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.
Motor impairments are the objectively most striking sequelae after stroke, but non-motor consequences represent a high burden for stroke survivors as well. Depression is reported in one third of ...patients, the fatigue prevalence ranges from 23 to 75% due to heterogenous definitions and assessments. Cognitive impairment is found in one third of stroke patients 3-12 months after stroke and the risk for dementia is doubled by the event. Aerobic exercise has been shown to reduce depressive symptoms, counteract fatigue, and improve cognitive functions in non-stroke patients. Furthermore, exercise is known to strengthen the immune system. It is unknown, though, if aerobic exercise can counteract poststroke depression, fatigue, poststroke dementia and poststroke immunosuppression. Therefore, we aim to analyse the effect of aerobic exercise on functional recovery, cognition, emotional well-being, and the immune system. Reorganization of topological networks of the brain shall be visualized by diffusion MRI fibre tracking.
Adults with mild to moderate stroke impairment (initial NIHSS or NIHSS determined at the moment of maximal deterioration 1-18) are recruited within two weeks of stroke onset. Study participants must be able to walk independently without risk of falling. All patients are equipped with wearable devices (smartwatches) measuring the heart rate and daily step count. The optimal heart rate zone is determined by lactate ergometry at baseline. Patients are randomized to the control or the intervention group, the latter performing a heart rate-controlled walking training on own initiative 5 times a week for 45 min. All patients receive medical care and stroke rehabilitation to the usual standard of care. The following assessments are conducted at baseline and after 90 days: Fugl Meyer-assessment for the upper and lower extremity, 6 min-walk test, neuropsychological assessment (cognition: MoCA, SDMT; fatigue and depression: FSMC, HADS-D, participation: WHODAS 2.0 12-items), blood testing (i.e. immune profiling to obtain insights into phenotype and functional features of distinct immune-cell subsets) and cranial magnetic resonance imaging (MRI) with grid-sampled diffusion weighted imaging, white matter fibre tracking and MR spectroscopy.
This study investigates the effect of smartwatch-controlled aerobic exercise on functional recovery, cognition, emotional well-being, the immune system, and neuronal network reorganization in stroke patients. Trial registration ClinicalTrials.gov NCT Number: NCT05690165. First posted19 January 2023. Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05690165.
As a whole, rare stroke causes represent a frequent stroke etiology. Since rare stroke causes affect primarily young patients, early diagnosis and treatment are of high socioeconomic relevance. In ...our everyday clinical practice, cervical artery dissection, which is the most common stroke etiology among patients < 45 years, and vasculitis are particularly important. In the case of vasculitis, devastating disease courses and potentially harmful treatment options complicate clinical decision-making. Non-vasculitic vasculopathies, infections, hematological disorders, coagulation disorders, metabolic disorders and malignancies are further rare causes of stroke with variable clinical manifestations, thus impeding an early diagnosis. If eligible, patients with rare stroke causes should be considered for thrombectomy. Except for infective endocarditis, most rare stroke causes are not per se a contraindication to thrombolysis, so that eligible patients should also be considered for thrombolysis. Evidence based recommendations for the secondary prevention of most rare stroke causes are still missing. In many cases, treatment regimens are adapted to the patients' individual risk of stroke recurrence and bleeding complications.
Zusammenfassung
Seltene Schlaganfallursachen sind in der Summe gar nicht so selten und betreffen oft junge Schlaganfallpatienten, sodass der frühzeitigen Diagnostik und Therapie auch deshalb eine ...besondere sozioökonomische Bedeutung zukommt. In unserem klinischen Alltag sind Dissektionen, die in der Altersgruppe bis 45 Jahre die häufigste Schlaganfallursache darstellen, und Vaskulitiden besonders bedeutsam. Die Vaskulitis ist dabei auch aufgrund der häufig schwerwiegenden klinischen Verläufe und der potenziell nebenwirkungsreichen Therapieoptionen relevant. Darüber hinaus sind aber auch nicht-vaskulitische Vaskulopathien, Infektionen, hämatologische Erkrankungen, Gerinnungsstörungen, Stoffwechselerkrankungen und Malignome gar nicht so seltene Schlaganfallursachen, die sich klinisch zum Teil sehr unterschiedlich präsentieren und aufgrund dessen eine diagnostische Herausforderung darstellen. In der Akuttherapie sollte auch beim Vorliegen einer seltenen Schlaganfallursache bei geeigneten Patienten eine Thrombektomie erfolgen. Mit Ausnahme der infektiösen Endokarditis stellen die meisten seltenen Schlaganfallursachen außerdem nicht per se eine Kontraindikation gegen die intravenöse Thrombolyse dar. Evidenzbasierte Empfehlungen zur Sekundärprophylaxe existieren für die meisten seltenen Schlaganfallursachen nicht. Das therapeutische Vorgehen im Einzelfall muss daher oft unter Berücksichtigung des Rezidivrisikos und des Blutungsrisikos individuell festgelegt werden.
Inflammatory causes of stroke are frequent and often pose diagnostic and therapeutic challenges due to the scarcity of randomized trials and the absence of clear guideline recommendations for many ...scenarios. Following the publication of the recommendations of the European Stroke Organization on primary angiitis of the central nervous system (PACNS) last year, the German Neurological Society (DGN) has issued very clear guidelines this year on the diagnostics and treatment of PACNS and updated the recommendations for systemic vasculitides; however, stroke often occurs not only as a result of primary vascular inflammation but also as a complication of another organ infection. Approximately 5% of all patients with sepsis, ca. 20% of patients with bacterial meningitis and up to 40% of patients with bacterial endocarditis suffer from a stroke as a complication. This article summarizes the key characteristics of these inflammatory causes of stroke and particularly focuses on the current recommendations for diagnostic and therapeutic management.Inflammatory causes of stroke are frequent and often pose diagnostic and therapeutic challenges due to the scarcity of randomized trials and the absence of clear guideline recommendations for many scenarios. Following the publication of the recommendations of the European Stroke Organization on primary angiitis of the central nervous system (PACNS) last year, the German Neurological Society (DGN) has issued very clear guidelines this year on the diagnostics and treatment of PACNS and updated the recommendations for systemic vasculitides; however, stroke often occurs not only as a result of primary vascular inflammation but also as a complication of another organ infection. Approximately 5% of all patients with sepsis, ca. 20% of patients with bacterial meningitis and up to 40% of patients with bacterial endocarditis suffer from a stroke as a complication. This article summarizes the key characteristics of these inflammatory causes of stroke and particularly focuses on the current recommendations for diagnostic and therapeutic management.
Zusammenfassung Entzündliche Schlaganfallursachen sind häufig und stellen oft eine diagnostische und therapeutische Herausforderung dar, da es hierzu kaum randomisierte Studien gibt und für viele ...Konstellationen keine klaren Leitlinienempfehlungen existieren. Nach Veröffentlichung der Empfehlungen der Europäischen Schlaganfallgesellschaft zur primären Angiitis des zentralen Nervensystems (PACNS) im letzten Jahr hat die Deutsche Gesellschaft für Neurologie (DGN) in diesem Jahr eine sehr klare Leitlinie zur Diagnostik und Therapie der PACNS herausgegeben und die Empfehlungen für die systemischen Vaskulitiden aktualisiert. Häufig treten Schlaganfälle jedoch nicht nur infolge einer primären Gefäßentzündung auf, sondern auch als Komplikation einer anderen Organinfektion. So erleiden ca. 5 % aller PatientInnen mit einer Sepsis, ca. 20 % der PatientInnen mit bakterieller Meningitis und bis zu 40 % der PatientInnen mit bakterieller Endokarditis als Komplikation einen Schlaganfall. Unser Artikel fasst die wichtigsten Charakteristika dieser entzündlichen Ursachen von Schlaganfällen zusammen und fokussiert hierbei insbesondere auch auf aktuelle Empfehlungen zum diagnostischen und therapeutischen Management.
Abstract Inflammatory causes of stroke are frequent and often pose diagnostic and therapeutic challenges due to the scarcity of randomized trials and the absence of clear guideline recommendations for many scenarios. Following the publication of the recommendations of the European Stroke Organization on primary angiitis of the central nervous system (PACNS) last year, the German Neurological Society (DGN) has issued very clear guidelines this year on the diagnostics and treatment of PACNS and updated the recommendations for systemic vasculitides; however, stroke often occurs not only as a result of primary vascular inflammation but also as a complication of another organ infection. Approximately 5% of all patients with sepsis, ca. 20% of patients with bacterial meningitis and up to 40% of patients with bacterial endocarditis suffer from a stroke as a complication. This article summarizes the key characteristics of these inflammatory causes of stroke and particularly focuses on the current recommendations for diagnostic and therapeutic management.
Although CSF analysis routinely enables the diagnosis of neurological diseases, it is mainly used for the gross distinction between infectious, autoimmune inflammatory, and degenerative disorders of ...the CNS. To investigate, whether a multi-dimensional cellular blood and CSF characterization can support the diagnosis of clinically similar neurological diseases, we analysed 546 patients with autoimmune neuroinflammatory, degenerative, or vascular conditions in a cross-sectional retrospective study. By combining feature selection with dimensionality reduction and machine learning approaches we identified pan-disease parameters that were altered across all autoimmune neuroinflammatory CNS diseases and differentiated them from other neurological conditions and inter-autoimmunity classifiers that subdifferentiate variants of CNS-directed autoimmunity. Pan-disease as well as diseases-specific changes formed a continuum, reflecting clinical disease evolution. A validation cohort of 231 independent patients confirmed that combining multiple parameters into composite scores can assist the classification of neurological patients. Overall, we showed that the integrated analysis of blood and CSF parameters improves the differential diagnosis of neurological diseases, thereby facilitating early treatment decisions.
Although several studies have suggested that anti-inflammatory strategies reduce secondary infarct growth in animal stroke models, clinical studies have not yet demonstrated a clear benefit of immune ...modulation in patients. Potential reasons include systematic differences of post-ischemic neuroinflammation between humans and rodents. We here performed a systematic review and meta-analysis to summarize and compare the spatial and temporal distribution of immune cell infiltration in human and rodent stroke. Data on spatiotemporal distribution of immune cells (T cells, macrophages, and neutrophils) and infarct volume were extracted. Data from all rodent studies were pooled by means of a random-effect meta-analysis. Overall, 20 human and 188 rodent stroke studies were included in our analyses. In both patients and rodents, the infiltration of macrophages and neutrophils preceded the lymphocytic influx. Macrophages and neutrophils were the predominant immune cells within 72 h after infarction. Although highly heterogeneously across studies, the temporal profile of the poststroke immune response was comparable between patients and rodents. In rodent stroke, the extent of the immune cell infiltration depended on the duration and location of vessel occlusion and on the species. The density of infiltrating immune cells correlated with the infarct volume. In summary, we provide the first systematic analysis and comparison of human and rodent post-ischemic neuroinflammation. Our data suggest that the inflammatory response in rodent stroke models is comparable to that in patients with stroke. However, the overall heterogeneity of the post-ischemic immune response might contribute to the translational failure in stroke research.
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