Neurological research and practice最新文献

Background: Comorbid autoimmune disorders, including rheumatoid arthritis (RA), are common in people with multiple sclerosis (MS). Both conditions share pathogenic similarities, enabling potential overlap in treatments. While numerous disease-modifying therapies (DMT) are approved for MS and new options are under clinical trial, their effectiveness in RA varies.

Main body: A PubMed literature review was conducted to evaluate the effects of approved and currently investigated MS-DMT on MS and RA and vice versa. Certain MS-DMT showed beneficial effects for RA, such as teriflunomide, anti-CD20 therapies, and cladribine, while others demonstrated no significant impact (type-I interferons, Bruton´s tyrosine kinase (BTK) inhibitors) or lacked trials (sphingosine-1-phosphate receptor modulators, glatiramer acetate). In contrast, BTK inhibitors were shown to be effective for inactive secondary progressive forms of MS, whereas secukinumab showed limited effects in relapsing MS. Concerning DMT for RA in MS, no significant benefit was observed for abatacept, and there are no trials for Janus kinase inhibitors, or interleukin-(IL)-6 receptor inhibitors (tocilizumab, sarilumab). Adverse events, including RA exacerbation, were reported for some MS-DMT like dimethyl fumarate, alemtuzumab, and natalizumab. Tumor necrosis factor alpha (TNFα) inhibitors increased disease activity in MS patients.

Conclusion: Among approved DMT for MS and RA, teriflunomide and anti-CD20 therapies are the most suitable options for moderately or highly active MS with comorbid RA. Cladribine may also be considered, while TNFα inhibitors are contraindicated.

Background: Although brain atrophy is a prevalent finding in Wilson disease (WD), its role as a contributing factor to clinical symptoms, especially cognitive decline, remains unclear. The objective of this study was to investigate different neuroimaging biomarkers related to grey matter atrophy and their relationship with neurological and cognitive impairment in WD.

Methods: In this study, 30 WD patients and 30 age- and sex-matched healthy controls were enrolled prospectively and underwent structural magnetic resonance imaging (MRI). Regional atrophy was evaluated using established linear radiological measurements and the automated workflow volumetric estimation of gross atrophy and brain age longitudinally (veganbagel) for age- and sex-specific estimations of regional brain volume changes. Brain Age Gap Estimate (BrainAGE), defined as the discrepancy between machine learning predicted brain age from structural MRI and chronological age, was assessed using an established model. Atrophy markers and clinical scores were compared between 19 WD patients with a neurological phenotype (neuro-WD), 11 WD patients with a hepatic phenotype (hep-WD), and a healthy control group using Welch's ANOVA or Kruskal-Wallis test. Correlations between atrophy markers and neurological and neuropsychological scores were investigated using Spearman's correlation coefficients.

Results: Patients with neuro-WD demonstrated increased third ventricle width and bicaudate index, along with significant striatal-thalamic atrophy patterns that correlated with global cognitive function, mental processing speed, and verbal memory. Median BrainAGE was significantly higher in patients with neuro-WD (8.97 years, interquartile range [IQR] = 5.62-15.73) compared to those with hep-WD (4.72 years, IQR = 0.00-5.48) and healthy controls (0.46 years, IQR = - 4.11-4.24). Striatal-thalamic atrophy and BrainAGE were significantly correlated with neurological symptom severity.

Conclusions: Our findings indicate advanced predicted brain age and substantial striatal-thalamic atrophy patterns in patients with neuro-WD, which serve as promising neuroimaging biomarkers for neurological and cognitive functions in treated, chronic WD.

Background: Acute stroke care has evolved markedly in recent decades, yet long-term trends across stroke subtypes remain understudied. This study analyzed national trends in inpatient stroke care for ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) in Germany from 2000 to 2021.

Methods: We conducted a retrospective analysis of nationwide hospital administrative data, assessing annual case counts, age-standardized rates, mean length of stay, and annual inpatient case days (AICD). Stroke unit (SU) treatments were analyzed from 2005 onward. Joinpoint regression identified changes in trends over time.

Results: IS case rates, length of stay, and AICD declined significantly until 2005/2006, after which they stabilized at remarkably high levels. Paralleled by a rapid expansion of SU care, in-hospital mortality from IS decreased significantly. Coding of unspecified stroke (I64) declined steeply, suggesting shifts in diagnostic precision. In contrast, ICH and SAH showed falling case rates but increasing lengths of stay, particularly among deceased patients. SU treatments rose continuously from 2005 to 2021, with age-standardized rates increasing by 7.1% annually.

Conclusions: Over two decades, total inpatient burden from stroke has declined, primarily due to reductions in IS admissions and mortality. However, longer hospital stays in SAH and ICH and an overall rising SU care indicate shifting but consistently high resource requirements. Thus, continued efforts in optimizing healthcare infrastructure seem reasonable and should consider a subtype-specific resource allocation in acute stroke care.

Introduction: A decade ago, endovascular therapy (EVT) for acute ischemic stroke (AIS) with large vessel occlusion (LVO) has been established as standard of care. It is still a matter of debate whether EVT is better and safe for patients with more distal occlusions (DMVO). Three randomized controlled trials investigated the role of EVT on top of best medical treatment (BMT) for patients with DMVO.

Methods: In a narrative review we present the results of 3 randomized controlled trials (RCT), (DISTAL, ESCAPE MeVO, DISCOUNT) of EVT plus BMT versus BMT alone. In addition, we performed a study level meta-analysis with a random-effects model for three endpoints: independent outcome, symptomatic intracranial hemorrhage (sICH) and death.

Results: There was neither a significant effect of EVT plus BMT versus BMT alone on functional outcome (RR 0.92, 95% CI 0.80-1.06, p = 0.272), nor did the odds of death differ (OR 1.23, 95% CI 0.76-1.99, p = 0.409). The odds for sICH were more than twice as high with EVT (OR 2.38, 95% CI 1.35-4.20, p = 0.003).

Conclusion: At present EVT for medium and distal vessel occlusions in AIS patients is not a standard of care. With equipoise for EVT in DMVO now an unbiased and rapid randomization into new and differently designed RCT should be a top priority.

Background: In the Find-AF 2 randomised controlled trial, we investigate whether a risk-adapted intensified heart rhythm monitoring with subsequent initiation of oral anticoagulation in ischaemic stroke patients leads to a reduction of recurrent ischaemic stroke and systemic embolism. The objective of this analysis is to present baseline characteristics of the overall Find-AF 2 study population and stratified by low or high risk for developing AF.

Methods: The Find-AF 2 trial included acute ischaemic stroke patients ≥ 60 years of age within 30 days of ischaemic stroke of any cause. Before randomisation, patients received a 24-h Holter-ECG to exclude those with easily detectable AF and to determine the presence or absence of enhanced supraventricular ectopic activity (ESVEA), used as a marker indicating high or low risk for developing AF. Those without AF were randomly assigned 1:1 to either usual care diagnostics for AF detection (control group) or enhanced, prolonged and intensified ECG monitoring (intervention group). In the intervention group, patients with ESVEA received an implantable cardiac monitor (ICM), whereas those without ESVEA received repeated annual 7-day Holter ECGs. We present baseline characteristics of the overall Find-AF 2 population and stratified by ESVEA.

Results: Between July 2020 and July 2024, 5227 patients (mean age 72.3 ± 7.5 years, 40% female, 2618 intervention group, 2609 control group) were randomised from 52 study centres in Germany within a median of 5 (IQR 3-7) days after the index stroke. The most frequent stroke aetiologies were cryptogenic (60%) and small vessel occlusion (19%). 1152 (22%) patients were at high risk for developing AF and 4075 (78%) at low risk. Patients within the high-risk stratum were significantly older (mean age 75.2 versus 71.5 years, p < 0.001), more often had moderate to severe stroke (34% versus 30%, p < 0.001), non-lacunar (70% versus 64%, p < 0.001) and of cryptogenic aetiology (64% vs 58%, p < 0.001).

Conclusions: The Find-AF 2 trial has successfully completed recruitment of a large acute ischaemic stroke population with different stroke subtypes. The follow-up is ongoing and results are expected within two years.

Trial registration: ClinicalTrials.gov, Identifier NCT04371055, registered 24 April 2020.

Background: An analysis of the cerebrospinal fluid (CSF) is essential for diagnosis of meningitis, headache, disturbance of conscience, cranial nerves or autoimmune-related conditions of the CNS. The initial treatment of pleocytosis usually consists of both antiviral therapy and antibiotics until laboratory results enable a more specific approach. Therefore, it is crucial to rapidly and accurately detect pathogens.

Methods: In this observatory, monocentric study of quality management data, we studied insourcing of ME-PCR, CXCL 13, Antibody-specific Index (AI) for HSV, VZV (G $_1^{}$ ) compared with outsourced laboratory measurements (G $_0^{}$ ) and its benefit for the work-up. Before the implementation of these parameters, data from 150 patients were sampled, followed by 210 after the introduction of ME-PCR, CXCL 13 and AI. Data were collected, anonymized, and analysed afterwards. All were treated in hospital for suspected infections of the Central Nervous System (CNS). The length of hospital stay (LOS), intervals from lumbar puncture, the cumulative dose of anti-infective agents, length of treatment and the potential impact on patients' safety parameters were examined.

Results: The G $_1^{}$ -group showed a significant decrease of LOS (p<0.001), exposure to antiviral, and antibiotic agents decreased significantly (p < 0.001, each). Insourcing of ME-PCR and CXCL 13 shortened the time-span from admission to diagnosis in patients with suspected inflammatory CNS disease from 13.6 (6.6) to 9.7 (6.7) days in mean (SD).

Conclusion: The shortened average LOS after changing the diagnostic pathway increased direct costs for test kits. However, these costs were by far outweighed the economical benefit of being able to treat more patients in the same time. This analysis should be replicated in a different Medical Care System than the one in which this analysis has been calculated.

Background: Idiopathic Normal Pressure Hydrocephalus (iNPH) is a potentially reversible cause of cognitive impairment, urinary incontinence, and gait disturbances, which typically present with a characteristic slow, shuffling, and wide-based gait. Gait velocity, which is reduced relative to healthy controls, improves in iNPH patients following a spinal tap test. This study aimed at evaluating the criterion of a 20% gait velocity improvement in the 10 m walk test to identify responders and non-responders in a cohort of patients with probable iNPH receiving a spinal tap test as well as the added value of instrument-supported gait analysis.

Methods: We assessed pace, rhythm, variability, postural control, and force in 59 patients with clinically suspected iNPH undergoing a spinal tap test, applying the 10 m walk test and an instrument-supported gait analysis. The change in gait velocity assessed in the 10 m walk test was used to differentiate patients with a positive response to the spinal tap (> 20% improvement, responders) from those with no relevant response (< 20% improvement, non-responders). Group differences were analyzed using chi-square tests, independent sample t-tests, Mann-Whitney-U tests and repeated measure ANOVAs.

Results: Unlike non-responders (n = 39), responders (n = 20) showed significant changes in the gait domain pace in the 10 m walk test. Moreover, instrument-supported gait analyses revealed additional improvements in the gait domains variability, rhythm, postural control and force in responders only.

Interpretation: This study confirmed the clinical utility of the 20% gait velocity improvement criterion for differentiating responders and non-responders in a cohort of patients with mostly probable iNPH, in whom clinical parameters alone were insufficient for classification. Notably, instrument-supported gait analysis validated this criterion by providing a more comprehensive characterization of gait disturbances compared to the 10 m walk test. However, further-especially longitudinal-studies are needed to reveal the full potential of the instrument-supported gait analysis in patients with (early/probable) iNPH.

Background: Admission glycemia has emerged as an important outcome predictor in the context of mechanical thrombectomy (MT) for large vessel occlusions (LVO) in ischemic stroke. However, a clinically relevant threshold of glucose levels to identify patients at risk for poor functional outcome has yet to be established.

Methods: We conducted a retrospective, monocentric, consecutive registry-based analysis of patients who underwent MT for anterior circulation LVO. Good outcome was defined as functional independence after 90 days (90d mRS < 3) or no deterioration from premorbid mRS. We performed a multiple logistic regression analysis to assess the association between admission glucose levels and functional outcome, including for well-established outcome predictors, i.e. age, NIHSS, Alberta Stroke Program Early CT Score (ASPECTS), time to reperfusion, unsuccessful recanalization, presence of bleeding, and diabetes. In addition, we conducted a receiver operating characteristic (ROC) analysis to determine the optimal admission glucose threshold that best discriminates patients at risk for poor outcome, maximizing sensitivity and specificity.

Results: We analyzed 509 patients (mean age = 74.3 ± 12.6 years, median previous mRS = 1.5, 48% male). 194 patients (38.1%) had good outcome and 315 (61.9%) had poor outcome. According to the logistic regression admission glucose (p = 0.012, OR 1.009 95% CI [1.002 1.016]) contributed to predicting poor outcome, while known diabetes did not show a significant contribution. The ROC analysis revealed an admission glucose of 117 mg/dL (59.7% sensitivity; 58% specificity) to be the optimal cut-off value to discriminate patients at risk for poor outcome with an OR of 2.3.

Conclusion: Admission hyperglycemia is an independent predictor of poor outcome after MT for LVO in the anterior circulation. We hypothesize, that optimal glucose values in patients undergoing MT will likely be in the low normoglycemic range. Prospective controlled studies with targeted glucose values will be needed for validation.