Annals of Clinical and Translational Neurology最新文献

{"title":"α-Synuclein species in plasma neuron-derived extracellular vesicles as biomarkers for iRBD","authors":"Xuemei Wang,&nbsp;Yuanchu Zheng,&nbsp;Huihui Cai,&nbsp;Wenyi Kou,&nbsp;Chen Yang,&nbsp;Siming Li,&nbsp;Bingxu Zhu,&nbsp;Jiayi Wu,&nbsp;Ning Zhang,&nbsp;Tao Feng,&nbsp;Xiaohong Li,&nbsp;Fulong Xiao,&nbsp;Zhenwei Yu","doi":"10.1002/acn3.52200","DOIUrl":"10.1002/acn3.52200","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Isolated REM sleep behavior disorder (iRBD) is considered as the strongest predictor of Parkinson's disease (PD). Reliable and accurate biomarkers for iRBD detection and the prediction of phenoconversion are in urgent need. This study aimed to investigate whether α-Synuclein (α-Syn) species in plasma neuron-derived extracellular vesicles (NDEVs) could differentiate between iRBD patients and healthy controls (HCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Nanoscale flow cytometry was used to detect α-Syn-containing NDEVs in plasma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 54 iRBD patients and 53 HCs were recruited. The concentrations of total α-Syn, α-Syn aggregates, and phosphorylated α-Syn at Ser129 (pS129)-containing NDEVs in plasma of iRBD individuals were significantly higher than those in HCs (<i>p</i> &lt; 0.0001 for all). In distinguishing between iRBD and HCs, the area under the receiver operating characteristic (ROC) curve (AUC) for an integrative model incorporating the levels of α-Syn, pS129, and α-Syn aggregate-containing NDEVs in plasma was 0.965. This model achieved a sensitivity of 94.3% and a specificity of 88.9%. In iRBD group, the concentrations of α-Syn aggregate-containing NDEVs exhibited a negative correlation with Sniffin’ Sticks olfactory scores (<i>r</i> = −0.351, <i>p</i> = 0.039). Smokers with iRBD exhibited lower levels of α-Syn aggregates and pS129-containing NDEVs in plasma compared to nonsmokers (<i>p</i>_{α-Syn aggregates} = 0.014; <i>p</i>_pS129 = 0.003).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The current study demonstrated that the levels of total α-Syn, α-Syn aggregates, and pS129-containing NDEVs in the plasma of individuals with iRBD were significantly higher compared to HCs. The levels of α-Syn species-containing NDEVs in plasma may serve as biomarkers for iRBD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 11","pages":"2891-2903"},"PeriodicalIF":4.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52200","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265424","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":"Language abnormalities in Alzheimer's disease indicate reduced informativeness","authors":"Sabereh Bayat,&nbsp;Mahya Sanati,&nbsp;Mehrdad Mohammad-Panahi,&nbsp;Amirhossein Khodadadi,&nbsp;Mahdieh Ghasimi,&nbsp;Sahar Rezaee,&nbsp;Sara Besharat,&nbsp;Zahra Mahboubi-Fooladi,&nbsp;Mostafa Almasi-Dooghaee,&nbsp;Morteza Sanei-Taheri,&nbsp;Bradford C. Dickerson,&nbsp;Neguine Rezaii","doi":"10.1002/acn3.52205","DOIUrl":"10.1002/acn3.52205","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aims to elucidate the cognitive underpinnings of language abnormalities in Alzheimer's Disease (AD) using a computational cross-linguistic approach and ultimately enhance the understanding and diagnostic accuracy of the disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Computational analyses were conducted on language samples of 156 English and 50 Persian speakers, comprising both AD patients and healthy controls, to extract language indicators of AD. Furthermore, we introduced a machine learning-based metric, Language Informativeness Index (LII), to quantify empty speech.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Despite considerable disparities in surface structures between the two languages, we observed consistency across language indicators of AD in both English and Persian. Notably, indicators of AD in English resulted in a classification accuracy of 90% in classifying AD in Persian. The substantial degree of transferability suggests that the language abnormalities of AD do not tightly link to the surface structures specific to English. Subsequently, we posited that these abnormalities stem from impairments in a more universal aspect of language production: the ability to generate informative messages independent of the language spoken. Consistent with this hypothesis, we found significant correlations between language indicators of AD and empty speech in both English and Persian.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The findings of this study suggest that language impairments in AD arise from a deficit in a universal aspect of message formation rather than from the breakdown of language-specific morphosyntactic structures. Beyond enhancing our understanding of the psycholinguistic deficits of AD, our approach fosters the development of diagnostic tools across various languages, enhancing health equity and biocultural diversity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 11","pages":"2946-2957"},"PeriodicalIF":4.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265420","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":"Assessment of central vein sign and paramagnetic rim lesions in pediatric multiple sclerosis","authors":"Monica Margoni,&nbsp;Paolo Preziosa,&nbsp;Elisabetta Pagani,&nbsp;Loredana Storelli,&nbsp;Mor Gueye,&nbsp;Lucia Moiola,&nbsp;Massimo Filippi,&nbsp;Maria A. Rocca","doi":"10.1002/acn3.52208","DOIUrl":"10.1002/acn3.52208","url":null,"abstract":"<p>The evaluation of white matter lesions (WMLs) showing the central vein sign (CVS) and paramagnetic rim lesions (PRLs) has been suggested to enhance the diagnostic work-up of adult multiple sclerosis (MS). We aimed to evaluate the fulfillment of different CVS criteria and the added value of PRLs in 22 pediatric MS patients. Eleven patients (50%) fulfilled the 40%-rule threshold. Nineteen (86%) patients had ≥3 CVS+ WMLs or ≥1 PRL, whereas 17 (77%) had ≥6 CVS+ WMLs or ≥1 PRL. A simplified CVS-based approach, with the combined evaluation of ≥1 PRL in patients with ≥6 CVS+ WMLs, may improve MS diagnosis in pediatric patients.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 11","pages":"3031-3036"},"PeriodicalIF":4.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52208","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265426","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":"Impact of paramagnetic rim lesions on disability and race in multiple sclerosis: mediation analysis","authors":"Nara M. Michaelson,&nbsp;Sandra H. Rúa,&nbsp;Ulrike W. Kaunzner,&nbsp;Melanie Marcille,&nbsp;Iliana Pliska-Bloch,&nbsp;Kimberly Markowitz,&nbsp;Thanh D. Nguyen,&nbsp;Susan A. Gauthier","doi":"10.1002/acn3.52203","DOIUrl":"10.1002/acn3.52203","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Black American (BA) multiple sclerosis (MS) patients experience greater disability compared to White American (WA) patients. Here, we investigated the role of paramagnetic rim lesions (PRLs), a subset of chronic active lesions, on race-related disability in MS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective observational study comparing BA and WA MS patients. PRLs were identified through Quantitative Susceptibility Mapping (QSM) MRI. A causal mediation analysis explored the impact of PRLs on the relationship between race and disability, as measured by the Expanded Disability Status Scale (EDSS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The prevalence of PRLs in BA patients with MS was higher at 55% compared to WA patients at 39% (<i>p</i> = 0.022). A higher percentage of PRLs among all white matter lesions was observed with BA (8.01%) patients compared to WA (3.4%) patients (<i>p</i> = 0.003). In a regression analysis, controlling for significant patient-level covariates and income-level demographics, the percentage of PRLs was, on average, 4.61 points higher for BA patients than for WA patients (<i>p</i> = 0.003). In a separate regression analysis, accounting for covariates, BA patients exhibited significantly higher EDSS scores (<i>p</i> &lt; 0.001). Further analysis demonstrated that the percentage of PRLs was a mediator in the association between BA patients and greater disability (<i>p</i> = 0.031). Higher proportion of PRLs in BA population accounted for 14% of the total effect of race on disability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>BA patients exhibit greater disability, in part, due to their higher proportion of PRLs. This study underscores the substantial impact of chronic active lesions on disability outcomes in this specific minority MS patient population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 11","pages":"2923-2931"},"PeriodicalIF":4.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52203","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265421","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":"Endogenous tPA levels: A biomarker for discriminating hemorrhagic stroke from ischemic stroke and stroke mimics","authors":"Melissa Jauquet,&nbsp;Pierre Gagnepain,&nbsp;Estelle La Porte,&nbsp;Audrey M. Thiebaut,&nbsp;Ambre Rochey,&nbsp;Helene Legros,&nbsp;Baptiste Laine,&nbsp;Marion Berthelot,&nbsp;Valerie Roussel,&nbsp;Joan Montaner,&nbsp;Barbara Casolla,&nbsp;Denis Vivien,&nbsp;Eloise Lemarchand,&nbsp;Richard Macrez,&nbsp;Benoit D. Roussel","doi":"10.1002/acn3.52197","DOIUrl":"10.1002/acn3.52197","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Stroke is the leading cause of death and disability. Timely differentiation between ischemic stroke, hemorrhagic stroke, and stroke mimics is critical for tailored treatment and triage. To accelerate the identification of stroke's subtype, we propose to use the levels of circulating tPA as a biomarker.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Biostroke is an observational study performed at the Caen Hospital. We quantified tPA levels in 110 patients with ischemic strokes, 30 patients with hemorrhagic strokes, and 67 stroke mimic patients upon their arrival at the emergency. Two logistic regression models were formulated: one with parameters measurable in an ambulance (Model A) and one with parameters measurable at the hospital (Model H). These models were both tested with or without plasma tPA measurements. Our initial assessment involved evaluating the effectiveness of both models in distinguishing between hemorrhagic strokes, ischemic strokes, and stroke mimics within our study cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Plasmatic tPA levels exhibit significant distinctions between hemorrhagic, ischemic, and mimic stroke patients (1.8; 2.5; 2.4 ng/mL, respectively). The inclusion of tPA in model A significantly enhances the classification accuracy of hemorrhagic patients only, increasing identification from 0.67 (95% CI, 0.59 to 0.75) to 0.78 (95% CI, 0.7 to 0.85) (<i>p</i> = 0.0098). Similarly, in model H, classification accuracy of hemorrhagic patients significantly increased with the addition of tPA, rising from 0.75 (95% CI, 0.67 to 0.83) without tPA to 0.86 (95% CI, 0.81 to 0.91) with tPA (<i>p</i> = 0.024).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretations</h3>\u0000 \u0000 <p>Our findings underscore the valuable role of tPA levels in distinguishing between stroke subtypes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 11","pages":"2877-2890"},"PeriodicalIF":4.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52197","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202689","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":"Muscular dystrophy patients show low exercise-induced blood flow in muscles with normal strength","authors":"Orna Gera,&nbsp;Efrat Shavit-Stein,&nbsp;Taly Amichai,&nbsp;Joab Chapman,&nbsp;Odelia Chorin,&nbsp;Lior Greenbaum,&nbsp;Amir Dori","doi":"10.1002/acn3.52194","DOIUrl":"10.1002/acn3.52194","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Neuromuscular evaluation increasingly employs muscle ultrasonography to determine muscle thickness, mean grayscale echointensity, and visual semiquantitative echotexture attenuation. However, these measures provide low sensitivity for detection of mild muscle abnormality. Exercise-induced intramuscular blood flow is a physiologic phenomenon, which may be impaired in mildly affected muscles, particularly in dystrophinopathies, and may indicate functional muscle ischemia. We aimed to determine if muscle blood flow is reduced in patients with neuromuscular disorders and preserved muscle strength, and if it correlates with echointensity and digital echotexture measurements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Peak exercise-induced blood flow, echointensity, and echotexture were quantified in the elbow flexor muscles of 15 adult patients with Becker muscular dystrophy (BMD) and 13 patients with other muscular dystrophies (OMD). These were compared to 17 patients with Charcot–Marie–Tooth type 1 (CMT1) neuropathy and 21 healthy adults from a previous study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Muscle blood flow was reduced in all patient groups compared to controls, most prominently in BMD patients (<i>p</i> &lt; 0.0001). Echointensity was similarly increased in all patient groups (<i>p</i> &lt; 0.05), while echotexture was reduced only in muscular dystrophy patients (p ≤ 0.002). In BMD, blood flow correlated with echotexture (Pearson <i>r</i> = 0.6098, <i>p</i> = 0.0158) and strength (Spearman <i>r</i> = 0.5471; <i>p</i> = 0.0370). In patients with normal muscle strength, reduced muscle blood flow was evident in all patient groups (<i>p</i> &lt; 0.001), echotexture was reduced in BMD and OMD (<i>p</i> &lt; 0.01), and echointensity was increased in CMT (<i>p</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Muscle blood flow is a sensitive measure to detect abnormality, even in muscles with normal strength. Increased echointensity may indicate a neurogenic disorder when strength is preserved, while low echotexture suggests a dystrophic disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 11","pages":"2866-2876"},"PeriodicalIF":4.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52194","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202690","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":"Clinicopathological and circulating cell-free DNA profile in myositis associated with anti-mitochondrial antibody","authors":"Yikang Wang,&nbsp;Yawen Zhao,&nbsp;Meng Yu,&nbsp;Luhua Wei,&nbsp;Wei Zhang,&nbsp;Zhaoxia Wang,&nbsp;Yun Yuan","doi":"10.1002/acn3.51901","DOIUrl":"10.1002/acn3.51901","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Anti-mitochondrial antibodies (AMAs) are associated with idiopathic inflammatory myopathies (IIMs). We aimed to summarize the clinicopathological characteristics, assess circulating cell-free mitochondrial DNA (ccf-mtDNA), and circulating cell-free nuclear DNA (ccf-nDNA) in AMA-associated IIMs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Medical records of 37 IIMs patients with AMAs were reviewed. Circulating cell-free mtDNA and ccf-nDNA levels in sera from IIMs patients with AMAs (<i>n</i> = 21), disease controls (<i>n</i> = 66) and healthy controls (HCs) (<i>n</i> = 23) were measured and compared. Twenty-eight immune-mediated necrotizing myopathy (IMNM) patients, 23 dermatomyositis (DM) patients, and 15 anti-synthetase syndrome (ASS) patients were enrolled as disease controls. Correlations between variables were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Limb weakness was observed in 75.7% and neck weakness in 56.8% of patients. Cardiac involvement occurred in 51.4% of patients. Muscle pathology revealed 81.1% of IMNM, 5.4% polymyositis, and 13.5% nonspecific myositis. Microinfarction was observed in 8.1% of patients. Serum ccf-mtDNA levels in AMA-associated IIMs were significantly higher than those in HCs (<i>p</i> &lt; 0.001), but no significant differences between AMA-associated IIMs and IMNM, DM, or ASS. Serum ccf-nDNA levels in AMA-associated IIMs were significantly higher than those in HCs (<i>p</i> = 0.02), and significantly lower than those in DM (<i>p</i> = 0.02). Serum ccf-nDNA levels correlated negatively with MMT8 total scores (<i>r</i>s = −0.458, <i>p</i> = 0.037) and positively with mRS scores (<i>r</i>s = 0.486, <i>p</i> = 0.025). Serum ccf-nDNA levels were significantly higher in the non-remission group (<i>p</i> &lt; 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>AMA-associated IIMs exhibit distinct clinicopathological features. Serum ccf-nDNA may serve as a potential marker for disease severity and prognosis in AMA-associated IIMs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 11","pages":"2127-2138"},"PeriodicalIF":5.3,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10647000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10657889","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":"Limbic network co-localization predicts pharmacoresistance in dysplasia-related epilepsy","authors":"Nathan T. Cohen,&nbsp;Phat Chang,&nbsp;Taha Gholipour,&nbsp;Chima Oluigbo,&nbsp;L. Gilbert Vezina,&nbsp;Hua Xie,&nbsp;Anqing Zhang,&nbsp;William D. Gaillard","doi":"10.1002/acn3.51892","DOIUrl":"10.1002/acn3.51892","url":null,"abstract":"<p>To evaluate the role of focal cortical dysplasia co-localization to cortical functional networks in the development of pharmacoresistance. One hundred thirty-six focal cortical dysplasia patients with 3.0 T or 1.5 T MRI were identified from clinical databases at Children's National Hospital. Clinico-radio-pathologic factors and network co-localization were determined. Using binomial logistic regression, limbic network co-localization (odds ratio 4.164 95% confidence interval 1.02–17.08, <i>p</i> = 0.048), and focal to bilateral tonic–clonic seizures (4.82, 1.30–18.03, <i>p</i> = 0.019) predicted pharmacoresistance. These findings provide clinicians with markers to identify patients with focal cortical dysplasia-related epilepsy at high risk of developing pharmacoresistance and should facilitate earlier epilepsy surgical evaluation.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 11","pages":"2161-2165"},"PeriodicalIF":5.3,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10646997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10224716","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":"Propensity matched comparison of omaveloxolone treatment to Friedreich ataxia natural history data","authors":"David R. Lynch,&nbsp;Angie Goldsberry,&nbsp;Christian Rummey,&nbsp;Jennifer Farmer,&nbsp;Sylvia Boesch,&nbsp;Martin B. Delatycki,&nbsp;Paola Giunti,&nbsp;J. Chad Hoyle,&nbsp;Caterina Mariotti,&nbsp;Katherine D. Mathews,&nbsp;Wolfgang Nachbauer,&nbsp;Susan Perlman,&nbsp;S.H. Subramony,&nbsp;George Wilmot,&nbsp;Theresa Zesiewicz,&nbsp;Lisa Weissfeld,&nbsp;Colin Meyer","doi":"10.1002/acn3.51897","DOIUrl":"10.1002/acn3.51897","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The natural history of Friedreich ataxia is being investigated in a multi-center longitudinal study designated the Friedreich ataxia Clinical Outcome Measures Study (FACOMS). To understand the utility of this study in analysis of clinical trials, we performed a propensity-matched comparison of data from the open-label MOXIe extension (omaveloxolone) to that from FACOMS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>MOXIe extension patients were matched to FACOMS patients using logistic regression to estimate propensity scores based on multiple covariates: sex, baseline age, age of onset, baseline modified Friedreich Ataxia Rating scale (mFARS) score, and baseline gait score. The change from baseline in mFARS at Year 3 for the MOXIe extension patients compared to the matched FACOMS patients was analyzed as the primary efficacy endpoint using mixed model repeated measures analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Data from the MOXIe extension show that omaveloxolone provided persistent benefit over 3 years when compared to an untreated, matched cohort from FACOMS. At each year, in all analysis populations, patients in the MOXIe extension experienced a smaller change from baseline in mFARS score than matched FACOMS patients. In the primary pooled population (136 patients in each group) by Year 3, patients in the FACOMS matched set progressed 6.6 points whereas patients treated with omaveloxolone in MOXIe extension progressed 3 points (difference = −3.6; nominal <i>p</i> value = 0.0001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>These results suggest a meaningful slowing of Friedreich ataxia progression with omaveloxolone, and consequently detail how propensity-matched analysis may contribute to understanding of effects of therapeutic agents. This demonstrates the direct value of natural history studies in clinical trial evaluations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 1","pages":"4-16"},"PeriodicalIF":5.3,"publicationDate":"2023-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.51897","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10205406","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":"Evidence-based consensus guidelines for ALS genetic testing and counseling","authors":"Jennifer Roggenbuck,&nbsp;Breda H. F. Eubank,&nbsp;Joshua Wright,&nbsp;Matthew B. Harms,&nbsp;Stephen J. Kolb,&nbsp;the ALS Genetic Testing and Counseling Guidelines Expert Panel","doi":"10.1002/acn3.51895","DOIUrl":"10.1002/acn3.51895","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Advances in amyotrophic lateral sclerosis (ALS) gene discovery, ongoing gene therapy trials, and patient demand have driven increased use of ALS genetic testing. Despite this progress, the offer of genetic testing to persons with ALS is not yet “standard of care.” Our primary goal is to develop clinical ALS genetic counseling and testing guidelines to improve and standardize genetic counseling and testing practice among neurologists, genetic counselors or any provider caring for persons with ALS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Core clinical questions were identified and a rapid review performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-P) 2015 method. Guideline recommendations were drafted and the strength of evidence for each recommendation was assessed by combining two systems: the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) System and the Evaluation of Genomic Applications in Practice and Prevention (EGAPP). A modified Delphi approach was used to reach consensus among a group of content experts for each guideline statement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 35 guideline statements were developed. In summary, all persons with ALS should be offered single-step genetic testing, consisting of a <i>C9orf72</i> assay, along with sequencing of <i>SOD1, FUS,</i> and <i>TARDBP,</i> at a minimum. The key education and genetic risk assessments that should be provided before and after testing are delineated. Specific guidance regarding testing methods and reporting for <i>C9orf72</i> and other genes is provided for commercial laboratories.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>These evidence-based, consensus guidelines will support all stakeholders in the ALS community in navigating benefits and challenges of genetic testing.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 11","pages":"2074-2091"},"PeriodicalIF":5.3,"publicationDate":"2023-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10646996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10257125","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}