Annals of Neurology最新文献

{"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}

{"title":"Survey of the Landscape of Society Practice Guidelines for Genetic Testing of Neurodevelopmental Disorders","authors":"Siddharth Srivastava MD,&nbsp;Jordan J. Cole MD,&nbsp;Julie S. Cohen ScM,&nbsp;Maya Chopra MBBS, FRACP,&nbsp;Hadley Stevens Smith PhD, MPSA,&nbsp;Matthew A. Deardorff MD, PhD,&nbsp;Ernest Pedapati MD, MS, FAAP,&nbsp;Brian Corner MS,&nbsp;Julia S. Anixt MD,&nbsp;Shafali Jeste MD,&nbsp;Mustafa Sahin MD, PhD,&nbsp;Christina A. Gurnett MD, PhD,&nbsp;Colleen A. Campbell PhD, MS,&nbsp;the Intellectual and Developmental Disabilities Research Center (IDDRC) Workgroup on Advocating for Access to Genomic Testing","doi":"10.1002/ana.27045","DOIUrl":"10.1002/ana.27045","url":null,"abstract":"<p>Genetic testing of patients with neurodevelopmental disabilities (NDDs) is critical for diagnosis, medical management, and access to precision therapies. Because genetic testing approaches evolve rapidly, professional society practice guidelines serve an essential role in guiding clinical care; however, several challenges exist regarding the creation and equitable implementation of these guidelines. In this scoping review, we assessed the current state of United States professional societies' guidelines pertaining to genetic testing for unexplained global developmental delay, intellectual disability, autism spectrum disorder, and cerebral palsy. We describe several identified shortcomings and argue the need for a unified, frequently updated, and easily-accessible cross-specialty society guideline. ANN NEUROL 2024;96:900–913</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 5","pages":"900-913"},"PeriodicalIF":8.1,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337706","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":"Loss-of-Function Variants in CUL3 Cause a Syndromic Neurodevelopmental Disorder.","authors":"Patrick R Blackburn, Frédéric Ebstein, Tzung-Chien Hsieh, Marialetizia Motta, Francesca Clementina Radio, Johanna C Herkert, Tuula Rinne, Isabelle Thiffault, Michele Rapp, Mariel Alders, Saskia Maas, Bénédicte Gerard, Thomas Smol, Catherine Vincent-Delorme, Benjamin Cogné, Bertrand Isidor, Marie Vincent, Ruxandra Bachmann-Gagescu, Anita Rauch, Pascal Joset, Giovanni Battista Ferrero, Andrea Ciolfi, Thomas Husson, Anne-Marie Guerrot, Carlos Bacino, Colleen Macmurdo, Stephanie S Thompson, Jill A Rosenfeld, Laurence Faivre, Frederic Tran Mau-Them, Wallid Deb, Virginie Vignard, Pankaj B Agrawal, Jill A Madden, Alice Goldenberg, François Lecoquierre, Michael Zech, Holger Prokisch, Ján Necpál, Robert Jech, Juliane Winkelmann, Monika Turčanová Koprušáková, Vassiliki Konstantopoulou, John R Younce, Marwan Shinawi, Chloe Mighton, Charlotte Fung, Chantal F Morel, Jordan Lerner-Ellis, Stephanie DiTroia, Magalie Barth, Dominique Bonneau, Ingrid Krapels, Alexander P A Stegmann, Vyne van der Schoot, Theresa Brunet, Cornelia Bußmann, Cyril Mignot, Giuseppe Zampino, Saskia B Wortmann, Johannes A Mayr, René G Feichtinger, Thomas Courtin, Claudia Ravelli, Boris Keren, Alban Ziegler, Linda Hasadsri, Pavel N Pichurin, Eric W Klee, Katheryn Grand, Pedro A Sanchez-Lara, Elke Krüger, Stéphane Bézieau, Hannah Klinkhammer, Peter Michael Krawitz, Evan E Eichler, Marco Tartaglia, Sébastien Küry, Tianyun Wang","doi":"10.1002/ana.27077","DOIUrl":"10.1002/ana.27077","url":null,"abstract":"<p><strong>Objective: </strong>De novo variants in cullin-3 ubiquitin ligase (CUL3) have been strongly associated with neurodevelopmental disorders (NDDs), but no large case series have been reported so far. Here, we aimed to collect sporadic cases carrying rare variants in CUL3, describe the genotype-phenotype correlation, and investigate the underlying pathogenic mechanism.</p><p><strong>Methods: </strong>Genetic data and detailed clinical records were collected via multicenter collaboration. Dysmorphic facial features were analyzed using GestaltMatcher. Variant effects on CUL3 protein stability were assessed using patient-derived T-cells.</p><p><strong>Results: </strong>We assembled a cohort of 37 individuals with heterozygous CUL3 variants presenting a syndromic NDD characterized by intellectual disability with or without autistic features. Of these, 35 have loss-of-function (LoF) and 2 have missense variants. CUL3 LoF variants in patients may affect protein stability leading to perturbations in protein homeostasis, as evidenced by decreased ubiquitin-protein conjugates in vitro. Notably, we show that 4E-BP1 (EIF4EBP1), a prominent substrate of CUL3, fails to be targeted for proteasomal degradation in patient-derived cells.</p><p><strong>Interpretation: </strong>Our study further refines the clinical and mutational spectrum of CUL3-associated NDDs, expands the spectrum of cullin RING E3 ligase-associated neuropsychiatric disorders, and suggests haploinsufficiency via LoF variants is the predominant pathogenic mechanism. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277498","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":"Laser Ablation of Periventricular Nodular Heterotopia for Medically Refractory Epilepsy","authors":"Ryan M. McCormack MD, PhD,&nbsp;Arjun S. Chandran MD,&nbsp;Samden D. Lhatoo MD,&nbsp;Sandipan Pati MD,&nbsp;Zhouxuan Li MS,&nbsp;Katherine Harris MD,&nbsp;Nuria Lacuey MD, PhD,&nbsp;Giridhar Kalamangalam MD, DPhil,&nbsp;Stephen Thompson MD,&nbsp;Nitin Tandon MD","doi":"10.1002/ana.27059","DOIUrl":"10.1002/ana.27059","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Periventricular nodular heterotopia (PVNH) is the most common neuronal heterotopia, frequently resulting in pharmaco-resistant epilepsy. Here, we characterize variables that predict good epilepsy outcomes following surgical intervention using stereo-electroencephalography (SEEG) -informed magnetic resonance-guided laser interstitial thermal therapy (MRgLITT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective review of consecutive cases from a single high-volume epilepsy referral center identified patients who underwent SEEG evaluation for PVNH to characterize the intervention and outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirty-nine patients underwent SEEG-guided MRgLITT of the seizure onset zone (SoZ) in PVNH and associated epileptic tissue. PVNH and polymicrogyria (PMG) were densely sampled with a mean of 16.5 (SD = 2)/209.4 (SD = 36.9) SEEG probes/recording contacts per patient. Ablation principally targeted just the PVNH and cortex that was abnormal on imaging was ablated (5 patients) only if implicated in the SoZ. Volumetric analyses revealed a high percentage of PVNH SoZ ablation (96.6%, SD = 5.3%) in unilateral and bilateral (92.9%, SD = 7.2%) cases. Mean follow-up duration was 31.4 months (SD = 20.9). Seizure freedom (ILAE 1) was excellent: unilateral PVNH without other imaging abnormalities, 80%; PVNH with mesial temporal sclerosis (MTS) or PMG, 63%; bilateral PVNH, 50%. SoZ ablation percentage significantly impacted surgical outcomes (<i>p</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>PVNH plays a central role in seizure genesis as revealed by dense recordings and selective targeting by LITT. MRgLITT represents a transformative technological advance in PVNH-associated epilepsy with seizure control outcomes consistent with those seen in focal lesional epilepsies. In localized unilateral cases and otherwise normal imaging, PVNH ablation without invasive recordings may be considered, and this approach deserves to be explored further. ANN NEUROL 2024;96:1174–1184</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 6","pages":"1174-1184"},"PeriodicalIF":8.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142266402","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":"Clinical, Radiological and Pathological Features of a Large American Cohort of Spinocerebellar Ataxia (SCA27B)","authors":"Widad Abou Chaar MD,&nbsp;Anirudh N. Eranki,&nbsp;Hannah A. Stevens,&nbsp;Sonya L. Watson MS,&nbsp;Darice Y. Wong PhD,&nbsp;Veronica S. Avila,&nbsp;Megan Delfeld,&nbsp;Alexander J. Gary,&nbsp;Sanjukta Tawde MS,&nbsp;Malia Triebold MS,&nbsp;Marcello Cherchi MD, PhD,&nbsp;Tao Xie MD, PhD,&nbsp;Paul J. Lockhart PhD,&nbsp;Melanie Bahlo PhD,&nbsp;David Pellerin MD, MSc,&nbsp;Marie-Josée Dicaire,&nbsp;Matt Danzi PhD,&nbsp;Stephan Zuchner MD, PhD,&nbsp;Bernard C. Brais MD, PhD,&nbsp;Susan Perlman MD,&nbsp;Margit Burmeister PhD,&nbsp;Henry Paulson MD, PhD,&nbsp;Sharan Srinivasan MD, PhD,&nbsp;Lawrence Schut MD,&nbsp;Matthew Bower MS,&nbsp;Khalaf Bushara MD,&nbsp;Chuanhong Liao MS,&nbsp;Vikram G. Shakkottai MD, PhD,&nbsp;John Collins MD, PhD,&nbsp;H. Brent Clark MD, PhD,&nbsp;Soma Das PhD,&nbsp;Brent L. Fogel MD, PhD,&nbsp;Christopher M. Gomez MD, PhD","doi":"10.1002/ana.27060","DOIUrl":"10.1002/ana.27060","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Spinocerebellar ataxia 27B due to GAA repeat expansions in the fibroblast growth factor 14 (<i>FGF14</i>) gene has recently been recognized as a common cause of late-onset hereditary cerebellar ataxia. Here we present the first report of this disease in the US population, characterizing its clinical manifestations, disease progression, pathological abnormalities, and response to 4-aminopyridine in a cohort of 102 patients bearing GAA repeat expansions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We compiled a series of patients with SCA27B, recruited from 5 academic centers across the United States. Clinical manifestations and patient demographics were collected retrospectively from clinical records in an unblinded approach using a standardized form. Post-mortem analysis was done on 4 brains of patients with genetically confirmed SCA27B.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In our cohort of 102 patients with SCA27B, we found that SCA27B was a late-onset (57 ± 12.5 years) slowly progressive ataxia with an episodic component in 51% of patients. Balance and gait impairment were almost always present at disease onset. The principal finding on post-mortem examination of 4 brain specimens was loss of Purkinje neurons that was most severe in the vermis most particularly in the anterior vermis. Similar to European populations, a high percent of patients 21/28 (75%) reported a positive treatment response with 4-aminopyridine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our study further estimates prevalence and further expands the clinical, imaging and pathological features of SCA27B, while looking at treatment response, disease progression, and survival in patients with this disease. Testing for SCA27B should be considered in all undiagnosed ataxia patients, especially those with episodic onset. ANN NEUROL 2024;96:1092–1103</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 6","pages":"1092-1103"},"PeriodicalIF":8.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142224663","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":"Mineralizing Lenticulostriate Vasculopathy and Traumatic Infarction","authors":"Mingyao Li, Tsecheng Chiu, Guofeng Ma, Ning Ma","doi":"10.1002/ana.27079","DOIUrl":"https://doi.org/10.1002/ana.27079","url":null,"abstract":"<h2> Potential Conflicts of Interest</h2>\u0000<p>Nothing to report.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"58 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189435","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":"Annals of Neurology: Volume 96, Number S32, September 2024","authors":"","doi":"10.1002/ana.27074","DOIUrl":"https://doi.org/10.1002/ana.27074","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 S32","pages":"C1"},"PeriodicalIF":8.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142169888","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":"Before, during, and after: An Argument for Safety and Improved Outcome of Thrombolysis in Acute Ischemic Stroke with Direct Oral Anticoagulant Treatment","authors":"Sanaz Monjazeb MD,&nbsp;Heather V. Chang BS,&nbsp;Patrick D. Lyden MD","doi":"10.1002/ana.27058","DOIUrl":"10.1002/ana.27058","url":null,"abstract":"<p>Direct oral anticoagulants are the primary stroke prevention option in patients with atrial fibrillation. Anticoagulant use before stroke, however, might inhibit clinician comfort with thrombolysis if a stroke does occur. Resuming anticoagulants after ischemic stroke is also problematic for fear of hemorrhage. We describe extensive literature showing that thrombolysis is safe after stroke with direct anticoagulant use. Early reinstitution of direct anticoagulant treatment is associated with lower risk of embolic recurrence and lower hemorrhage risk. The use of direct anticoagulants before, during, and after thrombolysis appears to be safe and is likely to promote improved outcomes after ischemic stroke. ANN NEUROL 2024;96:871–886</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 5","pages":"871-886"},"PeriodicalIF":8.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189453","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.27075","DOIUrl":"https://doi.org/10.1002/ana.27075","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 S32","pages":"i-iii"},"PeriodicalIF":8.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142169889","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":"149th Annual Meeting American Neurological Association","authors":"","doi":"10.1002/ana.27051","DOIUrl":"https://doi.org/10.1002/ana.27051","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 S32","pages":"S1-S310"},"PeriodicalIF":8.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142169890","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}