Neurology最新文献

Background and objectives: Patients with spinal cord injury (SCI) frequently experience dysphonia, leading to communication difficulties, social participation restrictions, and reduced quality of life. In the absence of consensus guidelines, we conducted a systematic review to synthesize evidence on diagnostic tools and rehabilitation protocols for dysphonia after SCI, with the aim of informing clinical practice and future research.

Methods: Six biomedical, rehabilitation, and speech pathology databases were searched, along with reference lists of relevant studies. Inclusion criteria were as follows: adults with acquired SCI of any etiology, studies reporting dysphonia assessments or rehabilitation protocols, and designs ranging from randomized controlled trials (RCTs) to case reports (English only). Two reviewers independently screened studies, extracted data, and assessed risk of bias (RoB) and level of evidence (LoE) using design-specific tools and Oxford Centre for Evidence-Based Medicine criteria. Dysphonia assessments-including instrumental, acoustic, perceptual, and self-reported measures-were summarized as frequencies and percentages; rehabilitation protocols were described narratively. The review was registered in the International Prospective Register of Systematic Reviews (CRD42024561809).

Results: From 626 unique records, 18 studies were included (total n = 303; mean age 39 years; 79.3% male), comprising 4 RCTs (LoE 2) and 14 observational or case studies (LoE 3-4). Most studies focused on cervical SCI with varied etiologies and American Spinal Injury Association Impairment Scale grades (A-D). RoB was generally low to moderate. Dysphonia assessments included instrumental evaluations (83%, mainly spirometry or plethysmography of lung volumes, pressures, and flows), acoustic analyses (83%, most commonly maximum phonation time and sound pressure level), perceptual measures (78%, using heterogeneous tools), and patient questionnaires (67%, mainly the Voice Handicap Index extended and short forms [VHI/VHI-10]). Reported rehabilitation protocols included the use of speech valves for ventilated patients, glossopharyngeal breathing, abdominal binding, and neurologic music therapy.

Discussion: Current research on dysphonia after SCI remains limited and methodologically heterogeneous. Evidence supports combining spirometry, indirect laryngoscopy, acoustic and perceptual analyses, and VHI-10 for comprehensive assessment. Among rehabilitation approaches, abdominal binding and neurologic music therapy show the most consistent benefits. High-quality, large-scale studies with longer follow-up are needed to standardize diagnostic and rehabilitation protocols and improve voice outcomes in this underexplored field.

Background and objectives: Multiple system atrophy (MSA) is a progressive neurodegenerative disorder presenting significant clinical heterogeneity, posing challenges in diagnosis and treatment. This study uses spatial independent component analysis (ICA) of ¹⁸F-fluorodeoxyglucose (FDG) PET to deconstruct disease heterogeneity and elucidate the large-scale brain network mechanisms of MSA.

Methods: This cross-sectional study included patients with MSA and healthy controls (HCs) from the Second Affiliated Hospital, Zhejiang University School of Medicine. MSA diagnosis was based on the 2022 Movement Disorder Society MSA criteria. All participants underwent FDG-PET imaging. Clinical assessments and dopamine transporter (DAT) PET were performed in patients with MSA. Spatial ICA was applied to identify metabolic covariance networks. Moderation analysis and structural equation modeling (SEM) were used to explore underlying pathway mechanisms.

Results: Ninety-five patients with MSA and 102 HCs were included (mean age: 62.25 vs 61.84 years; 51% vs 43% female). Five MSA-related ICs were identified: cerebellar network, salience network, compensatory network, default mode network (DMN), and basal ganglia network (all q < 0.05, false discovery rate-adjusted, vs controls). The combination of ICs aligns with the MSA metabolic abnormalities. The cerebellar network was associated with cognitive impairment (Mini-Mental State Examination: β = 13.87, 95% CI 5.86-21.88, p = 9.04 × 10^-4; Montreal Cognitive Assessment: β = 14.63, 95% CI 7.45-21.81, p = 1.13 × 10^-4), cerebellar symptoms (β = -38.58, 95% CI -73.37 to -3.78, p = 0.03), and posterior putamen DAT (β = -72.79, 95% CI -120.35 to -25.23, p = 0.0031). The compensatory network showed increased metabolism associated with more severe parkinsonian symptoms (β = 3.66, 95% CI 1.51-5.81, p = 1.08 × 10^-3). The basal ganglia network was associated with parkinsonian symptoms (β = -2.56, 95% CI -4.03 to -1.09, p = 8.37 × 10^-4) and posterior putamen DAT (β = 48.24, 95% CI 15.99-80.50, p = 0.0038). DMN moderated the relationship between the cerebellar network and cognitive function. SEM demonstrated that posterior putamen DAT and basal ganglia network contributed to motor symptoms while the compensatory network acted as a compensatory mechanism.

Discussion: This study demonstrated that the metabolic abnormalities in MSA can be decomposed into 5 large-scale brain networks, providing a comprehensive understanding of the disease's heterogeneous mechanisms.

Background and objectives: The highest incidence of epilepsy in childhood occurs in the first year of life. Infantile epilepsies are associated with substantial morbidity and mortality. Although most are presumed to have genetic etiologies, many infants with nonacquired epilepsy remain genetically unsolved after clinical genome sequencing. The yield of reanalysis after nondiagnostic genome sequencing in this population is unknown. We aimed to determine the diagnostic yield of comprehensive reanalysis after nondiagnostic genome sequencing in infants with unexplained epilepsy.

Methods: This cohort study included infants with unexplained epilepsy or complex febrile seizures who were recruited from 4 pediatric referral centers from September 2021 to March 2024 and had nondiagnostic clinical rapid genome sequencing. We performed comprehensive reanalysis of genome sequencing data from infants and available biological parents using multiple bioinformatics pipelines through July 2025 and clinically confirmed reanalysis findings. The primary outcome was diagnostic yield of genome sequencing reanalysis, defined as the percentage of infants who received genetic diagnoses from reanalysis. The secondary outcome was clinical utility of reanalysis findings.

Results: From an initial cohort of 312 infants with unexplained epilepsy who underwent clinical rapid genome sequencing, we performed comprehensive genome reanalysis in 176 infants with initially nondiagnostic results at a median age of 642 days, including 63 female patients (36%) and 30 (17%) with neonatal-onset seizures. The diagnostic yield of reanalysis was 5.1% (9/176, 95% CI 2.4%-9.5%), increasing the overall yield from 43.6% (136/312, 95% CI 38.0%-49.3%) to 46.5% (145/312, 95% CI 40.8%-52.2%). Of the new diagnoses, 6 involved variants not reported by clinical laboratories (2 single nucleotide variants, 2 structural variants, 1 tandem repeat expansion, 1 mosaic variant) and 3 involved previously reported variants of uncertain significance with new evidence. All diagnoses had clinical utility.

Discussion: Comprehensive reanalysis after nondiagnostic rapid genome sequencing has utility for infants with unexplained epilepsy. Our findings support implementation of reanalysis within 1-2 years after nondiagnostic genomic sequencing into routine clinical care of children with unexplained epilepsy and the expansion of clinically accredited genomic sequencing to include complex and noncoding variant detection.

Background and objectives: The residual recurrence risk after atrial fibrillation (AF)-related stroke is high despite anticoagulation, thereby necessitating new therapies. The importance of inflammation in AF is increasingly recognized. However, patients with AF-related stroke were excluded from recent trials of anti-inflammatory therapies. It is uncertain whether associations between IL-6/high-sensitivity C-reactive protein (hsCRP) and poststroke recurrence are modified by AF status. In this study, we aimed to analyze the association between IL-6/hsCRP and recurrence according to AF history.

Methods: We leveraged individual participant data from studies identified by systematic review. We analyzed associations between IL-6/hsCRP and recurrent stroke/major adverse cardiovascular events (MACEs) (defined as fatal or nonfatal recurrent stroke or major coronary events) using multivariable Cox regression analyses (conditional logistic regression for 1 study) adjusted for age, sex, index event, cardiovascular risk factors, and medication use, stratified by AF status.

Results: Data from 11 prospective studies with 10,080 patients (2,134 with AF, mean age 70 years, 59.3% male) were included. During 21,080 person-years of follow-up, 1,677 patients had MACEs and 1,342 had recurrent stroke. Inflammatory markers were higher in patients with AF, irrespective of stroke severity and timing of measurement, with elevated levels persisting well beyond the acute phase. hsCRP was associated with recurrent MACEs in patients with AF (adjusted risk ratio [aRR] 1.14, 95% CI 1.04-1.25, per log_e-unit increase) and without AF (aRR 1.08, 1.03-1.13) (P_interaction 0.30). There were similar associations on per-quarter analysis in patients with AF (aRR 1.51, 1.04-2.18) and without AF (aRR 1.32, 1.10-1.59) (Q4 vs Q1). No association was observed between hsCRP and recurrent stroke in either group. For IL-6, there was no evidence of interaction according to AF status for MACEs (P_interaction 0.57) or recurrent stroke (P_interaction 0.82). The aRR per log_e unit for MACE was 1.17 (1.07-1.27) in patients without AF and 1.10 (0.91-1.34) in those with AF. The corresponding aRR for recurrent stroke was 1.15 (1.05-1.25) and 1.12 (0.91-1.37) in patients without and with AF, respectively.

Discussion: These data highlight the importance of inflammatory mechanisms in vascular recurrence irrespective of AF, provide rationale for the inclusion of patients with AF in trials of anti-inflammatory therapy, and support a selection approach in future trials based on elevated inflammatory marker levels, rather than stroke etiology alone.