Therapeutic Advances in Neurological Disorders最新文献

Background: Post-stroke epilepsy (PSE) is a common complication after ischemic stroke (IS) that worsens prognosis and quality of life. The atherogenic index of plasma (AIP) is an emerging biomarker for cardiovascular and metabolic diseases, but its link with PSE is unknown.

Objective: This study aimed to evaluate the association between AIP and the risk of PSE in patients with IS.

Design: A multicenter retrospective cohort study.

Methods: We analyzed data from 21,459 IS patients in Southwest China (2017-2023). AIP was calculated as log10(triglycerides/high-density lipoprotein cholesterol) from baseline lipid profiles. The primary outcome was PSE occurrence within 1 year post-stroke. The relationship between AIP and PSE was assessed using multivariable logistic regression and restricted cubic spline (RCS) models, adjusting for demographic, clinical, and laboratory covariates. Subgroup and sensitivity analyses were performed to test robustness.

Results: Among 21,459 participants, 936 (4.36%) developed PSE. Higher AIP levels were significantly associated with increased PSE risk. After full adjustment, each 1-standard deviation increase in AIP was associated with a 1.56-fold higher PSE risk (odds ratio = 1.56; 95% confidence interval: 1.44-1.68). Patients in the highest AIP quartile (Q4) had a 3.89-fold increased risk compared to the lowest quartile (Q1). RCS analysis revealed a nonlinear dose-response relationship, with an inflection point at AIP = 0.193. Subgroup analyses indicated stronger associations in patients without diabetes, coronary artery disease, or specific subcortical lesions.

Conclusion: Elevated AIP is independently associated with an increased risk of PSE in IS patients, following a nonlinear dose-response pattern. AIP may serve as a valuable clinical tool for PSE risk stratification, facilitating early identification and preventive management. Prospective studies are warranted for validation.

Background: Guillain-Barré syndrome (GBS) is an acute autoimmune neuropathy with limited effective treatments. Efgartigimod, a neonatal Fc receptor (FcRn) antagonist, may offer a novel treatment by reducing pathogenic immunoglobulin G.

Objectives: To evaluate the efficacy, safety, and immunological effects of efgartigimod in patients with GBS.

Design: A retrospective, observational, monocentric study.

Methods: The study included 36 patients with GBS who received efgartigimod treatment. Efficacy was evaluated using the GBS-Disability Scale (GBS-DS) and Medical Research Council (MRC) scores over 8 weeks. Additionally, exploratory lymphocyte subset analysis was conducted on 13 patients before and after treatment.

Results: Patients were stratified into those receiving efgartigimod as first-line therapy (n = 17) and as escalation therapy after intravenous immunoglobulin or plasma exchange (n = 19). Both cohorts showed significant and sustained clinical improvement over 8 weeks (p < 0.05). More importantly, the first-line cohort demonstrated a more rapid initial response, with a significantly greater reduction in GBS-DS score (ΔGBS-DS: 2.0 vs 0.0 at week 1, p = 0.003) and increase in MRC score (ΔMRC: 9.0 vs 6.0, p = 0.016) compared to the escalation cohort. This led to a higher percentage of achieving a favorable outcome (GBS-DS ⩽2) and a shorter median time to this outcome (6 vs 25 days, p < 0.001) in the first-line cohort. Regression analysis within the entire cohort confirmed that greater baseline severity and need for mechanical ventilation were associated with a longer time to favorable outcome. Exploratory analysis suggested a decrease in the proportions of CD3+CD4+ and CD4+HLA-DR+ T cells following efgartigimod treatment. Only two mild adverse events were reported.

Conclusion: Efgartigimod shows efficacy as both a rapid-onset first-line therapy and a rescue option for refractory GBS, with a favorable safety profile and potential immunomodulatory effects, supporting further prospective evaluation.

Background: Ischemic stroke or transient ischemic attack (TIA) occurs in 1.4% of patients with atrial fibrillation (AF) per year despite treatment with direct oral anticoagulants (DOACs). This group of patients is poorly studied, and possible causes for this are not fully understood.

Objectives: The aim of the study was to analyze DOAC plasma levels in patients who had ischemic stroke or TIA despite treatment with DOAC.

Design: Monocentric retrospective study.

Methods: We selected consecutive DOAC-treated patients with acute ischemic stroke or TIA, admitted during a 2-year period, with measurement of DOAC levels ⩽24 h after hospital admission. Patients with and without low DOAC levels (<50 ng/mL) were compared.

Results: We included 163 patients with median age of 80 years, 46.6% of female sex. AF was the most frequent indication for DOAC (83.4%). Low DOAC levels were found in 42.3% of patients. Patients with low DOAC levels more frequently were being treated with an inappropriate low DOAC dose (29.4% vs 16.0%, p = 0.004), more frequently had unknown last DOAC intake or intake >48 h before admission (72.5% vs 57.5%, p = 0.004), and had higher baseline NIHSS (8 vs 4, p = 0.001). Lower DOAC levels were associated with large or medium vessel occlusion (LVO/MeVO; odds ratio per 10 ng/mL-increase = 0.89, 95% confidence interval = 0.85-0.94, p < 0.001). Cardiac pathology as the only potentially causal mechanism was more frequent in low DOAC levels patients (76.8% vs 60.6%, p = 0.029). Thirty patients (18.4%) had ⩾2 potentially causal mechanisms, 18 (11.0%) had potentially causal mechanisms other than cardiac pathology, and 5 (3.1%) had no identifiable potentially causal mechanism.

Conclusion: In DOAC-treated patients with ischemic stroke or TIA, low DOAC levels were found in 2/5 of patients. Lower DOAC levels are associated with increased stroke severity and the presence of LVO/MeVO. The profile of stroke etiology in DOAC-treated patients varies between groups with and without low DOAC levels.

Background: The necessity and optimal duration of post-thymectomy immunoregulatory medication (IM) in myasthenia gravis (MG) remain unclear.

Objectives: This study aimed to evaluate whether IM is required after thymectomy in MG patients and to determine the appropriate duration of IM in patients without postoperative deterioration by comparing long-term clinical outcomes.

Design: This triple-center, retrospective study included 1248 MG patients who underwent thymectomy. Among these patients, we compared outcomes between 483 patients without post-thymectomy IM and 765 patients receiving IM.

Methods: Efficacy outcomes included post-thymectomy deterioration and minimal manifestation status (MMS) at 1 year. Safety outcomes, tumor growth, and serious complications were assessed between groups. Subgroup analyses were performed in mild cases (Myasthenia Gravis Foundation of America clinical classification (MGFA) ⩽2a at discharge), patients receiving IM for >1 year, and patients receiving IM for >2 years. Propensity score matching (PSM) was conducted for validation.

Results: Relative to 438 MG patients underwent thymectomy with no-IM therapy, 756 thymectomized MG patients receiving concomitant IM showed significantly superior outcomes, including lower deterioration (hazard ratio (HR) = 0.44, adjusted p < 0.001), lower deteriorated MGFA class (adjusted coefficient = 0.94, p < 0.001), and higher odds of achieving MMS at 1 year (odds ratio = 2.06, adjusted p < 0.001). No significant differences were observed in tumor development (3 years: p = 0.78; 5 years: p = 0.27) or serious complications (p = 0.53). Similar trends were observed across subgroups. Among patients without postoperative deterioration, IM longer than 1 year reduced deterioration risk compared with ⩽1 year (HR = 0.67 (0.50-0.91), p = 0.01), whereas extending IM beyond 2 years offered no additional benefit (p = 0.137). PSM analysis confirmed these findings.

Conclusion: Our real-world analysis of 1248 MG patients suggests that thymectomy alone is not sufficient to achieve satisfactory outcomes. Post-thymectomy IM is recommended for at least 1 year, while extending treatment beyond 2 years appears to offer no further advantage in patients without deterioration.

Background: Cerebrovascular events are a potentially serious complication of giant cell arteritis (GCA) with intracranial involvement. However, diagnosing GCA in this context remains challenging, as classical clinical features may be absent.

Objectives: To identify characteristic cerebellar infarct patterns associated with intracranial GCA and to differentiate them from other common causes of posterior circulation stroke.

Design: Multicenter retrospective study.

Methods: A total of 125 patients with cerebellar infarctions of various etiologies were included. Among these, 19 patients had confirmed intracranial GCA. Infarct patterns were compared to those seen in strokes of cardioembolic origin (n = 42), arterio-arterial embolism from proximal vertebral artery atherosclerosis (n = 13), local atherosclerotic stenosis of the V4 segment (n = 21), and vertebral artery dissection (n = 30). Infarct topography was assessed using acute-phase diffusion-weighted magnetic resonance imaging. Sensitivity and specificity were calculated for individual imaging features.

Results: Distinct imaging signatures were observed in patients with GCA. A "corona-like" infarct pattern, defined by sparing of the medial branch of the proximal posterior inferior cerebellar artery (PICA), demonstrated a sensitivity of 79% and a specificity of 64%. A patchy infarct pattern, characterized by scattered non-confluent lesions, was present in 53% of GCA cases and showed high specificity (93%). When both features were present, specificity increased to 98% and sensitivity was reduced to 47%.

Conclusion: Our findings reveal a distinct cerebellar infarct pattern associated with intracranial GCA, characterized by a corona-like configuration and patchy lesions predominantly involving the lateral PICA territory. Recognition of this imaging phenotype may enhance diagnostic accuracy in challenging cases and facilitate the timely initiation of immunosuppressive therapy.

Background: Converging lines of preclinical evidence support the neuroprotective properties of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in Parkinson's disease (PD). Nevertheless, results from randomized-controlled clinical trials (RCTs) remain conflicting.

Objectives: To assess the safety and efficacy of GLP-1 RAs in PD.

Design: Systematic review and meta-analysis of randomized placebo-controlled clinical trials.

Data sources and methods: A systematic search of MEDLINE and Scopus databases was conducted on October 7, 2025, for randomized placebo-controlled clinical trials investigating GLP-1 RAs in adults with PD. Risk of bias was evaluated using the Cochrane Collaboration risk-of-bias (RoB2) tool.

Results: Four RCTs comprising 667 PD patients (377 receiving GLP-1 RAs) were included. Between baseline and end-of-treatment, no differences were observed in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III score change between GLP-1 RA- and placebo-treated patients in either off-medication (standardized mean difference (SMD): -0.16; 95% CI: -0.64 to 0.32; p = 0.52) or on-medication states (SMD: -0.13; 95% confidence interval (CI): -0.51 to 0.25; p = 0.49). No significant differences were uncovered in other MDS-UPDRS subscores, Non-Motor Symptoms Scale, Montreal Cognitive Assessment, or Parkinson's Disease Questionnaire scores. The risk of serious adverse events and odds of treatment discontinuation were similar between groups, but GLP-1 RAs were associated with an increased risk of weight loss compared to placebo (risk ratio: 1.44; 95% CI: 1.04-1.99; p = 0.03).

Conclusion: GLP-1 RAs were not associated with improvements in motor or non-motor domains of PD. However, robust preclinical evidence and promising findings in select subpopulations warrant further RCTs to evaluate their neuroprotective potential, prioritizing long-acting and brain-penetrant agents that effectively engage central GLP-1 circuits for PD treatment.

Registration: The pre-specified protocol of the present systematic review and meta-analysis has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (registration ID: CRD420251008703).

Background: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy has shown promising results in treating pharmaco-resistant essential tremor (ET). This incisionless, image-guided technique targets the ventralis intermedius nucleus of the thalamus with precision, sparing surrounding eloquent tissue.Objective: This study aims to assess the efficacy of MRgFUS thalamotomy in improving tremor among ET patients, as objectively measured by a tri-axis accelerometer, and to compare these objective measures with the conventional Clinical Rating Scale for Tremor (CRST).Design: Prospective observational study.

Methods: Ten ET patients (aged 68.1 ± 11.8 years) received the MRgFUS treatment. Improvements in tremor severity were assessed using primary (CRST), with additional measurements of kinematic feature obtained from a tri-axis accelerometer. Correlations between accelerometer-derived kinematic features and CRST scores were evaluated.

Results: Significant improvement in tremor severity was observed in the cohort, as measured by both the accelerometer and CRST (paired Student's t test, p < 0.05) before and 1 day after the treatment. A moderate-to-strong correlation was found between accelerometer measurements and CRST scores.

Conclusion: The tri-axis accelerometer provides an effective means of monitoring tremor reduction following MRgFUS and correlated well to the clinical scales like CRST. This study supports the feasibility of accelerometer-based monitoring in clinical practice for MRgFUS assessment.

Background: Basilar artery occlusion (BAO) is a rare but devastating form of ischaemic stroke, with high rates of disability and mortality. While randomized trials have demonstrated the benefit of mechanical thrombectomy (MT) in BAO, the optimal first-line technique - aspiration, stent retriever, or a combined approach - remains undefined.

Objectives: This multicentre study aimed to provide a three-way comparison of MT techniques in terms of efficacy, safety and subgroup-specific outcomes.

Design: A retrospective observational study.

Methods: We prospectively included 517 consecutive patients with acute isolated BAO treated with MT across seven comprehensive stroke centres between January 2019 and December 2023. Patients were grouped by first-line technique: aspiration (n = 200), stent retriever (n = 260), or combined approach (n = 57). The primary outcome was favourable functional outcome at 90 days (mRS 0-3). Inverse probability weighting (IPW) adjusted for baseline imbalances. Secondary outcomes included successful recanalization, excellent outcome (mRS 0-1), functional independence (mRS 0-2), mortality, symptomatic intracranial haemorrhage (sICH) and haemorrhagic transformation (HT). Predefined subgroup analyses were performed.

Results: After adjustment, 90-day outcomes were similar across groups. Stent retrievers achieved higher recanalization rates (RR 1.86 vs aspiration, p < 0.001), while the combined technique was associated with less HT (RR 0.39 vs aspiration, p = 0.008). In patients ⩾80 years, stent-retriever use led to better outcomes than aspiration (39.2% vs 18%; p = 0.021). No other significant subgroup interactions were found.

Conclusion: While overall functional outcomes were comparable, stent retrievers yielded superior recanalization and the combined technique reduced haemorrhagic complications. Technique selection may benefit from individualized, anatomy-driven decision-making. Randomized studies are warranted.

What is this summary about? This is a plain language summary of an article published in The Lancet Neurology in 2024. The article describes the results of the ADHERE clinical study, which involved people with chronic inflammatory demyelinating polyradiculoneuropathy, or CIDP for short. CIDP is a rare autoimmune disease that affects nerves in the arms and legs. There is a need for new treatment options for CIDP that reduce symptoms, are convenient to take, and have manageable side effects. What happened in this study? In this study, researchers looked at how well efgartigimod worked in people with CIDP and the side effects people had during the study. Stage A of the study aimed to find people who had signs of reduced symptoms and disability after receiving efgartigimod. People received weekly injections of efgartigimod under the skin (subcutaneous). Stage B compared efgartigimod with a placebo treatment to find out how well efgartigimod worked and the side effects that people had. What were the results? Overall, 66% of all participants in ADHERE showed signs of clinical improvement after receiving efgartigimod. Half of these people had first signs of clinical improvement in about 22 days. Compared to a placebo, people who received efgartigimod had a reduced risk of CIDP symptoms getting worse or returning (relapsing). More people who received efgartigimod were able to carry out their daily activities and maintained grip strength than those who took a placebo. Most side effects that people developed during the study were mild or moderate. What do the results mean? In this study, people who received efgartigimod had stable or improving symptoms for up to 48 weeks, while more people who received a placebo had worsening strength, disability, and quality of life. Subcutaneous injections of efgartigimod may offer a more convenient option for people with CIDP compared with current treatments.

Multi-system comorbidities are common in patients with multiple sclerosis (PwMS) and significantly influence the disease's presentation and progression. A comorbidity is defined as an illness other than the specific disease of interest (in this case, MS). Generally, chronic or recurrent conditions are included, while transient conditions such as infection or concussion are excluded. Certain modifiable metabolic diseases in PwMS, such as hypertension, diabetes, dyslipidemia, and modifiable health factors such as smoking, alcohol, and obesity, are also considered part of MS comorbidity in this review, since these are risk factors not only for poor outcomes in MS but also for other vascular comorbidities in PwMS. Cohort studies and clinical trials have reported that comorbidity could have multiple adverse effects on MS. The purpose of this review is to summarize studies investigating modifiable risk factors of comorbidity of MS, as well as multiple body system comorbidities in MS, focusing on the influence these comorbidities have on MS outcomes. We aim to emphasize that the management of MS involves not only disease-modifying therapy, but also requires controlling and preventing modifiable risk factors for comorbidities and appropriate treatment of comorbidities, as these interventions may be equally crucial in improving the prognosis of MS.