This study aimed to provide a clinimetric evaluation of the shortened Frontal Assessment Battery (FAB15) in a large cohort of patients with neurodegenerative disorders. FAB15 scores were retrospectively retrieved from 379 patients with neurocognitive disorders and 260 healthy controls (HCs). The clinical cohort included patients with mild cognitive impairment (MCI) and dementia due to Alzheimer’s disease (AD; n = 147), AD with mixed etiology (n = 26), frontotemporal lobar degeneration (FTLD; n = 52), and Lewy body disease (LBD; n = 32). First, we tested the discriminatory power of FAB15 across etiologies and disease severity. Then, optimal cutoffs were derived, and available normative thresholds were tested for their diagnostic performance. Within the clinical sample, factorial structure, internal consistency, construct validity, and ecological validity were also examined. After demographic adjustment, a FAB15 cutoff around 11 optimally discriminated HCs from patients with neurodegenerative disease. Importantly, discrimination was stronger for dementia than MCI and remained consistent across etiologies, with the best performance observed in LBD. Overall, normative cutoffs were highly specific but poorly sensitive, with their screening utility being largely prevalence-dependent. Psychometrically, the FAB15 showed a unidimensional factor structure, strong convergence with executive measures, and weaker associations with episodic memory tasks, as well as functional autonomies. The FAB15 is a clinimetrically and psychometrically sound screener for detecting executive dysfunction in neurodegenerative disorders.
The therapeutic landscape of myasthenia gravis (MG) has changed substantially with advances in immunopathogenesis and the introduction of targeted, mechanism-based immunotherapies. For decades, treatment relied primarily on corticosteroids and conventional immunosuppressive agents, which are effective but often limited by delayed onset, long-term toxicity, and incomplete disease control. This review summarizes current and emerging therapies for generalized MG, focusing on mechanisms of action, clinical efficacy, safety, and practical considerations, while also addressing real-world evidence, treatment switching and sequencing, and factors relevant to individualized decision-making. Complement-targeted therapies, including eculizumab, ravulizumab, zilucoplan, gefurulimab, and the emerging RNA interference-based agent cemdisiran, and neonatal Fc receptor (FcRn) inhibitors, including efgartigimod, rozanolixizumab, and nipocalimab, have substantially expanded therapeutic options. B cell-targeted therapies, particularly rituximab and inebilizumab, have also broadened the therapeutic landscape, especially for refractory disease and muscle-specific kinase antibody-positive MG. Emerging approaches, including chimeric antigen receptor T cell and chimeric autoantibody receptor T cell therapies, plasma cell-directed therapies, regulatory T cell-based therapies, and antigen-specific immune tolerance strategies, may further improve long-term disease control by targeting the underlying autoimmune process. Important unmet needs remain, including limited treatment accessibility, insufficient evidence for specific patient populations, and the lack of validated predictive biomarkers. In the absence of direct head-to-head trials or validated predictive biomarkers, individualized treatment selection should integrate autoantibody status, disease activity and urgency, clinical characteristics, prior treatment response and toxicity, comorbidities and safety considerations, treatment burden, reproductive considerations, patient preferences, and access. Future progress will depend on the development and validation of predictive biomarkers to enable biomarker-guided precision medicine, together with advances in targeted immunotherapy and immune tolerance-inducing strategies, with the ultimate goal of achieving durable remission and improving long-term outcomes and quality of life.
Multiple sclerosis (MS) management has increasingly favored earlier high-efficacy disease-modifying therapy (DMT). We examined diagnosis-era changes in relapse activity and disability accrual alongside evolving DMT use. We retrospectively analyzed two Italian cohorts of adults with MS onset in 2001–2024 across four diagnosis eras. Annualized relapse rate (ARR) was modeled by Poisson regression; confirmed disability accrual (CDA), relapse-associated worsening (RAW), and progression independent of relapse activity (PIRA) by Andersen–Gill Cox models. CDA was classified as RAW when relapse onset occurred from 90 days before through 30 days after the event, otherwise as PIRA. Treatment was time-varying: untreated, low-/moderate-efficacy therapy (LET/MET), or high-efficacy therapy (HET). Inverse probability-weighted models included residual adjustment. Sensitivity analyses examined a strict common 2-year horizon, MRI restriction/adjustment, relapsing-onset MS, first-event analyses, 90-day DMT lag, early-HET exclusion, pre-treatment versus never-treated person-time, visit frequency, and center stratification. Among 1096 patients (228, 214, 292, and 362 across eras 1–4), first-line HET use reached 45.9
Headache management in children and adolescents remains challenging, particularly in patients with high headache-related disability, medication overuse, and comorbid conditions, for whom evidence-based preventive treatment options are limited and often ineffective. This study aimed to evaluate the clinical outcomes and safety of a protocolized, repetitive bilateral greater and lesser occipital nerve block (GONB/LONB) strategy in pediatric patients with frequent and severe headaches. This retrospective study included adolescents aged 11–18 years who underwent bilateral GONB and LONB for headache between 2018 and 2025. At each treatment session, 1 mL of 2
Cerebrospinal fluid (CSF) biomarker ratios (amyloid-β [Aβ]42/Aβ40, phosphorylated-tau [pTau]/Aβ42, and total tau [tTau]/Aβ42) are lower-cost alternatives to amyloid positron-emission tomography (PET) for Alzheimer’s disease diagnosis. Among these CSF biomarker ratios, it is not clear whether concordance with amyloid PET is highest with Aβ42/Aβ40, pTau/Aβ42, or tTau/Aβ42. To evaluate this, we conducted a diagnostic test accuracy meta-analysis. Medline and Embase were searched for articles published between January 2008 and February 2026 reporting concordance of ≥ 1 CSF biomarker ratio with amyloid PET. Statistical analyses were performed using the bivariate model of Reitsma with the R package mada v0.5.11. This quantitative meta-analysis comprised 38 studies, including a total of 7504 participants, with 35 studies available for statistical analysis. All three CSF biomarker ratios (Aβ42/Aβ40, pTau/Aβ42, and tTau/Aβ42) were highly concordant with amyloid PET. However, the pTau/Aβ42 ratio showed numerically higher overall percent agreement with amyloid PET positivity (90.4
