Pericytes and Extracellular Vesicle Interactions in Neurovascular Adaptation to Chronic Arterial Hypertension.

Background: Chronic arterial hypertension restructures the vascular architecture of the brain, leading to a series of pathological responses that culminate in cerebral small-vessel disease. Pericytes respond dynamically to vascular challenges; however, how they manifest under the continuous strain of hypertension has not been elucidated.

Methods And Results: In this study, we characterized pericyte behavior alongside hypertensive states in the spontaneously hypertensive stroke-prone rat model, focusing on their phenotypic and metabolic transformation.

Discovery, Replicability, and Generalizability of a Left Anterior Hippocampus' Morphological Network Linked to Self-Regulation.

The human hippocampus is a key region in cognitive and emotional processing, but also a vulnerable and plastic region. Accordingly, there is a great interest in understanding how variability in the hippocampus' structure relates to variability in behavior in healthy and clinical populations. In this study, we aimed to link interindividual variability in subregional hippocampal networks (i.

Abatacept Induces Long-Term Reconstitution of the B-Cell Niche in a Patient With CTLA-4 Haploinsufficiency: A Case Report.

Objectives: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) haploinsufficiency is a rare genetic condition characterized by development of immune cytopenia, hypogammaglobulinemia, and/or lymphoproliferative disorder, as well as multiple autoimmunity. Treatment with abatacept was shown to alleviate autoimmune conditions, yet its long-lasting impact on bone marrow function remains undetermined.

Methods: We here present the case of a now 39-year-old woman with CTLA-4 haploinsufficiency with predominant CNS affection, yet multiorgan autoimmunity and lymphopenia.

Prehospital telemedicine support for urban stroke care: Analysis of current state of care and conceptualization.

Background: The reduction of processing times in the treatment of acute ischemic stroke is of outstanding importance. Our objective is to analyze the acute stroke care chain from onset to treatment in a city in Germany comprising three stroke units. Additionally, we discuss solutions for detected treatment delays.

Aggressive Lymphoma after CD19 CAR T-Cell Therapy.

The development of a fatal, clonal, autonomously proliferating CD4-CD8- chimeric antigen receptor (CAR)+ peripheral T-cell lymphoma (PTCL) occurred 1 month after a patient received treatment with tisagenlecleucel for relapsed primary central nervous system lymphoma. The PTCL had a clonal T-cell receptor rearrangement, which was already detectable in the apheresis product for CAR T-cell manufacturing and 7 months earlier for autologous transplantation. Somatic and mutations in CD34+ stem cells and their progeny were detected in the PTCL, in the apheresis specimen that was obtained for CAR T-cell production, and in the autotransplant.

Increased Disability Progression in rs10191329 Carriers with Multiple Sclerosis Is Preceded by Neurofilament Light Chain Elevations.

Objective: We examined the impact of the rs10191329 genetic risk variant on neuroaxonal damage as measured by serum neurofilament light chain (sNfL) levels, and disability progression in people with multiple sclerosis (pwMS).

Methods: In a cohort of pwMS (n = 740), 658 participants were prospectively monitored every 2 years for less than a decade while 82 of 740 pwMS were monitored retrospectively for up to 40 years. We investigated associations between rs10191329 variants and clinical outcome, including Expanded Disability Status Scale (EDSS), disability accrual (defined by EDSS-increase of at least 1.

MS brain health quality standards: a survey on the reality in clinical practice in Germany.

Background: The quality of treatment is especially critical in the context of complex and chronic diseases such as multiple sclerosis (MS). The Brain Health Initiative, an independent international consortium of neurologists, reached a consensus on time-based quality standards prioritizing brain health-focused care for people with MS.

Objectives: To gain deeper insights into the transferability of these quality standards to a specific area, we conducted a survey among MS experts across various MS centers in Germany.

Flow cytometry identifies changes in peripheral and intrathecal lymphocyte patterns in CNS autoimmune disorders and primary CNS malignancies.

Background: Immune dysregulation is a hallmark of autoimmune diseases of the central nervous system (CNS), characterized by an excessive immune response, and primary CNS tumors (pCNS-tumors) showing a highly immunosuppressive parenchymal microenvironment.

Methods: Aiming to provide novel insights into the pathogenesis of CNS autoimmunity and cerebral tumor immunity, we analyzed the peripheral blood (PB) and cerebrospinal fluid (CSF) of 81 autoimmune limbic encephalitis (ALE), 148 relapsing-remitting multiple sclerosis (RRMS), 33 IDH-wildtype glioma, 9 primary diffuse large B cell lymphoma of the CNS (CNS-DLBCL), and 110 controls by flow cytometry (FC). Additionally, an in-depth immunophenotyping of the PB from an independent cohort of 20 RRMS and 18 IDH-wildtype glioblastoma patients compared to 19 controls was performed by FC combined with unsupervised computational approaches.

Immune system activation and cognitive impairment in arterial hypertension.

Chronic arterial hypertension disrupts the integrity of the cerebral microvasculature, doubling the risk of age-related dementia. Despite sufficient antihypertensive therapy in still a significant proportion of individuals blood pressure lowering alone does not preserve cognitive health. Accumulating evidence highlights the role of inflammatory mechanisms in the pathogenesis of hypertension.

CSF and blood signatures support classification of limbic encephalitis subtypes.

Autoimmune limbic encephalitis (ALE) represents a heterogeneous disease associated with antibodies targeting extracellular (ALE) epitopes, intracellular (ALE) epitopes, anti-glutamic acid decarboxylase65 ALE (ALE), and ALE without detectable antibodies (ALE). Combining analysis of cellular parameters, investigated by flow cytometry, and soluble parameters in the blood and cerebrospinal fluid (CSF) from a large cohort of 148 ALE patients (33 ALE, 12 ALE, 28 ALE-GAD65, 37 ALE) in comparison to paradigmatic examples for neuro-inflammatory (51 relapsing remitting MS patients (RRMS)), and neuro-degenerative (34 Alzheimer's disease patients (AD)) diseases revealed discrete immune signatures in ALE subgroups. Identification of ALE-subtype specific markers facilitated classification of rare ALE-associated tumors, which may prompt further diagnostic efforts in clinical practice.

Cerebral vasculitis as clinical manifestation of neuroborreliosis: Pattern of vascular pathology and prognostic factors of outcome.

Background: Neuroborreliosis is a tick-borne condition that affects the central and/or peripheral nervous system. Cerebral infarction associated with neuroborreliosis-related vasculitis has been reported in only a handful of cases. Therefore, specific patterns of vascular pathology and prognostic outcome factors are still incompletely understood.

Neuropsychiatric symptoms and lifelong mental activities in cerebral amyloid angiopathy - a cross-sectional study.

Background: While several studies in cerebral amyloid angiopathy (CAA) focus on cognitive function, data on neuropsychiatric symptoms (NPS) and lifelong mental activities in these patients are scarce. Since NPS are associated with functional impairment, faster cognitive decline and faster progression to death, replication studies in more diverse settings and samples are warranted.

Methods: We prospectively recruited n = 69 CAA patients and n = 18 cognitively normal controls (NC).

Heterophoria in multiple sclerosis patients: a proof of principle cross-sectional study.

Objectives: The pathophysiology of multiple sclerosis (MS) involves inflammatory neurodegeneration in the brainstem, cerebellum, and retina. The clinical relevance of oculomotor involvement in MS, however, remains uncertain.

Methods: In this cross-sectional study, we evaluated heterophoria as a (sub)clinical tool in 54 MS patients and 55 age-matched healthy controls (HCs).

The Antidepressant- and Anxiolytic-Like Effects of the Phosphodiesterase Type-5 Inhibitor Tadalafil are Associated with the Modulation of the Gut-Brain Axis During CNS Autoimmunity.

Multiple Sclerosis (MS) is a debilitating disease that severely affects the central nervous system (CNS). Apart from neurological symptoms, it is also characterized by neuropsychiatric comorbidities, such as anxiety and depression. Phosphodiesterase-5 inhibitors (PDE5Is) such as Sildenafil and Tadalafil have been shown to possess antidepressant-like effects, but the mechanisms underpinning such effects are not fully characterized.

Retigabine, a potassium channel opener, restores thalamocortical neuron functionality in a murine model of autoimmune encephalomyelitis.

Background: Multiple Sclerosis (MS) is an autoimmune neurodegenerative disease, whose primary hallmark is the occurrence of inflammatory lesions in white and grey matter structures. Increasing evidence in MS patients and respective murine models reported an impaired ionic homeostasis driven by inflammatory-demyelination, thereby profoundly affecting signal propagation. However, the impact of a focal inflammatory lesion on single-cell and network functionality has hitherto not been fully elucidated.

Deficiency of the sphingosine-1-phosphate (S1P) transporter Mfsd2b protects the heart against hypertension-induced cardiac remodeling by suppressing the L-type-Ca channel.

The erythrocyte S1P transporter Mfsd2b is also expressed in the heart. We hypothesized that S1P transport by Mfsd2b is involved in cardiac function. Hypertension-induced cardiac remodeling was induced by 4-weeks Angiotensin II (AngII) administration and assessed by echocardiography.