Background: Corticospinal excitability, measured by motor-evoked potentials (MEPs), is often impaired in neurological and musculoskeletal conditions. Transcranial direct current stimulation (tDCS) can modulate cortical excitability and improve clinical outcomes, yet inconsistencies in parameter settings complicate identification of optimal protocols.
Objective: Our primary objective was to examine the effects of: (i) stimulation polarity, (ii) duration, (iii) intensity, (iv) frequency, (v) electrode montage, and (vi) electrode design (size/shape) on MEP size.
Methods: Nine databases were searched from inception to 24th November 2023. We identified 84 individual cohorts (1,709 participants) and assessed time-dependent effects of each parameter on M1 MEP-to-baseline ratio in healthy and clinical populations using multi-level longitudinal meta-analysis.
Results: Anodal tDCS increased MEP size, with effects lasting up to 120 min post-stimulation. Consistent effects were observed with anodal tDCS durations ≥ 20 min and intensities ≥ 1.5 mA. Despite cohorts being matched, cathodal tDCS reduced MEP size for approximately 15 min post-stimulation, with significant effects at durations ≥ 9 min, intensity effects were inconclusive. Electrode montage and electrode size/shape influenced MEP, with greatest effect for electrodes over both the primary motor cortex and the dorsolateral pre-frontal cortex or over the cerebellar region, using 4 cm2 ring and 35 cm2 rectangular electrodes.
Conclusion: tDCS effects on corticospinal excitability are parameter dependent. Anodal tDCS tends to facilitate excitability, whereas cathodal tDCS tends to inhibit excitability (depending on stimulation parameters). Specific durations, intensities, electrode placements and designs will ensure effectiveness and optimise safety. Findings support a parameter-specific approach to guide tailored neuromodulation interventions to enhance motor cortex rehabilitation outcomes.
Background: Guidelines generally advise against reperfusion therapy in patients with mild stroke (NIHSS ≤ 5) and non-disabling symptoms. However, stroke severity can fluctuate, and clinical scores may not fully capture tissue at risk. Reliance on non-contrast CT (NCCT), potentially missing perfusion deficits or large vessel occlusions (LVOs). Advanced imaging-including CT angiography (CTA) and CT perfusion (CTP)-can reveal significant hypoperfusion in otherwise mild presentations. This study aimed to quantify the proportion of increased tissue-at-risk volumes (Tmax + 6s ≥ 15 mL) in patients with mild acute ischaemic stroke and identify associated factors and outcomes.
Methods: We included consecutive AIS patients within 24 h of onset from multicentre stroke registries in Australia and Indonesia. Only those with baseline NCCT, CTA, and CTP were analysed. Patients were stratified into NIHSS ≤ 5 and > 5. Tissue-at-risk was defined as Tmax + 6s ≥ 15 mL. Clinical, imaging, and outcome data were compared, and predictors of poor functional outcome (mRS 3-6 at 90-day) were assessed.
Results: Of 655 patients, 314 had NIHSS ≤ 5. Among these, 22.9% exhibited Tmax + 6s ≥ 15 mL, indicating significant hypoperfusion. This subgroup had worse 90-day outcomes (26.4% mRS 3-6 vs. 9.5%, p < 0.001). Tmax + 6s ≥ 15 mL, hypertension, and LVO were independently associated with poor outcome (adjusted ORs: 2.51, 3.15, and 2.74 respectively). ROC analysis demonstrated moderate discrimination of Tmax + 6s volume for poor functional outcome.
Conclusions: A substantial proportion of mild stroke patients harbour treatable perfusion deficits. CT perfusion provides essential prognostic information beyond clinical severity, supporting its role in guiding therapeutic decisions-even in low NIHSS presentations where standard imaging may otherwise overlook tissue at risk.
Background: In the general population, cognitive impairment and dementia are more common in individuals with prior myocardial injury, defined as elevated levels of high-sensitive cardiac troponin (hs-cTn). In stroke patients, data on the link between myocardial injury and cognitive outcome are scarce. We aimed to analyze the association between the severity of myocardial injury (degree of hs-cTn elevation), presence of acute myocardial injury (dynamic change in elevated hs-cTn values > 20% in serial measurements) and cognitive performance over time after acute ischemic stroke.
Methods: This is a prespecified analysis of the prospective multicenter observational PRediction of Acute coronary syndrome in acute Ischemic StrokE (PRAISE) study. PRAISE included 254 patients with an acute ischemic stroke or transient ischemic attack (TIA) and myocardial injury in 26 centers in Germany. Patients underwent cognitive assessment at baseline and before hospital discharge using the Montreal Cognitive Assessment (MoCA) and at three and twelve months after the index event using the Telephone Interview for Cognitive Status (TICS). We used linear regression to analyze the associations between cognitive performance and (1) severity of myocardial injury and (2) presence of acute myocardial injury. The association between hs-cTn and TICS scores over time was examined using inverse probability weighted generalized linear models.
Results: Severity of myocardial Injury was associated with lower MoCA scores (adjusted beta - 2.6, 95% CI -4.0 - -1.2, p < 0.001) and higher proportion of cognitive impairment (i.e. MoCA score < 26 points) (adjusted OR 2.9, 95%CI 1.3-6.7, p = 0.012). Acute myocardial injury was associated with better cognitive performance (adjusted beta 1.8, 95% CI 0.4-3.1, p = 0.011). We found no association between hs-cTn and cognitive decline over twelve months.
Conclusions: In patients with ischemic stroke, the severity of myocardial injury in general but not the presence of acute myocardial injury at time of stroke is associated with cognitive impairment.
Trial registration: Clinicaltrials.gov NCT03609385 https://clinicaltrials.gov/study/NCT03609385?term=NCT03609385&rank=1 Date of registration 6th July 2018.
Background: Deciding on intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients with reported recent direct oral anticoagulant (DOAC) intake remains challenging due to concerns about hemorrhagic risk and the absence of randomized controlled trial evidence. This study aimed to provide a comprehensive characterization of all AIS patients with reported recent DOAC intake-regardless of IVT eligibility-treated at a comprehensive stroke center that routinely measures calibrated anti-facor IIa/Xa activity at admission.
Methods: In this retrospective study, clinical and procedural data from AIS patients with recent DOAC intake and calibrated anti-factor IIa/Xa activity measured within three hours of admission were analyzed. Patients were treated at the University Hospital Essen between March 2017 and October 2023.
Results: Among 469 included patients, anti-factor IIa/Xa activity was ≤ 30 ng/ml in 28%, > 30- ≤ 50 ng/ml in 9%, > 50- ≤ 75 ng/ml in 9%, > 75- ≤ 100 ng/ml in 9% and > 100 ng/ml in 45%. Lower DOAC levels correlated with severe stroke symptoms at admission (ρ = - 0.263, p < 0.001). IVT was administered to 33.5% of patients with DOAC levels ≤ 50 ng/ml, compared to only 4% among those with levels > 50 ng/ml, the majority of whom received prior reversal with idarucizumab. Symptomatic intracranial haemorrhage (sICH) occurred in 4% of IVT-treated and 1% of non-IVT-treated patients, without association to anticoagulation status.
Conclusions: A considerable proportion of AIS patients with recent DOAC intake exhibited minimal or no anticoagulant activity at presentation. Those with the lowest levels also showed highest stroke severity. IVT was safe across all DOAC level groups, with low and comparable sICH rates. These findings support the rationale for a randomized trial evaluating IVT without prior DOAC level testing.
Background: Previous studies have demonstrated that patients with Parkinson's disease (PD) exhibit pathologically increased beta band activity (12-35 Hz) in the basal ganglia, which peaks at an individual frequency and correlates with symptom severity. The purpose of this study was to determine whether different beta peak measures can serve as predictors for deep brain stimulation (DBS) contact selection.
Methods: Subthalamic local field potentials were acquired from 27 patients with PD (8 female, 59.0 ± 8.9 years) with (ON) and without (OFF) dopaminergic medication. Peak amplitudes and frequencies were detected in the low (12-20 Hz) and high beta band (21-35 Hz), and their predictive value for the motor symptom improvement, the therapeutic window and the optimal stimulation contact were analyzed.
Results: In particular, the power ratio of the highest low beta peak ON versus OFF medication explained 23.7% of the variance in the therapeutic window.
Conclusion: Our results demonstrate that beta peak measures can serve as valuable markers to estimate contact selection to achieve an optimal DBS outcome in patients with PD.
Trial registration: Not applicable.
Introduction: The German Dementia Registry (DEMREG) is a large-scale national prospective biomarker-based study for cognitive impairment and dementia, providing an integrated clinical research platform for research studies.
Methods: The DEMREG study longitudinally collects demographic, clinical, genetic, biological, and imaging data, along with risk factors and treatment information from real-world settings. Comprehensive clinical assessments are conducted yearly. This extensive resource enables researchers to investigate current diagnostic and treatment practices and explore the complex relationships between risk factors and outcomes. The registry is now active across 22 sites in Germany, all members of the the German Memory Clinic Network (DNG), with more than 500 patients recruited to date, and is expected to include up to 1.000 patients annually.
Perspective: The DEMREG study represents a large nationally harmonized cohort of detailed real-world clinical and biological data from patients with cognitive impairment and dementia, enabling insights into long-term dynamics and treatment responses. This infrastructure has the potential to foster collaborative research and roll out healthcare innovations across different settings in Germany. In this context, a substudy will soon be conducted to evaluate long-term safety and efficacy measures of the new monoclonal antibodies targeting amyloid plaques in a clinical setting.
Trial registration: The protocol is registered at German Clinical Trials Register (DRKS00027547), Date of Registration: 01.04.2022.
Background: Non-convulsive status epilepticus (NCSE) is a common definitive or exclusion diagnosis in patients with disorders of consciousness (DOC) on neurological or interdisciplinary intensive care units (ICU). Special expertise is required to ensure reliable diagnosis, targeted therapy management, and individual prognostication, particularly as NCSE is identified based solely on clinical and electroencephalographic findings.
Main body: This narrative state-of-the-art review compiles and critically discusses the existing literature on various aspects of NCSE. We focus on the reliable initial diagnosis and further monitoring of NCSE using the Salzburg criteria and the 2HELP2B score, therapy options beyond current guideline recommendations, and prognosis assessment using established scores and metrics, such as STESS, SACE, EMSE, and END-IT. With compact tables and clear illustrations, comprehensive insights are presented in a concise structure to provide clear guidance for daily practice.
Conclusion: NCSE is a common and complex disease entity observed in the ICU that requires dedicated and specialised diagnostics, therapy, monitoring, and outcome assessment. Evidence-based recommendations are now available for each of these critical processes to guide caregivers and relatives. However, the availability of continuous (cEEG), quantitative (qEEG) electroencephalography in the ICU and expertise in its interpretation are limiting factors in many clinical settings. This problem is becoming increasingly pronounced due to the reduced or complete lack of reimbursement for c/qEEG in the context of intensive care medicine in many countries.
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