Use of High-Efficacy Therapy in Children With Multiple Sclerosis to Prevent Long-Term Disability

在多发性硬化症儿童中使用高效疗法以预防长期残疾

Children with multiple sclerosis (MS) are increasingly treated with high-efficacy monoclonal antibody therapies; however, treatment approaches vary widely, largely because of regulatory restrictions that often delay access until adulthood. We hypothesized that initiating these therapies during childhood confers greater benefits than their initiation in adulthood. This study, therefore, evaluated long-term disability in patients with pediatric-onset MS treated with monoclonal antibodies before age 18 compared with those who initiated these therapies in adulthood. This study provides Class II evidence that, in children aged 12-17 years with MS, initiating therapy with monoclonal antibodies before age 18 (vs 20-22) is associated with less disability accrual between the ages of 23 and 27.

患有多发性硬化症（MS）的儿童越来越多地接受高效单克隆抗体治疗；然而，治疗方法差异很大，这主要是因为监管限制常常会延迟治疗，直到患者成年。我们假设在儿童时期开始使用这些疗法比成年后开始使用能带来更大的益处。因此，本研究评估了18岁之前接受单克隆抗体治疗的儿童期起病MS患者与成年后开始接受这些疗法的患者的长期残疾情况。这项研究提供了II级证据，表明在12 - 17岁的MS儿童中，18岁之前（与20 - 22岁相比）开始使用单克隆抗体治疗与23 - 27岁期间较少的残疾累积相关。

REF: Sharmin S, Roos I, Labauge PM, et al. Use of High-Efficacy Therapy in Children With Multiple Sclerosis to Prevent Long-Term Disability. Neurology. 2026;106(12):e218056. doi:10.1212/WNL.0000000000218056 PMID: 42214041

Associations of Baseline Clinical Phenotypes With White Matter Hyperintensity Volume Change: A Study of 4,329 UK Biobank Participants

基线临床表型与脑白质高信号体积变化的关联：一项针对4329名英国生物银行参与者的研究

White matter hyperintensities (WMHs) relate to cognitive and physical impairment. Although WMHs typically progress over time, regression has also been observed. Our aim was to explore baseline clinical phenotypes associated with subsequent WMH volume change in the UK Biobank (UKB). We established vascular risk factors associated with subsequent WMH volume change in the studied cohort. Distinct clinical and demographic profiles characterized WMH progression, regression, and stable groups. Results suggest that vascular factors relate to WMH change but are sensitive to covariate control. Further studies should establish factors differentially and causally related to WMH progression, regression, and stability.

白质高信号（WMHs）与认知和身体功能障碍相关。尽管白质高信号通常会随时间进展，但也观察到了其消退的情况。我们的目的是在英国生物银行（UKB）中探索与后续白质高信号体积变化相关的基线临床表型。我们确定了所研究队列中与后续白质高信号体积变化相关的血管危险因素。不同的临床和人口统计学特征分别对应白质高信号进展、消退和稳定组。研究结果表明，血管因素与白质高信号的变化有关，但对协变量控制较为敏感。进一步的研究应确定与白质高信号进展、消退和稳定存在差异关联和因果关联的因素。

REF: Kancheva AK, Millard LAC, Lyall DM, Wardlaw JM, Quinn TJ. Associations of Baseline Clinical Phenotypes With White Matter Hyperintensity Volume Change: A Study of 4,329 UK Biobank Participants. Neurology. 2026;106(12):e218085. doi:10.1212/WNL.0000000000218085 PMID: 42214040

Vamorolone for Duchenne Muscular Dystrophy: A Cross-Trial Efficacy Comparison With Classic Corticosteroids From the FOR-DMD Trial

瓦莫洛酮治疗杜氏肌营养不良症：基于FOR - DMD试验与经典皮质类固醇的跨试验疗效比较

Vamorolone demonstrated similar efficacy for Duchenne muscular dystrophy (DMD) compared with prednisone in a 24-week exploratory analysis and may reduce key side effects compared with classic corticosteroids. In this study, we compare the efficacy and anthropometric effect of vamorolone 6 mg/kg/d with prednisone 0.75 mg/kg/d and deflazacort 0.9 mg/kg/d in steroid-naïve boys aged 4 to <7 years using data from 2 trials. Vamorolone demonstrated numerically similar TTSTAND velocity changes to prednisone and deflazacort at 1 year; however, interpretations of differences are limited by 95% CIs crossing minimally important difference thresholds. Further evidence of the growth-protective effect of vamorolone was observed; however, all treatments increased BMI. Vamorolone provides a linear growth-protective classic corticosteroid alternative.

在一项为期24周的探索性分析中，伐莫洛酮治疗杜氏肌营养不良症（DMD）的疗效与泼尼松相似，且与传统皮质类固醇相比，可能会减少关键的副作用。在本研究中，我们利用两项试验的数据，比较了伐莫洛酮6 mg/（kg·d）、泼尼松0.75 mg/（kg·d）和地夫可特0.9 mg/（kg·d）对4至未满7岁未使用过类固醇的男孩的疗效和人体测量学影响。在1年时，伐莫洛酮的TTSTAND速度变化在数值上与泼尼松和地夫可特相似；然而，95%置信区间跨越最小重要差异阈值，限制了对差异的解读。进一步观察到了伐莫洛酮保护生长的效果；不过，所有治疗均使体重指数升高。伐莫洛酮是一种具有保护线性生长作用的传统皮质类固醇替代药物。

REF: Clemens PR, Berglund A, Schiava M, et al. Vamorolone for Duchenne Muscular Dystrophy: A Cross-Trial Efficacy Comparison With Classic Corticosteroids From the FOR-DMD Trial. Neurology. 2026;107(1):e214756. doi:10.1212/WNL.0000000000214756 PMID: 42202243 PMCID: PMC13225239

Diagnostic Revision From Primary Lateral Sclerosis to Amyotrophic Lateral Sclerosis: A Cohort Study

从原发性侧索硬化症到肌萎缩侧索硬化症的诊断修正：一项队列研究

Primary lateral sclerosis (PLS) is defined as a pure upper motor neuron syndrome and is a diagnosis of exclusion, amyotrophic lateral sclerosis (ALS) being the most likely alternative diagnostic consideration. A minimum disease duration of 2 years is required for the diagnosis of PLS, after which patients are classified as probable PLS (P-PLS) and subsequently as definite PLS (D-PLS) after 4 years. Our aim is to apply the current diagnostic criteria to a population-based cohort and investigate which clinical characteristics are associated with a diagnostic revision to ALS. In our cohort, most diagnostic revisions from PLS to ALS were in patients with a disease duration of less than 4 years. Besides disease duration, a faster progression rate was associated with diagnostic revision from PLS to ALS. Adding progression rate to the current diagnostic criteria could increase accuracy and help identify patients at higher risk of developing ALS.

原发性侧索硬化（PLS）被定义为一种单纯的上运动神经元综合征，是一种排他性诊断，肌萎缩侧索硬化（ALS）是最有可能的替代诊断考虑。诊断PLS需要至少2年的疾病病程，之后患者被归类为可能的PLS（P - PLS），4年后则归类为确诊的PLS（D - PLS）。我们的目的是将当前的诊断标准应用于一个基于人群的队列，并研究哪些临床特征与PLS诊断修订为ALS有关。在我们的队列中，大多数从PLS诊断修订为ALS的患者疾病病程少于4年。除了疾病病程外，较快的进展速度与PLS诊断修订为ALS有关。将进展速度纳入当前诊断标准可以提高诊断准确性，并有助于识别患ALS风险较高的患者。

REF: de Boer EMJ, Willemse SW, Veldink JH, et al. Diagnostic Revision From Primary Lateral Sclerosis to Amyotrophic Lateral Sclerosis: A Cohort Study. Neurology. 2026;106(12):e218055. doi:10.1212/WNL.0000000000218055 PMID: 42214042

Efficacy of Levetiracetam in Patients With Pediatric Epilepsy: A Systematic Review and Meta-Analysis

左乙拉西坦治疗小儿癫痫的疗效：系统评价与Meta分析

Levetiracetam (LEV) is widely used in pediatric epilepsies because of its favorable pharmacokinetics, ease of administration, and perceived tolerability. However, its comparative efficacy relative to established antiseizure medications (ASMs) in children remains uncertain. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate LEV efficacy in pediatric epilepsies and compare outcomes vs placebo and active comparators. LEV confers benefit vs placebo, mostly as adjunctive therapy, but does not consistently outperform established ASMs in pediatric epilepsies and may be inferior in some subgroups when higher-quality evidence is considered. Limitations include substantial heterogeneity, frequent high risk of bias, variable follow-up durations, publication bias, and limited pediatric-only comparative data.

左乙拉西坦（LEV）因其良好的药代动力学特性、易于给药以及被认为具有较好的耐受性，在儿童癫痫治疗中得到广泛应用。然而，与已确立的抗癫痫药物（ASMs）相比，其在儿童中的相对疗效仍不确定。我们对随机对照试验（RCTs）进行了系统评价和荟萃分析，以评估LEV在儿童癫痫中的疗效，并将其治疗结果与安慰剂和积极对照药物进行比较。与安慰剂相比，LEV具有一定益处，主要作为辅助治疗，但在儿童癫痫治疗中，它并非始终优于已确立的ASMs，在考虑更高质量证据时，在某些亚组中可能效果较差。局限性包括显著的异质性、频繁的高偏倚风险、随访时间不一、发表偏倚以及仅针对儿童的比较数据有限。

REF: Balestrini S, Puliti D, Lombardini M, et al. Efficacy of Levetiracetam in Patients With Pediatric Epilepsy: A Systematic Review and Meta-Analysis. Neurology. 2026;106(12):e218080. doi:10.1212/WNL.0000000000218080 PMID: 42202238 PMCID: PMC13225242

IV Thrombolysis Before Thrombectomy in Carotid Artery Dissection–Related Large-Vessel Occlusion

颈动脉夹层相关大血管闭塞患者取栓术前的静脉溶栓治疗

The benefit of IV thrombolysis (IVT) before thrombectomy in patients with anterior-circulation large-vessel occlusion (LVO) due to carotid artery dissection (CAD) remains uncertain. We aimed to evaluate the safety and efficacy of IVT in this specific population in clinical practice. This study provides Class III evidence that IVT before thrombectomy was associated with improved functional outcome and higher reperfusion success in patients with anterior-circulation LVO due to CAD, without an increase in sICH.

对于因颈动脉夹层（CAD）导致的前循环大血管闭塞（LVO）患者，在取栓术前进行静脉溶栓（IVT）的益处仍不确定。我们旨在评估在临床实践中对这一特定人群应用静脉溶栓的安全性和有效性。本研究提供了III级证据，表明对于因颈动脉夹层导致的前循环大血管闭塞患者，取栓术前进行静脉溶栓与改善功能结局和提高再灌注成功率相关，且不会增加症状性颅内出血（sICH）的发生。

REF: Hotz JF, Poli S, Giannakakis MP, et al. IV Thrombolysis Before Thrombectomy in Carotid Artery Dissection-Related Large-Vessel Occlusion. Neurology. 2026;106(12):e218125. doi:10.1212/WNL.0000000000218125 PMID: 42202237

A Validated Prognostic Score for Time to Loss of Ambulation in Patients With Duchenne Muscular Dystrophy

杜氏肌营养不良患者行走能力丧失时间的有效预后评分

Development of a prognostic score for time to loss of ambulation (LoA) may help guide treatment of patients with Duchenne muscular dystrophy (DMD). Information from clinical data sources was used to create a prognostic score for LoA for use in practice. Patients with DMD were classified into 5 risk groups for LoA using a simple, easy-to-use prognostic score based on RFF and 10MWR thresholds. The prognostic score replicated well in validation data and performed better than previously proposed classifications used in practice. Incorporating the prognostic score for time to LoA into a clinical visit may allow clinicians to counsel patients on trial eligibility, need for mobility devices, home adjustments, financial accommodations, and psychosocial needs. The prognostic score may also be used in trials to inform inclusion criteria and stratification. Study limitations included limited data for prediction of LoA risk beyond 4 years.

制定行走能力丧失（LoA）时间的预后评分有助于指导杜氏肌营养不良症（DMD）患者的治疗。利用临床数据源的信息创建了用于实际应用的LoA预后评分。根据快速起坐试验（RFF）和10米步行跑试验（10MWR）阈值，使用一个简单易用的预后评分将DMD患者分为5个LoA风险组。该预后评分在验证数据中表现良好，且比之前实际应用中提出的分类方法效果更好。将LoA时间的预后评分纳入临床就诊环节，可能使临床医生能够就试验入组资格、对移动辅助设备的需求、家庭环境调整、经济支持以及心理社会需求等方面为患者提供建议。该预后评分还可在试验中用于确定纳入标准和进行分层。研究的局限性包括缺乏超过4年的LoA风险预测数据。

REF: McDonald CM, Signorovitch J, Goemans NM, et al. A Validated Prognostic Score for Time to Loss of Ambulation in Patients With Duchenne Muscular Dystrophy. Neurology. 2026;106(12):e214705. doi:10.1212/WNL.0000000000214705 PMID: 42190145

Burst-Suppression EEG in Early Infantile Developmental and Epileptic Encephalopathies: Phenotype, Genotype, and Outcome

早期婴儿发育性和癫痫性脑病中的爆发 - 抑制脑电图：表型、基因型和结局

Developmental and epileptic encephalopathies (DEEs) with early burst-suppression EEG (EIDEE-BS) are among the most severe neonatal epileptic syndromes, typically presenting in the first months of life with refractory seizures and profound neurodevelopmental impairment. Although variants in the KCNQ2, STXBP1, and SCN2A genes are recognized as major causes, the full genetic spectrum remains uncertain. We aimed to delineate the electroclinical characteristics, genetic etiologies, and long-term outcomes in a large MRI-negative EIDEE-BS cohort. This large series highlights the strong monogenic basis of EIDEE-BS. KCNQ2, STXBP1, and SCN2A were the most commonly affected genes. Early EEG features, particularly BS timing and morphology, can help anticipate the underlying genotype and guide precision therapy, including the early use of sodium channel blockers in selected cases. These findings support recent ILAE reclassification efforts and underscore the importance of comprehensive genomic testing for improved diagnosis and counseling.

伴早期暴发 - 抑制脑电图表现的发育性癫痫性脑病（EIDEE - BS）是最严重的新生儿癫痫综合征之一，通常在出生后的头几个月发病，表现为难治性癫痫发作和严重的神经发育障碍。虽然KCNQ2、STXBP1和SCN2A基因变异被认为是主要病因，但完整的遗传谱仍不确定。我们旨在明确一个大型磁共振成像阴性的EIDEE - BS队列的电临床特征、遗传病因和长期结局。这一大型系列研究突显了EIDEE - BS强烈的单基因基础。KCNQ2、STXBP1和SCN2A是最常受累的基因。早期脑电图特征，尤其是暴发 - 抑制的时间和形态，有助于预测潜在的基因型并指导精准治疗，包括在某些病例中早期使用钠通道阻滞剂。这些发现支持国际抗癫痫联盟近期的重新分类工作，并强调了全面基因组检测对于改善诊断和遗传咨询的重要性。

REF: Riccardi F, Desnous B, Borloz E, et al. Burst-Suppression EEG in Early Infantile Developmental and Epileptic Encephalopathies: Phenotype, Genotype, and Outcome. Neurology. 2026;106(12):e218013. doi:10.1212/WNL.0000000000218013 PMID: 42190144

Comparative Study of Sporadic and Immune Checkpoint Inhibitor–Related Forms of Myasthenia Gravis-Myositis Overlap Syndrome

散发性和免疫检查点抑制剂相关型重症肌无力 - 肌炎重叠综合征的对比研究

Myasthenia gravis-inflammatory myopathy (MG-IM) overlap syndrome can occur as an immune-related adverse event (irAE) after immune checkpoint inhibitor (ICI) therapy. Before the advent of ICIs, a sporadic form of MG-IM (s-MG-IM), often thymoma-associated, was already described. This study compared clinical and serologic features, treatment strategies, and outcomes of s-MG-IM and ICI-related MG-IM (ir-MG-IM). Although they share some similarities, s-MG-IM represents a chronic, predominantly thymoma-associated overlap syndrome with classical MG and IM features, whereas ir-MG-IM is typically an aggressive, likely monophasic condition characterized by severe myositis, with frequent ocular and cardiac involvement, and lacking classical MG features. Study limitations include the retrospective design, small sample size, and limited serum availability, warranting confirmation in larger prospective cohorts.

重症肌无力 - 炎性肌病（MG - IM）重叠综合征可作为免疫检查点抑制剂（ICI）治疗后的免疫相关不良事件（irAE）出现。在ICI问世之前，就已经有散发型MG - IM（s - MG - IM）的报道，其常与胸腺瘤相关。本研究比较了s - MG - IM和ICI相关的MG - IM（ir - MG - IM）的临床和血清学特征、治疗策略及预后情况。尽管二者有一些相似之处，但s - MG - IM是一种慢性、主要与胸腺瘤相关的重叠综合征，具有典型的重症肌无力和炎性肌病特征；而ir - MG - IM通常是一种侵袭性、可能为单相的疾病，以严重的肌炎为特征，常累及眼部和心脏，且缺乏典型的重症肌无力特征。本研究的局限性包括回顾性研究设计、样本量小以及血清样本有限，需要在更大的前瞻性队列中进行验证。

REF: Lauletta A, Rossini E, Beretta F, et al. Comparative Study of Sporadic and Immune Checkpoint Inhibitor-Related Forms of Myasthenia Gravis-Myositis Overlap Syndrome. Neurology. 2026;106(12):e218081. doi:10.1212/WNL.0000000000218081 PMID: 42190146