Neurology最新文献

Background and objectives: Inflammation is an established risk factor in the development of cerebral small vessel disease (CSVD). This study aimed to investigate the associations between neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII) with progression of CSVD.

Methods: This prospective cohort study used data from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study between 2017 and 2024. Participants were excluded for a history of stroke or cancer or because of missing data on baseline systemic inflammatory markers or follow-up neuroimaging for CSVD. Baseline systemic inflammatory markers were calculated by neutrophils, monocytes, lymphocytes, and platelets count data, and categorized into 4 groups according to the quartiles. The progression of total CSVD burden, using Wardlaw and Rothwell ratings, along with progression of specific MRI markers were assessed between baseline and wave 3 follow-up (∼4.7 years). Assessment of the associations was performed using log-binomial regression models.

Results: The median follow-up duration was 4.7 years (interquartile range 4.5-4.8), and 2,267 participants were included. At baseline, the mean age of the participants was 60.4 years, with 50.6% being male. An elevation in NLR was associated with progression of total CSVD burden (Wardlaw: adjusted relative risk [aRR] 1.23, 95% CI 1.08-1.41; Rothwell: aRR 1.29, 95% CI 1.11-1.50) and incident cerebral microbleeds (CMBs) (aRR 1.43, 95% CI 1.16-1.78). High level of MLR was associated with incident lacunes (aRR 1.88, 95% CI 1.28-2.77) and incident CMBs (aRR 1.33, 95% CI 1.08-1.65). High level of SII was associated with progression of total CSVD burden (Wardlaw: aRR 1.15, 95% CI 1.01-1.31; Rothwell: aRR 1.17, 95% CI 1.01-1.35) and incident CMBs (aRR 1.34, 95% CI 1.10-1.64). Linear associations between these markers and progression of CSVD were demonstrated by restricted cubic spline analysis.

Discussion: This community-based prospective study demonstrated that elevated NLR, MLR, and SII were associated with progression of total CSVD burden and progression of white matter hyperintensity, incident lacunes, and CMBs over ∼4.7 years, supporting their potential to provide additional context for CSVD preventive considerations. Limitations include study's single-city population and the lack of dynamic changes in inflammatory markers.

Background and objectives: A monogenic, age-related cerebral small vessel disease (cSVD), retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S), causes accelerated vascular dementia, vision loss, and premature death. Given knowledge is limited regarding its pathophysiology, we examined the natural history of progression in imaging and cognitive endpoints to define the rate and variability of progression in a prospective RVCL-S cohort. We hypothesized that cerebral blood flow (CBF) and oxygen extraction fraction (OEF), as metrics of cerebral hypoxia-ischemia, would be associated with neurologic disease progression.

Methods: We performed sequential brain MRI and a cognitive battery in a prospective RVCL-S cohort. Arterial spin labeling and asymmetric spin echo quantified CBF and OEF in normal-appearing white matter (WM), respectively. Three neuroimaging endpoints of cSVD included the following: log-transformed, normalized fluid-attenuated inversion recovery WM hyperintensity (WMH) volume; WM microstructure using mean diffusivity; and normalized WM volume. Five cognitive and motor endpoints included Digit Symbol Substitution Test (DSST), category fluency, free recall, Montreal Cognitive Assessment (MoCA), and gait speed. Linear mixed-effects models examined age, CBF, and OEF in association with neuroimaging and cognitive progression.

Results: Twenty-five participants, aged 23-68 years (median 47 years, 56% female), underwent 151 scans over a median (25th, 75th) of 2.2 (1.8, 4.4) years. All neuroimaging and cognitive endpoints progressed over time, except for MoCA. Of neuroimaging endpoints, WMH volume demonstrated the largest rate of change (+31.3%/year, 95% CI 20.8%-42.3%). Of cognitive endpoints, DSST, a metric of processing speed, showed the steepest decline (-13.1 T-score points/decade, 95% CI -21.2 to -5.32), followed by free recall and category fluency (-5 [-7.9 to -2.4] and -4.1 [-7.2 to -1.2] T-score points per decade, respectively). The age at first brain lesion was estimated to be 30.6 (23.8, 35.8) years, modeled from individual WMH volume trajectories. In multivariable analysis, OEF, but not CBF, was independently associated with WMH growth (β = 3.73, 95% CI 0.63-6.83, p = 0.029) and change in WM microstructure (β = 0.175, 95% CI 0.029-0.32, p = 0.029). Neither OEF nor CBF was independently associated with cognitive decline.

Discussion: Elevated OEF in at-risk WM was associated with progression in WMH and impairment in WM microstructure, suggesting a role for tissue hypoxia-ischemia in underlying RVCL-S pathophysiology. Cerebral OEF holds promise as a predictive biomarker to risk-stratify patients with RVCL-S and other forms of cSVD.

Background and objectives: The 2024 McDonald criteria provide new recommendations for multiple sclerosis (MS) diagnosis, but validation of the criteria is lacking. We wanted to investigate the application and performance of the 2024 McDonald criteria in patients with suspected MS seen in routine clinical practice.

Methods: We retrospectively identified patients referred with clinical and/or radiologic suspicion for MS between January and December 2024. All patients had a minimum diagnostic evaluation with brain and spinal cord MRI. The 2017 McDonald criteria were applied prospectively, and the 2024 McDonald criteria were applied retrospectively after the initial diagnostic workup and at last follow-up. We investigated (1) the number of patients diagnosed with MS using the 2017 McDonald criteria or the 2024 McDonald criteria, and (2) the diagnostic performance of the 2024 McDonald criteria when applied during the initial diagnostic workup, with an MS diagnosis using the 2017 McDonald criteria as the reference-standard.

Results: In 347 patients (mean age 39.4 years, 66% female) with suspected MS followed up for mean 15.3 (range 8-20) months, 73 (21%) had alternative disorders and were excluded. After applying the 2024 McDonald criteria in the remaining 274 patients, more patients were diagnosed with MS after the initial diagnostic workup (220 vs 172, p < 0.01), and at follow-up (237 vs 204, p < 0.01), compared with the 2017 McDonald criteria, and fewer patients were diagnosed with clinically or radiologically isolated syndrome. The median time to diagnosis was 40 vs 84 days (p < 0.01), respectively. After initial diagnostic workup, the 2024 McDonald criteria demonstrated high sensitivity (92.6%, 95% CI 88.1%-95.8%) and accuracy (83.6%, 95% CI 78.7%-87.8%), for an MS diagnosis using 2017 McDonald criteria at last follow-up, but moderate specificity (57.8%, 95% CI 45.4%-69.4%). The increased rate of MS diagnosis and the diagnostic performance of the revised criteria was similar in children (<18 years) and older adults (>50 years).

Discussion: Use of the 2024 McDonald allows for earlier MS diagnosis, but also more frequent diagnosis including in patients with radiologically isolated syndrome. The revised criteria have similar performance across the lifespan. Limitations include the lack of data on central vein sign and kappa free light chains, and missing optic nerve assessment in some patients.

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.