identify predictors of good outcome (mRS ≤ 2)., Results: Of 1917 patients who underwent thrombectomy, 208 (11%) were treated within a time window ≥ 6-24 h and met the baseline trial criteria. Of these, 27 patients (13%) were eligible for DAWN and 39 (19%) for DEFUSE3 and 156 patients were not eligible for DAWN or DEFUSE3 (75%), mainly because there was no perfusion imaging (62%; n = 129). Good outcome was not significantly higher in trial-ineligible (27%) than in trial-eligible (20%) patients (p = 0.343). Patients with large trial-ineligible CT perfusion imaging (CTP) lesions had significantly more hemorrhagic complications (33%) as well as unfavorable outcomes., Conclusion: In clinical practice, the high number of patients with a good clinical outcome after endovascular therapy ≥ 6-24 h as in DAWN/DEFUSE3 could not be achieved. Similar outcomes are seen in patients selected for EVT ≥ 6 h based on factors other than CTP. Patients triaged without CTP showed trends for shorter arrival to reperfusion times and higher rates of independence., (© 2021. The Author(s).)

Background: Endovascular treatment (ET) in orally anticoagulated (OAC) patients has not been evaluated in randomized clinical trials and data regarding this issue are sparse., Methods: We analyzed data from the German Stroke Registry-Endovascular Treatment (GSR-ET; NCT03356392, date of registration: 22 Nov 2017). The primary outcomes were successful reperfusion defined as modified thrombolysis in cerebral infarction (mTICI 2b-3), good outcome at 3 months (modified Rankin scale [mRS] 0-2 or back to baseline), and intracranial hemorrhage (ICH) on follow-up imaging at 24 h analyzed by unadjusted univariate and adjusted binary logistic regression analysis. Additionally, we analyzed mortality at 3 months with adjusted binary logistic regression analysis., Results: Out of 6173 patients, there were 1306 (21.2%) OAC patients, 479 (7.8%) with vitamin K antagonists (VKA) and 827 (13.4%) with non-vitamin K antagonist oral anticoagulation (NOAC). The control group consisted of 4867 (78.8%) non-OAC patients. ET efficacy with the rates of mTICI 2b-3 was similar among the three groups (85.6%, 85.3% vs 84.3%, p = 0.93 and 1). On day 90, good outcome was less frequent in OAC patients (27.8%, 27.9% vs 39.5%, p < 0.005 and < 0.005). OAC status was not associated with ICH at 24 h (NOAC: odd's ratio [OR] 0.89, 95% confidence interval [CI] 0.67-1.20; VKA: OR 1.04, CI 0.75-1.46). Binary logistic regression analysis revealed no influence of OAC status on good outcome at 3 months (NOAC: OR 1.25, CI 0.99-1.59; VKA: OR 1.18, CI 0.89-1.56) and mortality at 3 months (NOAC: OR 1.03, CI 0.81-1.30; VKA: OR 1.04, CI 0.78-1.1.37)., Conclusions: ET can be performed safely and successfully in LVO stroke patients treated with OAC. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov . Unique identifier: NCT03356392.

Background and Purpose: The aim of the study was to identify the neuroanatomical correlates and associations of neuropsychological syndromes after acute unilateral right-hemisphere brain lesions. The neuropsychological syndromes considered were orientation in three-dimensional space such as tilts of the subjective visual vertical or of the subjective haptic vertical, pusher syndrome, visual neglect and unawareness of paresis (anosognosia for hemiparesis). These neuropsychological phenomena have been found to occur separately or in different combinations after lesions to the right insular cortex., Method: Magnetic resonance imaging scans were obtained from 82 patients with acute right-hemispheric stroke. A lesion-behavior mapping analysis was conducted to specify the neuroanatomical correlates of the above-mentioned neuropsychological syndromes., Results: In all analyses of the individual neuropsychological syndromes the insular cortex was affected., Conclusions: Thus, the insular cortex is involved in (self-)perception and orientation within a three-dimensional space. Since isolated lesions of the insular cortex did not induce the above neuropsychological phenomena, there have to be other regions involved., (© 2020 European Academy of Neurology.)

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Background and Purpose: Up to 30% of infective endocarditis (IE) patients have ischemic stroke as a complication. Standard treatment with mechanical thrombectomy (MT) with or without intravenous thrombolysis for large vessel occlusion (LVO) has not been evaluated formally in these patients., Methods: Patients enrolled in the German Stroke Registry-Endovascular Treatment (GSR-ET) between June 2015 and December 2019 were analyzed. Patients with stroke due to IE and patients with cardioembolic stroke and atrial fibrillation (AF) were compared using propensity score matching. Successful reperfusion was defined as modified Thrombolysis in Cerebral Infarction score = 2b-3. Modified Rankin Scale (mRS) = 0-2 at 3 months indicated good outcome., Results: Of 6635 patients, 55 patients (age = 69.0 ± 13.3 years, 43.6% female, median premorbid mRS (pmRS) = 1, interquartile range [IQR] = 0-1, National Institutes of Health Stroke Scale [NIHSS] = 15, IQR = 10-21) presented with septic embolic stroke due to IE and were compared to 104 patients (age = 66.5 ± 13.4 years, 39.4% female, pmRS = 0, IQR = 0-2, NIHSS = 16, IQR = 10-20) with cardioembolic stroke due to AF. Successful recanalization was achieved in 74.5% of endocarditis patients compared to 87.5% of controls (p = 0.039). Intracranial hemorrhage rates were comparable (30.9% vs. 21.6%, p = 0.175). Good functional outcome was 20.0% in patients with IE compared to 43.3% in matched patients (p = 0.006), with a significantly higher mortality (60.0% vs. 28.8%, p < 0.001). IE was strongly associated with poor outcome (odds ratio [OR] = 0.32, 95% confidence interval [CI] = 0.11-0.87, p = 0.03 for good outcome) and mortality (OR = 4.49, 95% CI = 1.80-10.68, p = 0.001)., Conclusions: Although MT results in high successful recanalization rates with acceptable safety profile, patients with LVO stroke due to IE have poor outcome., (© 2020 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Telemedicine stroke networks are mandatory to provide inter-hospital transfer for mechanical thrombectomy (MT). However, studies on patient selection in daily practice are sparse., Methods: Here, we analyzed consecutive patients from 01/2014 to 12/2018 within the supraregional stroke network "Neurovascular Network of Southwest Bavaria" (NEVAS) in terms of diagnoses after consultation, inter-hospital transfer and predictors for performing MT. Degree of disability was rated by the modified Rankin Scale (mRS), good outcome was defined as mRS ≤ 2. Successful reperfusion was assumed when the modified thrombolysis in cerebral infarction (mTICI) was 2b-3., Results: Of 5722 telemedicine consultations, in 14.1% inter-hospital transfer was performed, mostly because of large vessel occlusion (LVO) stroke. A total of n = 350 patients with LVO were shipped via NEVAS to our center for MT. While n = 52 recanalized spontaneously, MT-treatment was performed in n = 178 patients. MT-treated patients had more severe strokes according to the median National institute of health stroke scale (NIHSS) (16 vs. 13, p < 0.001), were more often treated with intravenous thrombolysis (64.5% vs. 51.7%, p = 0.026) and arrived significantly earlier in our center (184.5 versus 228.0 min, p < 0.001). Good outcome (27.5% vs. 30.8%, p = 0.35) and mortality (32.6% versus 23.5%, p = 0.79) were comparable in MT-treated versus no-MT-treated patients. In patients with middle cerebral artery occlusion in the M1 segment or carotid artery occlusion good outcome was twice as often in the MT-group (21.8% vs. 12.8%, p = 0.184). Independent predictors for performing MT were higher NIHSS (OR 1.096), higher ASPECTS (OR 1.28), and earlier time window (OR 0.99)., Conclusion: Within a telemedicine network stroke care can successfully be organized as only a minority of patients has to be transferred. Our data provide clinical evidence that all MT-eligible patients should be shipped with the fastest transportation modality as possible.

Objective: Structural reorganization following cerebellar infarcts is not yet known. This study aimed to demonstrate structural volumetric changes over time in the cortical vestibular and multisensory areas (i.e., brain plasticity) after acute cerebellar infarcts with vestibular and ocular motor symptoms. Additionally, we evaluated whether structural reorganization in the patients topographically correlates with cerebello-cortical connectivity that can be observed in healthy participants., Methods: We obtained high-resolution structural imaging in seven patients with midline cerebellar infarcts at two time points. These data were compared to structural imaging of a group of healthy age-matched controls using voxel-based morphometry (2×2 ANOVA approach). The maximum overlap of the infarcts was used as a seed region for a separate resting-state functional connectivity analysis in healthy volunteers., Results: Volumetric changes were detected in the multisensory cortical vestibular areas around the parieto-opercular and (retro-) insular cortex. Furthermore, structural reorganization was evident in parts of the frontal, temporal, parietal, limbic, and occipital lobes and reflected functional connections between the main infarct regions in the cerebellum and the cerebral cortex in healthy individuals., Conclusions: This study demonstrates structural reorganization in the parieto-opercular insular vestibular cortex after acute vestibulo-cerebellar infarcts. Additionally, the widely distributed structural reorganization after midline cerebellar infarcts provides additional in vivo evidence for the multifaceted contribution of cerebellar processing to cortical functions that extend beyond vestibular or ocular motor function., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To determine feasibility and safety of stroke care organization within our Neurovascular Network of Southwest Bavaria (NEVAS) in a rural area with distances of up to 100 kilometers, we compared patients who underwent mechanical thrombectomy (MT) in large vessel occlusion admitted directly to our center (direct to center [DTC]) to patients who were transferred for MT via NEVAS (drip and ship [DS])., Methods: This is a retrospective analysis of prospectively collected data of all MT patients between January 2015 and May 2018. Successful recanalization was defined as a thrombolysis in cerebral infarction score of 2b-3. Symptomatic intracerebral hemorrhage (sICH) was defined according to European Cooperative Acute Stroke Study 3. Modified Rankin Scale (mRS) score of 0-2 at 3 months indicated good outcome., Results: MT was performed in 410 patients: 221 DTC and 189 DS. Median NIH Stroke Scale (NIHSS) score was 16 and premorbid mRS score was 0. Thrombolysis was applied in 62.2% with the same time from symptom onset in both groups (94.5 vs 95 minutes). Successful recanalization (79.3% vs 77.8%) and NIHSS score reduction from admission to discharge (16-7 vs 17-6) were comparable. Time delay from onset to revascularization was 96 minutes in DS (212 vs 308 minutes, p = 0.001). At follow-up, DTC patients had a trend to better outcome (33.5% vs 24.3%, p = 0.056). Neither sICH (6.3% vs 5.9%, p = 0.840) nor mortality (31.2% vs 34.4%, p = 0.387) differed between the groups., Conclusion: DS patients benefit from MT without relevant safety concerns, but with a trend to unfavorable outcome compared to DTC patients. These results suggest that DS is suitable to provide MT in rural areas where DTC is not possible., (© 2019 American Academy of Neurology.)

Purpose of Review: To provide an update on diagnostic algorithms for differential diagnosis of acute vertigo and dizziness and swift identification of potentially harmful causes., Recent Findings: About 25% of patients with acute vertigo and dizziness have a potentially life-threatening diagnosis, including stroke in 4-15%. Diagnostic work-up relies on the combination of symptom features (triggers, duration, history of vertigo/dizziness, accompanying symptoms) and a comprehensive vestibular, ocular motor, and balance exam. The latter includes head impulse, head-shaking nystagmus, positional nystagmus, gaze-holding, smooth pursuit, skew deviation, and Romberg's test. Recent standardized diagnostic algorithms (e.g., HINTS, TriAGe+) suggest the combination of several elements to achieve a good diagnostic accuracy in differentiation of central and peripheral vestibular causes. Neuroimaging with MRI must be applied and interpreted with caution, as small strokes are frequently overlooked, especially in the acute setting (false-negative rate of up to 50%)., Summary: Diagnostic differentiation of acute vertigo and dizziness remains a complex task, which can be tackled by a structured clinical assessment focusing on symptom characteristics and constellations of ocular motor and vestibular findings. Specific challenges arise in cases of transient or atypical vestibular syndromes.

A retrospective clinical study focused on the frequency of rotational vertigo in 63 patients with acute unilateral midbrain strokes involving the vestibular and ocular motor systems. In contrast to unilateral pontomedullary brainstem lesions, rotational vertigo in midbrain lesions occurred with a low frequency (14%) and transient (< 1 day) course. Swaying vertigo or unspecific dizziness (22%) and postural imbalance (31%) were more frequent. Midbrain strokes with transient rotational vertigo manifested with lesions chiefly in the caudal midbrain tegmentum, while manifestations with swaying, unspecific, or no vertigo chiefly occurred in rostral mesencephalic or meso-diencephalic lesions. We hypothesize that these different manifestations can be explained by the distribution of two separate cell systems based on semicircular canal function: the angular head-velocity cells and the head direction cells, both of which code for head rotation. Animal experiments have shown that angular head-velocity cells are located mainly in the lower brainstem up to the midbrain, whereas the head direction cells are found from the midbrain and thalamic level up to cortical regions. Due to the differences in coding, unilateral dysfunction of the angular velocity cell system should result in the sensation of rotation, while unilateral dysfunction of the head direction cell system should result in dizziness and unsteadiness. We simulated the different manifestations of vestibular dysfunction using a mathematical neural network model of the head direction cell system. This model predicted and confirmed our clinical findings that unilateral caudal and rostral brainstem lesions have different effects on vestibular function.

Patients with anosognosia for visual field defect (AVFD) fail to recognize consciously their visual field defect. There is still unclarity whether specific neural correlates are associated with AVFD. We studied AVFD in 54 patients with acute stroke and a visual field defect. Nineteen percent of this unselected sample showed AVFD. By using modern voxelwise lesion-behaviour mapping techniques we found an association between AVFD and parts of the lingual gyrus, the cuneus as well as the posterior cingulate and corpus callosum. Damage to these regions appears to induce unawareness of visual field defects and thus may play a significant role for conscious visual perception.

In patients with left-sided lesions, anosognosia for hemiparesis (AHP) seems to be a rare phenomenon. It has been discussed whether this rareness might be due to an inevitable bias due to language dysfunction and whether the left hemisphere's role for our self-awareness of motor actions thus is underestimated. By applying functional magnetic resonance imaging (fMRI) we examined whether patients with AHP following a left hemisphere stroke show a regular, left-sided or a reversed, right-sided lateralization of language functions. Only the former observation would argue for an original role of the left hemisphere in self-awareness about limb function. In a consecutive series of 44 acute left-sided stroke patients, only one patient (=2%) was identified showing AHP. In this case, we could verify by using fMRI that lateralization of AHP and spatial neglect on the one hand and of language functions on the other hand were reversed. The present single case observation thus argues against an original role of the left hemisphere in self-awareness about limb function. We discuss the data in the context of previous observations in the literature., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background and Purpose: In previous imaging studies, the posterior insular cortex (IC) was identified as an essential part for vestibular otolith perception and considered as a core region of a human vestibular cortical network. However, it is still unknown whether lesions exclusively restricted to the posterior IC suffice to provoke signs of vestibular otolith dysfunction. Thus, present data aimed to test whether patients with lesions restricted to the IC showed vestibular otolith dysfunction., Methods: We studied 10 acute unilateral stroke patients with lesions restricted to the IC which were tested for signs of vestibular otolith dysfunction, such as tilts of subjective visual vertical, out of 475 stroke patients., Results: None of the patients was with stroke exclusively affecting the IC-specified vertigo as a symptom. In addition, neither showed a deficit in the perception of verticality (subjective visual vertical tilts) nor showed any further vestibular otolith deficits, such as ocular torsion or skew deviation., Conclusions: It seems that lesions of the posterior IC might have to be combined with lesions of adjacent regions of the cortical and subcortical vestibular network to cause vestibular otolith deficits.

Objective: Perception of verticality can be perturbed after cortical stroke. However, a relationship between lesion location and pathologic perception of verticality is still a matter of debate since previous studies revealed contradictory results. Thus, the aim of the current study was to test whether specific cortical lesions were associated with tilts of subjective visual vertical (SVV) and to determine the critical brain areas that cause such tilts in the case of a lesion., Methods: SVV was systematically studied in 54 patients (22 patients with left-sided and 32 patients with right-sided lesions) with acute unilateral strokes, analyzed by modern voxel-wise lesion-behavior mapping techniques., Results: The data give evidence for an association between tilt of SVV and the insular cortex (IC) and inferior frontal gyrus (IFG) in both hemispheres. Whereas the IC seems to be the prominent structure in the left hemisphere, the IFG is most affected in the right hemisphere. Furthermore, other cortical regions such as the superior temporal gyrus (STG) and the rolandic operculum as well as-subcortically-the inferior occipitofrontal fascicle and the superior longitudinal fascicle seem to be involved in the vestibulo-cortical network for the perception of verticality in the roll plane., Conclusion: Damage to these regions might lead to an imbalance within the vestibular network of one hemisphere due to a deficit in multimodal signal processing.

Unilateral stroke can lead to a disorder of postural balance that manifests as a pushing away toward the contralesional side. It is called "pusher syndrome" (PS). The aims of this study were first to assess the anatomical cortical regions that induce PS and second to clarify whether tilt of the subjective visual vertical (SVV)--a sign of vestibular otolith dysfunction--is associated with PS. Sixty-six patients with acute unilateral strokes (28 left-sided lesions, 38 right-sided lesions) were tested for PS, for tilts of the SVV, for hemineglect and for the anatomical lesion site by magnetic resonance imaging (MRI)-based voxelwise lesion-behavior mapping analysis. Our data indicated no significant voxels; however, there was a trend towards an association between lesions of the posterior part of the insula, the operculum and the superior temporal gyrus--key areas of the multisensory vestibular cortical network--and the extent of pushing in patients with right-sided lesions, whereas the rather anterior part of the insula, the operculum as well as the internal capsule reaching to the lateral thalamus seemed to be involved in PS in left-sided lesion patients. These data might point toward a link between the systems responsible for postural control and for processing vestibular otolith information. These findings indicate that vestibular information might be fundamental in right-sided lesion patients for maintaining body posture in space.

Successful remembering involves both hindering irrelevant information from entering working memory (WM) and actively maintaining relevant information online. Using a voxelwise lesion-behavior brain mapping approach in stroke patients, we observed that lesions of the left basal ganglia render WM susceptible to irrelevant information. Lesions of the right prefrontal cortex on the other hand make it difficult to keep more than a few items in WM. These findings support basal ganglia-prefrontal cortex models of WM whereby the basal ganglia play a gatekeeper role and allow only relevant information to enter prefrontal cortex where this information then is actively maintained in WM.

This study aimed at identifying gender-specific differences in stroke knowledge, stroke risk perception and the educational effects of a multimodal educational intervention. We performed computer-assisted telephone surveys among an average sample of 500 members of the general public (44.0% male, 56.0% female), before and immediately after an intense 3-month educational stroke campaign in a western German area of 400,000 inhabitants. The intervention was comprised of poster advertisements and various print media. Slogans and stroke interest stories appeared regularly in local newspapers, on television and radio and public events focussed on the subject. Even before the intervention, more women than men were able to name at least one stroke warning sign (71.3 vs. 57.8%, p < 0.01), to name the correct emergency call number (33.3 vs. 24.3%, p < 0.05) or to cite the correct action in acute stroke ("call emergency care", 87.2 vs. 70.1%, p < 0.001). In some aspects women showed a generally better improvement of knowledge after the campaign (e.g. correct emergency call number: +5.7 vs. +1.2%, p < 0.05). Fewer women than men considered themselves as being at risk of stroke (30.9 vs. 36.9%. p < 0.01) with a significant increase following the intervention in both sexes (38.9/46.0%, p < 0.01). The perception of different educational media varied between the sexes. For example, female sex was independently associated with a better recall of poster advertisements and flyers in pharmacies and at the doctor's office (OR 1.44). Our data indicate that educational programs do have gender-specific effects. Women show a better stroke knowledge and in some aspects a better chance to gain information from classical broad educational interventions. Future campaigns should be tailored economically, and should focus different media and educational messages on the two sexes accordingly.

To study the differential educational effects of a multimodal educational program on public stroke knowledge, we performed computer-assisted telephone surveys among a random sample of 500 members of the general public, before and immediately after an intense three-month educational campaign. The intervention comprised of poster advertisements, flyers, mail circular, slogans, stroke interest stories etc. in local newspapers, on television and radio, and public events. The main outcome measures were stroke knowledge, the intended behavior in acute stroke and the educational media remembered after the intervention. General knowledge of the nature of stroke (65.7% correct answers before versus 84.9 % after the campaign, p < 0.01) and the awareness of being at risk of stroke (32.7 % vs. 41.9%, p < 0.01) increased due to the campaign, especially in respondents of lower educational background. There was no significant effect on the number of patients who would seek emergency medical care after the intervention (81 % vs. 82 %) and hardly any effect on detailed knowledge of stroke warning signs or different risk factors. Mass media like newspapers, radio and television were most frequently reported as the main information source remembered (66.6 %). Our data indicate that educational programs do have differential effects on public stroke knowledge and individual stroke risk,which does not necessarily lead to a change in care-seeking behavior. Repeated information using short-tailored slogans and cues to action led to a gain in general stroke knowledge, especially in high-risk populations of lower educational background. Large educational campaigns seem unsuitable, however, for mediation of detailed information on stroke.

The embolic MCA occlusion model in rats is used for recanalisation studies in acute stroke. In addition to the determination of lesion size, the assessment of functional outcome may improve the value of this model. Male Wistar rats were submitted to MCA clot embolism or sham surgery. In order to achieve a larger variety of lesion volume, 2 subgroups (each 7 animals) were subjected to differently sized emboli (30 and 40 mm). Follow-up period was 6 days. Outcome assessment consisted of a test battery including parallel bar crossing, observation of behaviour in an open field and an 8-arm maze and a neurological score with ten different sensorimotor and coordinative items. Animals were perfusion-fixed on day 7 (blinded examination). For both subgroups, there were significant impairments with regard to performance on the Neuro score, parallel bar crossing and maze exploration. Improvement was only partial during the follow-up period. On follow-up day 6, there was still a significant correlation between total infarct volume and functional outcome on the Neuro score (R=0.80, p=0.0006) and the exploration behaviour in the maze (R=0.66, p=0.01). Application of emboli with a length of 40 mm caused more functional impairment and a more extended lesion volume compared with 30 mm. We present outcome tests that provide quantitative and objective tools to test functional impairment in rats following embolic stroke.

Background: Stroke accounts for 5-10% of all presentations with acute vertigo and dizziness. The objective of the current study was to examine determinants of long-termfunctioning and health-related quality of life (HRQoL) in a patient cohort with vestibular stroke. Methods: Thirty-six patients (mean age: 66.1 years, 39% female) with an MRI-proven vestibular stroke were followed prospectively (mean time: 30.2 months) in the context of the EMVERT (EMergency VERTigo) cohort study at the Ludwig-Maximilians Universität, Munich. The following scores were obtained once in the acute stage (<24 h of symptom onset) and once during long-term follow-up (preferably >1 year after stroke): European Quality of Life Scale-five dimensions-five levels questionnaire (EQ-5D-5L) and Visual Analog Scale (EQ-VAS) for HRQoL, Dizziness Handicap Inventory (DHI) for symptom severity, and modified Rankin Scale (mRS) for general functioning and disability. Anxiety state and trait were evaluated by STAI-S/STAI-T, and depression was evaluated by the Patient Health Questionnaire-9 (PHQ-9). Voxel-based lesion mapping was applied in normalized MRIs to analyze stroke volume and localization. Multiple linear regression models were calculated to determine predictors of functional outcome (DHI, EQ-VAS at follow-up). Results: Mean DHI scores improved significantly from 45.0 in the acute stage to 18.1 at follow-up (p < 0.001), and mean mRS improved from 2.1 to 1.1 (p < 0.001). Mean HRQoL (EQ-5D-5L index/EQ-VAS) changed from 0.69/58.8 to 0.83/65.2 (p = 0.01/p = 0.11). Multiple linear regression models identified higher scores of STAI-T and DHI at the time of acute vestibular stroke and larger stroke volume as significant predictors for higher DHI at follow-up assessment. The effect of STAI-T was additionally enhanced in women. There was a significant effect of patient age on EQ-VAS, but notDHI during follow-up. Conclusion: The average functional outcome of strokes with the chief complaint of vertigo and dizziness is favorable. The most relevant predictors for individual outcomes are the personal anxiety trait (especially in combination with the female sex), the initial symptom intensity, and lesion volume. These factors should be considered for therapeutic decisions both in the acute stage of stroke and during subsequent rehabilitation. [ABSTRACT FROM AUTHOR]

Background and purpose: We aimed to delineate common principles of reorganization after infarcts of the subcortical vestibular circuitry related to the clinical symptomatology. Our hypothesis was that the recovery of specific symptoms is associated with changes in distinct regions within the core vestibular, somatosensory, and visual cortical and subcortical networks. Methods: We used voxel‐ and surface‐based morphometry to investigate structural reorganization of subcortical and cortical brain areas in 42 patients with a unilateral, subcortical infarct with vestibular and ocular motor deficits in the acute phase. The patients received structural neuroimaging and clinical monitoring twice (acute phase and after 6 months) to detect within‐subject changes over time. Results: In patients with vestibular signs such as tilts of the subjective visual vertical (SVV) and ocular torsion in the acute phase, significant volumetric increases in the superficial white matter around the parieto‐opercular (retro‐)insular vestibular cortex (PIVC) were found at follow‐up. In patients with SVV tilts, spontaneous nystagmus, and rotatory vertigo in the acute phase, gray matter volume decreases were located in the cerebellum and the visual cortex bilaterally at follow‐up. Patients with saccade pathology demonstrated volumetric decreases in cerebellar, thalamic, and cortical centers for ocular motor control. Conclusions: The findings support the role of the PIVC as the key hub for vestibular processing and reorganization. The volumetric decreases represent the reciprocal interaction of the vestibular, visual, and ocular motor systems during self‐location and egomotion detection. A modulation in vestibular and ocular motor as well as visual networks was induced independently of the vestibular lesion site. [ABSTRACT FROM AUTHOR]

Stroke is the second leading cause of death and disability worldwide. Current treatments, such as pharmacological thrombolysis or mechanical thrombectomy, reopen occluded arteries but do not protect against ischemia‐induced damage that occurs before reperfusion or neuronal damage induced by ischemia/reperfusion. It has been shown that disrupting the conversion of glyoxal to glycolic acid (GA) results in a decreased tolerance to anhydrobiosis in Caenorhabditis elegans dauer larva and that GA itself can rescue this phenotype. During the process of desiccation/rehydration, a metabolic stop/start similar to the one observed during ischemia/reperfusion occurs. In this study, the protective effect of GA is tested in different ischemia models, i.e., in commonly used stroke models in mice and swine. The results show that GA, given during reperfusion, strongly protects against ischemic damage and improves functional outcome. Evidence that GA exerts its effect by counteracting the glutamate‐dependent increase in intracellular calcium during excitotoxicity is provided. These results suggest that GA treatment has the potential to reduce mortality and disability in stroke patients. [ABSTRACT FROM AUTHOR]

Objective: Patients with acute central vestibular syndrome suffer from vertigo, spontaneous nystagmus, postural instability with lateral falls, and tilts of visual vertical. Usually, these symptoms compensate within months. The mechanisms of compensation in vestibular infarcts are yet unclear. This study focused on structural changes in gray and white matter volume that accompany clinical compensation. Methods: We studied patients with acute unilateral brain stem infarcts prospectively over 6 months. Structural changes were compared between the acute phase and follow‐up with a group of healthy controls using voxel‐based morphometry. Results: Restitution of vestibular function following brain stem infarcts was accompanied by downstream structural changes in multisensory cortical areas. The changes depended on the location of the infarct along the vestibular pathways in patients with pathological tilts of the SVV and on the quality of the vestibular percept (rotatory vs graviceptive) in patients with pontomedullary infarcts. Patients with pontomedullary infarcts with vertigo or spontaneous nystagmus showed volumetric increases in vestibular parietal opercular multisensory and (retro‐) insular areas with right‐sided preference. Compensation of graviceptive deficits was accompanied by adaptive changes in multiple multisensory vestibular areas in both hemispheres in lower brain stem infarcts and by additional changes in the motor system in upper brain stem infarcts. Interpretation: This study demonstrates multisensory neuroplasticity in both hemispheres along with the clinical compensation of vestibular deficits following unilateral brain stem infarcts. The data further solidify the concept of a right‐hemispheric specialization for core vestibular processing. The identification of cortical structures involved in central compensation could serve as a platform to launch novel rehabilitative treatments such as transcranial stimulations. [ABSTRACT FROM AUTHOR]

Rationale: Treatment of aphasia is still challenging for clinicians and patients. So far, there is proven evidence for "face-to-face" speech therapy. However, the digital age potentially offers new and complementary strategies that may add to treatment outcome in a cost-effective way. Neolexon® is a commercial tablet-based software for treatment of aphasia, which can be applied with the help of a therapist or as self-training by the patient. Aims and hypothesis: In the Lexi study, we aim to determine whether treatment with Neolexon® is superior to standard therapy in acute post-stroke aphasia. Sample size estimates: A sample size of 180 patients, 90 for each group, will be included with an assumed dropout rate of ~20%. Methods and design: Prospective, randomized, parallel group, open-label, blinded-endpoint clinical, and experimental controlled non-invasive trial (PROBE). Adult German native speakers with acute aphasia after stroke are included. Computer-generated, blocked, and stratified randomization by aphasia severity will assign patients to one of two groups: 4 weeks of either standard logopedic speech therapy or logopedic speech therapy with the app version of Neolexon®. Both groups will be instructed in self-training: the frequency and duration of self-training will be documented. Screening for aphasia will be performed using the Language Screening Test (LAST). The severity of aphasia in general and in subitems will be assessed using the Bielefelder Aphasie Screening (BIAS) and the Aphasia Check List (ACL). Follow-up will be assessed after 3 months. Study outcomes: Based on the consensus in our study team, we considered a 10% mean difference in the change of percentile rank (PR) of BIAS to be a minimal and clinically important difference. The primary endpoint is defined as a significant difference in BIAS comparing the two groups. Differences in quality of life, Beck Depression Inventory (BDI), and modified Ranking Scale (mRS) will be evaluated as secondary outcome parameters. Discussion: This trial will determine whether speech therapy with the use of Neolexon® is superior to standard logopedic therapy. Subgroups with the greatest response to Neolexon® will be described. The trial was prospectively registered on the "EU Clinical Trials Register" (NCT04080817)1. [ABSTRACT FROM AUTHOR]

Background and Purpose: Therapeutic ultrasound as stand-alone therapy or in combination with rt-PA has proven to be an effective measure for recanalisation of acute vessel occlusion in different in vitro and in vivo studies. Uncertainty still exists concerning the optimal frequency and intensity with regard to the thrombolytic efficacy of ultrasound. The purpose of this study was a direct comparison of different ultrasound frequencies, when otherwise using identical measurement settings and parameters. Methods: Ultrasound-induced dissolution of fresh human blood clots was studied in a flow system using low-frequency continuous wave ultrasound of 20, 40 and 60 kHz. After calibration of each ultrasound probe, blood clots were exposed to local time average intensities of either 0.12 or 0.2 W/cm2. Exposure time of the clots to ultrasound was 10 min, the number of treated clots in each experimental group was 12. Results: As tested with 0.2 W/cm2, we found the most pronounced thrombolytic effect with the 20-kHz probe (weight loss of blood clots: 52.4%) and the 40-kHz probe (49.4%), as compared to the 60-kHz probe (21.4%) and the control group (18.5%). The difference between the 20- and 60-kHz probes was statistically significant (p < 0.001). The treatment effect was clearly intensity dependent with a less pronounced, but still significant treatment effect at 0.12 W/cm2 (24.5% at 20 kHz; p < 0.001 compared to 0.2 W/cm2; p = 0.045 compared to controls). Conclusions: These data show that therapeutic efficacy of ultrasound, in absence of a thrombolytic drug, is frequency and intensity dependent with best results at low frequencies. With continuous wave transmission, the benefit may be limited to the very low frequency range. The results are a basis for further evaluation in animal models. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article reports on acute cerebellar stroke cases. It adds that head and body posture and balance can be disturbed by acute supratentorial unilateral stroke that leads to pusher syndrome (PS) citing a case of a patient suffering from gait ataxia which eventually led to PS. It suggests that one of the reasons causing PS is a large cerebellar infarction the lesion site of which could only be documented by computed tomography (CT) scan.

Abstract: Introduction: Topographical disorientation is defined as the inability to recognize familiar or unfamiliar environments. While its slowly progressive development is a common feature of neurodegenerative processes like Alzheimer's dementia, acute presentations are less frequent and mostly caused by strategic lesions within the cerebral navigation network. Depending on the lesion site, topographical disorientation can originate from deficits in landmark recognition and utilization for route planning (egocentric navigation deficit), or disturbance of an overarching cognitive map of the spatial environment (allocentric navigation deficit). However, objective measurements of spatial navigation performance over time are largely missing in patients with topographical disorientation. Methods: We here report a 55‐year‐old patient with acute topographical disorientation as the single symptom of right‐sided hippocampal hemorrhage and present quantitative gaze‐monitoring head camera‐based analyses of his path‐finding strategy and visual exploration behavior in a real space navigation paradigm. Results: The patient exhibited severe allocentric and also egocentric navigation deficits during the acute phase, shown by higher error rates at finding target items. In addition, he showed a more extensive use of search saccades toward, and fixations on, landmarks that could potentially serve as spatial cues. These deficits had been completely compensated for after four months, when the patient performed unremarkably in the real space navigation task, and used even more strongly allocentric path optimization strategies than age‐matched controls. Conclusions: This case report highlights the integral function and right‐sided dominance of the hippocampal formation in the cerebral navigation network in humans. It shows that the cognitive map can be restored completely despite a residual hippocampal lesion, which illustrates the enormous plasticity of the cerebral navigation network in humans. [ABSTRACT FROM AUTHOR]