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Alongside biological, psychological, and social risk factors, psychotic syndromes may berelated to disturbances of neuronal migration. This highly complex process characterizesthe developing brain of the fetus, the early postnatal brain, and the adult brain, as reflectedby changes within the subventricular zone and the dentate gyrus of the hippocampus,where neurogenesis persists throughout life. Psychosis also appears to be linked tohuman cytomegalovirus (HCMV) infection. However, little is known about the connectionbetween psychosis, HCMV infection, and disruption of neuronal migration. The presentstudy addresses the hypothesis that HCMV infection may lead to mental disordersthrough mechanisms of autoimmune cross-reactivity. Searching for common peptidesthat underlie immune cross-reactions, the analyses focus on HCMV and human proteinsinvolved in neuronal migration. Results demonstrate a large overlap of viral peptides withhuman proteins associated with neuronal migration, such as ventral anterior homeobox 1and cell adhesion molecule 1 implicated in GABAergic and glutamatergicneurotransmission. The presentfindings support the possibility of immune cross-reactivity between HCMV and human proteins that—when altered, mutated, orimproperly functioning—may disrupt normal neuronal migration. In addition, thesefindings are consistent with a molecular and mechanistic framework for pathologicalsequences of events, beginning with HCMV infection, followed by immune activation,cross-reactivity, and neuronal protein variations that may ultimately contribute to theemergence of mental disorders, including psychosis
Socio-cognitive abilities and challenges change across the healthy lifespan and are essential for successful human interaction. Identifying effective socio-cognitive training approaches for healthy individuals may prevent development of mental or physical disease and reduced quality of life. A systematic search was conducted in MEDLINE Ovid, Web of Science Core Collection, CENTRAL, and PsycInfo databases. Studies that investigated different socio-cognitive trainings for healthy individuals across the human lifespan assessing effects on theory of mind, emotion recognition, perspective taking, and social decision making were included. A random-effects pairwise meta-analysis was conducted. Risk-of-Bias was assessed using the Cochrane Risk-of-Bias-2-Tool. Twenty-three intervention studies with N = 1835 participants were included in the systematic review; twelve randomized controlled trials in the meta-analysis (N = 875). Socio-cognitive trainings differed regarding duration and content in different age groups, with theory of mind being the domain most frequently trained. Results of the meta-analysis showed that trainings were highly effective for improving theory of mind in children aged 3–5 years (SMD = 2.51 (95%CI: 0.48–4.53)), children aged 7–9 years (SMD = 2.71 (95%CI: − 0.28 to 5.71)), and older adults (SMD = 5.90 (95%CI: 2.77–9.02). Theory of mind training was highly effective in all investigated age-groups for improving theory of mind, yet, more research on transfer effects to other socio-cognitive processes and further investigation of training effects in other socio-cognitive domains (e.g., emotion recognition, visual perspective taking, social decision making) is needed. Identified characteristics of successful socio-cognitive trainings in different age groups may help designing future training studies for other populations.
BACKGROUND Acute disseminated encephalomyelitis (ADEM) is a rare, acquired demyelination syndrome that causes cognitive impairment and
focal neurological deficits and may be fatal. The potentially reversible disease mainly affects children, often after vaccination or viral infection, but may
be seen rarely in adults.
OBSERVATIONS A 50-year-old woman presented with loss of visual acuity of the left eye. Magnetic resonance imaging (MRI) revealed an intra- and
suprasellar mass, which was removed successfully. On postoperative day 1, MRI showed gross total resection of the lesion and no surgery-related
complications. On postoperative day 2, the patient presented with a progressive left-sided hemiparesis, hemineglect, and decline of cognitive
performance. MRI showed white matter edema in both hemispheres. Cerebrospinal fluid analysis revealed mixed pleocytosis (355/mL) without further
evidence of infection. In synopsis of the findings, ADEM was diagnosed and treated with intravenous immunoglobulins. Shortly thereafter, the patient
recovered, and no sensorimotor deficits were detected in the follow-up examination.
LESSONS Pituitary gland pathologies are commonly treated by transsphenoidal surgery, with only minor risks for complications. A case of ADEM after
craniopharyngioma resection has not been published before and should be considered in case of progressive neurological deterioration with multiple
white matter lesions.
Manual sleep scoring for research purposes and for the diagnosis of sleep disorders is labor-intensive and often varies significantly between scorers, which has motivated many attempts to design automatic sleep stage classifiers. With the recent introduction of large, publicly available hand-scored polysomnographic data, and concomitant advances in machine learning methods to solve complex classification problems with supervised learning, the problem has received new attention, and a number of new classifiers that provide excellent accuracy. Most of these however have non-trivial barriers to use. We introduce the Greifswald Sleep Stage Classifier (GSSC), which is free, open source, and can be relatively easily installed and used on any moderately powered computer. In addition, the GSSC has been trained to perform well on a large variety of electrode set-ups, allowing high performance sleep staging with portable systems. The GSSC can also be readily integrated into brain-computer interfaces for real-time inference. These innovations were achieved while simultaneously reaching a level of accuracy equal to, or exceeding, recent state of the art classifiers and human experts, making the GSSC an excellent choice for researchers in need of reliable, automatic sleep staging.
Objective: This study was conducted to elucidate prevalence, clinical features, outcomes, and best treatment in patients with late-onset seizures due to autoimmune encephalitis (AE).
Methods: This is a single-institution prospective cohort study (2012–2019) conducted at the Epilepsy Center at the University of Greifswald, Germany. A total of 225 patients aged ≥50 years with epileptic seizures were enrolled and underwent an MRI/CT scan, profiling of neural antibodies (AB) in serum and cerebrospinal fluid (CSF), and neuropsychological testing. On the basis of their work-up, patients were categorized into the following three cohorts: definite, suspected, or no AE. Patients with definite and suspected AE were subsequently treated with immunosuppressive therapy (IT) and/or anti-seizure drug (ASD) therapy and were followed up (FU) regarding clinical and seizure outcome.
Results: Of the 225 patients, 17 (8%) fulfilled the criteria for definite or suspected AE according to their AB profile and MRI results. Compared with patients with no evidence of AE, those with AE were younger (p = 0.028), had mesial temporal neuropsychological deficits (p = 0.001), frequently had an active or known malignancy (p = 0.006) and/or a pleocytosis (p = 0.0002), and/or had oligoclonal bands in CSF (p = 0.001). All patients with follow-up became seizure-free with at least one ASD. The Modified Rankin scale (mRS) at hospital admission was low for patients with AE (71% with mRS ≤2) and further decreased to 60% with mRS ≤2 at last FU.
Significance: AE is an important etiology in late-onset seizures, and seizures may be the first symptom of AE. Outcome in non-paraneoplastic AE was favorable with ASD and IT. AB testing in CSF and sera, cerebral MRI, CSF analysis, and neuropsychological testing for mesial temporal deficits should be part of the diagnostic protocol for AE following late-onset seizures.
Free light chains kappa (FLCκ) in cerebrospinal fluid (CSF) are a part of the intrathecal immune response. This observational study was conducted to investigate the effects of different disease-modifying therapies (DMT) on the humoral intrathecal immune response in the CSF of patients with multiple sclerosis (MS). FLCκ were analyzed in CSF and serum samples from MS patients taking DMT (n = 60) and those in a control cohort of treatment-naïve MS patients (n = 90). DMT was classified as moderately effective (including INFß-1a, INFß-1b, glatiramer acetate, dimethyl fumarate, teriflunomide, triamcinolone); highly effective (including fingolimod, daclizumab) and very highly effective (alemtuzumab, natalizumab, rituximab/ocrelizumab, mitoxantrone). FLCκ were measured using a nephelometric FLCκ kit. Intrathecal FLCκ and IgG concentrations were assessed in relation to the hyperbolic reference range in quotient diagrams. Intrathecal FLCκ concentrations and IgG concentrations were significantly lower in samples from the cohort of MS patients taking very highly effective DMT than in samples from the cohort of MS patients taking highly effective DMT and in the treatment-naïve cohort (FLCκ: p = 0.004, p < 0.0001 respectively/IgG: p = 0.013; p = 0.021). The reduction in FLCκ could contribute to an anti-inflammatory effect in the CNS through this mechanism. There was no difference in the appearance of CSF-specific oligoclonal bands (p = 0.830). Longitudinal analyses are required to confirm these results.
Importance: Developing interventions against age-related memory decline and for older adults experiencing neurodegenerative disease is one of the greatest challenges of our generation. Spermidine supplementation has shown beneficial effects on brain and cognitive health in animal models, and there has been preliminary evidence of memory improvement in individuals with subjective cognitive decline.
Objective: To determine the effect of longer-term spermidine supplementation on memory performance and biomarkers in this at-risk group.
Design, Setting, and Participants: This 12-month randomized, double-masked, placebo-controlled phase 2b trial (the SmartAge trial) was conducted between January 2017 and May 2020. The study was a monocenter trial carried out at an academic clinical research center in Germany. Eligible individuals were aged 60 to 90 years with subjective cognitive decline who were recruited from health care facilities as well as through advertisements in the general population. Data analysis was conducted between January and March 2021.
Interventions: One hundred participants were randomly assigned (1:1 ratio) to 12 months of dietary supplementation with either a spermidine-rich dietary supplement extracted from wheat germ (0.9 mg spermidine/d) or placebo (microcrystalline cellulose). Eighty-nine participants (89%) successfully completed the trial intervention.
Main Outcomes and Measures: Primary outcome was change in memory performance from baseline to 12-month postintervention assessment (intention-to-treat analysis), operationalized by mnemonic discrimination performance assessed by the Mnemonic Similarity Task. Secondary outcomes included additional neuropsychological, behavioral, and physiological parameters. Safety was assessed in all participants and exploratory per-protocol, as well as subgroup, analyses were performed.
Results: A total of 100 participants (51 in the spermidine group and 49 in the placebo group) were included in the analysis (mean [SD] age, 69 [5] years; 49 female participants [49%]). Over 12 months, no significant changes were observed in mnemonic discrimination performance (between-group difference, −0.03; 95% CI, −0.11 to 0.05; P = .47) and secondary outcomes. Exploratory analyses indicated possible beneficial effects of the intervention on inflammation and verbal memory. Adverse events were balanced between groups.
Conclusions and Relevance: In this randomized clinical trial, longer-term spermidine supplementation in participants with subjective cognitive decline did not modify memory and biomarkers compared with placebo. Exploratory analyses indicated possible beneficial effects on verbal memory and inflammation that need to be validated in future studies at higher dosage.
Neuronal cells are specialists for rapid transfer and translation of information. Their electrical properties relay on a precise regulation of ion levels while their communication via neurotransmitters and neuropeptides depends on a high protein and lipid turnover. The endoplasmic Reticulum (ER) is fundamental to provide these necessary requirements for optimal neuronal function. Accumulation of misfolded proteins in the ER lumen, reactive oxygen species and exogenous stimulants like infections, chemical irritants and mechanical harm can induce ER stress, often followed by an ER stress response to reinstate cellular homeostasis. Imbedded between glial-, endothelial-, stromal-, and immune cells neurons are constantly in communication and influenced by their local environment. In this review, we discuss concepts of tissue homeostasis and innate immunity in the central and peripheral nervous system with a focus on its influence on ER stress, the unfolded protein response, and implications for health and disease.
Background:
Epileptic seizures can occur throughout the course of multiple sclerosis (MS) and are associated with increasing disability progression over time. However, there are no data on whether epileptic seizures at the onset of MS also lead to increasing disability.
Objective:
To examine disease progression over time for MS patients with epileptic seizures at onset.
Methods:
We analyzed the data of 30,713 patients on the German Multiple Sclerosis Register in a case–control study for more than 15 years. MS patients with seizures at onset were further divided into subgroups with polysymptomatic and monosymptomatic onset to assess the impact of additional symptoms on disease progression.
Results:
A total of 46 patients had seizures as onset symptoms. Expanded Disability Status Scale (EDSS) within the first year was lower in the group with seizures at onset compared to controls (0.75 versus 1.6, p < 0.05), which changed until the last reported visit (3.11 versus 3.0). Both subgroups revealed increased EDSS progression over time compared to controls.
Conclusion:
Epileptic seizures at MS onset are associated with a higher amount of disability progression over time. Additional longitudinal data are needed to further clarify the impact of seizures on the pathophysiology of MS disease progression.