Annals of Neurology最新文献

{"title":"Slowly Expanding Lesions Differentiate Pediatric Multiple Sclerosis from Myelin Oligodendrocyte Glycoprotein Antibody Disease","authors":"Giulia Fadda MD,&nbsp;Brenda Banwell MD,&nbsp;Colm Elliott PhD,&nbsp;Dumitru Fetco MD,&nbsp;Douglas L. Arnold MD,&nbsp;Patrick Waters PhD,&nbsp;E. Ann Yeh MD,&nbsp;Ruth Ann Marrie MD PhD,&nbsp;Amit Bar-Or MD,&nbsp;Sridar Narayanan PhD,&nbsp;the Canadian Pediatric Demyelinating Disease Network","doi":"10.1002/ana.27066","DOIUrl":"10.1002/ana.27066","url":null,"abstract":"<p>Slowly expanding lesions (SELs) in adults with multiple sclerosis (MS) indicate a progressive pathological process. Whether SELs are present in pediatric-onset MS (POMS) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is unknown. We studied 19 children with POMS and 14 with MOGAD (median age 14.3 and 9.4 years, respectively) recruited to the Canadian Pediatric Demyelinating Disease Study with: (1) ≥3 research scans 12 months apart; and (2) ≥1 T2-lesions on the earliest scan. A total of 70 SELs from 16 POMS participants and 1 SEL in the MOGAD group were detected. SELs are an early feature of POMS and essentially not a feature of MOGAD. ANN NEUROL 2024;96:1086–1091</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 6","pages":"1086-1091"},"PeriodicalIF":8.1,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144500","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":"Guanylate Kinase 1 Deficiency: A Novel and Potentially Treatable Mitochondrial DNA Depletion/Deletions Disease","authors":"Agustin Hidalgo-Gutierrez PhD,&nbsp;Jonathan Shintaku,&nbsp;Javier Ramon,&nbsp;Eliana Barriocanal-Casado,&nbsp;Alba Pesini,&nbsp;Russell P. Saneto,&nbsp;Gloria Garrabou,&nbsp;Jose Cesar Milisenda,&nbsp;Ana Matas-Garcia,&nbsp;Laura Gort,&nbsp;Olatz Ugarteburu,&nbsp;Yue Gu,&nbsp;Lahari Koganti,&nbsp;Tian Wang,&nbsp;Saba Tadesse,&nbsp;Megi Meneri,&nbsp;Monica Sciacco,&nbsp;Shuang Wang,&nbsp;Kurenai Tanji,&nbsp;Marshall S. Horwitz,&nbsp;Michael O. Dorschner,&nbsp;Mahesh Mansukhani,&nbsp;Giacomo Pietro Comi,&nbsp;Dario Ronchi,&nbsp;Ramon Marti,&nbsp;Antonia Ribes,&nbsp;Frederic Tort,&nbsp;Michio Hirano MD","doi":"10.1002/ana.27071","DOIUrl":"10.1002/ana.27071","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Mitochondrial DNA (mtDNA) depletion/deletions syndrome (MDDS) comprises a group of diseases caused by primary autosomal defects of mtDNA maintenance. Our objective was to study the etiology of MDDS in 4 patients who lack pathogenic variants in known genetic causes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Whole exome sequencing of the probands was performed to identify pathogenic variants. We validated the mitochondrial defect by analyzing mtDNA, mitochondrial dNTP pools, respiratory chain activities, and GUK1 activity. To confirm pathogenicity of GUK1 deficiency, we expressed 2 GUK1 isoforms in patient cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified biallelic <i>GUK1</i> pathogenic variants in all 4 probands who presented with ptosis, ophthalmoparesis, and myopathic proximal limb weakness, as well as variable hepatopathy and altered T-lymphocyte profiles. Muscle biopsies from all probands showed mtDNA depletion, deletions, or both, as well as reduced activities of mitochondrial respiratory chain enzymes. <i>GUK1</i> encodes guanylate kinase, originally identified as a cytosolic enzyme. Long and short isoforms of GUK1 exist. We observed that the long isoform is intramitochondrial and the short is cytosolic. In probands’ fibroblasts, we noted decreased GUK1 activity causing unbalanced mitochondrial dNTP pools and mtDNA depletion in both replicating and quiescent fibroblasts indicating that GUK1 deficiency impairs de novo and salvage nucleotide pathways. Proband fibroblasts treated with deoxyguanosine and/or forodesine, a purine phosphatase inhibitor, ameliorated mtDNA depletion, indicating potential pharmacological therapies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Primary GUK1 deficiency is a new and potentially treatable cause of MDDS. The cytosolic isoform of GUK1 may contribute to the T-lymphocyte abnormality, which has not been observed in other MDDS disorders. ANN NEUROL 2024;96:1209–1224</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 6","pages":"1209-1224"},"PeriodicalIF":8.1,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124302","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":"Comparison of Perfusion Imaging Definitions of the No-Reflow Phenomenon after Thrombectomy—What Is the Best Perfusion Imaging Definition?","authors":"Chloe A. Mutimer MD,&nbsp;Adnan Mujanovic MD,&nbsp;Johannes Kaesmacher MD,&nbsp;Leonid Churilov PhD,&nbsp;Timothy J. Kleinig PhD,&nbsp;Mark W. Parsons PhD,&nbsp;Peter J. Mitchell MMed,&nbsp;Bruce C.V. Campbell PhD,&nbsp;Felix Ng PhD","doi":"10.1002/ana.27073","DOIUrl":"10.1002/ana.27073","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <p>The no-reflow phenomenon is a potential contributor to poor outcome despite successful thrombectomy. There are multiple proposed imaging-based definitions of no-reflow leading to wide variations in reported prevalence. We investigated the agreement between existing imaging definitions and compared the characteristics and outcomes of patients identified as having no-reflow.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed an external validation of 4 existing published definitions of no-reflow in thrombectomy patients with extended Thrombolysis in Cerebral Infarction scale 2c to 3 (eTICI2c-3) angiographic reperfusion who underwent 24-hour perfusion imaging from 2 international randomized controlled trials (EXTEND-IA TNK part-1 and 2) and a multicenter prospective observational study. Receiver-operating-characteristic and Bayesian-information-criterion (BIC) analyses were performed with the outcome variable being dependent-or-dead at 90-days (modified Rankin Score [mRS] ≥3).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 131 patients analyzed, the prevalence of no-reflow significantly varied between definitions (0.8–22.1%; <i>p</i> &lt; 0.001). There was poor agreement between definitions (kappa 5/6 comparisons &lt;0.212). Among patients with no-reflow according to at least 1 definition, there were significant differences between definitions in the intralesional interside differences in cerebral blood flow (CBF) (<i>p</i> = 0.006), cerebral blood volume (CBV) (<i>p</i> &lt; 0.001), and mean-transit-time (MTT) (<i>p</i> = 0.005). No-reflow defined by 3 definitions was associated with mRS ≥3 at 90 days. The definition of &gt;15% CBV or CBF asymmetry was the only definition that improved model fit on BIC analysis (ΔBIC = −8.105) and demonstrated an association between no-reflow and clinical outcome among patients with eTICI3 reperfusion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Existing imaging definitions of no-reflow varied significantly in prevalence and post-treatment perfusion imaging profile, potentially explaining the variable prevalence of no-reflow reported in literature. The definition of &gt;15% CBV or CBF asymmetry best discriminated for functional outcome at 90 days, including patients with eTICI3 reperfusion. ANN NEUROL 2024;96:1104–1114</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 6","pages":"1104-1114"},"PeriodicalIF":8.1,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118506","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":"RAN Translation of C9orf72-Related Dipeptide Repeat Proteins in Zebrafish Recapitulates Hallmarks of Amyotrophic Lateral Sclerosis and Identifies Hypothermia as a Therapeutic Strategy","authors":"David J. Burrows PhD,&nbsp;Alexander McGown PhD,&nbsp;Olfat Abduljabbar PhD,&nbsp;Lydia M. Castelli PhD,&nbsp;Pamela J. Shaw MBBS, MD,&nbsp;Guillaume M. Hautbergue PhD,&nbsp;Tennore M. Ramesh DVM, PhD","doi":"10.1002/ana.27068","DOIUrl":"10.1002/ana.27068","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Hexanucleotide repeat expansions in the <i>C9orf72</i> gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). A large body of evidence implicates dipeptide repeats (DPRs) proteins as one of the main drivers of neuronal injury in cell and animal models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A pure repeat-associated non-AUG (RAN) translation zebrafish model of C9orf72-ALS/FTD was generated. Embryonic and adult transgenic zebrafish lysates were investigated for the presence of RAN-translated DPR species and adult-onset motor deficits. Using C9orf72 cell models as well as embryonic C9orf72-ALS/FTD zebrafish, hypothermic-therapeutic temperature management (TTM) was explored as a potential therapeutic option for C9orf72-ALS/FTD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Here, we describe a pure RAN translation zebrafish model of C9orf72-ALS/FTD that exhibits significant RAN-translated DPR pathology and progressive motor decline. We further demonstrate that hypothermic-TTM results in a profound reduction in DPR species in C9orf72-ALS/FTD cell models as well as embryonic C9orf72-ALS/FTD zebrafish.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The transgenic model detailed in this paper provides a medium throughput in vivo research tool to further investigate the role of RAN-translation in C9orf72-ALS/FTD and further understand the mechanisms that underpin neuroprotective strategies. Hypothermic-TTM presents a viable therapeutic avenue to explore in the context of C9orf72-ALS/FTD. ANN NEUROL 2024;96:1058–1069</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 6","pages":"1058-1069"},"PeriodicalIF":8.1,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102525","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":"Fetal Intraparenchymal Hemorrhage Imaging Patterns, Etiology, and Outcomes: A Single Center Cohort Study","authors":"Rachel Vassar MD,&nbsp;Elizabeth George MBBS,&nbsp;Andrew Mogga BS,&nbsp;Yi Li MD,&nbsp;Mary E. Norton MD,&nbsp;Orit Glenn MD,&nbsp;Dawn Gano MD, MAS","doi":"10.1002/ana.27072","DOIUrl":"10.1002/ana.27072","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study examines associations among fetal brain magnetic resonance imaging (MRI) injury patterns, etiologies, and outcomes in fetal intraparenchymal hemorrhage (IPH).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This is a retrospective, single-center cohort study of IPH diagnosed on fetal MRI (1996–2022). IPH and associated abnormalities were categorized by 2 pediatric neuroradiologists; electronic medical records were reviewed by 2 pediatric neurologists to classify etiology and outcomes including cerebral palsy, epilepsy, developmental delay, and death.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Forty-four fetuses with IPH were identified (34 singleton and 10 twin gestations) with MRI at median 24 weeks gestation (interquartile range [IQR] = 22–28 weeks). IPH was commonly supratentorial (84%) and focal (50%) or focal with diffuse injury (43%) and was often associated with germinal matrix hemorrhage (GMH; 75%) and/or intraventricular hemorrhage (IVH; 52%). An etiology was identified in 75%, including twin-twin transfusion syndrome (TTTS, n = 10), COL4A1/2 variants (n = 8), or other fetal/maternal conditions (n = 15). COL4A1/2 variants were associated with focal IPH and the presence of hemorrhagic porencephaly, and intrauterine transfusion was associated with infratentorial hemorrhage. Twenty-two fetuses were liveborn, and 18 pregnancies were terminated. Among those with follow-up ≥ 12 months (median = 7 years), 12 of 13 had cerebral palsy, 6 of 13 had developmental delay, and 5 of 13 had epilepsy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>An etiology for fetal IPH with or without GMH-IVH is identified in most cases in our cohort and is commonly TTTS, COL4A1/2 variants, or other maternal/fetal comorbidities. Pattern of fetal IPH on MRI is associated with etiology. Cerebral palsy and neurodevelopmental impairment were common in liveborn infants. Genetic studies should be considered in cases of fetal IPH without an otherwise apparent cause. ANN NEUROL 2024;96:1137–1147</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 6","pages":"1137-1147"},"PeriodicalIF":8.1,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102524","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":"Correction to “Mutations in CLCN6 as a Novel Genetic Cause of Neuronal Ceroid Lipofuscinosis in Patients and a Murine Model”","authors":"","doi":"10.1002/ana.27076","DOIUrl":"10.1002/ana.27076","url":null,"abstract":"<p>\u0000 <span>He, H</span>, <span>Cao, X</span>, <span>He, F</span>, et al. <span>Mutations in <i>CLCN6</i> as a novel genetic cause of neuronal ceroid lipofuscinosis in patients and a murine model</span>. <i>Ann Neurol</i> <span>2024</span>; <span>96</span>: <span>608</span>–<span>624</span>. https://doi.org/10.1002/ana.27002\u0000 </p><p>In the above article, the title was incorrectly published as “Mutations in <i>CLCN6</i> as a Novel Genetic Cause of Neuronal Ceroid Lipofuscinosis in a Murine Model.”</p><p>The correct title is “Mutations in <i>CLCN6</i> as a Novel Genetic Cause of Neuronal Ceroid Lipofuscinosis in Patients and a Murine Model.” The online version of this article has been corrected accordingly.</p><p>We apologize for this error.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 4","pages":"822"},"PeriodicalIF":8.1,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102523","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":"Single-Nucleus RNA Sequencing Unravels Early Mechanisms of Human Becker Muscular Dystrophy","authors":"Zhihao Xie PhD,&nbsp;Chang Liu MD,&nbsp;Chengyue Sun MD, PhD,&nbsp;Yilin Liu MD, PhD,&nbsp;Jieru Peng MD,&nbsp;Lingchao Meng MD,&nbsp;Jianwen Deng PhD,&nbsp;Zhaoxia Wang MD, PhD,&nbsp;Chunxia Yang PhD,&nbsp;Yun Yuan MD, PhD,&nbsp;Zhiying Xie MD, PhD","doi":"10.1002/ana.27070","DOIUrl":"10.1002/ana.27070","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The transcriptional heterogeneity at a single-nucleus level in human Becker muscular dystrophy (BMD) dystrophic muscle has not been explored. Here, we aimed to understand the transcriptional heterogeneity associated with myonuclei, as well as other mononucleated cell types that underly BMD pathogenesis by performing single-nucleus RNA sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We profiled single-nucleus transcriptional profiles of skeletal muscle samples from 7 BMD patients and 3 normal controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 17,216 nuclei (12,879 from BMD patients and 4,337 from controls) were classified into 13 known cell types, including 9 myogenic lineages and 4 non-myogenic lineages, and 1 unclassified nuclear type according to their cell identities. Among them, type IIx myonuclei were the first to degenerate in response to dystrophin reduction. Differential expression analysis revealed that the fibro-adipogenic progenitors (FAPs) population had the largest transcriptional changes among all cell types. Sub-clustering analysis identified a significantly compositional increase in the activated FAPs (aFAPs) subpopulation in BMD muscles. Pseudotime analysis, regulon inference, and deconvolution analysis of bulk RNA-sequencing data derived from 29 BMD patients revealed that the aFAPs subpopulation, a distinctive and previously unrecognized mononuclear subtype, was profibrogenic and expanded in BMD patients. Muscle quantitative real-time polymerase chain reaction and immunofluorescence analysis confirmed that the mRNA and protein levels of the aFAPs markers including <i>LUM</i>, <i>DCN</i>, and <i>COL1A1</i> in BMD patients were significantly higher than those in controls, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our results provide insights into the transcriptional diversity of human BMD muscle at a single-nucleus resolution and new potential targets for anti-fibrosis therapies in BMD. ANN NEUROL 2024;96:1070–1085</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 6","pages":"1070-1085"},"PeriodicalIF":8.1,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078526","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":"Reply to “Letter to the Editor: Assessing the Efficacy and Limitations of Rescue Thrombectomy in Acute Ischemic Stroke”","authors":"Aaron Rodriguez-Calienes MD,&nbsp;Fazeel M. Siddiqui MD,&nbsp;Milagros Galecio-Castillo MD,&nbsp;Mahmoud H. Mohammaden MD,&nbsp;Jaydevsinh N. Dolia MD,&nbsp;Jonathan A. Grossberg MD,&nbsp;Aqueel Pabaney MD,&nbsp;Ameer E. Hassan MD,&nbsp;Wondwossen G. Tekle MD,&nbsp;Hamzah Saei MD,&nbsp;Samantha Miller MD,&nbsp;Shahram Majidi MD,&nbsp;Johanna T. Fifi MD,&nbsp;Gabrielle Valestin MD,&nbsp;James E. Siegler MD,&nbsp;Mary Penckofer MD,&nbsp;Linda Zhang MD,&nbsp;Sunil A. Sheth MD,&nbsp;Sergio Salazar-Marioni MD,&nbsp;Ananya Iyyangar MD,&nbsp;Thanh N. Nguyen MD,&nbsp;Mohamad Abdalkader MD,&nbsp;Italo Linfante MD,&nbsp;Guilherme Dabus MD,&nbsp;Brijesh P. Mehta MD,&nbsp;Joy Sessa MD,&nbsp;Mouhammad A. Jumma MD,&nbsp;Rebecca M. Sugg MD,&nbsp;Guillermo Linares MD,&nbsp;Raul G. Nogueira MD,&nbsp;David S. Liebeskind MD,&nbsp;Diogo C. Haussen MD,&nbsp;Santiago Ortega-Gutierrez MD, MSc","doi":"10.1002/ana.27064","DOIUrl":"10.1002/ana.27064","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 4","pages":"820-821"},"PeriodicalIF":8.1,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078597","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":"Mapping Functional Connectivity Signatures of Pharmacoresistant Focal Cortical Dysplasia-Related Epilepsy.","authors":"Hua Xie, Venkata Sita Priyanka Illapani, L Gilbert Vezina, Taha Gholipour, Chima Oluigbo, William D Gaillard, Nathan T Cohen","doi":"10.1002/ana.27069","DOIUrl":"https://doi.org/10.1002/ana.27069","url":null,"abstract":"<p><strong>Objective: </strong>To determine common network alterations in focal cortical dysplasia pharmacoresistant epilepsy (FCD-PRE) using functional connectivity analysis of resting-state functional magnetic resonance imaging (rsfMRI).</p><p><strong>Methods: </strong>This is a retrospective imaging cohort from Children's National Hospital (Washington, DC, USA) from January, 2011 to January, 2022. Patients with 3-T MRI-confirmed FCD-PRE underwent rsfMRI as part of routine clinical care. Patients were included if they were age 5-22 years at the time of the scan, and had a minimum of 18 months of follow-up. Healthy, typically-developing controls were included from Children's National Hospital (n = 16) and matched from Human Connectome Project-Development public dataset (n = 100).</p><p><strong>Results: </strong>A total of 42 FCD-PRE patients (20 M:22 F, aged 14.2 ± 4.1 years) and 116 healthy controls (56 M:60 F, aged 13.7 ± 3.3 years) with rsfMRI were included. Seed-based functional connectivity maps were generated for each FCD, and each seed was used to generate a patient-specific z-scored connectivity map on 116 controls. FCD-PRE patients had mutual altered connectivity in regions of dorsal attention, default mode, and control networks. Functional connectivity was diminished within the FCD dominant functional network, as well as in homotopic regions. Cluster specific connectivity patterns varied by pathological subtype. Higher FCD connectivity to the limbic network was associated with increased odds of Engel I outcome.</p><p><strong>Interpretation: </strong>This study demonstrates diminished functional connectivity patterns in FCD-PRE, which may represent a neuromarker for the disease, independent of FCD location, involving the dorsal attention, default mode, and control functional networks. Higher connectivity to the limbic network is associated with a seizure-free outcome. Future multicenter, prospective studies are needed to allow for much earlier detection of signatures of treatment-resistant epilepsy. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078596","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":"Miyazaki Syndrome as a Complication of Shunt Drainage","authors":"Rick H. G. J. van Lanen MD, MSc,&nbsp;Jasper van Aalst MD, PhD,&nbsp;Mariël P. Ter Laak-Poort MD, PhD","doi":"10.1002/ana.27067","DOIUrl":"10.1002/ana.27067","url":null,"abstract":"&lt;p&gt;A 41-year-old female was referred to the neurosurgery outpatient clinic with progressive bipyramidal syndrome. Medical history included premature birth and prior intraventricular hemorrhage with hydrocephalus. Ventricular-peritoneal (VP) shunting was performed in the management of hydrocephalus. However, complications related to over-drainage, along with hyperostosis of the skull and craniosynostosis, caused scaphocephaly.&lt;/p&gt;&lt;p&gt;Over the course of several months, she experienced progressive difficulties walking and developed right-sided weakness. Neurological examination revealed right-sided hemiparesis, hyperreflexia, and bilateral Babinski's sign. Imaging of the brain and cervical spine (Fig 1) showed scaphocephaly with slit-like ventricles and myelopathy extending from the C1 to C3 levels, along with the presence of spinal epidural venous engorgement. In the absence of a diagnosis, she was placed under long-term follow-up care by her neurologist. Follow-up magnetic resonance imaging (MRI) of the cervical spine revealed progressive myelopathy, before the diagnosis of Miyazaki syndrome was made. She underwent VP-shunt revision, with implantation of a Miethke proGAV 2.0 0-20/20 (programmable valve pressure setting 8). Outpatient clinic follow-up at 6 months showed stabilization of the bipyramidal symptoms. Follow-up MRI showed improvement of the epidural venous engorgement.&lt;/p&gt;&lt;p&gt;Miyazaki syndrome arises as a complication of cerebrospinal fluid (CSF) hypotension caused by excessive drainage through VP-shunting. Although CSF hypotension is often associated with well-known symptoms, like orthostatic headache and cranial nerve palsies, the development of epidural venous engorgement leading to spinal cord compression is a less common but critical manifestation.&lt;/p&gt;&lt;p&gt;The syndrome is characterized by cervical myelopathy or radiculopathy due to cervical epidural venous congestion, results from complex pathophysiological mechanisms.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; These include changes in CSF pressure, consistent with the Monro-Kellie doctrine, and dysfunction in the Starling resistor, leading to the enlargement and dilation of the spinal epidural venous plexus.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Venous congestion can lead to spinal cord or nerve roots compression or circulation hampering,&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; causing neurological symptoms, whereas presenting a unique diagnostic challenge. One of the striking features of Miyazaki syndrome is that it can manifest without the typical symptom of orthostatic headache, which is commonly associated with CSF hypotension. Instead, patients with Miyazaki syndrome may develop myelopathy symptoms slowly over time, making it challenging to diagnose, potentially leading to misdiagnosis.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; This underlines the importance of considering Miyazaki syndrome in the differential diagnosis of patients with VP-shunts who present with myelopathy but do not experience headaches. Timely recognition is crucial and","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 6","pages":"1230-1231"},"PeriodicalIF":8.1,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071516","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}