Journal of the Neurological Sciences最新文献

Introduction: Nusinersen improves motor outcomes in SMA, but reliable biomarkers for treatment monitoring, especially in adults, are still lacking. We investigated cerebrospinal fluid (CSF) and plasma levels of glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF), exploring their potential as biomarkers in disease progression.

Methods: This single-centre observational study included adults with type 3 SMA treated with nusinersen over 30 months. GFAP and VEGF levels in CSF and plasma were measured using ELISA at baseline, 14 and 30 months. Functional evaluation included Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), and respiratory tests. Longitudinal data were evaluated using generalized linear mixed-effects models. A significance level of α = 0.05 was used in all analyses.

Results: Eleven patients were included (63.6% male, aged 19-60 at baseline). Improvements were observed in motor function, with an estimated non-linear increase of 9.02% (CI95%: 5.13-8.79) for RULM and an estimated average increase of 6.96 points (CI95%: 5.44-8.48) for HFMSE over 30 months of treatment. However, both CSF and plasma GFAP and VEGF levels changes at 14 and 30 months did not reach statistical significance, respectively (all p > 0.05).

Conclusion: CSF and plasma GFAP and VEGF trajectories over a 30-month period under nusinersen treatment were nonsignificant. This study confirms sustained motor function improvements in adult type 3 SMA patients treated with nusinersen. Future research in larger, multicentric, and internationally collaborative cohorts are essential to fully understand the role of these potential biomarkers in SMA pathogenesis.

Background: Plasma neurofilament light chain (pNfL) is increasingly investigated as a biomarker of axonal damage in several neurological disorders, including hereditary spastic paraplegias (HSPs). Currently, very few studies are focused on pediatric HSPs.

Methods: Plasma NfL levels were measured in 40 pediatric (e.g., <18 years) subjects affected by genetically solved or unsolved HSPs. For 31 subjects, longitudinal NfL evaluation was also available. Potential correlation between pNfL and disease-specific or non-specific features were explored.

Results: Median age at enrollment was 11.53 years, with a median disease duration of 9 years and a median NfL level of 8.5 pg/mL. At baseline, pNfL did not differ across SPG, vs non-SPG HSPs, GMFCS levels, pure vs complex phenotype (with a non-statistically significant increase in the latter) and early- vs childhood-onset forms. Higher levels were observed in subjects with shorter disease duration from onset. Genetically unsolved individuals exhibited non-significant reduced levels compared with genetically confirmed cases. Plasma NfL presented a similar age-related trajectory as in the healthy pediatric population, with a possible trend of increase in younger children. Finally, no differences were observed at longitudinal NfL evaluation after a median period of 9 months.

Conclusions: This study is the first pediatric-focused work exploring utility of pNfL in HSPs. NfL levels showed a tendency of increase especially in complex forms, in younger subjects and with shorter disease duration from onset. Lower levels were observed in genetically unsolved individuals. Larger and longer studies are warranted to further define NfL utility as a clinically relevant biomarker in pediatric HSPs.

Background: Leucine-rich glioma-inactivated 1 (LGI1) antibody-associated autoimmune encephalitis (AE) presents with cognitive and behavioral disturbances. Although most patients improve with immunotherapy, long-term domain-specific cognitive outcomes have not been thoroughly studied. We examined long-term cognitive trajectories in LGI1-AE, with a focus on executive dysfunction.

Methods: We conducted a retrospective study of 18 LGI1-AE patients followed at a single tertiary center (2015-2025) for a median of 44 months [range 6-82]. Cognitive function was assessed using Montreal Cognitive Assessment (MoCA) and its subscales, including a broad Executive Index Score (EIS), a narrow executive composite, and delayed recall. We studied the course of cognitive function using repeated evaluations on follow up visits. Longitudinal changes were analyzed using the Wilcoxon signed-rank test, and predictors of outcomes were evaluated by regression analysis.

Results: Global cognition improved significantly from first to last visit (median MoCA 20 to 24, p = 0.001). Executive function and delayed recall also showed gains (p = 0.001 and p = 0.024, respectively). Younger patients (≤65 y) outperformed older patients at presentation and follow-up, despite similar immunotherapy timing (MoCA: 26 vs. 19, p = 0.016 and EIS: 12.5 vs. 9.5, p = 0.009). Improvement magnitude was similar across ages. Regression showed initial MoCA predicted long-term global cognition (p = 0.001), while both initial EIS (p = 0.036) and age at onset (p = 0.007) independently predicted executive outcomes.

Conclusions: Cognitive outcomes in LGI1 autoimmune encephalitis improve after immunotherapy, yet executive dysfunction frequently persists as a long-term deficit. Older age independently predicts poorer outcomes, suggesting that age-related vulnerability may limit recovery.

Background: Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are promising biomarkers for Multiple Sclerosis (MS) disease activity. There is less known about their association with the symptomatic phenotypes such as depression and mental health outcomes.

Objectives: To investigate the association between sNfL and sGFAP and Patient-Reported Outcome (PRO) measures for depression and overall mental health in individuals with MS (iwMS).

Methods: Participants completed the Center for Epidemiological Studies Depression Scale (CESD) and MS Quality of Life-54 (MSQOL-54)- at the time of the blood draw. Linear regression was used to estimate the association between the PRO measures as the outcome and the log-transformed biomarkers as the predictor. The association between baseline biomarkers and longitudinal change in PROs was estimated using linear mixed-effect models.

Results: Cross-sectional analysis showed a significant correlation between sNFL and CES-D (p = 0.035) and MSQOL-54 Mental Health Composite (MHC) (p = 0.003) scores. This association remained statistically significant after adjusting for sex, age, EDSS and MS treatment. Neither cross-sectional nor longitudinal analysis of sGFAP levels showed significant correlation with PROs scores.

Conclusion: Serum NfL is associated with depression and overall mental health scores in iwMS. We did not find a significant relationship between sGFAP and PRO measures.

We commend Matsukawa et al. for their study on outcomes of endovascular treatment (EVT) for unruptured intracranial aneurysms (UIAs) across age groups. While their findings support EVT in the elderly, we highlight four areas for deeper consideration. First, the divergent 30- and 90-day outcomes in the ≥80-year group suggest a distinct recovery trajectory, warranting finer-grained functional assessments beyond the mRS to differentiate transient post-procedural stress from permanent injury. Second, we advocate for incorporating advanced morphological and hemodynamic analyses (e.g., CFD) to understand the interplay between age, aneurysm characteristics, and outcomes. Third, for long-term durability, we recommend using Kaplan-Meier curves and competing risk analysis to provide a more accurate estimate of EVT benefit in the elderly. Finally, we underscore the need to move beyond chronological age by integrating frailty scales (e.g., CFS) and call for prospective, multi-center registries to confirm these findings and establish best practices. A multi-faceted approach is crucial for personalizing UIA management in our aging population.

A 3D model using computational fluid dynamics may explain the mechanism by which pulsatile tinnitus in idiopathic intracranial hypertension occurs and persists even after successful treatment of the idiopathic intracranial hypertension.