Neurology最新文献

Objective: To quantify brain health using a measure of reserve that incorporates pre-existing pathology.

Methods: We analyzed 2 retrospective ischemic stroke cohorts (GASROS and SALVO) with neuroimaging and 90-day modified Rankin Scores (mRS) available. White matter hyperintensity (WMHv), brain, and intracranial volumes were automatically extracted and brain parenchymal fraction (BPF) calculated. The latent variable effective reserve (eR) was modeled using age, WMHv, and BPF or brain volume in GASROS. Models were compared using Bayes Information Criterion (BIC). The best model's eR estimates were categorized into quartiles and evaluated in SALVO.

Results: GASROS included 476 (median age: 65.8; 65.3% male) and SALVO included 43 (median age: 69.2; 62.8% male) patients. Inverse associations between eR and mRS was seen in both models, with brain volume outperforming BPF (path coefficients: -0.67, -0.48, respectively; p < 0.001; |ΔBIC| = 362). Quartile-based eR stratification in both studies showed a similar inverse trend, with worse outcomes in the low reserve group (mRS ≤2 - highest vs lowest quartile: 85/90% vs 59/45% for GASROS/SALVO).

Discussion: Expanding the concept of eR, highlights its clinical translational potential. The strong link between higher eR and better outcomes underscores its value as a protective brain health metric.

Objectives: Tools are needed to evaluate the risk of developing Parkinson disease (PD) in at-risk populations. In this study, we examine differences in alpha-synuclein seed amplification assay (αSyn-SAA) qualitative results and amplification parameters between nonmanifesting carriers (NMCs) of PD-related pathogenic variants, prodromal PD, and PD and the risk of developing a synucleinopathy in participants with prodromal PD.

Methods: Cross-sectional and longitudinal CSF αSyn-SAA results from participants in the Parkinson's Progression Markers Initiative were analyzed. αSyn-SAA positivity and amplification parameters (maximum fluorescence [Fmax], time-to-threshold [TTT], time-to-50% Fmax [T50], and area under the curve [AUC]) were compared between NMCs, participants with prodromal PD, and participants with PD, and their relationship with the likelihood of phenoconversion in participants with prodromal PD was investigated.

Results: Samples from 1,027 participants were analyzed (159 healthy controls [HCs], 247 NMCs, 96 participants with prodromal PD, and 525 participants with PD). TTT and T50 were faster, and AUC was higher in αSyn-SAA+ participants with prodromal PD and PD than αSyn-SAA+ NMCs and HC participants (Kruskal-Wallis χ² = 4.15-13.96, p < 0.0002-0.04). Participants with prodromal PD with positive αSyn-SAA tests and faster TTT had higher rates of phenoconversion (log-rank p = 0.001 and log-rank test-for-trend p < 0.0001). There were no changes in 48 participants with prodromal PD with longitudinal assays.

Discussion: αSyn-SAA positivity and faster seed amplification are associated with a greater risk of developing PD in at-risk individuals and may aid in predicting phenoconversion.

Background and objectives: Rapid eye movement sleep behavior disorder (RBD) is increasingly recognized in patients with tauopathies, but its significance and underpinnings remain unclear. To address this gap, we investigated the prevalence of self-reported RBD in patients with progressive supranuclear palsy (PSP) and explored its clinical and imaging correlates using ¹⁸F-florzolotau PET imaging.

Methods: We consecutively enrolled patients meeting the 2017 Movement Disorder Society clinical criteria for PSP at a Chinese tertiary hospital between May 2019 and March 2022. Patients underwent comprehensive clinical assessments and ¹⁸F-florzolotau PET to investigate tau deposition patterns. The presence of self-reported RBD was identified using the RBD Single-Question Screen, while its frequency was retrospectively collected from medical history.

Results: We examined 148 patients recruited in the ongoing Progressive Supranuclear Palsy Neuroimage Initiative cohort. Self-reported RBD was identified in 18.2% of the participants (27/148). Patients with PSP-Richardson syndrome and PSP-parkinsonism reported the highest frequencies of self-reported RBD (21.7% and 18.5%, respectively), compared with PSP-progressive gait freezing (9.7%). While age and sex were similar in patients with and without self-reported RBD, the former group exhibited greater disease severity, as indicated by higher PSP Rating Scale (PSPrs) scores (38.0 vs 27.0, effect size = 0.256, p = 0.002). Furthermore, patients with RBD had significantly higher ¹⁸F-florzolotau binding in the locus coeruleus (LC) (1.50 vs 1.38, effect size = 0.231, p = 0.003), which remained significant after false discovery rate correction (p = 0.042). The frequency of RBD was found to be correlated with tau pathology in the LC (n = 8, r = 0.752, p = 0.002). Notably, the presence of self-reported RBD symptoms mediated the relationship between LC tau pathology and PSPrs total scores (proportion-mediated = 2.09%, 95% CI 0.01%-10.00%, p = 0.044).

Discussion: Approximately one-fifth of patients with PSP reported RBD and exhibited more severe motor and nonmotor symptoms. The elevated ¹⁸F-florzolotau binding in the LC and its association with the presence of RBD symptoms underscore the critical role of tau pathology in disrupting sleep-regulating neural circuits. Future studies with larger sample sizes should incorporate polysomnography in patients with PSP with self-reported RBD to further elucidate this relationship.

Background and objectives: Previous studies on sport-related concussion (SRC) may have measured brain injury blood-based biomarker, glial fibrillary acidic protein (GFAP), either before or after its peak, potentially underestimating the diagnostic value. The primary aim of this study was to evaluate the diagnostic performance of serum GFAP at 24 hours post-SRC. Secondary objectives included assessing whether the timing of sample collection relative to an Australian football match (with or without SRC) affected GFAP levels, evaluating if combining GFAP with symptoms improved discrimination of SRC compared with symptoms alone, and determining the diagnostic utility of serum neurofilament light (NfL) levels at 24 hours post-SRC.

Methods: In a prospective cohort study, adult male and female Australian football players of the Victorian Amateur Football Association (Melbourne, Australia) with and without SRC had blood sampled around 24 hours postinjury/postmatch. GFAP and NfL levels were quantified using Simoa assays, and area under the curve (AUC) values were calculated for time bins of 16-24 hours, 24-32 hours, and 36-52 hours. Symptom severity at blood collection was assessed using the Sport Concussion Assessment Tool 5 (SCAT).

Results: A total of 151 athletes with SRC (median age 22.5 years; 85% male) and 97 controls (median age 24.3 years; 86% male) were sampled at a median of 24.5 hours (interquartile range [IQR] 21.7-28.0; min-max 16-51.5). Time to sample postmatch did not affect GFAP levels in controls; however, higher GFAP levels correlated with shorter time post-SRC (Spearman r = -0.25, 95% CI -0.40 to -0.09). Median GFAP concentrations were 65.9 pg/mL (IQR 49.1-81.3) in controls, and for SRC, 124.6 pg/mL (IQR 86.7-190.7) at 16-24 hours, 94.5 pg/mL (IQR 61.6-163.9) at 24-32 hours, and 59.9 pg/mL (IQR 49.1-94.7) at 36-52 hours. AUC values at 16-24 and 24-32 hours were 0.83 (95% CI 0.76-0.90) and 0.72 (95% CI 0.64-0.80), respectively. Furthermore, combining GFAP with SCAT symptoms at 16-24 hours enhanced discriminatory capability compared with SCAT symptoms alone (AUC increased from 0.91 to 0.97; z = 2.48, p = 0.01). Serum NfL had a limited diagnostic value (AUC ≤0.60).

Discussion: Serum GFAP measured at 16-24 hours following potential or suspected SRC may be a useful objective aid to SRC diagnosis.