Neurology and Therapy最新文献

Anti-IgLON5 disease is a rare neuronal surface antibody-associated encephalopathy characterized by complex and diverse clinical manifestations, including sleep disturbances, bulbar symptoms, abnormal movements, cognitive decline, and occasionally, neuropsychiatric abnormalities. Immunotherapy is a mainstay of treatment. However, most patients still experience poor outcomes. We report the case of a 72-year-old female who presented with intractable insomnia and progressive mutism. Upon further evaluation, anti-IgLON5 antibodies were detected in both serum and cerebrospinal fluid via cell-based assay, leading to the final diagnosis of anti-IgLON5 disease. The patient failed to improve with intravenous immunoglobulin at the outside hospital; similarly, high-dose intravenous methylprednisolone at our institution yielded no clear benefit. Subsequently, efgartigimod, a neonatal Fc receptor inhibitor, was incorporated into the treatment regimen, resulting in significant clinical improvement, as evidenced by substantial reductions in both the modified Rankin Scale score and anti-IgLON5 disease composite score. To our knowledge, this is the first case report on efgartigimod for treating anti-IgLON5 disease. As an adjuvant therapy, efgartigimod demonstrated promising efficacy, suggesting its potential as a treatment option, especially in patients with limited response to conventional immunotherapy.

Introduction: Cenobamate is a recent therapeutic option for epilepsy, but few studies have investigated its impact on cognitive and emotional/behavioral functioning. The aim of our study was to assess cognitive function, adaptive behavior, quality of life, and parental stress in late adolescents and young adults with tuberous sclerosis complex (TSC) and drug-resistant epilepsy, treated with add-on cenobamate over a 12-month period using standardized neuropsychological tests.

Methods: Our prospective observational study included 22 patients, aged 18 to 24 years with a diagnosis of TSC and drug-resistant epilepsy who started cenobamate add-on therapy for improving seizure control. At baseline and after 3- and 12-month follow-ups, participants completed a neuropsychological standardized assessment of executive functions (Epitrack©), adaptive behavior (VABS-II), quality of life (QOL), and parental stress (PSI). Cognitive functions (WAIS-IV) were reassessed only at the 12-month follow-up. Changes in standardized scores over time were analyzed using Friedman's two-way analysis of variance and post hoc analysis. Relationships between demographic/clinical variables and neuropsychological scores were analyzed using correlation analysis.

Results: Our study highlighted a statistically significant improvement in Epitrack, PSI-4-SF, and QOL scores after 3- or 12-month follow-ups (p < 0.05). Stability was maintained for the WAIS and VABS-II scores. The subjects with TSC2 mutations showed significantly lower IQ scores than those carrying TSC1 mutations (p < 0.001). Total parental stress (PSI) was significantly related to the total score of VABS-II at both baseline (p = 0.003) and 12 months (p = 0.001).

Conclusion: Our study suggested that cenobamate add-on therapy was effective and generally well tolerated in this cohort. Neuropsychological assessments suggest beneficial effects on executive functions, emotional well-being, social functioning, and quality of life. Furthermore, an improvement in parental stress also emerged. These findings could support clinicians in the decision-making process, evaluating cenobamate as an early treatment option in drug-resistant epilepsy.

Introduction: Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by progressive speech and language impairments that impact communication, independence, and psychosocial well-being. People with PPA (PwPPA) and their carers face communication difficulties that lead to social withdrawal. Speech and language therapy (SLT) offers non-pharmacological strategies to support communication, yet evidence regarding its perceived impact on daily life remains limited. This study explored the experiences of PwPPA and their carers following SLT, focusing on perceived changes in communication abilities, confidence, and psychosocial well-being.

Methods: PwPPA participated in a 5-week, tailored telerehabilitation program (Lexical Retrieval Cascade Treatment for logopenic PPA/semantic PPA; Video-Implemented Script Training for nonfluent/agrammatic PPA). Post-treatment questionnaires were developed to collect the opinions of PwPPA and their carers regarding the SLT. The questionnaires included 22 closed-ended Likert-scale items and two open-ended questions for each group. Quantitative data were analyzed for frequency and consistency between PwPPA and carers, while qualitative responses underwent reflexive thematic analysis. Twenty-five PwPPA and 24 carers completed the questionnaires.

Results: Quantitative findings showed consistent perceptions between PwPPA and carers, with approximately 30% reporting improvements in communication confidence, speaking ability, and stress. Thematic analysis revealed four shared themes: reduction in negative emotions/increased self-efficacy, proactivity, acquisition of compensatory strategies, and the importance of the treatment setting and patient-clinician relationship. Additional themes included enhanced communicative effectiveness for PwPPA and increased awareness and improved interpersonal relationships for carers. Participants emphasized the benefits of individualized, supportive therapy delivered in a comfortable environment, including via telerehabilitation.

Conclusion: Our study highlights the positive influence of SLT on both communication and psychosocial outcomes in PwPPA and their carers. Integrating subjective experiences with quantitative measures underscores the importance of person-centered, holistic interventions that address linguistic, emotional, and social dimensions, supporting everyday communication and quality of life.

Introduction: Multiple sclerosis (MS) is an autoimmune-mediated neurodegenerative disorder. The United States Food and Drug Administration recommends using clinical outcome assessments (COAs) to measure concepts that matter to patients in clinical trials and to document the content validity of the COAs using conceptual models of patient experience. This study aimed to explore and document the patient experience of signs, symptoms, and health-related quality of life impacts of relapsing-remitting MS (RRMS) and primary progressive MS (PPMS) to inform future COA validation research.

Methods: We conducted a targeted literature review (TLR) and qualitative semi-structured interviews of patients with RRMS and PPMS in the United States of America (USA). Publications and interview transcripts were analyzed, synthesized, and inductively categorized to develop a conceptual model of patient experiences of RRMS and PPMS.

Results: Ten publications were reviewed as part of the TLR, and 16 participants (RRMS, n = 7; PPMS, n = 9) were interviewed. Most participants reported fatigue, muscle weakness, difficulty walking, sleep disturbance, and bladder issues. Many participants experienced negative emotional, physical, and social impacts due to the disease. Most participants also described needing to rest and plan/avoid activities, as well as requiring support from their family to manage their symptoms.

Conclusion: This study highlights the multidimensional burden of living with RRMS and PPMS. A provisional conceptual model was developed, harmonizing the TLR and interview findings. This conceptual model may be used to promote a better understanding of the patient experience of RRMS and PPMS and to evaluate the content validity of COAs during the development of new drug treatments.

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: Duchenne muscular dystrophy (DMD) is a rare, X-linked neuromuscular disease. The first approved DMD gene therapy, delandistrogene moxeparvovec, was evaluated in the phase 3, two-part, randomized, placebo-controlled EMBARK trial (NCT05096221), which did not meet statistical significance for its primary endpoint assessed at the end of Part 1 (Week 52). To gather patient experience data possibly not captured by traditional clinical outcome assessments, a qualitative in-trial interview substudy was conducted among caregivers (parents) (≥ 18 years) of male patients (≥ 4 to < 8 years with DMD) who completed Part 1 (Week 52) of EMBARK.

Methods: Semi-structured interviews, conducted with 23 parents within 14 days after the last EMBARK Part 1 visit, assessed DMD-related symptoms and impacts prior to EMBARK, perceptions of meaningful outcomes based on hypothetical examples using DMD-specific Caregiver Global Impression measures for Severity (CaGI-S) and Change (CaGI-C), and observed changes during the trial. Initial analyses were blinded to treatment assignment; follow-up analyses examining changes in physical activities were unblinded.

Results: Debriefing questions demonstrated parents' understanding and correct interpretation of items and response options. Most parents indicated that "no change" or a 1-point improvement on CaGI-S items and "no change" or "minimal" improvement on CaGI-C items would be meaningful. Most (n = 17/23) reported improvements in ≥ 1 CaGI-C item 1 year after treatment; for patients receiving delandistrogene moxeparvovec, most parents (n = 7/10) rated ≥ 1 item as "very much" or "much" improved compared with placebo (n = 5/13). These differences were based on descriptive reporting and were not formally tested for statistical significance. Parents identified improvements in physical abilities (i.e., running, climbing stairs, jumping) as the "most important" types of improvement.

Conclusion: These findings underscore the importance of maintaining stability or achieving minimal improvements in treatment outcomes for patients with DMD. Parental experiences and perceptions provided additional insight beyond clinical outcome assessment measures, offering a complementary subjective perspective on treatment impact.

Trial registration: ClinicalTrials.gov identifier, NCT05096221.

Introduction: Widely used to treat multiple sclerosis, dimethyl fumarate (DMF) is a prodrug metabolized in vivo to monomethyl fumarate (MMF) and methanol; the latter is a gastrointestinal (GI) irritant. GI adverse events (AEs) commonly cause DMF discontinuation. Tegomil fumarate (TMF) comprises two MMF moieties joined by tetraethylene glycol, a low molecular polyethylene glycol (PEG). TMF is cleaved in vivo to MMF and the pharmacologically inactive PEG.

Methods: This randomised, double-blind study compared the GI tolerability of TMF 348 mg and DMF 240 mg, administered twice daily, in healthy adults (3:1 female:male ratio) aged 18-55 years. Participants completed daily questionnaires in an electronic diary, including the Modified Overall Gastrointestinal Symptom Scale (MOGISS), Modified Acute Gastrointestinal Symptom Scale, Flushing Symptom Questionnaire and an ad hoc quality of life assessment. The primary endpoint was the area under the curve (AUC) for each individual MOGISS symptom over 5 weeks of treatment. Between-group treatment differences for each MOGISS symptom AUC were analysed using hierarchical testing in a predefined sequence starting with abdominal pain.

Results: The study enrolled 210 participants; the full analysis set comprised 208 (155 females, 53 males). While AUC values were lower for TMF than DMF for most MOGISS symptoms, the between-group difference for abdominal pain was not statistically different (p = 0.0513) so all subsequent statistical analyses were considered exploratory. MOGISS total and composite score, the number of days with symptoms and number of symptoms were lower with TMF than DMF. Fewer participants receiving TMF (57.7%) versus DMF (73.6%) reported GI AEs or discontinued because of GI AEs (TMF n = 0, DMF n = 2).

Conclusions: The between-group difference for the AUC of MOGISS abdominal pain score was not statistically different. However, compared with DMF, TMF showed improved GI tolerability profile in terms of self-assessed GI events and GI AEs leading to discontinuation.

Introduction: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare autoimmune disorder of the peripheral nervous system. While some patients with CIDP respond to standard-of-care treatments, a significant proportion remains refractory or has partial response. Evidence on the disease burden of this patient group is limited. This retrospective study aimed to analyze the demographics, clinical characteristics, and healthcare resource use of patients with CIDP in the United States, focusing on those who switched therapies within 2 years of initiating first-line treatment (LOT1).

Methods: Integrated data from the Optum^® de-identified Market Clarity dataset were used to identify adults diagnosed with CIDP from 2008-2020.

Results: The CIDP cohort included 1942 treated patients (54% male, 75% aged ≥ 50 years). LOT1 included immunoglobulins (43%), corticosteroids (32%), combination of immunoglobulins and corticosteroids (11%), immunosuppressants (10%), and plasma exchange (5%). Within 2 years, 31% patients switched to second-line treatment (LOT2). The median time to switch from LOT1 to LOT2 was 5.6 months. Within 2 years after initiating LOT1, 92% patients had outpatient visits and 40% were hospitalized. Patients who switched treatments had more healthcare visits than those who did not switch (45.3 vs. 35.3/year).

Conclusion: Approximately one-third of the patients switched to a new treatment within 2 years after starting treatment, which could be partly due to limited efficacy of therapies in LOT1. The decrease in treatment duration after LOT1 may suggest limited utility of subsequent therapies. Frequent treatment changes and increased healthcare encounters in this subgroup highlight significant unmet needs in CIDP.

Introduction: AXIN1 (axis inhibition protein 1), as a rate-limiting component of canonical Wingless-type mouse mammary tumor virus integration site (Wnt)/β-catenin signaling pathway, may influence midbrain dopaminergic neurons. A recent genome-wide association study identified AXIN1 as a candidate gene for Parkinson's disease (PD). Our study aimed to investigate the potential relevance of AXIN1 single nucleotide polymorphisms (rs13337493 and rs9921222) in the risk, clinical characteristics, and pathology of PD.

Methods: Data were collected from the Northern Han Chinese and Parkinson's Progression Markers Initiative (PPMI) cohorts. Associations between AXIN1 variants, PD-related biomarkers, and clinical manifestations were analyzed.

Results: Both loci were identified as risk factors in the Northern Han Chinese population, and the A allele of rs13337493 [odds ratio (OR) 1.320, 95% confidence interval (CI) 1.052, 1.653, P_c = 0.036] and the T allele of rs9921222 (OR 1.351, 95% CI 1.045, 1.747, P_c = 0.042) showed increased susceptibility to PD. The risk effect of rs9921222 was predominant in the male cohort (OR 1.504, 95% CI 1.058, 2.139, P_c = 0.044). Rs13337493 was related to worse motor function in white individuals, which was represented by the Hoehn & Yahr stage (OR 2.775, 95% CI 1.195, 6.447, P_c = 0.036). It also correlated with compensatory elevation of cerebrospinal fluid (CSF) 3,4-dihydroxyphenylalanine (DOPA, β = 0.040, 95% CI 0.007, 0.073, P_c = 0.038).

Conclusion: Our findings support a gatekeeper role for AXIN1; its polymorphisms contribute to increased PD susceptibility and accelerated motor progression, yet may also trigger a compensatory presynaptic response, as evidenced by elevated CSF DOPA levels, to counteract neurodegeneration. Future studies should include larger sample sizes, more diverse ethnic populations, and protein-level investigations.

Introduction: Calcitonin gene-related peptide (CGRP) pathway-targeted monoclonal antibodies (mAbs) are first-line treatment options for migraine prevention. Data on persistence and patient-reported outcomes including satisfaction are limited. This real-world study aimed to report the experience of patients prescribed ≥ 1 self-injectable anti-CGRP mAb in a large United States healthcare network.

Methods: The Migraine Signature Study, an observational study, conducted at Sutter Health, utilized electronic health records (EHRs) to identify adult patients with migraine who were prescribed ≥ 1 self-injectable anti-CGRP mAb. These patients were invited to participate in a survey (October-December 2020) on sociodemographics, migraine attack characteristics, treatment patterns, and patient-reported outcomes, including the Migraine Disability Assessment Scale (MIDAS) and 4-item Migraine Interictal Burden Scale (MIBS-4). EHRs were used to assess persistence/discontinuation.

Results: Of 4683 eligible patients with migraine, 484 (10.3%) completed the survey. More than half (51%) were 30-54 years old, female (89.1%), and non-Hispanic white (79.1%). Most (53.5%) reported 1-10 headache days in the previous month; 58.2% had moderate or severe migraine-related disability. A total of 430 respondents reported having used ≥ 1 anti-CGRP mAbs, comprising 547 reports of anti-CGRP-mAb experience, 319 (58.3%) current use, and 228 (41.7%) past use. Among participants with prescription-dispensing data (n = 338), ongoing refills were documented for ≥ 2 months in 90.2%, ≥ 6 months in 73.7%, and ≥ 12 months in 54.7%. Greater reduction in number of headache/migraine attacks (62.1% vs. 17.5%), improved ability to function (62.1% vs. 18.0%), and better quality of life (62.4% vs. 17.5%) was reported for current use versus past.

Conclusion: Among patients who dispensed ≥ 1 anti-CGRP mAb for migraine, rates of sustained treatment over the course of a year were higher than expected; ~ 75% continued their index mAb at 6 months and > 50% at 12 months. Patients using anti-CGRP mAbs at the time of the survey reported higher satisfaction than patients who had discontinued anti-CGRP mAb.