Therapeutic Advances in Neurological Disorders最新文献

{"title":"Independent risk factors for in-hospital outcome of myasthenic crisis: a prospective cohort study.","authors":"Yuan Wang, Xiao Huan, Xinfang Zhu, Jie Song, Chong Yan, Lei Yang, Caihua Xi, Yafang Xu, Jianying Xi, Chongbo Zhao, Rong Xia, Sushan Luo","doi":"10.1177/17562864241226745","DOIUrl":"https://doi.org/10.1177/17562864241226745","url":null,"abstract":"<p><strong>Background: </strong>Myasthenic crisis (MC) is a life-threatening condition for myasthenia gravis (MG). Therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIg) efficaciously treat patients with MC. However, not every MC responds well to rescue therapies, and the determinants for outcome with the evidence from prospective cohorts are still lacking.</p><p><strong>Objectives: </strong>To explore the risk factors for in-hospital outcomes in patients with MC.</p><p><strong>Methods: </strong>Using a national neuromuscular center-based cohort of MG with prospective follow-ups from the crisis to the post-crisis phase, we finally included 90 MC episodes from 76 independent patients who received a standard regimen of rescue therapies.</p><p><strong>Results: </strong>The mean admission age was 52.89 ± 15.72 years. With a female predominance of 63.16% (48/76) and a high proportion of thymoma-associated MG (TMG) of 63.16% (48/76), the overall in-hospital mortality was 2.63% (2/76) and the average duration for mechanical ventilation (MV) use was 17.09 ± 13.36 days (0-53 days). In contrast to the patients with anti-acetylcholine receptor (AChR) antibodies, muscle-specific tyrosine kinase (MuSK)-associated MC exhibited a shorter MV support (5.20 ± 5.07 <i>versus</i> 17.40 ± 13.24 days, <i>p</i> = 0.023), length of intensive care units (ICU) stay (6.00 ± 4.64 <i>versus</i> 19.16 ± 17.54 days, <i>p</i> = 0.046), and hospital stay (16.00 ± 4.12 <i>versus</i> 34.43 ± 20.48 days, <i>p</i> = 0.011). Thymoma [odds ratio (OR): 0.200, 95% confidence interval (CI): 0.058-0.687, <i>p</i> = 0.011], partial pressure of carbon dioxide (PCO₂) in blood gas before MV (OR: 1.238, 95% CI: 1.015-1.510, <i>p</i> = 0.035), and pneumonia (OR: 0.204, 95% CI: 0.049-0.841, <i>p</i> = 0.028) were identified as independent risk factors for prolonged MV use. TMG patients with thymoma burden exhibited a notable longer MV use (22.08 ± 17.54 <i>versus</i> 8.88 ± 6.79 days, <i>p</i> = 0.001), a prolonged hospital stay (40.40 ± 26.13 <i>versus</i> 23.67 ± 13.83 days, <i>p</i> = 0.009) compared with non-TMG. Even with complete thymoma resection (R0), TMG exhibited an unfavorable outcome <i>versus</i> non-TMG.</p><p><strong>Conclusion: </strong>With timely rescue therapies and prospective follow-ups, the in-hospital outcome of MCs was substantially improved. Thymoma, PCO₂ in blood gas before MV, and pneumonia were identified as independent risk factors for prolonged MV use.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241226745"},"PeriodicalIF":5.9,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10858673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724051","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":"Prognostic relevance of MRI in early relapsing multiple sclerosis: ready to guide treatment decision making?","authors":"Olaf Hoffmann, Ralf Gold, Sven G Meuth, Ralf A Linker, Thomas Skripuletz, Heinz Wiendl, Mike P Wattjes","doi":"10.1177/17562864241229325","DOIUrl":"10.1177/17562864241229325","url":null,"abstract":"<p><p>Magnetic resonance imaging (MRI) of the brain and spinal cord plays a crucial role in the diagnosis and monitoring of multiple sclerosis (MS). There is conclusive evidence that brain and spinal cord MRI findings in early disease stages also provide relevant insight into individual prognosis. This includes prediction of disease activity and disease progression, the accumulation of long-term disability and the conversion to secondary progressive MS. The extent to which these MRI findings should influence treatment decisions remains a subject of ongoing discussion. The aim of this review is to present and discuss the current knowledge and scientific evidence regarding the utility of MRI at early MS disease stages for prognostic classification of individual patients. In addition, we discuss the current evidence regarding the use of MRI in order to predict treatment response. Finally, we propose a potential approach as to how MRI data may be categorized and integrated into early clinical decision making.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241229325"},"PeriodicalIF":5.9,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10851744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139707943","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":"Promising advances in Alzheimer's treatment: donanemab's impact on disease progression and amyloid clearance.","authors":"Abdul Wahid, Wajiha Fatima Khan, Yusra Khan","doi":"10.1177/17562864241228650","DOIUrl":"10.1177/17562864241228650","url":null,"abstract":"","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241228650"},"PeriodicalIF":4.7,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10829490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139651719","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":"Intrinsic brain activity differences in perampanel-responsive and non-responsive drug-resistant epilepsy patients: an EEG microstate analysis.","authors":"Chaofeng Zhu, Juan Li, Dazhu Wei, Luyan Wu, Yuying Zhang, Huapin Huang, Wanhui Lin","doi":"10.1177/17562864241227293","DOIUrl":"10.1177/17562864241227293","url":null,"abstract":"<p><strong>Background: </strong>Drug-resistant epilepsy (DRE) patients exhibit aberrant large-scale brain networks. Perampanel may be a therapeutic option for controlling seizures in these patients.</p><p><strong>Objective: </strong>We aim to explore the differences of resting-state electroencephalogram (EEG) microstate in perampanel-responsive and non-responsive DRE patients.</p><p><strong>Design: </strong>Retrospective study.</p><p><strong>Methods: </strong>Clinical data were collected from DRE patients who received perampanel treatment at the Fujian Medical University Union Hospital from June 2020 to September 2021, with a minimum follow-up of 6 months. Patients were classified into three groups based on the extent of reduction in seizure frequency: non-responsive (seizure reduction <50%), responsive (seizure reduction >50% but not seizure-free), and seizure-free. Resting-state EEG data sets of all participants were subjected to EEG microstate analysis. The study comprehensively compared the mean duration, frequency per second, and temporal coverage of each microstate among the three groups.</p><p><strong>Results: </strong>A total of 76 perampanel-treated DRE patients were categorized into three groups based on their response to treatment: non-responsive (<i>n</i> = 20), responsive (<i>n</i> = 36), and seizure-free (<i>n</i> = 20), according to the degree of seizure frequency reduction. The results of EEG microstate analysis revealed no statistically significant distinctions in frequency, duration, and coverage of microstate D in these DRE patients. However, the seizure-free group showed significantly increased duration and coverage of microstate A, frequency and coverage of microstate B, and significantly decreased duration, frequency, and coverage of microstate C when compared with the other groups.</p><p><strong>Conclusion: </strong>Microstate A, B, and D is associated with the sensorimotor network, visual network, salience network, and attention network, respectively. This study demonstrates statistically significant differences in the sensorimotor, visual, and salience networks, but not in the attention network, between perampanel-responsive and non-responsive DRE patients.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241227293"},"PeriodicalIF":4.7,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10829497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139651718","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":"Efficacy of bortezomib, cyclophosphamide, and dexamethasone for newly diagnosed POEMS syndrome patients.","authors":"Fang Fang, Xiao-Xi Lan, Rong-Hua Hu, Wu-Han Hui, Hong Zhao, Yi-Xian Guo, Bing-Xin Ji, Hong-Jun Liu, Li Su, Wan-Ling Sun","doi":"10.1177/17562864231219151","DOIUrl":"10.1177/17562864231219151","url":null,"abstract":"<p><strong>Background: </strong>Due to the rarity of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, the best first-line treatment has not been established, although there are several options in guidelines. The preferred treatments vary according to the preference of the physician and anecdote.</p><p><strong>Objectives: </strong>First, to analyze the efficacy of a new treatment mode in POEMS syndrome that uses the four-cycle treatment as the induction regimen, followed by sequential transplantation as the consolidation regimen for transplantation-eligible patients, or received another two-cycle treatment for transplantation-ineligible patients. Second, to compare the efficacy and safety of regimens with a proteasome inhibitor (bortezomib-cyclophosphamide-dexamethasone, BCD) or without a proteasome inhibitor (cyclophosphamide-dexamethasone ± thalidomide, CD ± T).</p><p><strong>Design: </strong>We conducted a retrospective study using real-world data from Capital Medical University, Xuanwu Hospital.</p><p><strong>Methods: </strong>A total of 34 newly diagnosed POEMS syndrome patients met Dispenzieri's diagnostic criteria, and those who completed at least four cycles of treatment from July 2013 to March 2021 were included.</p><p><strong>Results: </strong>The overall vascular endothelial growth factor (VEGF) response rate of this new treatment mode was 100%. The cumulative VEGF complete remission (CR_V) rate was 67.9%, and the cumulative complete hematological response (CR_H) rate was 55.6%. During the median 49-month follow-up, the 5-year-overall survival (OS) rate was 90.7%, the 3-year-progression-free survival (PFS) rate was 78.4%, and the 5-year-PFS rate was 73.8%. The BCD regimen achieved a 75% CR_V rate (median time from diagnosis to CR_V = 130 days) and 66.7% CR_H rate (median time from diagnosis to CR_H = 218 days). In addition, the VEGF response was less than the partial remission (PR_V) after four-cycle induction treatment, which, together with a decrease on the Overall Neurological Limitation Scale of less than three points 1 year after consolidation treatment, was an independent poor prognostic factor.</p><p><strong>Conclusion: </strong>Bortezomib was well-tolerated by patients with POEMS syndrome. Compared with CD ± T regimen, BCD as the induction regimen achieved better VEGF response and earlier hematological remission. Autologous stem cell transplantation used as consolidation therapy further improved the neurological and hematological remission rates, resulting in better OS and PFS.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864231219151"},"PeriodicalIF":4.7,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10823847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576258","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":"Effect of altered gene expression in lipid metabolism on cognitive improvement in patients with Alzheimer's dementia following fecal microbiota transplantation: a preliminary study.","authors":"Jun-Seob Kim, Hyelim Park, Jung-Hwan Lee, Jongbeom Shin, Boram Cha, Kye Sook Kwon, Yong Woon Shin, Yerim Kim, YeoJin Kim, Jong Seok Bae, Ju-Hun Lee, Seok-Jin Choi, Tae Jung Kim, Sang-Bae Ko, Soo-Hyun Park","doi":"10.1177/17562864231218181","DOIUrl":"10.1177/17562864231218181","url":null,"abstract":"<p><strong>Background: </strong>The brain-gut axis has emerged as a potential target in neurodegenerative diseases, including dementia, as individuals with dementia exhibit distinct gut microbiota compositions. Fecal microbiota transplantation (FMT), the transfer of fecal solution from a healthy donor to a patient, has shown promise in restoring homeostasis and cognitive enhancement.</p><p><strong>Objective: </strong>This study aimed to explore the effects of FMT on specific cognitive performance measures in Alzheimer's dementia (AD) patients and investigate the relationship between cognition and the gut microbiota by evaluating changes in gene expression following FMT.</p><p><strong>Methods: </strong>Five AD patients underwent FMT, and their cognitive function [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB)] was assessed before and after FMT. The patients' fecal samples were analyzed with 16S rRNA to compare the composition of their gut microbiota. We also assessed modifications in the serum mRNA expression of patients' genes related to lipid metabolism using serum RNA sequencing and quantitative real-time polymerase chain reaction.</p><p><strong>Results: </strong>Significant improvements in cognitive function, as measured by the MMSE (pre- and post-FMT was 13.00 and 18.00) and MoCA were seen. The MoCA scores at 3 months post-FMT (21.0) were the highest (12.0). The CDR-SOB scores at pre- and post-FMT were 10.00 and 5.50, respectively. Analysis of the gut microbiome composition revealed changes <i>via</i> 16S rRNA sequencing with an increase in Bacteroidaceae and a decrease in Enterococcaceae. Gene expression analysis identified alterations in lipid metabolism-related genes after FMT.</p><p><strong>Conclusion: </strong>These findings suggest a link between alterations in the gut microbiome, gene expression related to lipid metabolism, and cognitive function. The study highlights the importance of gut microbiota in cognitive function and provides insights into potential biomarkers for cognitive decline progression. FMT could complement existing therapies and show potential as a therapeutic intervention to mitigate cognitive decline in AD.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864231218181"},"PeriodicalIF":5.9,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10799597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511726","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":"Genetic and phenotypic analyses of PRRT2 positive and negative paroxysmal kinesigenic dyskinesia.","authors":"Yingying Zhang, Jiechuan Ren, Tianhua Yang, Weixi Xiong, Linyuan Qin, Dongmei An, Fayun Hu, Dong Zhou","doi":"10.1177/17562864231224110","DOIUrl":"10.1177/17562864231224110","url":null,"abstract":"<p><strong>Background: </strong>Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurological disorder, characterized by attacks of involuntary movements triggered by sudden action. Variants in proline-rich transmembrane protein 2 (<i>PRRT2</i>) are the most common genetic cause of PKD.</p><p><strong>Objective: </strong>The objective was to investigate the clinical and genetic characteristics of PKD and to establish genotype-phenotype correlations.</p><p><strong>Methods: </strong>We enrolled 219 PKD patients, documented their clinical information and performed <i>PRRT2</i> screening using Sanger sequencing. Whole exome sequencing was performed on 49 PKD probands without <i>PRRT2</i> variants. Genotype-phenotype correlation analyses were conducted on the probands.</p><p><strong>Results: </strong>Among 219 PKD patients (99 cases from 39 families and 120 sporadic cases), 16 <i>PRRT2</i> variants were identified. Nine variants (c.879+4A>G, c.879+5G>A, c.856G>A, c.955G>T, c.884G>C, c.649C>T, c.649dupC, c.649delC and c.696_697delCA) were previously known, while seven were novel (c.367_403del, c.347_348delAA, c.835C>T, c.116dupC, c.837_838insC, c.916_937del and c.902G>A). The mean interval from onset to diagnosis was 7.94 years. Compared to patients without <i>PRRT2</i> variants, patients with the variants were more likely to have a positive family history, an earlier age of onset and a higher prevalence of falls during pre-treatment attacks (27.14% <i>versus</i> 8.99%, respectively). Patients with truncated <i>PRRT2</i> variants tend to have bilateral attacks. We identified two transmembrane protein 151A (<i>TMEM151A</i>) variants including a novel variant (c.368G>C) and a reported variant (c.203C>T) in two PRRT2-negative probands with PKD.</p><p><strong>Conclusion: </strong>These findings provide insights on the clinical characteristics, diagnostic timeline and treatment response of PKD patients. PKD patients with truncated <i>PRRT2</i> variants may tend to have more severe paroxysmal symptoms. This study expands the spectrum of <i>PRRT2</i> and <i>TMEM151A</i> variants. Carbamazepine and oxcarbazepine are both used as a first-line treatment choice for PKD patients.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864231224110"},"PeriodicalIF":5.9,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10798112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511956","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":"Tenecteplase for the treatment of acute ischemic stroke in the extended time window: a systematic review and meta-analysis","authors":"L. Palaiodimou, A. Katsanos, Guillaume Turc, Michele Romoli, Aikaterini Theodorou, R. Lemmens, Simona Sacco, G. Velonakis, C. Vlachopoulos, G. Tsivgoulis","doi":"10.1177/17562864231221324","DOIUrl":"https://doi.org/10.1177/17562864231221324","url":null,"abstract":"Background: Outcome data regarding the administration of tenecteplase (TNK) to acute ischemic stroke (AIS) patients presenting in the extended time window are limited. Objectives: We aimed to assess the current evidence regarding the efficacy and safety of TNK at a dose of 0.25 mg/kg for AIS treatment in the extended time window. Design: A systematic review and meta-analysis was conducted including all available randomized-controlled clinical trials (RCTs) that compared TNK 0.25 mg/kg versus no thrombolysis in AIS patients presenting in the extended time window (>4.5 h after last-seen-well or witnessed onset). Data sources and methods: Eligible studies were identified by searching Medline, Scopus, and international conference abstracts. The predefined efficacy outcomes of interest were 3-month excellent functional outcome [defined as the modified Rankin Scale (mRS) score ⩽1; primary outcome], 3-month good functional outcome (mRS ⩽ 2), 3-month reduced disability (⩾1-point reduction across all mRS scores). We determined symptomatic intracranial hemorrhage (sICH), any ICH and 3-month mortality as safety endpoints. A random-effects model was used to calculate risk ratios (RRs) and common odds ratios (cORs) with corresponding 95% confidence intervals (CIs). Results: Three RCTs were included comprising 556 patients treated with TNK versus 560 controls. TNK 0.25 mg/kg was associated with a higher likelihood of 3-month excellent functional outcome compared to controls (RR = 1.17; 95% CI = 1.01–1.36; I2 = 0%), whereas there was no difference regarding good functional outcome (RR = 1.05; 95% CI = 0.94–1.17; I2 = 0%) and reduced disability (adjusted cOR = 1.14; 95% CI = 0.92–1.40; I2 = 0%) at 3 months. The risks of sICH (RR = 1.67; 95% CI = 0.70–4.00; I2 = 0%), any ICH (RR = 1.08; 95% CI = 0.90–1.29; I2 = 0%) and 3-month mortality (RR = 1.10; 95% CI = 0.81–1.49; I2 = 0%) were similar between the groups. Conclusion: Based on data from three RCTs showing increased efficacy and a favorable safety profile of TNK in the treatment of AIS in the extended time window, continuing efforts of ongoing RCTs in the field are clearly supported. Trial registration: PROSPERO registration ID: CRD42023448707.","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":" 1147","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139391710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guideline for the management of myasthenic syndromes.","authors":"Heinz Wiendl, Angela Abicht, Andrew Chan, Adela Della Marina, Tim Hagenacker, Khosro Hekmat, Sarah Hoffmann, Hans-Stefan Hoffmann, Sebastian Jander, Christian Keller, Alexander Marx, Arthur Melms, Nico Melzer, Wolfgang Müller-Felber, Marc Pawlitzki, Jens-Carsten Rückert, Christiane Schneider-Gold, Benedikt Schoser, Bettina Schreiner, Michael Schroeter, Bettina Schubert, Jörn-Peter Sieb, Fritz Zimprich, Andreas Meisel","doi":"10.1177/17562864231213240","DOIUrl":"10.1177/17562864231213240","url":null,"abstract":"<p><p>Myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS), and congenital myasthenic syndromes (CMS) represent an etiologically heterogeneous group of (very) rare chronic diseases. MG and LEMS have an autoimmune-mediated etiology, while CMS are genetic disorders. A (strain dependent) muscle weakness due to neuromuscular transmission disorder is a common feature. Generalized MG requires increasingly differentiated therapeutic strategies that consider the enormous therapeutic developments of recent years. To include the newest therapy recommendations, a comprehensive update of the available German-language guideline 'Diagnostics and therapy of myasthenic syndromes' has been published by the German Neurological society with the aid of an interdisciplinary expert panel. This paper is an adapted translation of the updated and partly newly developed treatment guideline. It defines the rapid achievement of complete disease control in myasthenic patients as a central treatment goal. The use of standard therapies, as well as modern immunotherapeutics, is subject to a staged regimen that takes into account autoantibody status and disease activity. With the advent of modern, fast-acting immunomodulators, disease activity assessment has become pivotal and requires evaluation of the clinical course, including severity and required therapies. Applying MG-specific scores and classifications such as Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, and Myasthenia Gravis Foundation of America allows differentiation between mild/moderate and (highly) active (including refractory) disease. Therapy decisions must consider age, thymic pathology, antibody status, and disease activity. Glucocorticosteroids and the classical immunosuppressants (primarily azathioprine) are the basic immunotherapeutics to treat mild/moderate to (highly) active generalized MG/young MG and ocular MG. Thymectomy is indicated as a treatment for thymoma-associated MG and generalized MG with acetylcholine receptor antibody (AChR-Ab)-positive status. In (highly) active generalized MG, complement inhibitors (currently eculizumab and ravulizumab) or neonatal Fc receptor modulators (currently efgartigimod) are recommended for AChR-Ab-positive status and rituximab for muscle-specific receptor tyrosine kinase (MuSK)-Ab-positive status. Specific treatment for myasthenic crises requires plasmapheresis, immunoadsorption, or IVIG. Specific aspects of ocular, juvenile, and congenital myasthenia are highlighted. The guideline will be further developed based on new study results for other immunomodulators and biomarkers that aid the accurate measurement of disease activity.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"16 ","pages":"17562864231213240"},"PeriodicalIF":5.9,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10752078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049342","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":"Late-onset stiff-person syndrome: challenges in diagnosis and management.","authors":"Marinos C Dalakas, Jessica Yi","doi":"10.1177/17562864231214315","DOIUrl":"10.1177/17562864231214315","url":null,"abstract":"<p><strong>Background: </strong>Stiff person syndrome (SPS) is a rare slowly progressive autoimmune neuronal hyperexcitability disease with very-high GAD-65 antibody titers that most commonly presents above the age of 20, with muscle stiffness, painful muscle spasms, slow gait, and falls leading to disability. In other autoimmune disorders, late-onset disease has different symptom-spectrum and outcomes, but there is no information regarding late-onset SPS (LOSPS).</p><p><strong>Objective: </strong>Highlight delayed diagnosis and poor tolerance or incomplete response to therapies of patients with LOSPS and outline how best to increase disease awareness early at onset.</p><p><strong>Design a retrospective chart reviewmethods: </strong>We reviewed GAD-positive SPS patients with symptom onset above age 60, identified among 54 SPS patients, examined, treated and followed-up by the same clinicians, focused on clinical presentation, misdiagnoses, response and tolerance to therapies, and evolved disability.</p><p><strong>Results: </strong>Nine patients had LOSPS with symptom onset at median age of 61 years (range 60-78), and current median age of 73. The median time from symptom onset to SPS diagnosis was 3 years; prior to diagnosis, five patients were treated for lumbosacral radiculopathies (one with laminectomy), two for Parkinson's disease, one for multiple sclerosis, and another for cerebellar degeneration. Progressive decline occurred rapidly in all patients; at time of diagnosis, six patients were already using a cane or walker and two were wheelchair-bound. Tolerance and response to treatment were limited; two patients did not respond to IVIg, two discontinued IVIg despite early response due to comorbidities (cardiac disease, thrombosis), four others partially responded to IVIg and one to rituximab; several could not tolerate high doses of oral antispasmodics due to somnolence; and two patients died.</p><p><strong>Conclusions: </strong>LOSPS is almost always misdiagnosed for other similar conditions commonly seen in the elderly. Patients with LOSPS decline quickly to clinically severe disease due to delayed treatment initiation, poor response or tolerance, other comorbidities, and possibly immunosenescence. Increased awareness that SPS can occur in the elderly mimicking other disorders is important for early diagnosis and treatment, even necessitating earlier immunotherapy initiation, compared to their younger counterparts, to prevent faster-evolving severe disability.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"16 ","pages":"17562864231214315"},"PeriodicalIF":5.9,"publicationDate":"2023-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10752047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049343","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}