Therapeutic Advances in Neurological Disorders最新文献

Background: Tobacco smoking is an established risk factor for accelerated multiple sclerosis (MS) progression and worse MS symptoms. Generic smoking cessation programs might not fully meet the needs of people with MS (pwMS), as they don't address MS-specific barriers influencing smoking behavior (e.g., worries about relapses when quitting). Yet, no MS-specific smoking cessation interventions have been evaluated.

Objective: This study aimed to develop an MS-specific smoking cessation intervention.

Design: This is an intervention development and initial feasibility study, informed by the Behavior Change Wheel and the design and evaluation framework for digital health interventions, which have been successfully utilized before, including in MS contexts.

Method: Between January and December 2024, we developed MS-specific information videos to supplement an existing smoking cessation intervention. We used identified intervention functions and results from preceding studies to identify the most effective way to change smoking behavior in pwMS. For the evaluation of the videos, we developed a theory-based questionnaire, and recruited pwMS and MS experts via our MS day clinic for assessment. The evaluation informed final revised videos for integration into the existing program to form a MS-tailored smoking cessation intervention.

Results: We identified five out of nine intervention functions from the behavior change wheel to be relevant and created six videos based on these functions. The content of the videos includes, among other things, education about the connection of smoking and MS, and persuasion and incentivization about the positive effects of quitting. Eleven pwMS and five MS experts assessed the material. Overall, the videos were perceived as understandable and appropriate in length in both groups. The modified smoking cessation intervention includes all videos, integrating them into a structure of five online-meetings across 3 weeks.

Conclusion: The successful development of education videos using the Behavior Change Wheel, as well as the positive findings from our feasibility testing underline the potential of our video-based approach in the context of smoking cessation for pwMS. Next, the modified smoking cessation intervention should be tested for feasibility, acceptability, and efficacy. If successful, this approach could be implemented widely for people with MS.

Background: Two principal methods for detecting anti-John Cunningham virus (JCV) antibodies are currently utilized in clinical practice: STRATIFY JCV™, an ELISA developed by Biogen, and IMMUNOWELL™, a solid-phase ELISA assay by Polpharma Biologics/GenBio.

Objective: We aimed to evaluate the concordance between STRATIFY and IMMUNOWELL in detecting anti-JCV antibodies in a real-world population of patients with relapsing-remitting multiple sclerosis (RRMS) undergoing natalizumab therapy.

Design: This monocentric observational study screened all patients treated with natalizumab for at least 6 months, referring to the MS Center of the University Hospital of Catania.

Methods: Each patient's serum was tested simultaneously using STRATIFY-2 (STRATIFY JCV DxSelect) and IMMUNOWELL assays. The qualitative results (positive/negative) were compared, and the index values were analyzed using Pearson's correlation and Bland-Altman plots. Inter-method agreement was calculated using Cohen's kappa coefficient.

Results: Among the 120 patients tested, 82 were positive and 31 negative with both STRATIFY and IMMUNOWELL. Four cases were STRATIFY-negative but IMMUNOWELL-positive, and three were the opposite. Overall concordance was 94.2%, with a Cohen's Kappa of 0.86, indicating strong agreement. The index values showed strong correlation (Pearson r = 0.79, p < 0.001) and the coefficient of determination (r ²) was 0.62.

Conclusion: STRATIFY and IMMUNOWELL demonstrate a high level of agreement in the detection of anti-JCV antibodies in patients with RRMS receiving natalizumab. IMMUNOWELL may serve as a reliable complementary method, especially in cases where borderline serostatus could influence therapeutic strategy. Regular and accurate monitoring of JCV status remains essential for guiding long-term treatment safety and optimizing individual patient outcomes.

Background: Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder globally. Deep brain stimulation (DBS) has become a critical therapeutic option for advanced PD. The efficacy of DBS has been well established for up to 1 or 2 years; however, long-term outcome data for Chinese cohorts are limited, and the duration of the "DBS honeymoon" remains underexplored.

Objective: This study aimed to evaluate the long-term efficacy (⩾10 years) of subthalamic nucleus (STN)-DBS in patients with PD in Southern China, and to investigate the duration of "DBS honeymoon."

Design: Retrospective study.

Methods: Thirty-one patients who underwent bilateral STN-DBS between 2010 and 2011 were assessed. Motor symptoms were evaluated using the Unified Parkinson's Disease Rating Scale-Part III (UPDRS-III) in the off- and on-medication states with stimulation. Nonmotor symptoms and the quality of life (QOL) were measured using validated scales. The levodopa equivalent daily dose (LEDD), stimulation parameters, and adverse events were recorded. Genetic testing was performed for seven patients.

Results: Thirteen patients completed the follow-up at 1, 3, and ⩾10 years. The UPDRS-III (off-state) scores improved by 53.02%, 44.79%, and 22.56% at 1, 3, and ⩾10 years, respectively. Tremor and rigidity showed sustained improvement; sleep remained stable postoperatively. In contrast, emotion, cognition, and QOL improved at 3 years; however, they returned to baseline or declined beyond 10 years. The LEDD reductions were 36.29%, 40.40%, and 29.10% at 1, 3, and ⩾10 years, respectively. Stimulation frequency decreased from 141.70 ± 15.72 Hz at 1 year to 110.00 ± 18.22 Hz ⩾10 years. Additionally, genetic testing identified three mutation carriers and rare complications such as DBS withdrawal syndrome appeared beyond 10 years.

Conclusion: STN-DBS provided sustained motor improvement, with tremor and rigidity showing the most significant benefits after 10 years. The initial 3 years likely represented a "DBS honeymoon," with peak improvements in motor and nonmotor symptoms. Genotype may influence the efficacy of DBS, and monitoring rare complications is essential. These findings should be interpreted with caution, given the small sample size and the retrospective design of the study.

Chimeric antigen receptor T-cells (CAR T-cells) have revolutionized the treatment of hematologic malignancies and are now being explored in autoimmune diseases, including neuroimmunological disorders. The first clinical applications of CAR T-cell therapy for autoimmune diseases have demonstrated promising efficacy, particularly in systemic lupus erythematosus and myasthenia gravis. While CAR T-cell therapy can induce profound B-cell depletion, leading to durable remission, concerns remain regarding cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. However, neuroimmunological conditions with lower target cell burdens may carry a reduced risk of these adverse events. Recent evidence suggests CAR T-cells could offer a transformative approach for stiff-person syndrome (SPS), a rare but debilitating autoimmune neurological disorder characterized by muscle rigidity and spasms. The first reported case of anti-CD19 CAR T-cell therapy in a treatment-refractory SPS patient resulted in substantial clinical improvement, including increased mobility and reduced dependence on symptomatic medication. A newly launched phase II clinical trial (NCT06588491) aims to further evaluate the safety and efficacy of anti-CD19 CAR T-cell therapy in SPS. In this review, we examine the current evidence supporting the use of CAR T-cells in neuroimmunological conditions, discuss the clinical picture and pathophysiological processes associated with stiff person spectrum disorders (SPSD), and elaborate on perspectives and limitations of CAR T-cell therapy in SPSD and beyond.

Background: Perampanel (PER) is effective in treating focal and generalised seizures. The PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) Extension study was a large, pooled analysis of PER clinical practice studies that assessed the effectiveness and safety/tolerability of PER in over 6800 people with epilepsy.

Objectives: To determine clinical factors associated with PER retention, response, seizure freedom and tolerability when used in clinical practice.

Design: An exploratory post hoc analysis of data from all individuals included in PERMIT Extension.

Methods: Univariate and multivariable logistic regression analyses were performed to identify baseline factors associated with retention rate, responder rate (⩾50% seizure frequency reduction), seizure freedom rate (no seizures since at least the previous visit) and incidence of adverse events (AEs).

Results: A total of 6822 people with epilepsy treated with PER were included. Baseline factors associated with retention were absence of psychiatric comorbidity (odds ratio [95% confidence interval], 1.99 [1.403-2.825]; p < 0.001), fewer focal seizures (1.01 [1.004-1.014]; p < 0.001) and fewer previous antiseizure medications (ASMs; 1.06 [1.013-1.119]; p = 0.013). Factors associated with response were absence of focal seizures (2.12 [1.532-2.924]; p < 0.001), fewer previous ASMs (1.19 [1.136-1.250]; p < 0.001) and absence of concomitant sodium channel blocker (SCB) ASM(s) (1.96 [1.455-2.628]; p < 0.001). Factors associated with seizure freedom were fewer total seizures (1.04 [1.020-1.061]; p < 0.001), absence of focal seizures (3.45 [2.387-4.979]; p < 0.001), fewer previous ASMs (1.11 [1.028-1.205]; p = 0.008), absence of concomitant SCB ASM(s) (1.46 [1.051-2.028]; p = 0.024) and absence of concomitant gamma-aminobutyric acid (GABA)-ergic ASM(s) (2.08 [1.266-3.412]; p = 0.004). Factors associated with occurrence of AEs were older age (1.01 [1.006-1.015]; p < 0.001), longer epilepsy duration (1.01 [1.010-1.012]; p = 0.044), presence of psychiatric comorbidity (1.74 [1.469-2.062]; p < 0.001) and greater number of previous ASMs (1.09 [1.069-1.119]; p < 0.001).

Conclusion: This study identified clinical factors associated with PER's real-world effectiveness and tolerability, which may help inform treatment decisions in clinical practice.

Background: The ADAPT trial demonstrated the benefit of efgartigimod, a neonatal Fc receptor (FcRn) inhibitor, in acetylcholine receptor antibody (AChRAb) positive patients with generalized myasthenia gravis (MG). Information regarding the benefits in those lacking pathogenic antibodies is sparse.

Objectives: We aimed to investigate the safety and efficacy of efgartigimod in patients with double-seronegative (SN) generalized MG.

Design: An open-label 6-month prospective study, conducted at our center.

Methods: Patients aged at least 18 years with clinical and electrodiagnostic features of MG and negative results for AChRAb and muscle-specific tyrosine kinase antibodies were included. Efgartigimod was administered weekly for 4 weeks and then biweekly for 5 months followed by an observation period. The primary endpoint was the change in MG impairment index (MGII) at 6 months compared to baseline. Secondary endpoints include the change in MG activities of daily living (MG-ADL), other MG scores, overall responders, and early responders. The safety analysis included all patients who received at least one dose of efgartigimod.

Results: We enrolled 30 patients with SN MG who were resistant to other treatments and had unacceptable MGII scores. The MGII decreased by 11.92 points (p < 0.01) with efgartigimod treatment. The MG-ADL also improved. Seventy-two percent of patients were responders with 31% being early responders. Adverse events were reported in 83.3% of patients, and in 90.6%, they were mild. Headache was the most common, reported in 26.7%, followed by flu/common cold in 20%, and urinary tract infection in 13.3%.

Conclusion: Efgartigimod was well tolerated and efficacious in patients with SN MG. Future randomized, placebo-controlled studies are needed.

Trial registration: This trial is registered at ClinicalTrials.gov (NCT06587867), accessed via https://clinicaltrials.gov/study/NCT06587867?locStr=Toronto,%20ON,%20Canada&country=Canada&state=Ontario&city=Toronto&cond=Myasthenia%20Gravis&intr=efgartigimod&rank=1.

Background: Stiff person syndrome spectrum disorders (SPSD) are a disabling group of immune-mediated disorders that most commonly cause progressive rigidity and painful spasms. Botulinum neurotoxin (BoNT) has anecdotally improved SPSD symptoms, though evidence regarding treatment strategy and clinical efficacy is scarce.

Objectives: To characterize the location, frequency, dosage, and clinical response to BoNT injections in patients with SPSD.

Design: We conducted a retrospective observational cohort study.

Methods: SPSD patients who received BoNT treatments between August 2018 and February 2024 were included. Detailed information about the injections (formulation, dose, muscle), subjective patient-reported response, and concurrent therapies was recorded and compared between the first, third, and eighth BoNT visits.

Results: Thirty-seven SPSD patients were included. The majority had classic SPS (83.8%), were female (67.7%), white (78.4%), and on immune therapies (70.3%). The paraspinal muscles, hip flexors, distal leg flexors, and shoulder girdle muscles were most frequently injected. Supramaximal total doses up to 980 units of BoNT were used safely. The most common side effect was transient worsening of pain/spasms, which resolved with peak dose effect. Subjective clinical response was positive, with a median patient-reported 5-point Likert rating of 4, 5, and 5 after visits 1, 3, and 8.

Conclusion: BoNT may be an effective and durable adjunctive symptomatic therapy for people with SPSD with targeted muscle selection based on specific symptomatology. Injections into multiple body regions and use of supramaximal dosages may be required for adequate symptom control in this patient population. As our data lacked objective measures and relied on semiqualitative self-reported patient responses, conclusions about the utility of BoNT are limited and randomized placebo-controlled trials are needed to evaluate the impact of BoNT on improving quality of life, mobility, and burden of systemic symptomatic treatment.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy characterized by autoantibodies against aquaporin-4 (AQP) that predominantly affecting women of childbearing potential. Unlike multiple sclerosis, NMOSD poses a higher risk of severe and irreversible postpartum relapse, making pregnancy a significant concern in affected women. Historically, in Japan, immunosuppressive treatments were contraindicated in women who could become pregnant, leading many to discontinue therapy before conception. This often resulted in relapse and sometimes required pregnancy termination or abandonment. At present, immunosuppressants such as azathioprine, tacrolimus, and cyclosporine are considered beneficial during pregnancy. Five monoclonal antibody therapies have now been approved and are covered by national insurance for the treatment of NMOSD. These developments have expanded treatment options, enabling safer pregnancies and allowing more women with NMOSD to consider childbirth. To ensure optimal outcomes, individualized, evidence-based treatment plans are essential. Shared decision-making between patients and healthcare providers is critical, particularly when evaluating the safety of monoclonal antibody therapies during pregnancy and their potential impact on fetal development. This review outlines recent insights into the impact of NMOSD on patients of childbearing age, including family planning, postpartum management, and breastfeeding. It emphasizes the importance of balancing disease control with reproductive goals through informed and collaborative care strategies that also encompass AQP4-antibody-negative NMOSD and myelin oligodendrocyte glycoprotein antibody-associated disease.

Background: Idiopathic intracranial hypertension (IIH) is a condition with elevated intracranial pressure, leading to headaches and vision issues. Current treatments offer limited relief. Glucagon-like peptide-1 (GLP-1) agonists, known for their established metabolic benefits including weight loss and an emerging potential to lower intracranial pressure, may provide a novel approach for managing IIH.

Objectives: This systematic review and meta-analysis aimed to assess the effectiveness of GLP-1 agonists in improving IIH symptoms.

Design: A systematic review and meta-analysis.

Data sources and methods: A systematic search of PubMed, Scopus, Web of Science, and Cochrane was conducted until March 2025. Dichotomous outcomes were pooled using risk ratio (RR), while continuous outcomes were pooled using standardized mean difference. PROSPERO ID: CRD420251008614.

Results: The meta-analysis of four studies assessed the efficacy of GLP-1 agonists across various outcomes. Results showed a significant reduction in Body Mass Index (BMI) over 24 months, with mean differences of -0.36, -1.08, -1.18, and -1.42 at 3, 6, 12, and 24 months, respectively, with 95% CI, and low heterogeneity (I² = 0.0%). GLP-1 agonists also reduced headache risk, with the most significant effect at 3 months (RR: 0.69), remaining statistically significant at 6, 12, and 24 months. The risk of papilledema was reduced across all time points, with the lowest RR at 3 months (RR: 0.69 (95% CI: 0.55, 0.86)), and the effect remained significant through 24 months. Additionally, GLP-1 agonists consistently reduced the risk of visual disturbances and refractory IIH, with statistically significant effects sustained up to 24 months, demonstrating a sustained benefit throughout the treatment period.

Conclusion: This meta-analysis demonstrates that GLP-1 receptor agonists are a promising therapeutic option for patients with IIH, demonstrating significant efficacy in reducing intracranial pressure-related symptoms such as BMI, headache frequency, papilledema, and visual disturbances.