Annals of Neurology最新文献

{"title":"Ferroptosis of Microglia in Aging Human White Matter Injury","authors":"Philip A. Adeniyi PhD,&nbsp;Xi Gong MD,&nbsp;Ellie MacGregor BS,&nbsp;Kiera Degener-O'Brien MD,&nbsp;Evelyn McClendon PhD,&nbsp;Mariel Garcia BA,&nbsp;Oscar Romero BA,&nbsp;Joshua Russell PhD,&nbsp;Taasin Srivastava PhD,&nbsp;Jeremy Miller PhD,&nbsp;C. Dirk Keene MD, PhD,&nbsp;Stephen A. Back MD, PhD","doi":"10.1002/ana.26770","DOIUrl":"10.1002/ana.26770","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Because the role of white matter (WM) degenerating microglia (DM) in remyelination failure is unclear, we sought to define the core features of this novel population of aging human microglia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed postmortem human brain tissue to define a population of DM in aging WM lesions. We used immunofluorescence staining and gene expression analysis to investigate molecular mechanisms related to the degeneration of DM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that DM, which accumulated myelin debris were selectively enriched in the iron-binding protein light chain ferritin, and accumulated PLIN2-labeled lipid droplets. DM displayed lipid peroxidation injury and enhanced expression for TOM20, a mitochondrial translocase, and a sensor of oxidative stress. DM also displayed enhanced expression of the DNA fragmentation marker phospho-histone H2A.X. We identified a unique set of ferroptosis-related genes involving iron-mediated lipid dysmetabolism and oxidative stress that were preferentially expressed in WM injury relative to gray matter neurodegeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Ferroptosis appears to be a major mechanism of WM injury in Alzheimer's disease and vascular dementia. WM DM are a novel therapeutic target to potentially reduce the impact of WM injury and myelin loss on the progression of cognitive impairment. ANN NEUROL 2023;94:1048–1066</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"94 6","pages":"1048-1066"},"PeriodicalIF":11.2,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26770","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10230659","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":"Familial Mesial Temporal Lobe Epilepsy: Clinical Spectrum and Genetic Evidence for a Polygenic Architecture","authors":"Rebekah V. Harris BSc (Hons),&nbsp;Karen L. Oliver MSc,&nbsp;Piero Perucca MD, PhD,&nbsp;Pasquale Striano MD, PhD,&nbsp;Angelo Labate MD,&nbsp;Antonella Riva MD,&nbsp;Bronwyn E. Grinton BSc (Hons),&nbsp;Joshua Reid BSc,&nbsp;Jessica Hutton GradDip (Psych),&nbsp;Marian Todaro PhD,&nbsp;Terence J. O'Brien MD,&nbsp;Patrick Kwan MD, PhD,&nbsp;Lynette G. Sadleir MBChB, MD,&nbsp;Saul A. Mullen MBBS, PhD,&nbsp;Emanuela Dazzo PhD,&nbsp;Douglas E. Crompton MBBS, PhD,&nbsp;Ingrid E. Scheffer MBBS, PhD,&nbsp;Melanie Bahlo PhD,&nbsp;Carlo Nobile PhD,&nbsp;Antonio Gambardella MD,&nbsp;Samuel F. Berkovic MD, FRS","doi":"10.1002/ana.26765","DOIUrl":"10.1002/ana.26765","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Familial mesial temporal lobe epilepsy (FMTLE) is an important focal epilepsy syndrome; its molecular genetic basis is unknown. Clinical descriptions of FMTLE vary between a mild syndrome with prominent déjà vu to a more severe phenotype with febrile seizures and hippocampal sclerosis. We aimed to refine the phenotype of FMTLE by analyzing a large cohort of patients and asked whether common risk variants for focal epilepsy and/or febrile seizures, measured by polygenic risk scores (PRS), are enriched in individuals with FMTLE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We studied 134 families with ≥ 2 first or second-degree relatives with temporal lobe epilepsy, with clear mesial ictal semiology required in at least one individual. PRS were calculated for 227 FMTLE cases, 124 unaffected relatives, and 16,077 population controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The age of patients with FMTLE onset ranged from 2.5 to 70 years (median = 18, interquartile range = 13–28 years). The most common focal seizure symptom was déjà vu (62% of cases), followed by epigastric rising sensation (34%), and fear or anxiety (22%). The clinical spectrum included rare cases with drug-resistance and/or hippocampal sclerosis. FMTLE cases had a higher mean focal epilepsy PRS than population controls (odds ratio = 1.24, 95% confidence interval = 1.06, 1.46, <i>p</i> = 0.007); in contrast, no enrichment for the febrile seizure PRS was observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>FMTLE is a generally mild drug-responsive syndrome with déjà vu being the commonest symptom. In contrast to dominant monogenic focal epilepsy syndromes, our molecular data support a polygenic basis for FMTLE. Furthermore, the PRS data suggest that sub-genome-wide significant focal epilepsy genome-wide association study single nucleotide polymorphisms are important risk variants for FMTLE. ANN NEUROL 2023;94:825–835</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"94 5","pages":"825-835"},"PeriodicalIF":11.2,"publicationDate":"2023-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26765","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10473374","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":"CCNK Gene Deficiency Influences Neural Progenitor Cells Via Wnt5a Signaling in CCNK-Related Syndrome","authors":"Weiqian Dai PhD,&nbsp;He Wang PhD,&nbsp;Yongkun Zhan PhD,&nbsp;Nan Li MM,&nbsp;Fei Li PhD,&nbsp;Jingmin Wang PhD,&nbsp;Huifang Yan PhD,&nbsp;Yu Zhang PhD,&nbsp;Junyu Wang PhD,&nbsp;Lingqian Wu PhD,&nbsp;Huili Liu MM,&nbsp;Yanjie Fan PhD,&nbsp;Yue Tao PhD,&nbsp;Xi Mo PhD,&nbsp;Jian-Jun Yang PhD,&nbsp;Kun Sun PhD,&nbsp;Guiquan Chen PhD,&nbsp;Yongguo Yu PhD","doi":"10.1002/ana.26766","DOIUrl":"10.1002/ana.26766","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Rare variants of <i>CCNK</i> (cyclin K) give rise to a syndrome with intellectual disability. The purpose of this study was to describe the genotype–phenotype spectrum of CCNK-related syndrome and the underlying molecular mechanisms of pathogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We identified a number of de novo <i>CCNK</i> variants in unrelated patients. We generated patient-induced pluripotent stem cells (iPSCs) and neural progenitor cells (NPCs) as disease models. In addition, we constructed NPC-specific <i>Ccnk</i> knockout (KO) mice and performed molecular and morphological analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 2 new patients harboring <i>CCNK</i> missense variants and followed-up 3 previous reported patients, which constitute the largest patient population analysis of the disease. We demonstrate that both the patient-derived NPC models and the <i>Ccnk</i> KO mouse displayed deficient NPC proliferation and enhanced apoptotic cell death. RNA sequencing analyses of these NPC models uncovered transcriptomic signatures unique to CCNK-related syndrome, revealing significant changes in genes, including <i>WNT5A</i>, critical for progenitor proliferation and cell death. Further, to confirm <i>WNT5A</i>'s role, we conducted rescue experiments using NPC and mouse models. We found that a Wnt5a inhibitor significantly increased proliferation and reduced apoptosis in NPCs derived from patients with CCNK-related syndrome and NPCs in the developing cortex of <i>Ccnk</i> KO mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>We discussed the genotype–phenotype relationship of CCNK-related syndrome. Importantly, we demonstrated that <i>CCNK</i> plays critical roles in NPC proliferation and NPC apoptosis in vivo and in vitro. Together, our study highlights that Wnt5a may serve as a promising therapeutic target for the disease intervention. ANN NEUROL 2023;94:1136–1154</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"94 6","pages":"1136-1154"},"PeriodicalIF":11.2,"publicationDate":"2023-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10568467","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":"Distinct Patterns of Hippocampal Pathology in Alzheimer's Disease with Transactive Response DNA-binding Protein 43","authors":"Grace Minogue BA,&nbsp;Allegra Kawles BA,&nbsp;Antonia Zouridakis BS,&nbsp;Rachel Keszycki MS,&nbsp;Alyssa Macomber BS,&nbsp;Vivienne Lubbat,&nbsp;Nathan Gill PhD,&nbsp;Qinwen Mao MD,&nbsp;Margaret E. Flanagan MD,&nbsp;Hui Zhang PhD,&nbsp;Rudolph Castellani MD,&nbsp;Eileen H. Bigio MD,&nbsp;M.-Marsel Mesulam MD,&nbsp;Changiz Geula PhD,&nbsp;Tamar Gefen PhD","doi":"10.1002/ana.26762","DOIUrl":"10.1002/ana.26762","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Age-related dementia syndromes are often not related to a single pathophysiological process, leading to multiple neuropathologies found at autopsy. An amnestic dementia syndrome can be associated with Alzheimer's disease (AD) with comorbid transactive response DNA-binding protein 43 (TDP-43) pathology (AD/TDP). Here, we investigated neuronal integrity and pathological burden of TDP-43 and tau, along the well-charted trisynaptic hippocampal circuit (dentate gyrus [DG], CA3, and CA1) in participants with amnestic dementia due to AD/TDP, amnestic dementia due to AD alone, or non-amnestic dementia due to TDP-43 proteinopathy associated with frontotemporal lobar degeneration (FTLD-TDP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 48 extensively characterized cases (14 AD, 16 AD/TDP, 18 FTLD-TDP) were analyzed using digital HALO software (Indica Labs, Albuquerque, NM, USA) to quantify pathological burden and neuronal loss.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In AD/TDP and FTLD-TDP, TDP-43 immunoreactivity was greatest in the DG. Tau immunoreactivity was significantly greater in DG and CA3 in AD/TDP compared with pure AD. All clinical groups showed the highest amounts of neurons in DG, followed by CA3, then CA1. The AD and AD/TDP groups showed lower neuronal counts compared with the FTLD-TDP group across all hippocampal subregions consistent with the salience of the amnestic phenotype.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>We conclude that AD/TDP can be distinguished from AD and FTLD-TDP based on differential regional distributions of hippocampal tau and TDP-43. Findings suggest that tau aggregation in AD/TDP might be enhanced by TDP-43. ANN NEUROL 2023;94:1036–1047</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"94 6","pages":"1036-1047"},"PeriodicalIF":11.2,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26762","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10503488","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":"Search Strategies for Alzheimer Protector Genes","authors":"Kenneth S. Kosik MA, MD","doi":"10.1002/ana.26764","DOIUrl":"https://doi.org/10.1002/ana.26764","url":null,"abstract":"<p>Large families with autosomal dominant mutations leading to Alzheimer's disease and related conditions can show putative protective gene variants; however, no systematic search strategy exists to find these genes. Described here are the unique demographic circumstances and genetic setting in which the discovery of protective variants is likely. The identification of these genes may reveal pathways with therapeutic implications. ANN NEUROL 2023;94:613–617</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"94 4","pages":"613-617"},"PeriodicalIF":11.2,"publicationDate":"2023-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26764","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41084549","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":"Neutrophils Are Associated with Higher Risk of Incident Amyotrophic Lateral Sclerosis in a BMI- and Age-Dependent Manner","authors":"Wen Cao PhD,&nbsp;Zhi Cao PhD,&nbsp;Yao Tian MS,&nbsp;Linjing Zhang PhD,&nbsp;Wenjing Wang PhD,&nbsp;Lu Tang PhD,&nbsp;Chenjie Xu PhD,&nbsp;Dongsheng Fan MD, PhD","doi":"10.1002/ana.26760","DOIUrl":"10.1002/ana.26760","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Peripheral immune markers have been associated with the progression and prognosis of amyotrophic lateral sclerosis (ALS). However, whether dysregulation of peripheral immunity is a risk factor for ALS or a consequence of motor neuron degeneration has not yet been clarified. We aimed to identify longitudinal associations between prediagnostic peripheral immunity and the risk of incident ALS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 345,000 individuals from the UK Biobank between 2006 and 2010 were included at the baseline. The counts of peripheral immune markers (neutrophils, lymphocytes, monocytes, platelets, and CRP) and its derived metrics (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR], and systemic immune-inflammation index [SII]) were analyzed in relation to the following incident ALS by Cox proportional hazard models. Subgroup and interaction analyses were performed to explore the covariates of these relationships further.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After adjusting for all covariates, the multivariate analysis showed that high neutrophil counts and their derived metrics (NLR and SII) were associated with an increased risk of ALS incidence (per SD increment hazard ratio [HR] = 1.15, 95% confidence interval [CI] = 1.02–1.29 for neutrophils; HR = 1.15, 95% CI = 1.03–1.28 for NLR; and HR = 1.17, 95% CI = 1.05–1.30 for SII). Subgroup and interaction analyses revealed that body mass index (BMI) and age had specific effects on this association. In participants with BMI ≥ 25 or age &lt; 65 years, higher neutrophil counts, and their metrics increased the risk of incident ALS; however, in participants with BMI &lt; 25 or age ≥ 65 years, neutrophils had no effect on incident ALS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our study provides evidence that increased neutrophil levels and neutrophil-derived metrics (NLR and SII) are associated with an increased risk of developing ALS. ANN NEUROL 2023;94:942–954</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"94 5","pages":"942-954"},"PeriodicalIF":11.2,"publicationDate":"2023-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10076773","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":"Tuberculous Meningitis with the Soap Bubble Appearance Abscess Formation Resulting from a Paradoxical Reaction during Treatment in an Immunocompetent Host","authors":"Priabprat Jansem MD,&nbsp;Noppachai Siranart MD,&nbsp;Thanakit Pongpitakmetha MD,&nbsp;Prakit Anukoolwittaya MD","doi":"10.1002/ana.26759","DOIUrl":"https://doi.org/10.1002/ana.26759","url":null,"abstract":"previously healthy 18-year-old Thai woman presented with a progressive and diffuse headache she had for 3 weeks. The pain intensi fi ed upon neck and eye movements, accompanied by mild fever, nausea","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"94 4","pages":"803-805"},"PeriodicalIF":11.2,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26759","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41084546","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":"Severity of GNAO1-Related Disorder Correlates with Changes in G-Protein Function","authors":"Jana Domínguez-Carral MD,&nbsp;William Grant Ludlam PhD,&nbsp;Mar Junyent Segarra BS,&nbsp;Montserrat Fornaguera Marti BS,&nbsp;Sol Balsells MsC,&nbsp;Jordi Muchart MD,&nbsp;Dunja Čokolić Petrović MD,&nbsp;Iván Espinoza MD,&nbsp;Juan Dario Ortigoza-Escobar MD, PhD,&nbsp;Kirill A. Martemyanov PhD,&nbsp;GNAO1-Study Group","doi":"10.1002/ana.26758","DOIUrl":"10.1002/ana.26758","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p><i>GNAO1</i>-related disorders (OMIM #615473 and #617493), caused by variants in the <i>GNAO1</i> gene, are characterized by developmental delay or intellectual disability, hypotonia, movement disorders, and epilepsy. Neither a genotype–phenotype correlation nor a clear severity score have been established for this disorder. The objective of this prospective and retrospective observational study was to develop a severity score for <i>GNAO1</i>-related disorders, and to delineate the correlation between the underlying molecular mechanisms and clinical severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 16 individuals with <i>GNAO1</i>-related disorders harboring 12 distinct missense variants, including four novel variants (p.K46R, p.T48I, p.R209P, and p.L235P), were examined with repeated clinical assessments, video-electroencephalogram monitoring, and brain magnetic resonance imaging. The molecular pathology of each variant was delineated using a molecular deconvoluting platform.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The patients displayed a wide variability in the severity of their symptoms. This heterogeneity was well represented in the <i>GNAO1</i>-related disorders severity score, with a broad range of results. Patients with the same variant had comparable severity scores, indicating that differences in disease profiles are not due to interpatient variability, but rather, to unique disease mechanisms. Moreover, we found a significant correlation between clinical severity scores and molecular mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The clinical score proposed here provides further insight into the correlation between pathophysiology and phenotypic severity in <i>GNAO1</i>-related disorders. We found that each variant has a unique profile of clinical phenotypes and pathological molecular mechanisms. These findings will contribute to better understanding <i>GNAO1</i>-related disorders. Additionally, the severity score will facilitate standardization of patients categorization and assessment of response to therapies in development. ANN NEUROL 2023;94:987–1004</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"94 5","pages":"987-1004"},"PeriodicalIF":11.2,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26758","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10117168","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":"Histopathological Correlates of Lobar Microbleeds in False-Positive Cerebral Amyloid Angiopathy Cases","authors":"Valentina Perosa MD,&nbsp;Corinne A. Auger BM,&nbsp;Maria Clara Zanon Zotin MD PhD,&nbsp;Jan Oltmer MD,&nbsp;Matthew P. Frosch MD PhD,&nbsp;Anand Viswanathan MD PhD,&nbsp;Steven M. Greenberg MD PhD,&nbsp;Susanne J. van Veluw PhD","doi":"10.1002/ana.26761","DOIUrl":"10.1002/ana.26761","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>A definite diagnosis of cerebral amyloid angiopathy (CAA), characterized by the accumulation of amyloid β in walls of cerebral small vessels, can only be obtained through pathological examination. A diagnosis of probable CAA during life relies on the presence of hemorrhagic markers, including lobar cerebral microbleeds (CMBs). The aim of this project was to study the histopathological correlates of lobar CMBs in false-positive CAA cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In 3 patients who met criteria for probable CAA during life, but showed no CAA upon neuropathological examination, lobar CMBs were counted on ex vivo 3T magnetic resonance imaging (MRI) and on ex vivo 7T MRI. Areas with lobar CMBs were next sampled and cut into serial sections, on which the CMBs were then identified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Collectively, there were 25 lobar CMBs on in vivo MRI and 22 on ex vivo 3T MRI of the analyzed hemispheres. On ex vivo MRI, we targeted 12 CMBs for sampling, and definite histopathological correlates were retrieved for 9 of them, of which 7 were true CMBs. No CAA was found on any of the serial sections. The “culprit vessels” associated with the true CMBs instead showed moderate to severe arteriolosclerosis. Furthermore, CMBs in false-positive CAA cases tended to be located more often in the juxtacortical or subcortical white matter than in the cortical ribbon.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>These findings suggest that arteriolosclerosis can generate lobar CMBs and that more detailed investigations into the exact localization of CMBs with respect to the cortical ribbon could potentially aid the diagnosis of CAA during life. ANN NEUROL 2023;94:856–870</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"94 5","pages":"856-870"},"PeriodicalIF":11.2,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10156740","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":"Guy McKhann, First Head of Hopkins' Department of Neurology","authors":"Justin C. McArthur MBBS, MPH,&nbsp;Rebecca F. Gottesman MD, PhD","doi":"10.1002/ana.26735","DOIUrl":"https://doi.org/10.1002/ana.26735","url":null,"abstract":". His accomplishments in neurology were both broad and deep leading to changes in practice that have persisted today. These include important contributions in the pathogenesis and treatment of Guillain-Barre syndrome, de fi ning the criteria for Alzheimer disease","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"94 3","pages":"417-420"},"PeriodicalIF":11.2,"publicationDate":"2023-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6144654","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}