Annals of Neurology最新文献

{"title":"Different Genetic Signatures of Small-Cell Lung Cancer Characterize Anti-GABABR and Anti-Hu Paraneoplastic Neurological Syndromes","authors":"Alberto Vogrig MD, PhD,&nbsp;Antoine Pegat MD,&nbsp;Macarena Villagrán-García MD,&nbsp;Valentin Wucher PhD,&nbsp;Valéry Attignon PhD,&nbsp;Emilie Sohier PhD,&nbsp;Marie Brevet MD, PhD,&nbsp;Veronique Rogemond PhD,&nbsp;Anne-Laurie Pinto MSc,&nbsp;Sergio Muñiz-Castrillo MD, PhD,&nbsp;Elise Peter MD,&nbsp;Melisse Robert PhD,&nbsp;Géraldine Picard MSc,&nbsp;Lucie Hopes MD,&nbsp;Dimitri Psimaras MD,&nbsp;Anthony Terra,&nbsp;Corinne Perrin PhD,&nbsp;Dominique Cogne,&nbsp;Severine Tabone-Eglinger PharmD, PhD,&nbsp;Séverine Martinez,&nbsp;Delphine Jury,&nbsp;Julie Valantin,&nbsp;Nicolas Gadot,&nbsp;Jessie Auclair-Perrossier,&nbsp;Alain Viari PhD,&nbsp;Bertrand Dubois PhD,&nbsp;Virginie Desestret MD, PhD,&nbsp;Jérôme Honnorat MD, PhD","doi":"10.1002/ana.26784","DOIUrl":"10.1002/ana.26784","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Small-cell lung cancer (SCLC) is the malignancy most frequently associated with paraneoplastic neurological syndromes (PNS) and can trigger different antibody responses against intracellular (Hu) or neuronal surface (GABA_BR) antigens. Our aim was to clarify whether the genomic and transcriptomic features of SCLC are different in patients with anti-GABA_BR or anti-Hu PNS compared with SCLC without PNS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 76 SCLC tumor samples were collected: 34 anti-Hu, 14 anti-GABA_BR, and 28 SCLC without PNS. The study consisted of 4 steps: (1) pathological confirmation; (2) next generation sequencing using a panel of 98 genes, including those encoding the autoantibodies targets <i>ELAVL1-4</i>, <i>GABBR1</i>-<i>2</i>, and <i>KCTD16</i>; (3) genome-wide copy number variation (CNV); and (4) whole-transcriptome RNA sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CNV analysis revealed that patients with anti-GABA_BR PNS commonly have a gain in chromosome 5q, which contains <i>KCTD16</i>, whereas anti-Hu and control patients often harbor a loss. No significantly different number of mutations regarding any onconeural genes was observed. Conversely, the transcriptomic profile of SCLC was different, and the differentially expressed genes allowed effective clustering of the samples into 3 groups, reflecting the antibody-based classification, with an overexpression of <i>KCTD16</i> specific to anti-GABA_BR PNS. Pathway analysis revealed that tumors of patients with anti-GABA_BR encephalitis were enriched in B-cell signatures, as opposed to those of patients with anti-Hu, in which T-cell- and interferon-γ-related signatures were overexpressed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>SCLC genetic and transcriptomic features differentiate anti-GABA_BR, anti-Hu, and non-PNS tumors. The role of <i>KCTD16</i> appears to be pivotal in the tumor immune tolerance breakdown of anti-GABA_BR PNS. ANN NEUROL 2023;94:1102–1115</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"94 6","pages":"1102-1115"},"PeriodicalIF":11.2,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10286593","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":"Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex: The PREVeNT Trial","authors":"Elizabeth Martina Bebin MD, MPA,&nbsp;Jurriaan M. Peters MD, PhD,&nbsp;Brenda E. Porter MD, PhD,&nbsp;Tarrant O. McPherson PhD,&nbsp;Sarah O'Kelley PhD,&nbsp;Mustafa Sahin MD, PhD,&nbsp;Katherine S. Taub MD,&nbsp;Rajsekar Rajaraman MD,&nbsp;Stephanie C. Randle MD,&nbsp;William M. McClintock MD,&nbsp;Mary Kay Koenig MD,&nbsp;Mike D. Frost MD,&nbsp;Hope A. Northrup MD,&nbsp;Klaus Werner MD, PhD,&nbsp;Danielle A. Nolan MD,&nbsp;Michael Wong MD, PhD,&nbsp;Jessica L. Krefting RN, BSN,&nbsp;Fred Biasini PhD,&nbsp;Kalyani Peri MS,&nbsp;Gary Cutter PhD,&nbsp;Darcy A. Krueger MD, PhD,&nbsp;the PREVeNT Study Group","doi":"10.1002/ana.26778","DOIUrl":"10.1002/ana.26778","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study was undertaken to test the hypothesis that early vigabatrin treatment in tuberous sclerosis complex (TSC) infants improves neurocognitive outcome at 24 months of age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A phase IIb multicenter randomized double-blind placebo-controlled trial was conducted of vigabatrin at first epileptiform electroencephalogram (EEG) versus vigabatrin at seizure onset in infants with TSC. Primary outcome was Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive assessment score at 24 months. Secondary outcomes were prevalence of drug-resistant epilepsy, additional developmental outcomes, and safety of vigabatrin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 84 infants enrolled, 12 were screen failures, 4 went straight to open label vigabatrin, and 12 were not randomized (normal EEG throughout). Fifty-six were randomized to early vigabatrin (n = 29) or placebo (n = 27). Nineteen of 27 in the placebo arm transitioned to open label vigabatrin, with a median delay of 44 days after randomization. Bayley-III cognitive composite scores at 24 months were similar for participants randomized to vigabatrin or placebo. Additionally, no significant differences were found between groups in overall epilepsy incidence and drug-resistant epilepsy at 24 months, time to first seizure after randomization, and secondary developmental outcomes. Incidence of infantile spasms was lower and time to spasms after randomization was later in the vigabatrin group. Adverse events were similar across groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Preventative treatment with vigabatrin based on EEG epileptiform activity prior to seizure onset does not improve neurocognitive outcome at 24 months in TSC children, nor does it delay onset or lower the incidence of focal seizures and drug-resistant epilepsy at 24 months. Preventative vigabatrin was associated with later time to onset and lower incidence of infantile spasms. ANN NEUROL 2024;95:15–26</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"95 1","pages":"15-26"},"PeriodicalIF":11.2,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26778","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10439722","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":"Perimesencephalic Hemorrhage from A Superior Cerebellar Artery Dissection","authors":"Eelco F. M. Wijdicks MD, PhD,&nbsp;Sherri Braksick MD,&nbsp;Lorenzo Rinaldo MD, PhD","doi":"10.1002/ana.26779","DOIUrl":"10.1002/ana.26779","url":null,"abstract":"A 44-year-old women presented with a thunderclap-type headache and brie fl y lost consciousness. She became agitated and required brief intubation. Computed tomography scan of the brain (Figure A,B) showed a large clot in the right perimesencephalic cistern extending into the prepontine, quadrigeminal, and suprasellar cisterns, but not into the lateral Sylvian fi ssures. There was a small clot in the upper part of the third ventricle and early hydrocephalus. Ventriculostomy was placed and cerebro-spinal fl uid came out under high pressure. The 3D cerebral angiogram on day 2 (Figure C) showed some indistinct caliber changes in the superior cerebellar artery. Magnetic resonance imaging of the brain vessel imaging was normal, but the second cerebral angiogram, on day 7, revealed a dissecting aneurysm (Figure D) and was treated with a coil placed in the superior cerebellar artery at its origin. The ventriculostomy could be weaned. The patient made an excellent recovery (she provided written informed consent for publication of deidenti fi ed personal data).","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"94 6","pages":"1164-1165"},"PeriodicalIF":11.2,"publicationDate":"2023-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10232269","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":"Detection of High-Risk Paraneoplastic Antibodies against TRIM9 and TRIM67 Proteins","authors":"Christopher M. Bartley MD, PhD,&nbsp;Thomas T. Ngo BS,&nbsp;Le Duy Do PhD,&nbsp;Anastasia Zekeridou MD, PhD,&nbsp;Ravi Dandekar BS, MS,&nbsp;Sergio Muñiz-Castrillo MD, PhD,&nbsp;Bonny D. Alvarenga BA,&nbsp;Kelsey C. Zorn BA, MHS,&nbsp;Asritha Tubati BS,&nbsp;Anne-Laurie Pinto MSc,&nbsp;Weston D. Browne BS,&nbsp;Patrick W. Hullett MD, PhD,&nbsp;Mark Terrelonge MD, MPH,&nbsp;Ryan D. Schubert MD,&nbsp;Amanda L. Piquet MD,&nbsp;Binxia Yang PhD,&nbsp;Mayra Montalvo MD,&nbsp;Andrew F. Kung BA,&nbsp;Sabrina A. Mann BS,&nbsp;Maulik P. Shah MD, MHS,&nbsp;Michael D. Geschwind MD, PhD,&nbsp;Jeffrey M. Gelfand MD, MAS,&nbsp;Joseph L. DeRisi PhD,&nbsp;Sean J. Pittock MD,&nbsp;Jérôme Honnorat MD, PhD,&nbsp;Samuel J. Pleasure MD, PhD,&nbsp;Michael R. Wilson MD, MAS","doi":"10.1002/ana.26776","DOIUrl":"10.1002/ana.26776","url":null,"abstract":"Co‐occurring anti‐tripartite motif‐containing protein 9 and 67 autoantibodies (TRIM9/67‐IgG) have been reported in only a very few cases of paraneoplastic cerebellar syndrome. The value of these biomarkers and the most sensitive methods of TRIM9/67‐IgG detection are not known.","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"94 6","pages":"1086-1101"},"PeriodicalIF":11.2,"publicationDate":"2023-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26776","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10303370","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":"Risk of Parkinson's Disease in Celiac Disease: A Swedish Population-Based Study","authors":"Xiaoying Kang PhD, MPH,&nbsp;Alexander Ploner PhD,&nbsp;Bjorn Roelstraete PhD,&nbsp;Jonas F. Ludvigsson MD, PhD,&nbsp;Karin Wirdefeldt MD, PhD","doi":"10.1002/ana.26780","DOIUrl":"10.1002/ana.26780","url":null,"abstract":"<p>Using a population-based matched cohort design, we assessed the association of celiac disease (CeD) with risk of PD by comparing patients with biopsy-confirmed CeD in Sweden to a biopsy-free population and their unaffected siblings, separately. No overall association was observed but CeD diagnosed before age 60 associated positively with incident diagnosis of PD (hazard ratio [HR] = 1.29; 95% confidence interval [CI]: 1.02–1.62), which was mainly attributed to the significantly elevated risk detected after 10–15 years since biopsy (HR = 1.68; 95% CI: 1.05–2.68). Our findings imply an increased vulnerability to long-term PD development among patients with CeD diagnosed before 60s. ANN NEUROL 2023;94:911–916</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"94 5","pages":"911-916"},"PeriodicalIF":11.2,"publicationDate":"2023-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26780","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10170160","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":"Role of Blood–Brain Barrier Dysfunction in Delirium following Non-cardiac Surgery in Older Adults","authors":"Michael J. Devinney MD, PhD,&nbsp;Megan K. Wong MD,&nbsp;Mary Cooter Wright MS,&nbsp;Edward R. Marcantonio MD, SM,&nbsp;Niccolò Terrando PhD,&nbsp;Jeffrey N. Browndyke PhD,&nbsp;Heather E. Whitson MD, MHS,&nbsp;Harvey J. Cohen MD,&nbsp;Andrea G. Nackley PhD,&nbsp;Marguerita E. Klein BS,&nbsp;E. Wesley Ely MD, MPH,&nbsp;Joseph P. Mathew MD, MHSc, MBA,&nbsp;Miles Berger MD, PhD,&nbsp;for the MADCO-PC and INTUIT Study Teams","doi":"10.1002/ana.26771","DOIUrl":"10.1002/ana.26771","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Although animal models suggest a role for blood–brain barrier dysfunction in postoperative delirium-like behavior, its role in postoperative delirium and postoperative recovery in humans is unclear. Thus, we evaluated the role of blood–brain barrier dysfunction in postoperative delirium and hospital length of stay among older surgery patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cognitive testing, delirium assessment, and cerebrospinal fluid and blood sampling were prospectively performed before and after non-cardiac, non-neurologic surgery. Blood–brain barrier dysfunction was assessed using the cerebrospinal fluid-to-plasma albumin ratio (CPAR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 207 patients (median age = 68 years, 45% female) with complete CPAR and delirium data, 26 (12.6%) developed postoperative delirium. Overall, CPAR increased from before to 24 hours after surgery (median change = 0.28, interquartile range [IQR] = −0.48 to 1.24, Wilcoxon <i>p</i> = 0.001). Preoperative to 24 hours postoperative change in CPAR was greater among patients who developed delirium versus those who did not (median [IQR] = 1.31 [0.004 to 2.34] vs 0.19 [−0.55 to 1.08], <i>p</i> = 0.003). In a multivariable model adjusting for age, baseline cognition, and surgery type, preoperative to 24 hours postoperative change in CPAR was independently associated with delirium occurrence (per CPAR increase of 1, odds ratio = 1.30, 95% confidence interval [CI] = 1.03–1.63, <i>p</i> = 0.026) and increased hospital length of stay (incidence rate ratio = 1.15, 95% CI = 1.09–1.22, <i>p</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Postoperative increases in blood–brain barrier permeability are independently associated with increased delirium rates and postoperative hospital length of stay. Although these findings do not establish causality, studies are warranted to determine whether interventions to reduce postoperative blood–brain barrier dysfunction would reduce postoperative delirium rates and hospital length of stay. ANN NEUROL 2023;94:1024–1035</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"94 6","pages":"1024-1035"},"PeriodicalIF":11.2,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26771","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10517314","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":"Assessments of the Utilities of CSF NPTX2 for Disease Progression in Cognitively Normal Individuals Who Progress to Clinical MCI and AD","authors":"Leslie M. Shaw PhD,&nbsp;Douglas Galasko MD","doi":"10.1002/ana.26768","DOIUrl":"https://doi.org/10.1002/ana.26768","url":null,"abstract":"Cerebrospinal fluid (CSF) amyloid and tau biomarkers provide reliable detection of amyloid plaque and, to a lesser extent, tau pathology across the Alzheimer’s disease continuum; however, they predict risk for progression from cognitively normal to mild cognitive impairment (MCI) or to dementia with limited accuracy. Amyloid pathology as detected using CSF Aβ42 occurs substantially earlier than does tau pathology. Reliable detection of amyloid plaque burden alone has limited ability to accurately predict time to cognitive decline and MCI in cognitively normal individuals. Synaptic dysfunction and loss is considered to be one of the earliest pathological mechanisms – and consequences-of Alzheimer disease (AD) and may be a sensitive measure of neurodegeneration. Thus measurements of synaptic biomarkers in biofluids have attracted heightened interest for the potential to improve upon the accuracy in prediction of risk for disease progression, beyond Aβ42 and tau, in cognitively normal individuals. The possibility that a marker of synaptic integrity such as Neuronal pentraxin-2 (NPTX2) becomes abnormal earlier than a CSF measure of tau and adds predictive value in cognitively normal individuals on an AD trajectory is a major aim of the study reported by Soldan et al. Of note, these authors developed and validated an LC/MSMS methodology based upon a composite of 3 NPTX2-specific peptides produced by trypsinization to quantify CSF NPTX2 and found that levels correlate highly with the author’s previously described immunoassay. They included measurements of CSF Aβ42/40, t-tau, and p-tau181 by highly validated fully automated immunoassays. Soldan et al. conducted their study in BIOCARD study participants (269 cognitively normal individuals with average age at baseline of 57.7 years with average follow-up time of 16.3 years; 77 progressed to MCI or to dementia). The average age of this cohort is lower compared to the vast majority of AD biofluid biomarker studies and is a very important feature as it enables disease detection and biomarker transitions at an earlier age. The major findings in this study include: (A) association of lower CSF NPTX2 concentration values with the onset of MCI clinical symptoms, a finding consistent with prior reports across AD disease progression, e.g. from MCI to dementia; (B) the relationship between lower NPTX2 concentration and risk for disease progression was similar for males and females and did not differ between apolipoprotein E (ApoE) ε4 carriers and non-carriers; (C) CSF NPTX2 added predictive value to p-tau181 or t-tau for predicting progression to MCI consistent with the hypothesis that this is as early a marker for cognitive decline as is Aβ42/40, thus adding to predictive power of these biomarkers alone and providing a tauindependent added biomarker measure. These are encouraging findings, although the extent of increased predictive value was relatively small after including amyloid and p-tau181 in the model. A si","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"94 4","pages":"618-619"},"PeriodicalIF":11.2,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41084531","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":"Association Between Fat Depletion and Prognosis of Amyotrophic Lateral Sclerosis: CT-Based Body Composition Analysis","authors":"Seok-Jin Choi MD,&nbsp;Soon Ho Yoon MD, PhD,&nbsp;Jung-Joon Sung MD, PhD,&nbsp;Jong Hyuk Lee MD, PhD","doi":"10.1002/ana.26775","DOIUrl":"10.1002/ana.26775","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The purpose of this study was to present the results of our investigation of the prognostic value of adipopenia and sarcopenia in patients with amyotrophic lateral sclerosis (ALS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Consecutive patients with ALS with abdominal computed tomography (CT) were retrospectively identified at a single tertiary hospital between January 2010 and July 2021. Deep learning-based volumetric CT body composition analysis software was used to obtain abdominal waist fat volume, fat attenuation, and skeletal muscle area at the L3 level, then normalized to the fat volume index (FVI) and skeletal muscle index (SMI). Adipopenia and sarcopenia were defined as the sex-specific lowest quartile and SMI reference values, respectively. The associations of CT-derived body composition parameters with clinical variables, such as body mass index (BMI) and creatinine, were evaluated by Pearson correlation analyses, and associations with survival were assessed using the multivariable Cox regression analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eighty subjects (40 men, 65.5 ± 9.4 years of age) were investigated (median interval between disease onset and CT examination = 25 months). The mean BMI at the CT examination was 20.3 ± 4.3 kg/m². The BMI showed a positive correlation with both FVI (<i>R</i> = 0.70, <i>p</i> &lt; 0.001) and SMI (<i>R</i> = 0.63, <i>p</i> &lt; 0.001), and the serum creatinine level was associated with SMI (<i>R</i> = 0.68, <i>p</i> &lt; 0.001). After adjusting for sex, age, King's stage, BMI, creatinine, progression rate, and sarcopenia, adipopenia was associated with shorter survival (hazard ratio [HR] = 5.94, 95% confidence interval [CI] = 1.01, 35.0, <i>p</i> = 0.049). In a subgroup analysis for subjects with nutritional failure (stage 4a), the HR of adipopenia was 15.1 (95% CI = 2.45, 93.4, <i>p</i> = 0.003).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Deep learning-based CT-derived adipopenia in patients with ALS is an independent poor prognostic factor for survival. ANN NEUROL 2023;94:1116–1125</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"94 6","pages":"1116-1125"},"PeriodicalIF":11.2,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10150891","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":"Temporal Pattern of Cortical Hypoxia in Multiple Sclerosis and Its Significance on Neuropsychological and Clinical Measures of Disability","authors":"Damilola D. Adingupu PhD,&nbsp;Taelor Evans MSc,&nbsp;Ateyeh Soroush BSc,&nbsp;Ayden Hansen BSc,&nbsp;Scott Jarvis MD, PhD, FRCPC,&nbsp;Lenora Brown PhD, ABPP,&nbsp;Jeff F. Dunn PhD","doi":"10.1002/ana.26769","DOIUrl":"10.1002/ana.26769","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Multiple sclerosis (MS) is a degenerative disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal damage. It has been hypothesized that hypoxia plays a role in the pathogenesis of MS. This study was undertaken to investigate the reproducibility of non-invasively measured cortical microvascular hemoglobin oxygenation (S_tO₂) using frequency domain near-infrared spectroscopy (fdNIRS), investigate its temporal pattern of hypoxia in people with MS (pwMS), and its relationship with neurocognitive function and mood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We investigated the reproducibility of fdNIRS measurements. We measured cortical hypoxia in pwMS, and the relationships between S_tO₂, neurocognitive function, fatigue, and measures of physical disability. Furthermore, we cataloged the temporal pattern of S_tO₂ measured at 1-week intervals for 4 weeks, and at 8 weeks and ~1 year.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We show that fdNIRS parameters were highly reproducible in 7 healthy control participants measured over 6 days (<i>p</i> &gt; 0.05). There was low variability between and within subjects. In line with our previous findings, we show that 33% of pwMS (n = 88) have cortical microvascular hypoxia. Over 8 weeks and at ~1 year, S_tO₂ values for normoxic and hypoxic groups did not change significantly. There was no significant association between cognitive function and S_tO₂. This conclusion should be revisited as only a small proportion of the relapsing-remitting MS group (21%) was cognitively impaired.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The fdNIRS parameters have high reproducibility and repeatability, and we have demonstrated that hypoxia in MS is a chronic condition, lasting at least a year. The results show a weak relationship between cognitive functioning and oxygenation, indicating future study is required. ANN NEUROL 2023;94:1067–1079</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"94 6","pages":"1067-1079"},"PeriodicalIF":11.2,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26769","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10096871","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":"Sudden Unexpected Death in Epilepsy and Respiratory Defects in a Mouse Model of DEPDC5-Related Epilepsy","authors":"Hsin-Yi Kao PhD,&nbsp;Yilong Yao PhD,&nbsp;Tao Yang PhD,&nbsp;Julie Ziobro MD, PhD,&nbsp;Mary Zylinski BS,&nbsp;Mohd Yaqub Mir PhD,&nbsp;Shuntong Hu MD, PhD,&nbsp;Runnan Cao PhD,&nbsp;Nurun Nahar Borna MD, PhD,&nbsp;Rajat Banerjee PhD,&nbsp;Jack M. Parent MD,&nbsp;Shuo Wang PhD,&nbsp;Daniel K. Leventhal,&nbsp;Peng Li PhD,&nbsp;Yu Wang MD, PhD","doi":"10.1002/ana.26773","DOIUrl":"10.1002/ana.26773","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p><i>DEPDC5</i> is a common causative gene in familial focal epilepsy with or without malformations of cortical development. Its pathogenic variants also confer a significantly higher risk for sudden unexpected death in epilepsy (SUDEP), providing opportunities to investigate the pathophysiology intersecting neurodevelopment, epilepsy, and cardiorespiratory function. There is an urgent need to gain a mechanistic understanding of DEPDC5-related epilepsy and SUDEP, identify biomarkers for patients at high risk, and develop preventive interventions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p><i>Depdc5</i> was specifically deleted in excitatory or inhibitory neurons in the mouse brain to determine neuronal subtypes that drive epileptogenesis and SUDEP. Electroencephalogram (EEG), cardiac, and respiratory recordings were performed to determine cardiorespiratory phenotypes associated with SUDEP. Baseline respiratory function and the response to hypoxia challenge were also studied in these mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>Depdc5</i> deletion in excitatory neurons in cortical layer 5 and dentate gyrus caused frequent generalized tonic–clonic seizures and SUDEP in young adult mice, but <i>Depdc5</i> deletion in cortical interneurons did not. EEG suppression immediately following ictal offset was observed in fatal and non-fatal seizures, but low amplitude rhythmic theta frequency activity was lost only in fatal seizures. In addition, these mice developed baseline respiratory dysfunction prior to SUDEP, during which ictal apnea occurred long before terminal cardiac asystole.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p><i>Depdc5</i> deletion in excitatory neurons is sufficient to cause <i>DEPDC5</i>-related epilepsy and SUDEP. Ictal apnea and respiratory dysregulation play critical roles in SUDEP. Our study also provides a novel mouse model to investigate the underlying mechanisms of DEPDC5-related epilepsy and SUDEP. ANN NEUROL 2023;94:812–824</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"94 5","pages":"812-824"},"PeriodicalIF":11.2,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26773","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10224144","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}