Neurology最新文献

Background and objectives: Cerebral small vessel disease (cSVD) is a major contributor to stroke and dementia, often beginning decades before clinical symptoms appear. While MRI markers offer critical insight into cSVD burden, blood-based biomarkers may offer a more accessible complement to neuroimaging. We investigated whether plasma glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are associated with MRI markers of cSVD in middle-aged adults and whether they are associated with longitudinal progression.

Methods: We conducted a retrospective analysis of prospectively collected data from the UK Biobank cohort. Participants aged 40-60 years at baseline (2006-2010) with plasma biomarker measurements and follow-up MRI scans (2014-2019) were included. Individuals with prevalent neurologic conditions were excluded. We assessed 3 MRI markers of cSVD: white matter hyperintensities (WMHs), fractional anisotropy (FA), and mean diffusivity (MD). Three analytical approaches were used: associations between baseline biomarkers and future MRI markers, associations between baseline biomarkers and longitudinal MRI changes, and correlations between longitudinal biomarker and MRI changes. Robust regression models were adjusted for age, sex, and cerebrovascular risk factors.

Results: Among 5,270 participants (mean age 54.2 ± 7.8 years; 53.4% female), higher baseline GFAP levels were significantly associated with all 3 MRI cSVD markers-WMH volume (β = 0.06, 95% CI 0.01-0.10, p = 0.014), FA (β = 0.08, 95% CI 0.03-0.13, p = 0.001), and MD (β = 0.14, 95% CI 0.09-0.18, p < 0.001)-after a follow-up of 9 years. Among 1,317 participants with longitudinal MRI data, baseline GFAP was associated with progression of FA (β = 0.012, 95% CI 0.001-0.023, p = 0.033) and MD (β = 0.020, 95% CI 0.003-0.038, p = 0.025) over 3 years. NfL was not significantly associated with any MRI cSVD marker. Longitudinal changes in both biomarkers showed no significant associations with concurrent MRI progression.

Discussion: Plasma GFAP levels were associated with subsequent changes in white matter integrity among middle-aged adults, suggesting potential utility as an early indicator of cSVD vulnerability. These associations, observed nearly a decade after biomarker measurement, highlight GFAP's potential for long-term risk stratification. Blood-based biomarkers may support earlier identification of individuals at heightened risk of cSVD, enabling preventive strategies when interventions may be most effective.

Background and objectives: "Motor reserve" refers to the brain's dynamic resilience against dopaminergic degeneration in Parkinson disease (PD). However, its clinical significance remains unclear because of critical limitations, including the lack of data on its longitudinal trajectories. Using Parkinson's Progression Markers Initiative data with serial dopamine transporter (DAT) imaging from the drug-naive stage, we investigated its trajectories, determinants, and prognostic implications.

Methods: This retrospective observational cohort study assessed motor reserve using 2 complementary approaches. The residual-based approach calculated deviations in Movement Disorders Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 3 scores from expected values derived from a linear regression model incorporating putamen DAT specific binding ratio (putamen SBR), age, sex, and disease duration. The interaction-based approach extended this model by introducing interaction terms between putamen SBR and each factor, analyzing the corresponding β coefficients. We examined motor reserve's cross-sectional associations with clinical parameters, its mediation effects, and its longitudinal trajectories-up to 4 years-based on DAT imaging data availability, while identifying factors influencing its changes. Finally, we assessed its impact on long-term prognosis using Cox proportional hazards and linear mixed-effects models (LMEMs).

Results: We included 566 drug-naive patients with PD (median age 62.3 [interquartile range 56.3-69.6] years; 33.7% female). At baseline, regular physical activity was significantly associated with motor reserve in both approaches, with mediation analysis indicating that motor reserve largely mediated the effect of physical activity on motor symptom improvement. Longitudinally, adequate medication and sustained regular physical activity levels were strongly associated with a slower early-years decline in motor reserve. It is important to note that early-years average motor reserve, not the baseline value, was a strong predictor of long-term motor outcomes (Cox: Hoehn/Yahr stage 3, hazard ratio = 0.50, 95% CI 0.37-0.66; LMEMs: MDS-UPDRS Part 3 score, fixed-effects standardized interaction coefficient = -0.57, 95% CI -0.79 to -0.35). These findings were further validated through propensity score matching.

Discussion: Maintaining motor reserve in the early years after diagnosis strongly predicts favorable long-term motor outcomes, with adequate treatment and regular physical activity-both modifiable factors-supporting this maintenance. Because our study includes early-stage, drug-naive PD, further research in later stages is warranted.

Trial registration information: ClinicalTrials.gov (NCT01141023). A link to the trial registry page is clinicaltrials.gov/ct2/show/NCT01141023.

Background and objectives: Macrocephaly is among the most common findings in neurofibromatosis type 1 (NF1) and may be associated with other clinical manifestations of the genetic syndrome. NF1-specific growth charts that account for expected macrocephaly may increase sensitivity for detecting atypical growth. We aimed to produce NF1-specific growth charts of head circumference for the age range of 0-3 years and to assess their potential clinical impact.

Methods: Using electronic health records from the Children's Hospital of Philadelphia, we collected head circumference measurements from children with NF1 and a community control cohort seen at scheduled well-child visits. We compared head circumference normalized using Centers for Disease Control (CDC) growth charts between these groups over time. We constructed NF1-specific growth charts using 2 independent methods. Finally, we used mixed-effects models to relate the resulting centile scores to developmental delay assessed with the Survey of Well-being of Young Children.

Results: Our data set contained 2,180 observations from 305 individuals (167 male) with NF1 and 104,750 observations from 16,742 individuals (8,809 male) in the community control cohort, all aged 0-3 years. Head circumference was significantly elevated in the NF1 cohort across the age range (p-adjusted <0.05), but the Cohen effect size d varied nonlinearly with age, starting moderate at 1 month (d = 0.56), then small at 4 months (d = 0.28), moderate again at 15 months (d = 0.58), and finally large at 28 months (d = 0.80). NF1-specific growth curves demonstrated slower increases in head circumference in the first 2 months of life, yet more sustained growth over time. Although none of the children with NF1 met the standard for microcephaly according to CDC charts, smaller head circumference benchmarked against NF1-specific charts was correlated with developmental delay (standardized β = 0.24; p < 0.02).

Discussion: We present the first NF1-specific growth charts for head circumference covering the age range of 0-3 years. Macrocephaly in NF1 becomes more exaggerated over time as rate of growth is sustained compared with controls. Smaller head size relative to NF1 growth expectations is not captured by CDC charts yet it nevertheless relates to developmental delay, suggesting that NF1-specific charts may increase sensitivity to clinically concerning patterns of growth in children with NF1.