Annals of Neurology最新文献

{"title":"Annals of Neurology: Volume 96, Number S33, November 2024","authors":"","doi":"10.1002/ana.27085","DOIUrl":"https://doi.org/10.1002/ana.27085","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 S33","pages":"C1"},"PeriodicalIF":8.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142664607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"53rd Child Neurology Society Annual Meeting","authors":"","doi":"10.1002/ana.27080","DOIUrl":"10.1002/ana.27080","url":null,"abstract":"<p>\u0000 \u0000 </p><p>Abatkun, M.  199</p><p>Abdelmoity, A.  PL2-5</p><p>Abdelmoity, L.  316</p><p>Abdullahi, S.  92</p><p>Abe, K.  41</p><p>Abend, N.  PL2-3</p><p>Abera, S.  64</p><p>Abler, V.  87</p><p>Aboulsaoud, P.  79</p><p>Abreu, N.  280</p><p>Abushanab, E.  241</p><p>Acosta, M.  GAT1-2, 222</p><p>Adams, D.  222</p><p>Adams, H.  76</p><p>Adams, S.  241</p><p>Adanene, A.  199</p><p>Adeniyi-Jones, S.  85</p><p>Aduru, C.  285</p><p>Agarwal, R.  53</p><p>Agarwal, S.  156</p><p>Aggarwal, M.  170</p><p>Aghai, Z.  85</p><p>Agner, S.  187</p><p>Aguilar, S.  GAT2-1</p><p>Ahmadi, S.  23</p><p>Ahmed, A.  232</p><p>Ahmed, M.  7</p><p>Ahn, S.-H.  131</p><p>Ahsan, N.  248</p><p>Ailion, A.  98</p><p>Aimetti, A.  9, 205</p><p>Aitken, A.  235</p><p>Aiuti, A.  GAT1-1</p><p>Al Nimir, H.  89</p><p>Al Shouli, R.  329</p><p>Albazron, F.  51</p><p>Albor, L.  54, 107, 120</p><p>Alcaraz, W.  240</p><p>Aldana, P.  32</p><p>Aldinger, K.  30</p><p>Alecu, J.  PL1-3, 145</p><p>Alfano, L.  280</p><p>Algee, S.  107</p><p>Alhadid, K.  196</p><p>Ali, E.  125</p><p>Alleman, K.  8</p><p>Allen, S.  207</p><p>Allhusen, V.  185</p><p>Allison, T.  307</p><p>Almashnu, S.  GAT2-4</p><p>Alosi, S.  235</p><p>Alsayouf, H.  6</p><p>Al-Yahia, M.  128</p><p>Amin, H.  35</p><p>Amin, S.  9</p><p>Amoah, N.  20</p><p>Anand, P.  111</p><p>Ananth, A.  242</p><p>Andrade-Machado, R.  241</p><p>Andrews, A.  20, 153</p><p>Andrews, C.  214</p><p>Andringa-Seed, R.  221</p><p>Angelis, D.  121</p><p>Ankar, A.  57</p><p>Annesley, C.  117</p><p>Anwar, S.  164</p><p>Anwar, T.  17, 38, 69, 86, 254</p><p>Aquino, P.  PL3-1, 270</p><p>Aradhya, S.  GAT2-1, 209</p><p>Aras, S.  PL2-5, 279</p><p>Aravamuthan, B.  75</p><p>Arellano, J.  191, 286, 319</p><p>Arias, J.  169</p><p>Arkalgud, A.  269</p><p>Armstrong, D.  281</p><p>Aronin, N.  207</p><p>Arroyave-Wessel, M.  221</p><p>Arroyo, M.  127</p><p>Asarnow, R.  49</p><p>Aschbacher-Smith, L.  93</p><p>Asmar, Y.  26, 154</p><p>Astorga, G.  201</p><p>Atkinson, S.  81, 102</p><p>Au, J.  126</p><p>Augustine, E.  268</p><p>Austin, C.  295</p><p>Autio, K.  137</p><p>Auvin, S.  118, 219, 228</p><p>Avula, S.  292</p><p>Aykanat, A.  167</p><p>Bach, A.  PL2-7</p><p>Bacon, G.  243</p><p>Bacon, K.  168</p><p>Bacus, P.  15</p><p>Badh, R.  64</p><p>Bae, G.  8</p><p>Baiandurova, A.  298</p><p>Bailey, K.  208</p><p>Baim, A.  PL1-5</p><p>Bain, J.  183</p><p>Bajikar, S.  PL2-5</p><p>Baker, F.  PL1-7</p><p>Baker, M.  157</p><p>Bakulski, K.  16</p><p>Balamurugan, C.  42</p><p>Balasubramaniam, S.  85</p><p>Baldoli, C.  GAT1-1</p><p>Ballance, E.  3</p><p>Ballou, E.  253</p><p>Balls-Berry, J.  252</p><p>Banerjee, A.  PL2-4</p><p>Bansal, S.  84</p><p>Banwell, B.  PL2-7, PL3-4</p><p>Barber, J.  20, 66</p><p>Barisano, G.  PL1-7, 49</p><p>Barnfather, A.  GAT2-3</p><p>Baronio, D.  122</p><p>Barrett, E.  20</p><p>Barry, D.  231</p><p>Barry, M.  246, 266</p><p>Barsh, G.  312</p><p>Bartscherer, A.  48</p><p>Bass, N.  241</p><p>Bassan, H.  GAT2-4</p><p>Batschelett, M.  93</p><p>Batt","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 S33","pages":"S1-S162"},"PeriodicalIF":8.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information – TOC","authors":"","doi":"10.1002/ana.27086","DOIUrl":"https://doi.org/10.1002/ana.27086","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 S33","pages":"i-iii"},"PeriodicalIF":8.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142664608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polygenic Landscape of Cryptogenic New-Onset Refractory Status Epilepticus: A Comprehensive Whole-Genome Sequencing Study","authors":"Yoonhyuk Jang,&nbsp;Sung Eun Hong,&nbsp;Soo Hyun Ahn,&nbsp;Su Yee Mon,&nbsp;Ji Hye You,&nbsp;Kon Chu,&nbsp;Sang Kun Lee,&nbsp;Murim Choi,&nbsp;Soon-Tae Lee","doi":"10.1002/ana.27100","DOIUrl":"10.1002/ana.27100","url":null,"abstract":"<p>Cryptogenic new-onset refractory status epilepticus (cNORSE) is a devastating condition with unclear pathogenesis. Here, we analyzed the genetic underprints of 31 cNORSE patients from an autoimmune encephalitis observational cohort through whole-genome sequencing. Compared to their controls, cNORSE patients exhibited elevated polygenic risk scores (PRS) for traits associated with autoimmune diseases. The individual PRS against these diseases were correlated with specific clinical phenotypes of cNORSE. The variants were enriched in genes expressed in the central nervous system and lymphocytes. These results suggest a shared genetic framework between cNORSE and other autoimmune/autoinflammatory diseases, and its involvement in the disease pathogenesis. ANN NEUROL 2024;96:1201–1208</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 6","pages":"1201-1208"},"PeriodicalIF":8.1,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Relationship between Framingham Stroke Risk Profile on Incident Dementia and Alzheimer's Disease: A 40-Year Follow-Up Study Highlighting Female Vulnerability","authors":"Jing Yuan MD, MPH,&nbsp;Qiushan Tao MD, MS,&nbsp;Ting Fang Alvin Ang MD, MPH,&nbsp;Chunyu Liu PhD,&nbsp;Sherral Devine PhD,&nbsp;Sanford H. Auerbach MD,&nbsp;Jesse Mez MD,&nbsp;Lindsay A. Farrer PhD,&nbsp;Wei Qiao Qiu MD, PhD,&nbsp;Rhoda Au PhD","doi":"10.1002/ana.27108","DOIUrl":"10.1002/ana.27108","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Sex differences in the association between cardiovascular risk factors and the incident all-cause dementia and the subtype Alzheimer's disease (AD) risk are unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Framingham Heart Study (FHS) participants (n = 4,171, 54% women, aged 55 to 69 years) were included at baseline and followed up to 40 years. The Framingham Stroke Risk Profile (FSRP) was dichotomized into 2 levels (cutoff: 75th percentile of the FSRP z-scores). Cause-specific hazard models, with death as a competing event, and restricted mean survival time (RMST) model were used to analyze the association between FSRP levels and incident all-cause dementia and AD. Interactions between FSRP and sex were estimated, followed by a sex-stratified analysis to examine the sex modification effect.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>High FSRP was significantly associated with all-cause dementia (hazard ratio [HR] = 1.25, robust 95% confidence interval [CI] = 1.21 to 1.29, <i>p &lt;</i> 0.001) and AD (HR = 1.58, robust 95% CI = 1.57 to 1.59, <i>p &lt;</i> 0.001) in cause-specific hazard models. High FSRP was significantly associated with incident dementia (HR = 2.81, robust 95% CI = 2.75 to 2.87, <i>p</i> &lt; 0.001) and AD (HR = 2.96, robust 95% CI = 2.36 to 3.71, <i>p</i> &lt; 0.001) in women, but not in men. Results were consistent in the RMST models. Current diabetes and high systolic blood pressure as FSRP components were significantly associated with dementia and AD in women but not in men.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>High FSRP in mid- to early late life is a critical risk factor for all-cause dementia and AD, particularly in women. Sex-specific interventions and further research to elucidate underlying mechanisms are warranted. ANN NEUROL 2024;96:1124–1134</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 6","pages":"1124-1134"},"PeriodicalIF":8.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Priorities and Recommendations to Make ALS a Livable Disease Emanating from the 2024 National Academies of Sciences, Engineering, and Medicine Report Living with ALS","authors":"Ileana M. Howard MD,&nbsp;Suma Babu MBBS, MPH,&nbsp;Chelsey Carter PhD, MPH,&nbsp;Stacey A. Sakowski PhD,&nbsp;Jerome E. Kurent MD, MS, MPH,&nbsp;Merit E. Cudkowicz MD, MSC,&nbsp;Eva L. Feldman MD, PhD","doi":"10.1002/ana.27097","DOIUrl":"10.1002/ana.27097","url":null,"abstract":"<p>Amyotrophic lateral sclerosis (ALS) is a relentless, fatal neurodegenerative disease. The progressive loss of voluntary muscle function, diagnostic delays, lack of effective treatments, and challenges accessing multidisciplinary care and resources have tremendous impact on quality of life. The congressionally directed ALS committee of the National Academies of Science, Engineering, and Medicine, in their 2024 report “Living with ALS,” recommends critical actions for specific United States stakeholders to make ALS a livable disease over the next decade. This review summarizes the context and recommendations of the report. Advocacy efforts are critical to make these recommendations a reality for the ALS community. ANN NEUROL 2024;96:1035–1039</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 6","pages":"1035-1039"},"PeriodicalIF":8.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pro-Ictal EEG Scheduling Improves the Yield of Epilepsy Monitoring: Validating the Use of Multiday Seizure Cycles to Optimize Video-EEG Timing","authors":"Jodie Naim-Feil PhD,&nbsp;Rachel E. Stirling PhD,&nbsp;Philippa J. Karoly PhD,&nbsp;Daniel Payne PhD,&nbsp;Nicholas Winterling MEng,&nbsp;Dominique Eden BEng(Hons),&nbsp;Mark J. Cook MBBS, MD,&nbsp;David B. Grayden PhD,&nbsp;Matias Maturana PhD,&nbsp;Dean R. Freestone PhD,&nbsp;Ewan S. Nurse PhD","doi":"10.1002/ana.27078","DOIUrl":"10.1002/ana.27078","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>A significant challenge of video-electroencephalography (vEEG) in epilepsy diagnosis is timing monitoring sessions to capture epileptiform activity. In this study, we introduce and validate “pro-ictal EEG scheduling”, a method to schedule vEEG monitoring to coincide with periods of increased seizure likelihood as a low-risk approach to enhance the diagnostic yield.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A database of long-term ambulatory vEEG monitoring sessions (n = 5,038) of adults and children was examined. Data from linked electronic seizure diaries were extracted (minimum 10 self-reported events) to generate cycle-based estimates of seizure risk. In adults, vEEG monitoring sessions coinciding with periods of estimated high-risk were allocated to the high-risk group (n = 305) and compared to remaining studies (baseline: n = 3,586). Test of proportions and risk-ratios (RR) were applied to index differences in proportions and likelihood of capturing outcome measures (abnormal report, confirmed seizure, and diary event) during monitoring. The impact of clinical and demographic factors (age, sex, epilepsy-type, and medication) was also explored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>During vEEG monitoring, the high-risk group was significantly more likely to have an abnormal vEEG report (190/305:62% vs 1,790/3,586:50% [%change = 12%], RR = 1.25, 95% confidence interval [CI] = [1.137–1.370], <i>p</i> &lt; 0.001), present with a confirmed seizure (56/305:18% vs 424/3,586:11% [%change = 7%], RR = 1.63, 95% CI = [1.265–2.101], <i>p</i> &lt; 0.001) and report an event (153/305:50% vs 1,267/3,586:35% (%change = 15%), RR = 1.420, 95% CI = [1.259:1.602], <i>p</i> &lt; 0.001). Similar effects were observed across clinical and demographic features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This study provides the first large-scale validation of pro-ictal EEG scheduling in improving the yield of vEEG. This innovative approach offers a pragmatic and low-risk strategy to enhance the diagnostic capabilities of vEEG monitoring, significantly impacting epilepsy management. ANN NEUROL 2024;96:1148–1159</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 6","pages":"1148-1159"},"PeriodicalIF":8.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and Distribution of Intracranial Vessel Occlusion on Angiography and Its Association with Functional Outcome in Patients with Atrial Fibrillation Presenting with Ischemic Stroke","authors":"Alexander P. Benz,&nbsp;Thomas R. Meinel,&nbsp;Alexander Salerno,&nbsp;Morin Beyeler,&nbsp;Davide Strambo,&nbsp;Johannes Kaesmacher,&nbsp;Alexandros A. Polymeris,&nbsp;Timo Kahles,&nbsp;Mira Katan,&nbsp;Stefan T. Engelter,&nbsp;Emmanuel Carrera,&nbsp;Elisabeth Dirren,&nbsp;Nils Peters,&nbsp;Carlo W. Cereda,&nbsp;Georg Kägi,&nbsp;Susanne Renaud,&nbsp;Susanne Wegener,&nbsp;Manuel Bolognese,&nbsp;Leo H. Bonati,&nbsp;Urs Fischer,&nbsp;Marcel Arnold,&nbsp;Patrik Michel,&nbsp;Ashkan Shoamanesh,&nbsp;Stuart J. Connolly,&nbsp;David J. Seiffge,&nbsp;the Swiss Stroke Registry Investigators","doi":"10.1002/ana.27084","DOIUrl":"10.1002/ana.27084","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To determine the prevalence and distribution of intracranial vessel occlusion identified on computed tomography (CT) or magnet resonance (MR) angiography and to explore its association with functional outcome in patients with atrial fibrillation (AF) and ischemic stroke.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Multicenter cohort study enrolling consecutive patients with AF with imaging-confirmed ischemic stroke who underwent CT- or MR-angiography on admission (2014–2022). Multivariable regression was used to explore the association between intracranial vessel occlusion and poor functional outcome (modified Rankin Scale score 3–6) at 90 days.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The analysis included 10,164 patients (median age 81.5 years, 47.8% female, median National Institutes of Health Stroke Scale score on admission 6; 14.7% on a vitamin K antagonist [VKA], 27.5% on a direct oral anticoagulant [DOAC], 57.8% not receiving oral anticoagulation). Angiography showed intracranial vessel occlusion in 5,190 patients (51.1%), affecting the anterior cerebral circulation in 87.4%. Overall, 29.2% and 29.4% of patients received thrombolysis and mechanical thrombectomy, respectively. The proportion of patients with poor functional outcome at 90 days was 60.6% and 42.7% in those with and without vessel occlusion, respectively. In multivariable analyses, vessel occlusion was associated with poor functional outcome (adjusted odds ratio [aOR]: 1.95, 95% confidence interval [CI]: 1.71–2.22) with consistent results in subgroups according to oral anticoagulation use (VKA, aOR: 1.98, 95% CI: 1.40–2.80; DOAC, aOR: 2.35, 95% CI: 1.83–3.03; none, aOR: 1.76, 95% CI: 1.49–2.09).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Intracranial vessel occlusion is common in patients with AF with ischemic stroke, mainly affects the anterior circulation and is associated with poor functional outcome. ANN NEUROL 2024;96:1115–1123</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 6","pages":"1115-1123"},"PeriodicalIF":8.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MEK Pathway Inhibitor-Mediated Response in BRAF V600-Mutant Melanoma with Brain Parenchymal and Leptomeningeal Metastases","authors":"Saud Alhusaini MD, PhD,&nbsp;Lewis Naya BA,&nbsp;Sunil A. Reddy MD,&nbsp;Chirag B. Patel MD, PhD","doi":"10.1002/ana.27062","DOIUrl":"10.1002/ana.27062","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 6","pages":"1227-1229"},"PeriodicalIF":8.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon Stimulated Gene Expression Is a Biomarker for Primary Mitochondrial Disease","authors":"Nandaki Keshavan MRCPCH, PhD,&nbsp;Lana Mhaldien MSc,&nbsp;Kimberly Gilmour PhD,&nbsp;Shamima Rahman FRCP, PhD","doi":"10.1002/ana.27081","DOIUrl":"10.1002/ana.27081","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Mitochondria are implicated in regulation of the innate immune response. We hypothesized that abnormalities in interferon signaling may contribute to pathophysiology in patients with primary mitochondrial disease (PMD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Expression of interferon stimulated genes (ISGs) was measured by real-time polymerase chain reaction (PCR) in whole blood samples from a cohort of patients with PMD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Upregulated ISG expression was observed in a high proportion (41/55, 75%) of patients with PMD on at least 1 occasion, most frequently <i>IFI27</i> upregulation, seen in 50% of the samples. Some patients had extremely high <i>IFI27</i> levels, similar to those seen in patients with primary interferonopathies. A statistically significant correlation was observed between elevated <i>IFI27</i> gene expression and PMD, but not between <i>IFI27</i> and secondary mitochondrial dysfunction, suggesting that ISG upregulation is a biomarker of PMD. In some patients with PMD, ISG abnormalities persisted on repeat measurement over several years, indicative of ongoing chronic inflammation. Subgroup analyses suggested common ISG signatures in patients with similar mitochondrial disease mechanisms and positive correlations with disease severity among patients with identical genetic diagnoses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Dysregulated interferon signaling is frequently seen in patients with PMD suggesting that interferon dysregulation is a contributor to pathophysiology. This may indicate a role for repurposing of immunomodulatory therapies for the treatment of PMDs by targeting interferon signaling. ANN NEUROL 2024;96:1185–1200</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 6","pages":"1185-1200"},"PeriodicalIF":8.1,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}