Neurology and Therapy最新文献

Introduction: This study aimed to compare clinical outcomes between recombinant tissue plasminogen activator plus tirofiban (rt-PA + T) and rt-PA alone in patients with acute non-cardioembolic posterior circulation ischemic stroke (APCIS) treated within 24 h.

Methods: In this retrospective, propensity score-matched cohort study, we analyzed data from patients with acute non-cardioembolic posterior circulation ischemic stroke. The intervention group (rt-PA + T) received standard-dose rt-PA followed by intravenous tirofiban, whereas the control group (rt-PA) received rt-PA alone. The primary outcome was a favorable functional outcome (modified Rankin Scale [mRS] 0-1) at 90 days.

Results: After propensity score matching, 256 patients (128 per group) were included in the final analysis. The proportion of patients achieving a favorable functional outcome (mRS 0-1) at 90 days was significantly higher in the rt-PA + T group than in the rt-PA group (63.3% vs. 50.0%; OR 1.72, 95% CI 1.05-2.84, P = 0.033). Functional independence (mRS 0-2) was also more common in the rt-PA + T group (73.4% vs. 60.9%; OR 1.77, 95% CI 1.04-3.01, P = 0.034). No significant differences were observed in symptomatic intracranial hemorrhage (1.6% vs. 0.0%, P = 0.498), any bleeding (6.3% vs. 5.5%, P = 0.454), or 90-day mortality (2.3% vs. 1.6%, P = 0.654). Subgroup analysis indicated greater benefit in patients with baseline NIHSS < 10 (P for interaction = 0.029).

Conclusion: In patients with acute non-cardioembolic posterior circulation ischemic stroke treated within 24 h of onset, adjunctive tirofiban following standard intravenous thrombolysis was associated with significantly improved 90-day functional outcomes without a notable increase in major bleeding risk, particularly in patients with lower baseline NIHSS scores.

Progressive supranuclear palsy (PSP) is an adult-onset neurodegenerative disorder characterized by postural instability, ocular motor dysfunction, akinesia, and cognitive impairment. The accumulation of tau protein disrupts microtubule dynamics and axonal transport, leading to neurodegeneration in subcortical structures such as the basal ganglia and brainstem. These effects result in the clinical features of motor dysfunction and cognitive impairment associated with PSP. Dementia in patients with PSP is common but may be difficult to diagnose. This narrative review describes the cognitive decline and dementia associated with PSP. The pathological hallmarks of PSP, clinical features, and diagnostic criteria are also discussed to provide additional context for the diagnosis of PSP dementia.

This is a summary of the original article "Overview of acute seizure management in US nursing homes." Nursing home residents are more likely than community-dwelling individuals to be diagnosed with epilepsy or seizures. These conditions often complicate care and are associated with an increased likelihood of illness and death. The objective of this survey was to investigate acute seizure management practices in nursing homes in the USA, identify gaps in knowledge, and guide future educational efforts, including acute seizure action plans. The survey was completed by 91 nursing home directors. Overall, 52% of nursing homes had a seizure protocol in place. These protocols were most often put into action by nurses. Most residents with seizures were given rescue medications, primarily older formulations of benzodiazepines, regardless of seizure history. Levetiracetam was the most prescribed antiseizure medication. Staff training/in-service education was infrequent, and 55% of respondents agreed that no-cost seizure education would be highly beneficial. This study highlights the need to improve the treatment of acute seizures in nursing homes, including the adoption of acute seizure action plans.

Introduction: Inflammation plays a critical role in the pathophysiology of acute ischemic stroke (AIS). Ratios derived from routine blood counts, especially the neutrophil-to-lymphocyte ratio (NLR), have been proposed as prognostic biomarkers, but their value in patients receiving reperfusion therapies-intravenous thrombolysis (IVT) or mechanical thrombectomy (MT)-remains uncertain.

Methods: We systematically searched PubMed, Cochrane Library, Web of Science, and Scopus on November 30, 2024, following PRISMA guidelines. Eligible studies included patients with AIS treated with IVT or MT that reported associations between pre-treatment blood cell ratios and outcomes measured by the modified Rankin Scale (mRS). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models.

Results: Fifty-seven studies with 17,394 patients were included. NLR was the predominantly studied biomarker. In the MT subgroup, elevated NLR predicted poor 3-month outcome (OR 1.09, 95% CI 1.04-1.15) and higher mortality (OR 1.05, 95% CI 1.01-1.08). In IVT-treated patients, higher NLR also predicted poor outcome (OR 1.11, 95% CI 1.01-1.21) with lower heterogeneity across studies. Other ratios showed variable associations: lymphocyte-to-monocyte ratio (LMR) appeared protective, while platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-neutrophil ratio (PNR) showed inconsistent or null results. Data regarding hemorrhagic transformation were heterogeneous and unsuitable for meta-analysis.

Conclusions: Elevated pre-treatment NLR consistently predicted poor outcome and mortality after reperfusion therapy for AIS, supporting its role as a simple biomarker for early risk stratification. Future large, prospective multicenter studies with standardized methods are needed to confirm the clinical utility of these inflammatory ratios in stroke management.

Information on pregnancy and infant outcomes after cladribine tablets exposure is limited, as its use is not recommended during pregnancy. This is a summary of the original published article 'Pregnancy and infant outcomes in multiple sclerosis: findings from the Global MAPLE-MS Pharmacovigilance Program'. The primary outcome is the prevalence of major congenital anomalies (MCAs) in babies. Secondary outcomes include other pregnancy outcomes (live birth, elective termination, spontaneous abortion, ectopic pregnancy, and stillbirth).

Introduction: Delandistrogene moxeparvovec is a recombinant adeno-associated virus rhesus isolate serotype 74 vector-based gene therapy that addresses the absence of functional dystrophin in Duchenne muscular dystrophy (DMD). EMBARK is a phase 3, two-part, crossover, randomized, placebo-controlled trial assessing the safety and efficacy of delandistrogene moxeparvovec (single intravenous dose 1.33 × 10¹⁴ vector genomes/kg) in ambulatory male patients with DMD aged 4 to < 8 years; N = 125. One-year results demonstrated the manageable safety of delandistrogene moxeparvovec, consistent with previous clinical trials. The primary endpoint (change from baseline in North Star Ambulatory Assessment [NSAA] total score at 52 weeks compared with placebo) did not meet statistical significance. However, key secondary endpoints, comprising timed function tests, suggested slowing or stabilization of disease progression with delandistrogene moxeparvovec, which could become increasingly evident over longer periods of time. We report 2-year follow-up of safety and functional outcomes in patients receiving delandistrogene moxeparvovec in EMBARK part 1.

Methods: As a result of the crossover study design, 2-year functional outcomes of patients receiving delandistrogene moxeparvovec in part 1 of EMBARK were compared, by pre-specified analysis, with a matched propensity score-weighted external control (EC).

Results: At 2 years, EMBARK patients showed statistically significant benefit versus the EC cohort in functional outcomes prognostic for delaying loss of ambulation (NSAA, Time to Rise, 10-m Walk/Run), demonstrating sustained stabilization or slowing of disease progression. Delandistrogene moxeparvovec micro-dystrophin expression and sarcolemmal localization were maintained over 64 weeks. No new safety signals were observed between week 52 and week 104. Between baseline and week 104, there were no treatment-related deaths, study discontinuations due to adverse events, or clinically significant complement-mediated adverse events.

Conclusions: At 2 years, stabilization or slowing of DMD disease progression was observed in ambulatory male patients with DMD aged 4 to < 8 years receiving delandistrogene moxeparvovec versus a matched EC cohort. Safety was consistent with EMBARK 1-year data and manageable with appropriate monitoring.

Clinicaltrials: GOV: NCT05096221.

Dravet syndrome (DS) is a rare and severe form of epilepsy, characterised by recurrent seizures that begin during the first year of life, leading to motor, cognitive and behavioural impairments. This article provides the perspectives of a parent of a child with DS ('Ethan') and the treating neuropaediatrician. Ethan's seizures began when he was 9 months old, and were a mixture of focal seizures and status epilepticus. Numerous treatments were tried, including standard anti-seizure medications (such as levetiracetam, clobazam and fenfluramine), other medications (cannabidiol) and nonpharmacological approaches (ketogenic diet), with little success. When Ethan was 3 years old, a prolonged episode of status epilepticus precipitated by coronavirus disease 2019 (COVID-19) led to brain damage. Rehabilitation allowed Ethan to regain some of his previous functioning and, at the age of 38 months, combination therapy with clobazam, sodium valproate and stiripentol was begun and has successfully controlled Ethan's seizures. Ethan's father describes the stress that the diagnosis of DS, interactions with the healthcare system, and the search for effective treatment imposed on the family. Since Ethan's seizures have been better controlled, the family has been able to lead a more normal life, and is now focused on supporting Ethan and looking to the future. Ethan's neuropaediatrician outlines the approach she takes to the diagnosis and management of DS, including the importance of the clinician-parent relationship in imparting the diagnosis and making initial and ongoing treatment decisions. The preferred first-line treatment is sodium valproate, which is followed by sodium valproate-clobazam-stiripentol combination therapy, topiramate or a ketogenic diet as second-line options. In children > 2 years, cannabidiol and fenfluramine can also be considered. The aim of maintenance treatment (which will invariably be polytherapy) is to reduce the number of seizures, particularly status epilepticus, given the significant impact of this seizure type on patients and caregivers.

Introduction: Our preliminary study identified two metabolically distinct thrombus subtypes, demonstrating enhanced lipid metabolic signatures but downregulated folate biosynthesis pathways associated with poor prognosis. This study aimed to assess the prognostic value of routine laboratory parameters involved in lipid and folate metabolism for predicting 90-day futile recanalization (FR) in patients with anterior circulation acute ischemic stroke caused by large vessel occlusion (AIS-LVO) who achieved successful recanalization by endovascular thrombectomy.

Methods: Consecutive patients with anterior circulation AIS-LVO who achieved successful recanalization (modified Thrombolysis in Cerebral Infarction score of 2b-3) were retrospectively screened from April 2019 to February 2024. Admission serum levels of traditional and non-traditional lipid parameters, folate, and homocysteine (Hcy) were measured. FR was defined as a 90-day modified Rankin Scale score of 3-6, despite successful recanalization. Multivariable logistic regression was performed to identify predictors for FR, which were incorporated into a predictive nomogram.

Results: Among 446 enrolled patients [median age 65 (IQR, 56-72.75) years; 32.1% female], 210 (47.1%) experienced 90-day FR. Multivariate logistic regression analysis revealed that lower admission serum folate and higher Hcy levels were independently associated with increased 90-day FR risk. In contrast, neither admission traditional or non-traditional lipid parameters were independent predictors. The addition of folate and Hcy, individually or combined, significantly improved the predictive performance of conventional clinical factor-based model, as reflected by significant increases in net reclassification improvement and integrated discrimination improvement. Finally, a predictive nomogram was developed incorporating age, admission National Institute of Health Stroke Scale, puncture-to-recanalization time, and admission serum glucose, folate, and Hcy levels.

Conclusions: Admission serum folate and Hcy levels are independent predictors of 90-day FR risk and may enhance risk stratification and guide personalized secondary prevention strategies in patients with successfully recanalized AIS-LVO.

Introduction: The concurrent use of direct oral anticoagulants (DOACs) and antiseizure medications (ASMs) is increasingly common, particularly among patients with atrial fibrillation, stroke, and epilepsy. Certain ASMs may affect the pharmacokinetics of DOACs through enzyme induction or modulation of P-glycoprotein, potentially altering their effectiveness and safety. However, evidence regarding these interactions and their impact on clinical outcomes remains limited, heterogeneous, and inconsistently reported. The objective of this systematic review is to synthesize current evidence on cerebrovascular outcomes, bleeding risk, and pharmacokinetic effects in patients treated concurrently with DOACs and ASMs.

Methods: This protocol outlines a systematic review and meta-analysis of randomized controlled trials, observational studies, case-control studies, and pharmacokinetic investigations involving patients aged 8 years or older treated with DOACs in combination with ASMs. Databases including MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and clinical trial registries (ClinicalTrials.gov, WHO ICTRP) will be searched without language restrictions. Additional studies will be identified via reference screening, expert contact, and AI-assisted evidence discovery (Elicit). Dual independent review will be applied for study selection, data extraction, and risk of bias assessment using validated tools (Newcastle-Ottawa Scale (NOS), the Quality In Prognosis Studies (QUIPS) tool, and the Cochrane Risk of Bias 2.0 tool). Where appropriate, meta-analysis will be performed using random-effects models; otherwise, results will be synthesized narratively in accordance with SWiM (Synthesis Without Meta-analysis) guidelines.

Planned outcomes: Primary effectiveness outcome: composite of ischemic stroke and systemic embolism (IS/SE).

Secondary outcomes: ischemic stroke alone, systemic embolism alone, transient ischemic attack (TIA), major bleeding, intracranial hemorrhage, pharmacokinetic measures, and seizure occurrence. Subgroup analyses will stratify by ASM type, pharmacokinetic interaction potential, age groups (8-17, ≥ 18 years), and DOAC indications (e.g., non-valvular atrial fibrillation, venous thromboembolism, left ventricular thrombus). An individual participant data (IPD) meta-analysis is planned if sufficient eligible data are available. A summary table of outcomes and definitions (Table 1) and an overview flow diagram of the planned process (Fig. 1) are provided.

Systematic review registration: PROSPERO CRD4201050986.

Introduction: People with advanced Parkinson's disease (aPD) frequently experience unpredictable "Off" time and debilitating motor fluctuations. Foslevodopa/foscarbidopa (LDp/CDp), a levodopa/carbidopa (LD/CD) prodrug, is delivered as a 24-h continuous subcutaneous infusion. This post hoc analysis evaluated the efficacy of LDp/CDp in achieving consistent motor symptom control and stable motor states in people with aPD.

Methods: Diaries of people with aPD treated with LDp/CDp participating in a 12-week, phase 3, randomized controlled trial (RCT) were evaluated versus oral LD/CD, and in a 52-week open-label, single-arm trial (OLT) with LDp/CDp alone. Motor symptom control was assessed by frequency (30-min intervals) and duration (4-h blocks) of motor states (good "On" time [without dyskinesia or troublesome dyskinesia] or "Off" time) over a 16-h waking day. Motor state stability was evaluated by changes in daily motor fluctuations and extreme fluctuations (defined as transition from "Off" to "On" with troublesome dyskinesia, or vice versa). Outcomes were analyzed using adjusted regression models.

Results: Analysis included 47 (RCT) and 55 (OLT) people with aPD on LDp/CDp. In the RCT, LDp/CDp had an approximately 1-h gain in good "On" time in the mornings versus a quarter-hour gain for those on LD/CD (P = 0.001), with > 80% of participants on LDp/CDp waking up in good "On." At week 12, fewer motor fluctuations/day occurred with LDp/CDp versus LD/CD (3.2 vs 5.3; nominal P = 0.001), and twice as many participants on LDp/CDp had ≤ 3 fluctuations/day (53.2% vs 25.8%). In the OLT, the results seen at 12 weeks were sustained through week 52, with fewer mean fluctuations/day (3.1) than baseline (7.4) and more participants reporting ≤ 3 fluctuations/day at 52 weeks (66.6%) versus baseline (12.9%).

Conclusion: LDp/CDp provided consistent motor symptom control throughout the day, enhanced motor state stability, and reduced motor fluctuation, highlighting LDp/CDp's potential to significantly improve the management of unpredictable motor states and overall quality of life for people with aPD.

Trial information: Clinicaltrials.gov ID: NCT04380142, NCT03781167.