Therapeutic Advances in Neurological Disorders最新文献

{"title":"Secondary stroke prevention beyond antiplatelets: The role of colchicine and GLP-1RA - an ounce of prevention is worth a pound of cure.","authors":"Milija D Mijajlović, Natan M Bornstein, Vuk Aleksić","doi":"10.1177/17562864251326769","DOIUrl":"https://doi.org/10.1177/17562864251326769","url":null,"abstract":"<p><p>Stroke remains a major global health concern, ranking as the second most common cause of death and the third leading cause of disability worldwide. Despite advances in therapy and management, ischemic stroke patients continue to face high risks of recurrence, cardiovascular events, and mortality. Effective secondary stroke prevention is critical, encompassing antithrombotic therapy, management of vascular risk factors such as hypertension, dyslipidemia, and diabetes mellitus, and conducting healthy lifestyle. Approximately 80% of strokes are ischemic, with a significant proportion attributable to large-artery atherosclerosis of the extra- and intracranial arteries, particularly in the internal carotid artery. Atherothrombotic strokes, linked to plaque rupture and thrombus formation, present a notably high risk of recurrence. Inflammatory and immune mechanisms play pivotal roles in both the initiation and progression of atherosclerosis and stroke. Colchicine, an anti-inflammatory agent, has shown potential in managing cardiovascular disease, though its effects on stroke reduction and prevention have been inconsistent across studies. Its possible protective role against stroke is attributed to its anti-inflammatory actions, which include disrupting microtubule dynamics, inhibiting immune cell movement, and lowering inflammatory markers like L-Selectin and E-Selectin, while also suppressing interleukin release. Glucagon-like peptide-1 receptor agonists (GLP-1RA) agents have emerged as effective therapies for type 2 diabetes with notable cardiovascular benefits. These agents enhance glucose control while also providing protective effects against atherosclerosis and stroke. GLP-1RA drugs work by mimicking the effects of GLP-1, a peptide that regulates insulin release and glucose metabolism. They also exhibit anti-inflammatory properties, potentially reducing stroke risk through mechanisms such as improved endothelial function and reduced plaque formation. Clinical trials have indicated that GLP-1RA agents can significantly lower the incidence of nonfatal strokes and major adverse events. This narrative review underscores the importance of targeting inflammation to reduce the risk of recurrent stroke, emphasizing recent studies on colchicine and GLP-1RA. It consolidates evidence regarding the efficacy of these agents in secondary stroke prevention; however, future studies are needed to further explore their mechanisms and roles in comprehensive stroke management strategies.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251326769"},"PeriodicalIF":4.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Walking reduces the risk of dementia in patients with Parkinson's disease: a longitudinal follow-up study.","authors":"Cheng-Yu Wei, Ray-Chang Tzeng, Hsu-Chih Tai, Chun-Hsien Su, Pai-Yi Chiu","doi":"10.1177/17562864251330251","DOIUrl":"https://doi.org/10.1177/17562864251330251","url":null,"abstract":"<p><strong>Background: </strong>Physical activity, particularly regular aerobic exercise, is effective in preventing dementia. However, such activities are less feasible for patients with Parkinson's disease (PD) or other motor dysfunctions.</p><p><strong>Objectives: </strong>In this study, we investigated whether the minimal amount of exercise (MAE) through walking, which is practical for individuals with motor dysfunction, can reduce the risk of dementia in patients with PD.</p><p><strong>Design: </strong>For this retrospective longitudinal study, we enrolled 470 patients with PD without dementia from 3 centers in Taiwan.</p><p><strong>Methods: </strong>In total, 187 (39.8%) subsequently developed dementia, whereas 283 (60.2%) did not; the mean follow-up periods for these cohorts were 3.1 (range 0.3-6.1) and 2.4 (range 0.3-6.0) years, respectively. MAE was defined as walking approximately 1500-3000 steps or for 15-30 min. The patients were further stratified by the weekly frequency of MAE into MAE-no (frequency: 0), MAE-weekly (frequency: 1 or 2), and MAE-daily (frequency: ⩾3) groups, respectively. The incidence rates of dementia were compared among the three groups. Cox proportional-hazards analyses were performed to measure the effect of MAE on the incidence of dementia. The statistical model was adjusted for age, sex, education level, cognition level, activities of daily living, neuropsychiatric symptoms, vascular risk factors, and relevant medications.</p><p><strong>Results: </strong>The MAE-weekly and MAE-daily groups were 0.69 (95% confidence interval (CI): 0.41-1.17) and 0.59 (95% CI: 0.41-0.84) times, respectively, less likely to develop dementia than the MAE-no group. When the MAE-weekly and MAE-daily groups were combined, the hazard ratio for dementia was 0.62 (95% CI: 0.45-0.85). Cox regression revealed that older age, female sex, atrial fibrillation, antidiabetic drug use, and poor daily function were associated with an increased incidence of dementia.</p><p><strong>Conclusion: </strong>MAE may help prevent dementia in patients with PD. This finding highlights the benefits of walking for patients with PD and, potentially, older adults with motor dysfunction due to various disorders.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251330251"},"PeriodicalIF":4.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atypical adverse events in a real-world study of long-term immunomodulation for multiple sclerosis and neuromyelitis optica spectrum disorder.","authors":"Amelie Kirschbaum, Felix Luessi, Arda Civelek, Stefan Bittner, Johannes Piepgras, Frauke Zipp","doi":"10.1177/17562864251320206","DOIUrl":"https://doi.org/10.1177/17562864251320206","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapies are integral in managing multiple sclerosis (MS) and related demyelinating diseases, but adverse drug reactions significantly affect the tolerability of disease-modifying therapies (DMTs).</p><p><strong>Objectives: </strong>This study aims to assess the safety profile of DMTs within a real-world cohort affected by MS and related diseases and to identify atypical adverse events (AEs) and those of exceptional severity.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 3850 patients with MS, neuromyelitis optica spectrum disorder (NMOSD), and related conditions (2009-2022). Demographic and clinical data were analyzed for patients treated with DMTs. Parameters included prior treatments, AEs, treatment durations, and reasons for discontinuation.</p><p><strong>Results: </strong>Of the cohort, 1989 patients (71.1% female) with a median follow-up of 46.3 months during DMT use were included. Monotherapy was employed in 987 patients, while 1002 received sequential DMTs, totaling 3850 treatments. Adverse reactions led to discontinuation in 24.2% of cases, while disease progression accounted for 22.9%. Among 1878 AEs, 31 (1.7%) were atypical, and 59 (3.1%) were unusually severe, which was systematically categorized based on type, timing, and remission.</p><p><strong>Conclusion: </strong>Within the confines of this real-world study, DMT administration emerged as generally well tolerated in MS, related demyelinating diseases and NMOSD. The identification of a limited number of atypical AEs, nevertheless, broadens the spectrum of potential complications associated with DMTs. Although weaker evidence for causal associations between drug exposure and observed AEs remains a limitation in observational studies without comparable control groups, this study underscores the value of real-world investigations in offering insights into the long-term safety of DMTs, particularly for rare events.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251320206"},"PeriodicalIF":4.7,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated management of atypical parkinsonism: a home-based patient-centered healthcare delivery based on telenursing-the IMPACT study protocol.","authors":"Roberto Cilia, Fabiana Colucci, Antonio Suppa, Francesca Valentino, Carmen Terranova, Catia Leuzzi, Jessica Cordasco, Giulia Fusi, Simona Floridia, Francesca De Giorgi, Roberta Telese, Arianna Braccia, Alessandro Zampogna, Giulia Pinola, Martina Patera, Giorgio Belluscio, Sara Crivellari, Elisa Antoniazzi, Simona Cascino, Antonio Giaco, Alessio Masaracchio, Giacomina Clara Moreschi, Marisa Catotti, Roberto Eleopra","doi":"10.1177/17562864241299347","DOIUrl":"10.1177/17562864241299347","url":null,"abstract":"<p><strong>Background: </strong>People with atypical parkinsonism, such as multiple system atrophy and progressive supranuclear palsy, experience a wide range of motor and non-motor symptoms associated with the increasing complexity of care delivery and the increased risk of complications and hospital admissions.</p><p><strong>Objectives: </strong>To investigate the efficacy and cost-effectiveness of a 12-month remote home-based integrated program aiming to improve healthcare delivery coordinated by a nurse specialized in the management of individuals with atypical parkinsonism (parkinsonism nurse specialist, PKNS) compared to the standard-of-care model.</p><p><strong>Design: </strong>Multicenter, randomized, single-blind, controlled clinical trial involving 164 individuals with atypical parkinsonism.</p><p><strong>Methods and analysis: </strong>Participants will be randomized 1:1 in intervention (PKNS) and control (standard-of-care) arms. Assessments will be undertaken at baseline and after 6 and 12 months. Primary outcome measure is the Parkinson's Disease Questionnaire 39-items scale total score. Secondary measures include the clinical scales testing motor and non-motor symptoms, caregiver burden, adherence to therapy, cumulative disease burden and the number of unplanned hospital visits/admissions during the study period. The cost-effectiveness of this method will be evaluated by using the EuroQoL-5, which estimates the incremental cost per quality-adjusted life-years gain. Real-life motor autonomy will be objectively measured by collecting waist-worn wearable data on gait parameters (automatically detecting motor patterns indicative of freezing of gait and falls) in all subjects for five consecutive days each month during the 12-month duration of the study.</p><p><strong>Ethic: </strong>Study protocol has been approved by the ethics committee of all participating centers. The study is conducted according to good clinical practice and the Declaration of Helsinki.</p><p><strong>Discussion: </strong>An integrated remote care model at home coordinated by a specialized nurse in the management of parkinsonism (Telenursing) could offer significant benefits to patients and healthcare professionals through better health education, continuity of care, and careful monitoring of complications.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier NCT05792332.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864241299347"},"PeriodicalIF":4.7,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anterior nucleus of thalamus deep brain stimulation for medication refractory epilepsy modulates theta and low-frequency gamma activity: a case study.","authors":"Zachary T Sanger, Xinbing Zhang, Ilo E Leppik, Thomas Lisko, Theoden I Netoff, Robert A McGovern","doi":"10.1177/17562864251323052","DOIUrl":"10.1177/17562864251323052","url":null,"abstract":"<p><p>A 35-year-old gentleman with a traumatic brain injury was diagnosed with refractory epilepsy with electroencephalogram and imaging findings supporting a broad seizure onset pattern in bilateral frontotemporal regions. He therefore received a Medtronic Percept PC Deep Brain Stimulator (DBS) placed bilaterally in the anterior nucleus of the thalamus (ANT). While most refractory epilepsy patients' stimulation parameters use the SANTE trial standard clinical settings of 145 Hz, 90 μs, with cycling 1-min stimulation on and 5 min stimulation off, this participant underwent 7 different stimulation parameter tests at home following testing in the clinic of 24 different stimulation parameters across 12 neurologist visits. This device allows for simultaneous stimulation of the ANT while recording the ANT local field potential (LFP) response under different stimulation parameters. Slepian multitaper analysis, modified Fitting Oscillations, and One Over F method for detrending the aperiodic component were performed to analyze neural oscillations in the frequency domain captured in the clinic. This participant was participating in a clinical study examining the effectiveness of nonstandard DBS settings to minimize broadband neural activity in the ANT. Statistically significant neuromodulatory suppression of gamma oscillations was observed in the clinic under multiple stimulation settings. We compared the ability of these research stimulation parameters to suppress at-home ANT neural activity against the standard clinical settings and examined the effects of both sets of parameters on LFP power nonstationarity. At home, theta/alpha LFP power suppression was statistically significantly reduced under the 125 Hz, 50 μs setting as opposed to the clinical setting of 145 Hz, 90 μs. The participant has achieved greater than 50% seizure reduction for over 1 year since the last neurology visit. Suppression of gamma in the clinic in the right hemisphere and suppression of theta at home in the left hemisphere show promise as quantitative feedback biomarkers for ANT-DBS. Understanding the local and network relationships of theta and slow gamma oscillations in the thalamus would further explain how these modulated oscillations may relate to the onset and propagation of seizures.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251323052"},"PeriodicalIF":4.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efgartigimod for induction and maintenance therapy in muscle-specific kinase myasthenia gravis.","authors":"Yufan Zhou, Qian Zhou, Yaoxian Yue, Sushan Luo, Jie Song, Chong Yan, Dingxian He, Jialong Zhang, Wenhua Zhu, Chongbo Zhao, Huan Yang, Qinzhou Wang, Jianying Xi","doi":"10.1177/17562864251326778","DOIUrl":"10.1177/17562864251326778","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of efgartigimod in treating myasthenia gravis (MG) patients with muscle-specific kinase (MuSK) antibodies has not been demonstrated in the clinical trial, existing case reports, or observational studies.</p><p><strong>Objectives: </strong>To evaluate the efficacy and safety of efgartigimod combined with immunotherapies such as tacrolimus or B-cell depleting agents, as maintenance treatment for MuSK-MG patients.</p><p><strong>Design: </strong>This retrospective study included 14 MuSK-MG patients treated with efgartigimod at three tertiary hospitals from 2023 to 2024.</p><p><strong>Methods: </strong>Data on the activities of daily living (ADL) scores, Quantitative Myasthenia Gravis scores, and the time reaching minimal symptom expression (MSE) were collected. The combined use of steroids, immunosuppressants, and rescue therapies, as well as the adverse event incidence, were also recorded.</p><p><strong>Results: </strong>The mean age at first efgartigimod treatment was 55 ± 18 years old with a median follow-up time of 28 weeks. From baseline to week 4, MG-ADL scores decreased significantly from 10.1 ± 4.0 to 2.2 ± 3.1 (<i>n</i> = 14, <i>p</i> = 0.001). The majority of patients (92.9%) maintains a reduction of at least 2 points for more than 8 weeks. The median time to achieve MSE was 4 weeks, with 71.4% (10/14) of patients reaching MSE by week 12. In patients receiving CD20 B cell depleting therapy or tacrolimus as maintenance, the time-weighted average dosage of prednisone was 16 mg while that in those with prednisone alone was 37 mg. Of all the 14 patients, one developed an upper respiratory tract infection 4 weeks after rituximab (RTX), and one was infected with herpes zoster virus 13 weeks after RTX.</p><p><strong>Conclusion: </strong>A single-cycle efgartigimod as an induction therapy, combined with immunotherapies such as tacrolimus or B cell depleting agents, as maintenance treatment, could benefit MuSK-MG patients.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251326778"},"PeriodicalIF":4.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating natalizumab first-line and later-line use in multiple sclerosis: a US claims database analysis.","authors":"Robin L Avila, Nicole S Croteau, Fei Tang, Jason C Simeone, Khalil Jomaa, Boyang Bian, Mattia Gianinazzi","doi":"10.1177/17562864251317949","DOIUrl":"10.1177/17562864251317949","url":null,"abstract":"<p><strong>Background: </strong>Limited information exists on the healthcare resource utilization (HCRU) associated with real-world natalizumab used as a first-line (1L) versus later-line (2L+) treatment in multiple sclerosis (MS).</p><p><strong>Objectives: </strong>To describe natalizumab use in newly diagnosed MS patients treated as 1L or 2L+ and evaluate unadjusted annualized relapse rates (ARR) and MS-related HCRU before and after treatment initiation.</p><p><strong>Design: </strong>This retrospective observational study utilized Komodo Health Sentinel claims data from October 2015 to August 2022. The study included adults diagnosed with incident MS who initiated natalizumab treatment, with insurance coverage for at least 12 months before diagnosis and 24 months after. The index date was the first natalizumab claim on or after the diagnosis. Baseline was defined as the 365 days prior to the index date, truncated at the time of diagnosis. Follow-up ended at the earliest occurrence of death, insurance disenrollment, treatment discontinuation (gap ⩾45 days), switch to another disease-modifying therapy before natalizumab discontinuation, or study end.</p><p><strong>Methods: </strong>Relapses and HCRU were assessed using person-time methods to account for varying follow-up times. Relapses were identified using a validated claims-based algorithm, and time to first relapse was analyzed using Kaplan-Meier methods. Hazard ratios for relapse were estimated using univariate Cox models. Mean differences (MD) in HCRU between baseline and follow-up and between 1L and 2L+ treatment groups were calculated.</p><p><strong>Results: </strong>A total of 1174 patients in the 1L group (mean age 39.0, 72.0% female) and 394 in the 2L+ group (mean age 39.7, 79.4% female) were included. Patients in the 1L group had a significantly higher baseline ARR (1.48 vs 0.92, <i>p</i> < 0.001) and lower on-treatment ARR (0.28 vs 0.41 for 2L+, <i>p</i> < 0.001). HCRU decreased significantly in the 1L group from baseline to follow-up: hospitalizations (MD 17.01 visits/year), length of stay (LOS; MD 20.96 days/year), emergency room visits (MD 9.83 visits/year), non-natalizumab outpatient visits (MD 12.11 visits/year) and long-term care facility stays (MD 22.18 days/year, <i>p</i> = 0.002). The 1L group showed greater reductions in inpatient visits (MD 10.01 visits//year), LOS (MD 16.73 days/year) and non-natalizumab outpatient visits (MD 11.64 visits/year) compared to the 2L+ group.</p><p><strong>Conclusion: </strong>Natalizumab as a first-line treatment was associated with greater reductions in ARR and MS-related HCRU compared to later-line use.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251317949"},"PeriodicalIF":4.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential use of plasma NfL as a diagnostic and prognostic biomarker of fatigue in early Parkinson's disease.","authors":"Ningning Che, Jingxuan Huang, Shichan Wang, Qirui Jiang, Tianmi Yang, Yi Xiao, Junyu Lin, Jiajia Fu, Ruwei Ou, Chunyu Li, Xueping Chen, Huifang Shang","doi":"10.1177/17562864251324406","DOIUrl":"10.1177/17562864251324406","url":null,"abstract":"<p><strong>Background: </strong>Fatigue is a prevalent non-motor symptom that often appears in the early stages of Parkinson's disease (PD). Plasma neurofilament light chain (NfL) was elevated in PD patients and may be considered a potential biomarker for both motor and cognitive progression.</p><p><strong>Objectives: </strong>In this study, we explored the association between plasma NfL levels and various fatigue subtypes and the prediction of baseline plasma NfL levels for fatigue subtype conversion.</p><p><strong>Methods: </strong>Patients with PD were classified into four categories: persistent fatigue, never fatigue, non-persistent fatigue, and new-onset fatigue. They underwent detailed neurological evaluations at baseline and a 2-year follow-up. Plasma NfL, glial fibrillary acidic protein, phosphorylated tau181, amyloid beta 42, and Aβ40 levels in both PD patients and control subjects were measured using an ultrasensitive single molecule array.</p><p><strong>Results: </strong>The study enrolled 174 PD patients and 95 control subjects. Plasma NfL levels were significantly higher in the persistent fatigue group compared to the never fatigue group at the 2-year follow-up (<i>p</i> <i><</i> 0.05). Longitudinally, 45.16% of baseline fatigue patients converted to non-fatigue at the 2-year follow-up. Additionally, 22.12% of patients initially without-figure patients converted to fatigue patients at the 2-year follow-up. Baseline plasma NfL levels were significantly higher in both the persistent fatigue and new-onset fatigue groups compared to the never fatigue group (<i>p</i> <i><</i> 0.05). Higher baseline NfL levels were significantly associated with new-onset fatigue (odds ratio = 1.127, <i>p</i> = 0.034) after adjusting for confounders.</p><p><strong>Conclusion: </strong>Baseline plasma NfL levels may serve as a biomarker for predicting fatigue subtype conversion and the progression of fatigue in PD.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251324406"},"PeriodicalIF":4.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy-mediated modulation of the gut microbiota in multiple sclerosis and associations with diet and clinical response-the effect of dimethyl fumarate therapy.","authors":"Elsebeth Staun-Ram, Anat Volkowich, Ariel Miller","doi":"10.1177/17562864241306565","DOIUrl":"https://doi.org/10.1177/17562864241306565","url":null,"abstract":"<p><strong>Background: </strong>Accumulating evidence supports a role of the microbiota in health and disease, including in multiple sclerosis (MS). How MS drugs affect the microbiota and whether this is part of their mode of action is yet unknown.</p><p><strong>Objectives: </strong>To assess how dimethyl fumarate (DMF) affects the gut microbiota and whether the microbiota is associated with clinical response or adverse events (AEs) to DMF or diet.</p><p><strong>Design: </strong>An observational cohort study, in which the microbiota from 45 patients with relapsing-remitting MS pre-DMF initiation and following 6 months of DMF therapy, and from 47 matched healthy controls, were compared, and associations with clinical and dietary data assessed.</p><p><strong>Data sources and methods: </strong>Microbial DNA was sequenced and analyzed using MicrobiomeAnalyst. The clinical response was assessed after 1-year DMF therapy based upon evidence of disease activity (relapse, ΔEDSS increase >1, or MRI activity compared to pre-treatment). Dietary data were obtained by food questionnaires.</p><p><strong>Results: </strong>Alterations in relative abundance of several microbes were identified post 6-month DMF therapy compared to pre-treatment, including an increase in Firmicutes, <i>Lachnospiraceae</i>, and <i>Ruminococcaceae</i>, while reduction in Bacteroidetes and Proteobacteria. Patients who showed disease activity within 1 year from DMF initiation had pre-treatment higher abundance of Proteobacteria, <i>Flavonifractor</i>, and <i>Acidaminococcaceae</i>, while lower abundance of Firmicutes, <i>Ruminococcaceae</i>, <i>Butyricicoccus</i>, and <i>Massiliprevotella massiliensis</i>, compared to patients without disease activity. Patients who discontinued DMF therapy due to AEs had pre-treatment higher abundance of Proteobacteria, Bacteroidetes, <i>Eggerthella</i>, and <i>Lachnoclostridium</i> and lower abundance of <i>Ruminococcaceae</i>, <i>Megamonas</i>, and <i>Holdemanella</i>, among others. Differentially abundant microbes correlated with intake of several nutrients.</p><p><strong>Conclusion: </strong>DMF immunotherapy is associated with modifications of the microbiota. The microbiota may affect the severity of AEs and the clinical response to DMF, and is potentially modulated by diet. Microbiota-based, personalized treatment approach, integrating pharmacotherapy with dietary components, carries potential to improved clinical outcome.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864241306565"},"PeriodicalIF":4.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatigue, sleep quality, depression symptoms, and antiseizure medication resistance in patients with newly diagnosed epilepsy.","authors":"Rui Zhong, Teng Zhao, Nan Li, Jing Li, Guangjian Li, Xinyue Zhang, Weihong Lin","doi":"10.1177/17562864251325338","DOIUrl":"10.1177/17562864251325338","url":null,"abstract":"<p><strong>Background: </strong>Complaints of fatigue and poor sleep quality are common in patients with epilepsy. Fatigue may precipitate seizures, and patients with poor sleep quality have higher frequency of seizures and are more likely to have symptoms of depression.</p><p><strong>Objectives: </strong>This study aims to determine the association of baseline fatigue and sleep quality with antiseizure medication (ASM) resistance in patients with newly diagnosed epilepsy (PWNDE). We also evaluate whether the association is mediated by depression symptoms.</p><p><strong>Methods: </strong>We performed a prospective cohort study of PWNDE at comprehensive epilepsy center in Northeast China between June 2020 and May 2024. Fatigue, sleep quality, and depression symptoms were assessed at baseline. All patients were followed for 24 months for ASM-resistant epilepsy. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) of ASM resistance. Models fitted with restricted cubic spline were performed to test for linear and nonlinear shapes of each association. Mediation analysis was used to estimate the mediating effects of depression severity on association between fatigue, sleep quality, and ASM resistance.</p><p><strong>Results: </strong>A total of 189 patients (59 ASM-resistant cases and 130 ASM-responsive controls) were included in the final analysis. Baseline fatigue (HR, 1.98; 95% confidence interval (CI), 1.094-3.583, <i>p</i> = 0.024) and poor sleep quality (HR, 2.193; 95% CI, 1.29-3.729, <i>p</i> = 0.004) were associated with an increased hazard of ASM resistance in PWNDE after full adjustments. There exists a nonlinear association between Fatigue Severity Scale score and the hazard of ASM resistance (<i>P</i> for nonlinear = 0.012). Depression severity partly mediated the effect of fatigue and sleep quality on ASM resistance, with mediated proportions of 18.5% for the fatigue and 23.7% for the sleep quality.</p><p><strong>Conclusion: </strong>Baseline fatigue and poor sleep quality were associated with an increased risk of ASM resistance. The association between fatigue, sleep quality, and ASM resistance were partly mediated by depression severity. These findings emphasize that patients with ASM-resistant epilepsy are more likely to have fatigue, depression, and poor sleep quality at baseline and this may be unrelated to ASM intake.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251325338"},"PeriodicalIF":4.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}