Neurology and Therapy最新文献

Introduction: The spinocerebellar ataxia composite score (SCACOMS) comprises items from the functional Scale for the Assessment and Rating of Ataxia (f-SARA) and the Clinician Global Impression of Change (CGI-C). In the derivation of SCACOMS, weights reflecting 1-year responsiveness were assigned to each item using partial least squares (PLS) regression modeling. The current objective was to incorporate patient-feedback into the SCACOMS item weights, examine corresponding responsiveness of the composite scale, and discuss potential implications for future use.

Methods: Item weights derived by PLS regression were compared to each item's relative importance as assigned by 16 patients with SCA during semi-structured interviews. SCACOMS item weights were adjusted using the following combinations: (1) 50/50 weighted combination of PLS and patient weights and (2) reducing the weight of CGI-C to 20% and averaging individual item weights obtained from each perspective. The 1-year mean to standard deviation ratios (MSDRs) for the resulting reweighted scales were compared, with larger MSDRs indicating greatest sensitivity to disease progression.

Results: The PLS-derived SCACOMS had the highest MSDR (0.99). When item weights were averaged across the two sources, the resulting MSDR was 0.91. When the weight of CGI-C was set to 20%, reflecting patient preferences for higher weights on the discrete symptoms, the MSDR was 0.79.

Conclusions: This study took a novel approach to enhance the face validity of SCACOMS by incorporating patient feedback into the statistically optimized item weights. The result is the merging of objectively derived item weightings (reflecting optimal scale responsiveness) with patient-assigned relevance. While this update may increase the patient centricity of a composite measure, this comes at the expense of reduced sensitivity. This potential trade-off in sensitivity to detect change should be evaluated in the context of the composite measure's intended use.

Multiple sclerosis (MS) is a chronic sex-biased (3♀:1♂) immune-mediated demyelinating disease of the central nervous system (CNS). Disease-modifying therapies targeting the peripheral immune cells efficiently limit relapses in early MS but cannot abrogate the chronic progressive component of the disease. The exact cause of MS remains elusive but interactions between predisposing genetic and environmental risk factors result in aberrant activation of pro-inflammatory immune cells targeting the CNS, leading to the formation of multifocal demyelinating lesions in the brain and spinal cord. MS-related genetic polymorphisms and viral triggers are currently not amenable to intervention. In contrast, obesity and gut dysbiosis represent potential modifiable risk factors contributing to MS pathogenesis and disease course. Diet influences obesity and metabolic diseases, shapes gut microbiota composition, modulates oxidative stress, and affects biological aging and inflammatory processes. Dietary patterns have emerged as factors modifying MS risk, disease activity, and progression. Therapeutic dietary interventions represent a promising avenue to promote healthy aging and regulate neuroinflammatory and neurodegenerative processes in MS. Here we describe the impact of diet on MS course and review the nutritional interventions investigated in MS and its animal models, with a focus on the mechanisms implicated including the impact on the gut microbiota.

Introduction: Tysabri (natalizumab) is a recombinant humanized IgG4 monoclonal antibody for the treatment of adults with highly active relapsing-remitting multiple sclerosis (RRMS). A subcutaneous (SC) formulation administered by healthcare professionals (HCPs) is expected to save time for patients and healthcare staff compared with intravenous (IV) delivery. This observational study quantifies HCP and patient time with natalizumab IV vs natalizumab SC in patients with RRMS.

Methods: Seven sites across France (n = 3), Spain (n = 3), and the United Kingdom (UK) (n = 1) participated in this study. Primary endpoints were active HCP time for tasks related to preparation and administration processes of natalizumab, all tasks combined, and time in the infusion chair. The target sample was 15 observations each of natalizumab IV and SC per site. Results were extrapolated per patient per year. HCP satisfaction and preference were assessed via a one-time survey.

Results: A total of 213 observations were collected (102 IV and 111 SC). Mean total active HCP time (min) per visit (and annually) was 15.8 (205.8) for IV and 9.1 (118.4) for SC (- 42.5% [pooled], - 29.3% [Spain], - 48.1% [France], and - 56.5% [UK]). Mean time in the infusion chair (min) was 95.2 for IV and 33.5 for SC (- 64.9% [pooled], - 60.4% [Spain], - 67.3% [France], and - 69.2% [UK]). Mean HCP satisfaction score for administration was higher for SC than for IV (9.2 vs 8.2; p = 0.026). Seventy percent of HCPs stated a preference for SC, of which 56.3% stated a very strong and 18.8% a fairly strong preference.

Conclusions: Natalizumab SC offers substantial savings in active HCP time and patient chair time compared with natalizumab IV. HCPs reported higher satisfaction and a preference for natalizumab SC. The HCP time and infusion chair capacity made available with natalizumab SC could be reallocated to other patient-care activities or used to treat additional patients, thereby improving overall healthcare efficiency.

Introduction: Assessing the environmental impact on multiple sclerosis (MS) is complex because of long disease latency and potential recall bias, especially for perinatal exposures. This study aimed to investigate the association between parental smoking and the development of pediatric MS (PedMS).

Methods: As part of the Italian multicenter PEDIGREE study, the PEQ-IT questionnaire was used for prospective data collection. We enrolled subjects under 18 years with PedMS (2013 Krupp criteria) and disease duration ≤ 5 years from onset, along with matched controls.

Results: The study included 114 PedMS cases and 121 controls. Female participants represented 77.2% of cases and 54.4% of controls, with a mean (SD) age of 16.8 (2.7) and 13.5 (4.9) years, respectively. The mean (SD) age at MS onset was 14.2 (2.6) years, and the median EDSS score was 1.0 (range 0-4.0). PedMS risk was higher in subjects with fathers who were current smokers (crude OR 1.94, 95% CI 1.10-3.40) or who smoked 3 months' pre-pregnancy (crude OR 1.79, 95% CI 1.03-3.11). The risk increased when both parents smoked (crude OR 2.03, 95% CI 1.12-3.68) and was highest when both smoked 3 months before pregnancy (crude OR 10.79, 95% CI 1.30-89.54), even after adjustments. No significant association was found with maternal smoking.

Conclusion: Parental smoking, particularly paternal smoking current habit and before pregnancy, may increase the risk of PedMS. Promoting smoke-free behaviors among parents could therefore represent a feasible preventive approach to limit early-life environmental factors involved in disease susceptibility.

Introduction: Inflammation plays a critical role in the pathophysiology of acute ischemic stroke (AIS). Ratios derived from routine blood counts, especially the neutrophil-to-lymphocyte ratio (NLR), have been proposed as prognostic biomarkers, but their value in patients receiving reperfusion therapies-intravenous thrombolysis (IVT) or mechanical thrombectomy (MT)-remains uncertain.

Methods: We systematically searched PubMed, Cochrane Library, Web of Science, and Scopus on November 30, 2024, following PRISMA guidelines. Eligible studies included patients with AIS treated with IVT or MT that reported associations between pre-treatment blood cell ratios and outcomes measured by the modified Rankin Scale (mRS). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models.

Results: Fifty-seven studies with 17,394 patients were included. NLR was the predominantly studied biomarker. In the MT subgroup, elevated NLR predicted poor 3-month outcome (OR 1.09, 95% CI 1.04-1.15) and higher mortality (OR 1.05, 95% CI 1.01-1.08). In IVT-treated patients, higher NLR also predicted poor outcome (OR 1.11, 95% CI 1.01-1.21) with lower heterogeneity across studies. Other ratios showed variable associations: lymphocyte-to-monocyte ratio (LMR) appeared protective, while platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-neutrophil ratio (PNR) showed inconsistent or null results. Data regarding hemorrhagic transformation were heterogeneous and unsuitable for meta-analysis.

Conclusions: Elevated pre-treatment NLR consistently predicted poor outcome and mortality after reperfusion therapy for AIS, supporting its role as a simple biomarker for early risk stratification. Future large, prospective multicenter studies with standardized methods are needed to confirm the clinical utility of these inflammatory ratios in stroke management.

Secondary stroke prevention focuses on managing vascular risk factors such as hypertension, hyperglycemia, and dyslipidemia. However, the impact of exercise training regimens (ETR) on these factors post-stroke remains unclear. We conducted a network meta-analysis (NMA) to compare the effects of different ETR on vascular risk factors and adverse events in patients following stroke or transient ischemic attacks (TIA). We performed a systematic review following PRISMA criteria, searching multiple databases until March 2024. The outcomes of interest included systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), total cholesterol (TC), fasting blood glucose (FBG), and body mass index (BMI). A Bayesian network meta-analysis approach was used to estimate mean differences (MD) and 95% credible intervals (CrI). We analyzed 20 randomized clinical trials involving 1653 patients. Moderate intensity continuous training (MICT) and comprehensive training program (CTP) showed the greatest effects on SBP and DBP. Resistance training (RT) was most effective for improving lipid profiles. ETR had no significant effect on post-stroke FBG and BMI. For secondary stroke prevention, MICT and CTP may be beneficial for managing hypertension, while RT could be the primary strategy for improving lipid profiles.Trial Registration: CRD42024554934.

Introduction: Psychiatric comorbidities increase the risk of migraine disease progression. These post hoc analyses explored whether self-reported psychiatric comorbidities at screening had an impact on the short- and long-term efficacy of eptinezumab in the DELIVER trial.

Methods: DELIVER was a multinational trial that evaluated eptinezumab in adults with migraine with 2-4 prior preventive treatment failures. Participants were initially randomized to intravenous eptinezumab 100 mg, 300 mg, or placebo every 12 weeks. Participants receiving placebo during the 24-week double-blind placebo-controlled period were switched to eptinezumab 100 mg or 300 mg for the 48-week dose-blinded extension, while those initially randomized to eptinezumab continued their assigned dose. Subgroups included participants self-reporting a psychiatric condition at screening, within which participants self-reporting a depressive condition at screening were also analyzed. Outcomes were changes from baseline in monthly migraine days (MMDs), ≥ 50% migraine responder rates (MRRs), and participants who improved per Patient Global Impression of Change (PGIC; much or very improved). As post hoc analyses, no p-values were generated.

Results: Of the total population, 122/890 (13.7%) self-reported ≥ 1 psychiatric comorbidity, including 68/890 (7.6%) who self-reported depression. The mean change from baseline in MMDs over Weeks 1-12 in the psychiatric comorbidity subgroup was - 4.6 with eptinezumab versus - 0.9 with placebo, with similar mean changes observed in those with comorbid depression (eptinezumab, - 4.7; placebo, 0.0). In the psychiatric comorbidity subgroup, ≥ 50% MRRs over Weeks 1-12 were higher with eptinezumab (42%; odds ratio [OR] vs placebo = 25.3) than with placebo (3%), as were the proportions of participants with PGIC improvement (eptinezumab, 60%, OR = 6.7; placebo, 19%). During the extension period, participants switching from placebo to eptinezumab reported similar improvements to the eptinezumab-eptinezumab group, with similar outcomes in the subgroups with psychiatric comorbidities.

Conclusions: Psychiatric comorbidities, including depressive conditions, did not appear to impact the short- or long-term efficacy of eptinezumab in participants with migraine for whom 2-4 prior preventive treatments had failed.

Trial registration: EudraCT (2019-004497-25); ClinicalTrials.gov (NCT04418765).

Relapsing multiple sclerosis (RMS) is most often diagnosed in young adulthood but may also manifest during childhood or later in life. The number of older people living with RMS (pwMS) continues to grow as life expectancy increases and MS incidence rises among older adults. This review summarises the principal challenges in managing pwMS at different stages of life. Paediatric-onset RMS: RMS onset in childhood and adolescence is typically characterised by a higher relapse rate. Early diagnosis, timely intervention, and specialised care are essential. Management also requires close collaboration among healthcare providers, families, and educational institutions to help children balance the disease burden with academic, social, and family life. Young adults with RMS: In young adulthood, MS can disrupt education, employment, relationships, and family planning. Individualised treatment strategies and shared decision-making are essential to align disease management with evolving personal and professional goals. Older pwMS: Age-related issues such as immunosenescence, disability progression, comorbidities, polypharmacy, and menopause become increasingly relevant. Vaccination is particularly important given both immunomodulatory therapies and reduced immune resilience associated with immunosenescence. As pwMS age, treatment strategies may include disease-modifying therapy (DMT) de-escalation, discontinuation, or immune reconstitution therapies to reduce long-term immunosuppression. In conclusion, a holistic, pwMS-centred approach is essential to tailor MS management across the lifespan, adjusting to the medical, functional, and psychosocial needs of pwMS at each stage of life.

Relapsing multiple sclerosis (RMS) is a chronic inflammatory disease usually diagnosed at a young age. Most patients receive several disease-modifying therapies (DMTs) over time, but evidence-based guidelines to support treatment sequencing are limited, particularly for switches between high-efficacy DMTs. An international group of experts in the care of RMS reviewed the current evidence and their clinical practice in order to provide recommendations on the optimal therapeutic use of cladribine tablets (CladT, an immune reconstitution therapy for RMS) in patients previously managed on anti-trafficking agents (S1P modulators, natalizumab) or an anti-CD20 agent. Recommendations relate to switching due to breakthrough RMS disease activity or safety/tolerability issues, to reduce the risk of safety concerns, including de-risking in older people with stable RMS, and to facilitate family planning. We propose that CladT is a rational option for people with RMS presenting with intractable safety/tolerability issues during treatment with a high-efficacy DMT, for older patients with stable RMS who have received long-term DMT, or for patients with breakthrough RMS disease activity despite treatment with an S1P modulator. In selected cases, CladT may be considered for patients with breakthrough RMS disease activity on anti-CD20 treatment. It is important to keep the interval between withdrawal of a previous anti-trafficking DMT (especially S1P modulators) and initiation of CladT as short as possible if the switch is intended to address breakthrough RMS disease activity, especially with regard to the prevention of rebound RMS disease activity. Immune reconstitution therapy with CladT may also provide an opportunity to plan for pregnancy in the absence of continuous DMT.

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Accumulating evidence indicates that immune inflammation and oxidative stress may be involved in the pathogenesis of ASD. Intravenous immunoglobulin (IVIG), a well-established immunomodulatory agent, has demonstrated potential in ameliorating neuroinflammatory and behavioral symptoms in neuroimmune disorders. This prospective, open-label, single-arm study aimed to evaluate the short-term efficacy and safety of IVIG in children with ASD who have peripheral blood immune dysregulation.

Methods: A total of 41 children with ASD (aged 3-8 years) were enrolled. Participants received IVIG at a dose of 1 g/kg per infusion 1 month apart, resulting in a cumulative dose of 2 g/kg. The Social Responsiveness Scale-2 (SRS-2) was used to assess symptom changes at baseline, 1 month, and 2 months, and adverse events were recorded.

Results: The SRS-2 total score and the scores of the Social Cognition, Social Communication and Social Motivation domains were significantly reduced at 2 months after IVIG intervention (P < 0.05). In terms of safety, two participants presented with a transient low-grade fever, two participants experienced vomiting, and one participant exhibited abdominal distension and poor appetite. All adverse events (AEs) were classified as Common Terminology Criteria for Adverse Events (CTCAE) grade 1 and resolved spontaneously without medical intervention.

Conclusion: This exploratory single-arm open-label study demonstrated that IVIG is well tolerated and may be associated with improvements in social behavior among children with ASD with immune dysregulation. However, since the primary outcome measure (SRS-2) was caregiver-reported, response bias should be taken into consideration. As an exploratory and hypothesis-generating study, no definitive conclusions regarding therapeutic efficacy or causal relationships can be drawn from these findings. Therefore, its therapeutic efficacy remains inconclusive, and the results should be interpreted with caution. Further multicenter, double-blind controlled trials are warranted to confirm the efficacy of IVIG and explore the underlying mechanisms involved.

Trial registration: chictr.org.cn (registration number ChiCTR2500111846).