Therapeutic Advances in Neurological Disorders最新文献

{"title":"The impact of COVID-19 infection on multiple sclerosis disease course across 12 countries: a propensity-score-matched cohort study.","authors":"David Levitz, Yi Chao Foong, Paul Sanfilippo, Tim Spelman, Louise Rath, Angie Roldan, Anoushka Lal, Mastura Monif, Vilija Jokubaitis, Serkan Ozakbas, Raed Alroughani, Cavit Boz, Murat Terzi, Tomas Kalincik, Yolanda Blanco, Matteo Foschi, Andrea Surcinelli, Katherine Buzzard, Olga Skibina, Guy Laureys, Liesbeth Van Hijfte, Cristina Ramo-Tello, Aysun Soysal, Jose Luis Sanchez-Menoyo, Mario Habek, Elisabetta Cartechini, Juan Ignacio Rojas, Rana Karabudak, Barbara Willekens, Talal Al-Harbi, Yara Fragoso, Tamara Castillo-Triviño, Danny Decoo, Maria Cecilia Aragon de Vecino, Eli Skromne, Carmen-Adella Sirbu, Chao Zhu, Daniel Merlo, Melissa Gresle, Helmut Butzkueven, Anneke Van Der Walt","doi":"10.1177/17562864241278496","DOIUrl":"https://doi.org/10.1177/17562864241278496","url":null,"abstract":"<p><strong>Background: </strong>The relationship between coronavirus disease 2019 (COVID-19) infection and multiple sclerosis (MS) relapse and disease progression remains unclear. Previous studies are limited by small sample sizes and most lack a propensity-matched control cohort.</p><p><strong>Objective: </strong>To evaluate the effect of COVID-19 infection on MS disease course with a large propensity-matched cohort.</p><p><strong>Design: </strong>This multi-centre cohort study analysed relapse and disability outcomes post-COVID-19 infection after balancing covariates using a propensity score matching method. The study period was from the 11th of September 2019 to the 16th of February 2023. The mean follow-up period was 1.7 years.</p><p><strong>Methods: </strong>Data were retrieved from the MSBase Registry. Propensity scores were obtained based on age, sex, disease duration, baseline Expanded Disability Status Scale (EDSS), MS course, relapses pre-baseline, disease-modifying therapy (DMT) class and country. Primary outcomes were time to first relapse, annualised relapse rate (ARR) and time to confirm EDSS progression. Secondary outcomes were time to EDSS of 3, 4 or 6. Sensitivity analyses with baseline DMT classes were performed.</p><p><strong>Results: </strong>The study included 2253 cases and 6441 controls. After matching, there were 2161 cases and an equal number of matched controls. Cases had a significantly higher ARR (ARR = 0.10 [95% CI 0.09-0.11]) compared to controls (ARR = 0.07 [95% CI 0.06-0.08]). Cases had a significantly greater hazard of time to first relapse compared to controls (hazard ratio (HR) = 1.54 [95% CI 1.29-1.84]). There was no association between COVID-19 infection and 24-week EDSS progression (HR = 1.18 [95% CI 0.92-1.52]), or time to EDSS of 3, 4 or 6. For patients on interferons and glatiramer acetate (BRACE), COVID-19 infection was associated with a greater hazard of time to first relapse (HR = 1.83 [95% CI 1.25-2.68]) and greater hazard of time to EDSS of 3 (HR = 2.04 [95% CI 1.06-3.90]) compared to patients on BRACE therapy without COVID-19 infection.</p><p><strong>Conclusion: </strong>COVID-19 infection was associated with a significantly increased MS relapse rate and a shorter time to first relapse. There was no effect on confirmed EDSS progression over the short term. These results support ongoing COVID-19 risk minimisation strategies to protect patients with MS.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241278496"},"PeriodicalIF":4.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628952","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":"SCALA: a randomized phase I trial comparing subcutaneous and intravenous alemtuzumab in patients with progressive multiple sclerosis.","authors":"Xavier Montalban, Breogan Rodriguez-Acevedo, Carlos Nos, Mireia Resina, Mireia Forner, Yanzhen Wu, Magdalena Chirieac","doi":"10.1177/17562864241291655","DOIUrl":"https://doi.org/10.1177/17562864241291655","url":null,"abstract":"<p><strong>Background: </strong>Alemtuzumab is administered intravenously (IV) for relapsing-remitting multiple sclerosis (RRMS), with limited studies of subcutaneous (SC) treatment.</p><p><strong>Objectives: </strong>We sought to evaluate the pharmacodynamics (PD), pharmacokinetics (PK), and safety profile of SC-administered alemtuzumab in people with progressive multiple sclerosis (PMS).</p><p><strong>Design: </strong>SCALA was a phase I, open-label, randomized, parallel-group study with two 12-month periods and a safety monitoring phase to 60 months.</p><p><strong>Methods: </strong>Of 29 screened participants, 24 were enrolled and randomized 2:1 to two 12 mg/day alemtuzumab treatments (60 and 36 mg total; SC:IV). Key inclusion criteria: ⩾18 years with a PMS diagnosis. Key exclusion criteria included RRMS diagnosis and prior treatment with anti-CD52 antibodies. Primary endpoint: CD3⁺ lymphocyte count. Secondary endpoints: PD and PK parameters.</p><p><strong>Results: </strong>Demographics were broadly similar for participants in the SC (16) and IV (8) arms; more participants with primary PMS received SC (44%) versus IV (25%) treatment. After the first course, the mean CD3⁺ cell count/µL was reduced at month 1 in both arms (SC: baseline (BL) 1326 to 48 vs IV: BL 1155 to 84). Lymphocyte counts partially repopulated by month 12, with mean CD3⁺ cell counts/µL of SC 599 versus IV 528. The mean lymphocyte counts/µL decreased again after the second course at month 13 in both arms (SC: 90 vs IV: 129), with partial repopulation by month 24. Alemtuzumab serum concentrations were lower following SC administration relative to IV, with 32% bioavailability. There were no adverse events leading to permanent treatment discontinuation or death.</p><p><strong>Conclusion: </strong>In SCALA, there were similar patterns of lymphocyte depletion and repopulation for participants receiving SC or IV alemtuzumab. In both arms, alemtuzumab had a manageable safety profile, with no emerging safety concerns. The general stabilization of neurological outcomes observed over 60 months underscores the potential long-term benefits of alemtuzumab treatment.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov identifier: NCT02583594.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241291655"},"PeriodicalIF":4.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605310","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":"Identification of alemtuzumab-suitable multiple sclerosis patients in Slovakia and sequencing of post-alemtuzumab immunomodulatory treatment.","authors":"Ema Kantorová, Marianna Vítková, Martina Martiníková, Andrea Cimprichová, Miriam Fedicˇová, Slavomíra Kovácˇová, Miroslav Mako, Juraj Cisár, Viera Hancˇinová, Jarmila Szilasiová, Peter Koleda, Jana RoháIˇová, Jana Polóniová, Martin Karlík, Darina Slezáková, Eleonóra Klímová, Matúš Maciak, Egon Kurcˇa, Petra Hnilicová","doi":"10.1177/17562864241285556","DOIUrl":"10.1177/17562864241285556","url":null,"abstract":"<p><strong>Background: </strong>Alemtuzumab (ALEM) is a humanised monoclonal antibody that depletes circulating lymphocytes by selectively targeting CD52, which is expressed in high levels on T- and B-lymphocytes. This depletion is followed by lymphocyte repopulation and a cytokine expression shift towards a lesser inflammatory profile, both of which may contribute to prolonged efficacy. National recommendations for enrolling and treating multiple sclerosis (MS) patients with ALEM have been established. However, there are no recommendations in place for the treatment of MS reactivation after the ALEM treatment.</p><p><strong>Objectives: </strong>To evaluate the effectiveness and safety of the use of ALEM and to analyse subsequent disease-modifying treatments (DMTs). A multidimensional prediction model was developed to make a patient-specific prognosis regarding the response to ALEM.</p><p><strong>Design: </strong>A multicentre, prospective, non-controlled, non-interventional, observational cohort study.</p><p><strong>Methods: </strong>Relapsing multiple sclerosis patients (RMSp) who received ⩾1 dose of ALEM were enrolled. In each treatment year, the following baseline and prospective data were collected: age, MS history, number, type and duration of previous disease-modifying treatment (PDMT), relapse rate (REL), expanded disability status scale (EDSS), magnetic resonance imaging and serious adverse events (AE). In cases of reactivation of MS, all data about the subsequent DMT were collected.</p><p><strong>Results: </strong>A total of 142 RMSp from 10 MS Slovak Centres fulfilled the inclusion criteria. The average age was 35 years (standard error 8.56). The overall average EDSS was 3.87 (1.46) when ALEM was started. The average duration of PDMT was 6.0 (4.04) years, and the median number of PDMTs was 3 (0-5), while the patients were mostly treated with 2 or 3 DMTs (>65.00%). Post-ALEM treatment was needed in 39 cases (27.46%). The most frequent post-ALEM treatment indicated was ocrelizumab, followed by natalizumab (NAT), siponimod and cladribine. The ocrelizumab and NAT treatment bring little benefit to patients. Siponimod showed less EDSS increase in contrast to ocrelizumab and NAT. Another repopulation therapy, cladribine, may also be an effective option. Statistically significant predictors for the expected EDSS are age (<i>p</i>-value <0.0001), number of ALEM cycles (0.0066), high number of PDMT (0.0459) and the occurrence of relapses (<0.0001). There was no statistically significant effect on the patient's gender (0.6038), duration of disease-modifying treatment before alemtuzumab (0.4466), or the occurrence of AE (0.6668).</p><p><strong>Conclusion: </strong>The study confirms the positive effect of ALEM on clinical and radiological outcomes. We need more data from long-term sequencing studies.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241285556"},"PeriodicalIF":4.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569645","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":"Link between post-stroke psychopathology and scope-of-action awareness.","authors":"Benjamin Stahl, Kristina Becker, Kevser Kocyigit, Petra Denzler, Paula Röder","doi":"10.1177/17562864241282633","DOIUrl":"10.1177/17562864241282633","url":null,"abstract":"<p><strong>Background: </strong>Epidemiological research has failed to confirm laterality of lesion site as a neurobiological source of post-stroke psychopathology. However, acquired communication disorders have proved to be a key risk factor for depression, apart from established parameters such as pre-stroke psychopathology and physical immobility.</p><p><strong>Objectives: </strong>The present work examines a new predictor of post-stroke psychopathology: psychological flexibility. This concept describes an accepting attitude toward irreversible loss following stroke while using remaining agency.</p><p><strong>Design: </strong>Overall, 70 individuals engaged in a cross-sectional study conducted in the subacute stage after an ischemic or hemorrhagic event, a period with elevated prevalence of mental-health problems (2 weeks to 6 months after stroke).</p><p><strong>Methods: </strong>Outcomes included standardized self-report and clinician-rated measures of depression, anxiety disorders, and general psychopathology (Beck Depression Inventory; Hospital Anxiety and Depression Scale; ICD-10 Symptom Rating; Hamilton Depression Rating Scale) alongside lack of psychological flexibility (Acceptance and Action Questionnaire II). The study design controlled for pre-stroke psychopathology and physical immobility (Barthel Index).</p><p><strong>Results: </strong>Partial correlation analyses revealed a significant medium-to-large association between the entire set of clinical outcomes and lack of psychological flexibility (<i>r</i> ⩽ 0.62, <i>p</i> < 0.001). In moderator analyses, the magnitude of this association did not vary significantly with diagnosis of acquired communication disorders (i.e., aphasia, apraxia of speech or dysarthria; separately or combined).</p><p><strong>Conclusion: </strong>The current results demonstrate a substantial link between post-stroke psychopathology and psychological flexibility. This finding opens new avenues for research on depression and other mental-health problems in stroke survivors with and without acquired communication disorders.</p><p><strong>Registration: </strong>www.drks.de; identifier: DRKS00031204.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241282633"},"PeriodicalIF":4.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569649","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":"Therapeutic effect of an inhaled levodopa dry powder formulation on off episodes in patients with Parkinson's disease.","authors":"Lara de Jong, Marianne Luinstra, Angela Francesca Aalbers, Alide Johanna Wijma-Vos, Emile D'Angremont, Anne Aline Elisabeth van der Meulen, Antonie Wijnand Frederik Rutgers, Luc Steenhuis, Paul Hagedoorn, Teus van Laar, Hendrik Willem Frijlink","doi":"10.1177/17562864241289207","DOIUrl":"10.1177/17562864241289207","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Limited treatment options with a rapid onset of action are available to treat off episodes in Parkinson's disease (PD) patients. Therefore, the development of rapid onset formulations, for instance with levodopa, is warranted, which was the reason to investigate an inhalable formulation of levodopa.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;The primary objective was to determine the duration until maximum effect is reached of inhaled levodopa on the improvement of motor function of PD patients. The secondary objective was to compare the time until maximal effect and the maximal effect of inhaled levodopa versus oral levodopa.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;Open-label randomized two-way one-period crossover trial.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Nine PD patients in the 'off state' received one dose of inhaled levodopa (90 mg) from Cyclops® and one dose of levodopa orodispersible tablet (100 mg) on two consecutive days in a randomized order. A timed tapping test, Timed Up and Go test (TUG test) and Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III score were performed pre-dose and on set time points up to 90 min post-dose as measure for motor function. In addition, blood samples were taken for a pharmacokinetic evaluation (&lt;i&gt;T&lt;/i&gt; &lt;sub&gt;max&lt;/sub&gt;, &lt;i&gt;C&lt;/i&gt; &lt;sub&gt;max&lt;/sub&gt; and area under the concentration time curve (AUC) 0-3 h).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The maximal effect of inhaled levodopa was reached at 30 min (tapping test), at 75 min (TUG test) and at 60 min (UPDRS III). The positive effect on the UPDRS was statistically significant within 20 min after inhalation. After oral administration, &lt;i&gt;C&lt;/i&gt; &lt;sub&gt;max&lt;/sub&gt; and AUC 0-3 h were found to be significant higher (&lt;i&gt;p&lt;/i&gt; = 0.028 and &lt;i&gt;p&lt;/i&gt; = 0.028, respectively) than after pulmonary administration. &lt;i&gt;T&lt;/i&gt; &lt;sub&gt;max&lt;/sub&gt; was achieved significantly (&lt;i&gt;p&lt;/i&gt; = 0.028) faster after inhalation. The motor function examinations showed a similar maximum clinical improvement after pulmonary and oral administration and although not significant, inhaled levodopa results in a shorter median duration to maximum clinical effect for the TUG and timed finger-tapping test compared with oral administration (TUG: inhalation 55.0 and oral 67.5 min, timed finger-tapping test: inhalation 35.0 and oral 57.5 min). After the levodopa inhalation, there were no adverse events observed and no significant differences found in long-function parameters.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Inhaled levodopa from Cyclops&lt;sup&gt;®&lt;/sup&gt; shows promising data as a rescue therapy for PD patients with off episodes, not responsive to the current oral therapies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Trial registration: &lt;/strong&gt;The study protocol was approved by the local ethics board 'Regionale toetsingscommissie patiëntgebonden onderzoek' (RTPO) in Leeuwarden, The Netherlands (approval number RTPO1019). The study was registered in in the Dutch trial register (LTR) with identification numbe","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241289207"},"PeriodicalIF":4.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558850","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":"Lower leukocytes pretreatment as a possible risk factor for therapy-induced leukopenia in interferon-beta-treated patients with multiple sclerosis.","authors":"Maria Protopapa, Samantha Schmaul, Muriel Schraad, Katrin Pape, Frauke Zipp, Stefan Bittner, Timo Uphaus","doi":"10.1177/17562864241286497","DOIUrl":"10.1177/17562864241286497","url":null,"abstract":"<p><strong>Background: </strong>Interferon-beta (IFN-β) still plays a fundamental role in immunomodulation of people with multiple sclerosis (MS) with low disease activity and in clinically isolated syndrome (CIS). In 2014, pegylated (PEG) interferon was licensed by the European Medicines Agency (EMA) for relapsing-remitting MS (RRMS), enabling a lower dosing frequency.</p><p><strong>Objectives: </strong>Our retrospective study compares laboratory findings and adverse events between subcutaneous (sc.) PEG-IFN-β-1a and IFN-β-1a in RRMS and CIS patients.</p><p><strong>Design: </strong>Patients with CIS or RRMS fulfilling the revised McDonald criteria from 2017 visiting the neurology department of the University Medical Center of the Johannes Gutenberg University Mainz from 2010 to 2019 and treated with sc. PEG-IFN-β-1a or sc. IFN-β-1a (<i>n</i> = 202) were screened for eligibility. Patients who underwent regular laboratory controls in-house were included in our analysis (<i>n</i> = 128).</p><p><strong>Methods: </strong>We evaluate disease progression through clinical examination, relapse history, and magnetic resonance imaging (MRI) disease activity (gadolinium-enhancing or new T2 lesions). Relevant laboratory findings such as leukopenia (leukocyte count < 3.5/nl) and neutropenia (neutrophil count <43% of lymphocytes or <1500/µl) were assessed. Telephone interviews evaluated the side effects of the respective medication. A subgroup of patients was analyzed regarding neutrophil quantities and qualities.</p><p><strong>Results: </strong>Patients treated with sc. PEG-IFN-β-1a had significantly lower leukocyte counts (<i>p</i> = 0.046) and higher incidences of leukopenia (<i>p</i> = 0.006) and neutropenia (<i>p</i> = 0.03) compared to sc. IFN-β-1a. Clinical and MRI disease activity showed no significant differences, but people treated with sc. PEG-IFN-β-1a reported more common adverse events such as joint/muscle pain, injection-site reaction, and infections. No serious adverse events were reported.</p><p><strong>Conclusion: </strong>Treatment with sc. PEG-IFN-β-1a compared to unpegylated sc. IFN-β resulted in a significantly greater reduction in leukocyte and neutrophil levels with a higher incidence of side effects. We suggest mandatory monitoring of differential blood counts before and during treatment.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241286497"},"PeriodicalIF":4.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547612","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 impact of different lifestyle factors on disability in multiple sclerosis at older ages: a monocentric retrospective study.","authors":"Sophie Wecker, David Freudenstein, Iris Ganser, Klemens Angstwurm, De-Hyung Lee, Ralf A Linker","doi":"10.1177/17562864241284166","DOIUrl":"10.1177/17562864241284166","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system affecting approximately 2.8 million people worldwide. In addition to genetic and environmental factors, various lifestyle factors contribute to disease development and progression.</p><p><strong>Objectives: </strong>We performed a monocentric retrospective study and investigated the effect of lifestyle factors such as obesity, smoking, alcohol consumption, physical activity, and dietary habits on the degree of disability in a cohort of people with MS (pwMS) with an average onset of disease after the age of 55.</p><p><strong>Design: </strong>This late-onset MS (LOMS) study group (<i>n</i> = 47) was characterized by a mean age of 60.9 years and a mean duration of disease of 5.0 years. The LOMS study group was compared with two control groups. The study participants in the \"old control group\" (C_old) were on average as old and in the \"young control group\" (C_young) as long suffering from MS as the pwMS in the LOMS group.</p><p><strong>Methods: </strong>Data from medical documentation and a questionnaire were analyzed using descriptive frequency analyses and testing for correlation between different variables also by generalized estimating equations. The Expanded Disabilty Status Scale (EDSS) score and the progression index were used as a measure of disability.</p><p><strong>Results: </strong>We found a significant association between smoking history and the current EDSS score in the C_young group, but not in the two older study groups. For physical activity, there was a significant negative correlation with EDSS score in the study group and the C_old group, alcoholic beverage consumption correlated with decreased EDSS in the C_old group. The intake of meat negatively correlated with the progression index in the LOMS group.</p><p><strong>Conclusion: </strong>In summary, different life-style factors correlated with disability depending on patient age and disease duration. These life-style factors may be considered in the future counseling of pwMS at older ages.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241284166"},"PeriodicalIF":4.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569652","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":"Possible clinical and radiological predictors of haemorrhagic transformation in acute stroke patients undergoing dual antiplatelet therapy: a clinical study.","authors":"Maria Rosaria Bagnato, Ilaria Maestrini, Leonardo Bruno, Ilaria Ciullo, Federica D'Agostino, Giordano Lacidogna, Federico Marrama, Alfredo Paolo Mascolo, Alessandro Rocco, Marina Diomedi","doi":"10.1177/17562864241289735","DOIUrl":"https://doi.org/10.1177/17562864241289735","url":null,"abstract":"<p><strong>Background: </strong>The predictors of intracranial haemorrhagic transformation (HT) in acute ischaemic stroke (AIS) patients undergoing dual antiplatelet therapy (DAPT) are not well known.</p><p><strong>Objectives: </strong>The aim of this study is to identify the possible clinical and radiological predictors of HT in patients, irrespective of clinical indication for this treatment.</p><p><strong>Design: </strong>This study is a monocentric cohort retrospective study.</p><p><strong>Methods: </strong>We enrolled consecutive AIS patients, from our prospective register, admitted to Stroke Unit between June 2021 and June 2023 undergoing DAPT with Acetylsalicylic Acid and Clopidogrel within 72 h from symptoms onset. According to current guidelines, DAPT indication was for patients with a minor stroke, symptomatic intracranial artery stenosis and carotid angioplasty stenting. We collected clinical, demographical and radiological data. We used ABC/2 method to measure stroke volume in magnetic resonance imaging (MRI)/Diffusion-weighted imaging (DWI) sequences performed within 48 h. The primary outcome was the presence of HT at non-contrast brain computed tomography, performed 7 days after commencing DAPT.</p><p><strong>Results: </strong>One hundred ninety-four patients were included. Twenty-eight (14.4%) presented HT. Higher NIH Stroke Scale (NIHSS) and MRI/DWI lesion volume related to increased risk of HT (<i>p</i> < 0.001). Reperfusion therapy and mechanical thrombectomy (MT), stent placement and a loading dose (LD) of dual antiplatelet or Clopidogrel were associated with a higher occurrence of HT (<i>p</i> < 0.05). Furthermore, we individuated an NIHSS cut-off value >4 (area under the curve (AUC) 0.80, sensitivity 0.82, specificity 0.65) and a volume cut-off value >8.2 ml (AUC 0.82, sensitivity 0.79, specificity 0.80) associated with an increased risk of HT (respectively, adjusted odds ratio (adj. OR) 6.5, confidence interval (CI) 1.3-32.7, <i>p</i> = 0.024 and adj. OR 11.0, CI 3.1-39.2, <i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>In clinical practice, MT treatment, antiplatelet LD administration, stent placement and clinical severity may relate to a higher risk of HT in patients with AIS and DAPT in the acute phase. In particular, we found that lesion volume cut-off could help to identify patients at greater risk of HT, regardless of the indication for DAPT.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241289735"},"PeriodicalIF":4.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508510","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":"Beyond lines of treatment: embracing early high-efficacy disease-modifying treatments for multiple sclerosis management.","authors":"Celia Oreja-Guevara, Sergio Martínez-Yélamos, Sara Eichau, Miguel Ángel Llaneza, Jesús Martín-Martínez, Joaquín Peña-Martínez, Virginia Meca-Lallana, Ana María Alonso-Torres, Ester Moral-Torres, Jordi Río, Carmen Calles, Adrián Ares-Luque, Lluís Ramió-Torrentà, María Eugenia Marzo-Sola, José María Prieto, María Luisa Martínez-Ginés, Rafael Arroyo, María Ángeles Otano-Martínez, Luis Brieva-Ruiz, Montserrat Gómez-Gutiérrez, Alfredo Rodríguez-Antigüedad, Victoria Galán Sánchez-Seco, Lucienne Costa-Frossard, Miguel Ángel Hernández-Pérez, Lamberto Landete-Pascual, Montserrat González-Platas, José E Meca-Lallana","doi":"10.1177/17562864241284372","DOIUrl":"10.1177/17562864241284372","url":null,"abstract":"<p><p>Recent advances in multiple sclerosis (MS) management have shifted perspectives on treatment strategies, advocating for the early initiation of high-efficacy disease-modifying therapies (heDMTs). This perspective review discusses the rationale, benefits, and challenges associated with early heDMT initiation, reflecting on the obsolescence of the traditional \"first-line\" and \"second-line\" treatment classifications. The article emerges from the last update of the consensus document of the Spanish Society of Neurology on the treatment of MS. During its development, there was a recognized need to further discuss the concept of treatment lines and the early use of heDMTs. Evidence from randomized controlled trials and real-world studies suggests that early heDMT initiation leads to improved clinical outcomes, including reduced relapse rates, slowed disease progression, and decreased radiological activity, especially in younger patients or those in early disease stages. Despite the historical belief that heDMTs involve more risks and adverse events compared to moderate-efficacy DMTs (meDMTs), some studies have reported comparable safety profiles between early heDMTs and meDMTs, though long-term safety data are still lacking. The review also addresses the need for a personalized approach based on patient characteristics, prognostic factors, and preferences, explores the importance of therapeutic inertia, and highlights the evolving landscape of international and national guidelines that increasingly advocate for early intensive treatment approaches. The article also addresses the challenges of ensuring access to these therapies and the importance of further research to establish long-term safety and effectiveness of DMTs in MS.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241284372"},"PeriodicalIF":4.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558849","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":"Nerve decompression for diabetic peripheral neuropathy with nerve entrapment: a narrative review.","authors":"Chenlong Liao, Wenchuan Zhang","doi":"10.1177/17562864241265287","DOIUrl":"https://doi.org/10.1177/17562864241265287","url":null,"abstract":"<p><p>Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes which primarily affects the sensory nervous system. Pain is the most common complaint that prompts patients to seek medical advice. With various presentations and intricate pathological mechanisms, diabetic peripheral neuropathic pain is currently the most crucial and challenging aspect of managing diabetic complications. As a heterogeneous disorder, there is no medication or treatment modality that is effective for all types of DPN and its associated neuropathic pain. Peripheral nerve decompression provides a new option for treating patients with diabetic peripheral neuropathic pain in the lower extremities. However, the clinical applicability of nerve decompression has been debated since it was first proposed. This review discusses the theoretical basis of nerve decompression, the clinical indications, and the progress of basic research based on the pathological mechanisms and nerve impairment patterns of diabetic peripheral neuropathic pain. The heterogeneity of DPN patients is summarized in terms of three aspects: complex pathophysiological mechanisms, multilevel nervous system involvement, and various nerve impairment properties. Identifying the presence of nerve entrapment among complex pathophysiological mechanisms is the key to successful outcomes. Tinel signs, focal pain, mechanical allodynia, and two-point discrimination were reported to be prognostic factors for good surgical outcomes, and their predictive ability might stem from their association with the early stage of entrapment neuropathy.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241265287"},"PeriodicalIF":4.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11475385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475385","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}