Annals of Clinical and Translational Neurology最新文献

{"title":"Nomogram to predict unfavorable outcome of endovascular thrombectomy for large ischemic core","authors":"Nannan Han,&nbsp;Xiaobo Zhang,&nbsp;Yu Zhang,&nbsp;Yu Liu,&nbsp;Yongqin Zhang,&nbsp;Haojun Ma,&nbsp;Hanming Ge,&nbsp;Shilin Li,&nbsp;Xiao Zhang,&nbsp;Xudong Yan,&nbsp;Tengfei Li,&nbsp;Bin Gao,&nbsp;Chengxue Du,&nbsp;Xinchao Ji,&nbsp;Wenzhen Shi,&nbsp;Ye Tian,&nbsp;Mingze Chang","doi":"10.1002/acn3.51826","DOIUrl":"https://doi.org/10.1002/acn3.51826","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The prognosis for patients presenting with a large ischemic core (LIC) following endovascular thrombectomy is relatively poor. This study aimed to construct and validate a nomogram for predicting 3-month unfavorable outcome in patients with anterior circulation occlusion-related LIC who underwent endovascular thrombectomy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective training cohort and a prospective validation cohort of patients with a large ischemic core were studied. The diffusion weighted imaging related radiomic features and pre-thrombectomy clinical features were collected. After the selection of relevant features, a nomogram predicting modified Rankin Scale score of 3–6 as an unfavorable outcome was established. The discriminatory value of the nomogram was evaluated with a receiver operating characteristic curve.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 140 patients (mean age 66.3 ± 13.4 years, 35% female) were included in this study, consisting of a training cohort (<i>n</i> = 95) and a validation cohort (<i>n</i> = 45). The percentage of patients with an mRS scores of 0–2 was 30%, 0–3 was 40.7%, and 32.9% were dead. Age, National Institute of Health Stroke Scale (NIHSS) score, and two radiomic features, Maximum2DDiameterColumn and Maximum2DDiameterSlice, were identified as factors associated with unfavorable outcome in the nomogram. The nomogram demonstrated an area under the curve of 0.892 (95% confidence interval [CI], 0.812–0.947) in the training dataset and 0.872 (95% CI, 0.739–0.953) in the validation dataset.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This nomogram, which includes age, NIHSS score, Maximum2DDiameterColumn, and Maximum2DDiameterSlice, may predict the risk of unfavorable outcome in patients with LIC caused by anterior circulation occlusion.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 8","pages":"1353-1364"},"PeriodicalIF":5.3,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.51826","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5687657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical features and brain MRI volumetric changes in anti-mGluR5 encephalitis","authors":"Yueqian Sun,&nbsp;James X. Tao,&nbsp;Xiong Han,&nbsp;Xiangqing Wang,&nbsp;Yulan Zhu,&nbsp;Yajun Lian,&nbsp;Guoping Ren,&nbsp;Qun Wang","doi":"10.1002/acn3.51831","DOIUrl":"https://doi.org/10.1002/acn3.51831","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Anti-metabotropic glutamate receptor 5 (mGluR5) encephalitis is a rare and under-recognized autoimmune encephalitis. This study is conducted to characterize its clinical and neuroimaging features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-nine patients with anti-mGluR5 encephalitis (15 new cases identified in this study and 14 previously reported cases) were included in this study and their clinical features were characterized. Brain MRI volumetric analysis using FreeSurfer software was performed in 9 new patients and compared with 25 healthy controls at both early (≤6 months of onset) and chronic (&gt;1 year of onset) disease stages.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The common clinical manifestations of anti-mGluR5 encephalitis included cognitive deficits (<i>n</i> = 21, 72.4%), behavioral and mood disturbances (<i>n</i> = 20, 69%), seizures (<i>n</i> = 16, 55.2%), and sleep disorder (<i>n</i> = 13, 44.8%). Tumors were observed in 7 patients. Brain MRI T2/FLAIR signal hyperintensities were observed predominantly in mesiotemporal and subcortical regions in 75.9% patients. MRI volumetric analysis demonstrated significant amygdala enlargement in both early and chronic disease stages compared to healthy controls (<i>P</i> &lt; 0.001). Twenty-six patients had complete or partial recovery, one remained stable, one died and one was lost to follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings demonstrated that cognitive impairment, behavioral disturbance, seizures, and sleep disorder are the prominent clinical manifestations of anti-mGluR5 encephalitis. Most patients showed a good prognosis with full recovery, even in the paraneoplastic disease variants. The amygdala enlargement in the early and chronic disease stages is a distinct MRI feature, which exploratively offer a valuable perspective for the study of the disease processes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 8","pages":"1407-1416"},"PeriodicalIF":5.3,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.51831","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5686053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of perampanel in pediatric epilepsy with known and presumed genetic etiology","authors":"Pu Miao,&nbsp;Xueying Zhu,&nbsp;Wenqin Jin,&nbsp;Lingyan Yu,&nbsp;Yanfang Li,&nbsp;Ye Wang,&nbsp;Qunyan Su,&nbsp;Sha Xu,&nbsp;Shuang Wang,&nbsp;Jianhua Feng","doi":"10.1002/acn3.51828","DOIUrl":"https://doi.org/10.1002/acn3.51828","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The efficacy of perampanel (PER) in pediatric epilepsy with specific etiologies has not been well established. Here, we investigated outcome and predictors of PER treatment in a pediatric cohort with known and presumed genetic etiology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included pediatric patients with potential genetic epilepsy who received PER treatment and underwent whole-exome sequencing (WES) from January 2020 to September 2021. All patients were followed up for &gt;12 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 124 patients were included. Overall response rates were 51.6% and 49.6% at 6 months and 12 months, respectively. Pathogenic or likely pathogenic variants in 27 multiple genes were detected among 58 patients (46.8%) by WES. On performing multivariate logistic regression analysis, only developmental delay (OR = 0.406, <i>P</i> = 0.042) was a negative predictor of treatment response. However, the seizure onset age, positive WES results, and number of ASMs before PER administration were not significantly. Thirteen carriers with variants in the <i>SCN1A</i> gene showed a better response compared to eight patients with other sodium channels (<i>P</i> = 0.007), and to the other 45 patients with positive WES results (OR = 7.124, 95% CI = 1.306–38.860, <i>P</i> = 0.023). Adverse events were only reported in 23 patients, the most common being emotional problems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>PER is safe and efficacious in pediatric patients with known and presumed genetic etiology. The response rate is comparable to that reported in other pediatric populations, and lower among those with developmental delay. A gene-specific response to PER is found along with better efficacy links to pathogenic variants in the <i>SCN1A</i> gene.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 8","pages":"1374-1382"},"PeriodicalIF":5.3,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.51828","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5687655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The kynurenine pathway relates to post-acute COVID-19 objective cognitive impairment and PASC","authors":"Lucette A. Cysique,&nbsp;David Jakabek,&nbsp;Sophia G. Bracken,&nbsp;Yasmin Allen-Davidian,&nbsp;Benjamin Heng,&nbsp;Sharron Chow,&nbsp;Mona Dehhaghi,&nbsp;Ananda Staats Pires,&nbsp;David R. Darley,&nbsp;Anthony Byrne,&nbsp;Chansavath Phetsouphanh,&nbsp;Anthony Kelleher,&nbsp;Gregory J. Dore,&nbsp;Gail V. Matthews,&nbsp;Gilles J. Guillemin,&nbsp;Bruce J. Brew","doi":"10.1002/acn3.51825","DOIUrl":"https://doi.org/10.1002/acn3.51825","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To determine the prevalence and natural history of post-acute COVID-19 objective cognitive impairment and function, and their relationship to demographic, clinical factors, post-acute sequelae of COVID-19 (PASC), and biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 128 post-acute COVID-19 patients (age = 46 ± 15; 42% women, acute disease severity: not hospitalized: 38.6% mild: 0–1 symptoms, 52% 2+ symptoms; 9.4% hospitalized) completed standard cognition, olfaction, and mental health examinations 2-, 4-, and 12-month post diagnosis. Over the same time frame, WHO-defined PASC was determined. Blood cytokines, peripheral neurobiomarkers, and kynurenine pathway (KP) metabolites were measured. Objective cognitive function was demographically/practice corrected, and impairment prevalence was determined using the evidence-based Global Deficit Score method to detect at least mild cognitive impairment (GDS &gt; 0.5). Linear mixed effect regression models with time effect (month post diagnosis) evaluated the relationships to cognition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Across the 12-month study period, mild to moderate cognitive impairment ranged from 16% to 26%, and 46.5% were impaired at least once. Impairment associated with poorer work capacity (<i>p</i> &lt; 0.05), and 2-month objectively tested anosmia (<i>p</i> &lt; 0.05). PASC with (<i>p</i> = 0.01) and without disability (<i>p</i> &lt; 0.03) associated with acute COVID-19 severity. KP measures showed prolonged activation (2 to 8 months) (<i>p</i> &lt; 0.0001) linked to IFN-beta in those with PASC. Of the blood analytes, only the KP metabolites (elevated quinolinic acid, 3-hydroxyanthranilic acid, kynurenine, the kynurenine/tryptophan ratio) associated (<i>p</i> &lt; 0.001) with poorer cognitive performance and greater likelihood of impairment. PASC, independent of disability associated with abnormal kynurenine/tryptophan (<i>p</i> &lt; 0.03).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The kynurenine pathway relates to post-acute COVID-19 objective cognitive impairment and PASC, thereby enabling biomarker and therapeutic possibilities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 8","pages":"1338-1352"},"PeriodicalIF":5.3,"publicationDate":"2023-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.51825","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5670464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The case of a 49-year-old man with involuntary toe movements","authors":"Gabriela F. Pucci,&nbsp;Aaron L. Berkowitz","doi":"10.1002/acn3.51778","DOIUrl":"https://doi.org/10.1002/acn3.51778","url":null,"abstract":"<p>A 49-year-old man presented with 3 years of leg pain and involuntary toe movements. He described the pain as mild burning, radiating from the left foot upward to the leg. On examination, there were involuntary continuous flexion-extension movements of his left toes (video). Strength, sensation, and reflexes were normal. Lumbosacral MRI demonstrated diffuse degenerative disc disease with multi-level mild-to-moderate foraminal stenosis. Nerve conduction studies were normal. EMG showed neurogenic potentials and active denervation changes in the left anterior tibial and soleus muscles consistent with radiculopathy. The diagnosis of painful legs and moving toes is discussed.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 7","pages":"1260"},"PeriodicalIF":5.3,"publicationDate":"2023-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.51778","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5865094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MeCP2 dysfunction prevents proper BMP signaling and neural progenitor expansion in brain organoid","authors":"Hyowon Hong,&nbsp;Sae-Bom Yoon,&nbsp;Jung Eun Park,&nbsp;Jung In Lee,&nbsp;Hyun Young Kim,&nbsp;Hye Jin Nam,&nbsp;Heeyeong Cho","doi":"10.1002/acn3.51799","DOIUrl":"https://doi.org/10.1002/acn3.51799","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Sporadic mutations in MeCP2 are a hallmark of Rett syndrome (RTT). Many RTT brain organoid models have exhibited pathogenic phenotypes such as decreased spine density and small size of soma with altered electrophysiological signals. However, previous models are mainly focused on the phenotypes observed in the late phase and rarely provide clues for the defect of neural progenitors which generate different types of neurons and glial cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We newly established the RTT brain organoid model derived from MeCP2-truncated iPS cells which were genetically engineered by CRISPR/Cas9 technology. By immunofluorescence imaging, we studied the development of NPC pool and its fate specification into glutamatergic neurons or astrocytes in RTT organoids. By total RNA sequencing, we investigated which signaling pathways were altered during the early brain development in RTT organoids.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Dysfunction of MeCP2 caused the defect of neural rosette formation in the early phase of cortical development. In total transcriptome analysis, BMP pathway-related genes are highly associated with MeCP2 depletion. Moreover, levels of pSMAD1/5 and BMP target genes are excessively increased, and treatment of BMP inhibitors partially rescues the cell cycle progression of neural progenitors. Subsequently, MeCP2 dysfunction reduced the glutamatergic neurogenesis and induced overproduction of astrocytes. Nevertheless, early inhibition of BMP pathway rescued <i>VGLUT1</i> expression and suppressed astrocyte maturation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our results demonstrate that MeCP2 is required for the expansion of neural progenitor cells by modulating BMP pathway at early stages of development, and this influence persists during neurogenesis and gliogenesis at later stages of brain organoid development.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 7","pages":"1170-1185"},"PeriodicalIF":5.3,"publicationDate":"2023-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.51799","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5805759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing facial weakness in myasthenia gravis with facial recognition software and deep learning","authors":"Annabel M. Ruiter,&nbsp;Ziqi Wang,&nbsp;Zhao Yin,&nbsp;Willemijn C. Naber,&nbsp;Jerrel Simons,&nbsp;Jurre T. Blom,&nbsp;Jan C. van Gemert,&nbsp;Jan J. G. M. Verschuuren,&nbsp;Martijn R. Tannemaat","doi":"10.1002/acn3.51823","DOIUrl":"https://doi.org/10.1002/acn3.51823","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Myasthenia gravis (MG) is an autoimmune disease leading to fatigable muscle weakness. Extra-ocular and bulbar muscles are most commonly affected. We aimed to investigate whether facial weakness can be quantified automatically and used for diagnosis and disease monitoring.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this cross-sectional study, we analyzed video recordings of 70 MG patients and 69 healthy controls (HC) with two different methods. Facial weakness was first quantified with facial expression recognition software. Subsequently, a deep learning (DL) computer model was trained for the classification of diagnosis and disease severity using multiple cross-validations on videos of 50 patients and 50 controls. Results were validated using unseen videos of 20 MG patients and 19 HC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Expression of anger (<i>p</i> = 0.026), fear (<i>p</i> = 0.003), and happiness (<i>p</i> &lt; 0.001) was significantly decreased in MG compared to HC. Specific patterns of decreased facial movement were detectable in each emotion. Results of the DL model for diagnosis were as follows: area under the curve (AUC) of the receiver operator curve 0.75 (95% CI 0.65–0.85), sensitivity 0.76, specificity 0.76, and accuracy 76%. For disease severity: AUC 0.75 (95% CI 0.60–0.90), sensitivity 0.93, specificity 0.63, and accuracy 80%. Results of validation, diagnosis: AUC 0.82 (95% CI: 0.67–0.97), sensitivity 1.0, specificity 0.74, and accuracy 87%. For disease severity: AUC 0.88 (95% CI: 0.67–1.0), sensitivity 1.0, specificity 0.86, and accuracy 94%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Patterns of facial weakness can be detected with facial recognition software. Second, this study delivers a ‘proof of concept’ for a DL model that can distinguish MG from HC and classifies disease severity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 8","pages":"1314-1325"},"PeriodicalIF":5.3,"publicationDate":"2023-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.51823","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6167975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered extracellular matrices facilitate brain organoids from human pluripotent stem cells","authors":"Ay?e J. Mu?iz,&nbsp;Tu?ba Topal,&nbsp;Michael D. Brooks,&nbsp;Angela Sze,&nbsp;Do Hoon Kim,&nbsp;Jacob Jordahl,&nbsp;Joe Nguyen,&nbsp;Paul H. Krebsbach,&nbsp;Masha G. Savelieff,&nbsp;Eva L. Feldman,&nbsp;Joerg Lahann","doi":"10.1002/acn3.51820","DOIUrl":"https://doi.org/10.1002/acn3.51820","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Brain organoids are miniaturized in vitro brain models generated from pluripotent stem cells, which resemble full-sized brain more closely than conventional two-dimensional cell cultures. Although brain organoids mimic the human brain's cell-to-cell network interactions, they generally fail to faithfully recapitulate cell-to-matrix interactions. Here, an engineered framework, called an engineered extracellular matrix (EECM), was developed to provide support and cell-to-matrix interactions to developing brain organoids.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We generated brain organoids using EECMs comprised of human fibrillar fibronectin supported by a highly porous polymer scaffold. The resultant brain organoids were characterized by immunofluorescence microscopy, transcriptomics, and proteomics of the cerebrospinal fluid (CSF) compartment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The interstitial matrix-mimicking EECM enhanced neurogenesis, glial maturation, and neuronal diversity from human embryonic stem cells versus conventional protein matrix (Matrigel). Additionally, EECMs supported long-term culture, which promoted large-volume organoids containing over 250 μL of CSF. Proteomics analysis of the CSF found it superseded previous brain organoids in protein diversity, as indicated by 280 proteins spanning 500 gene ontology pathways shared with adult CSF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Engineered EECM matrices represent a major advancement in neural engineering as they have the potential to significantly enhance the structural, cellular, and functional diversity that can be achieved in advanced brain models.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 7","pages":"1239-1253"},"PeriodicalIF":5.3,"publicationDate":"2023-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.51820","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5747798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enlarged perivascular spaces in patients with migraine: a case–control study based on 3T MRI","authors":"Ziyu Yuan,&nbsp;Wei Li,&nbsp;Hefei Tang,&nbsp;Yanliang Mei,&nbsp;Dong Qiu,&nbsp;Min Zhang,&nbsp;Qian Sun,&nbsp;Wei Wang,&nbsp;Peng Zhang,&nbsp;Zhaochao Ma,&nbsp;Xueyan Zhang,&nbsp;Yaqing Zhang,&nbsp;Yonggang Wang,&nbsp;Xueying Yu","doi":"10.1002/acn3.51798","DOIUrl":"https://doi.org/10.1002/acn3.51798","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To explore whether MRI-visible enlarged perivascular spaces (EPVS) are associated with migraine and may serve as a predictor of migraine. Then further explore its correlation with migraine chronification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 231 participants (healthy control [HC] = 57, episodic migraine [EM] = 59, chronic migraine [CM] = 115) were included in this case–control study. A 3T MRI device and the validated visual rating scale were used to assess the grades of EPVS in centrum semiovale (CSO), midbrain (MB), and basal ganglia (BG). Comparisons between the two groups were made using the chi-square or Fisher's exact tests to initially determine whether high-grade EPVS were associated with migraine and migraine chronification. A multivariate logistic regression model was constructed to further investigate the role of high-grade EPVS in migraine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The prevalence of high-grade EPVS in CSO and MB were significantly higher in patients with migraine than in HCs (CSO: 64.94% vs. 42.11%, <i>P</i> = 0.002; MB: 55.75% vs. 29.82%, <i>P</i> = 0.001). Subgroup analysis showed no statistical difference between patients with EM and CM (CSO: 69.94% vs. 62.61%, <i>P</i> = 0.368; MB: 50.85% vs. 58.26%, <i>P</i> = 0.351). Individuals with high-grade EPVS in CSO (odds ratio [OR]: 2.324; 95% confidence interval [CI]: 1.136–4.754; <i>P</i> = 0.021) and MB (OR: 3.261; 95% CI: 1.534–6.935; <i>P</i> = 0.002) were more likely to suffer from migraine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This case–control study showed that high-grade EPVS in CSO and MB in clinical practice with the underlying mechanism of dysfunction of the glymphatic system could be a predictor of migraine, but no significant correlation had been found with migraine chronification.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 7","pages":"1160-1169"},"PeriodicalIF":5.3,"publicationDate":"2023-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.51798","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5727971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward an early clinical diagnosis of MM2-type sporadic Creutzfeldt–Jakob disease","authors":"Zhongyun Chen,&nbsp;Yu Kong,&nbsp;Jing Zhang,&nbsp;Min Chu,&nbsp;Li Liu,&nbsp;Kexin Xie,&nbsp;Yue Cui,&nbsp;Hong Ye,&nbsp;Junjie Li,&nbsp;Lin Wang,&nbsp;Liyong Wu","doi":"10.1002/acn3.51802","DOIUrl":"https://doi.org/10.1002/acn3.51802","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To assess the proportion of clinically diagnosed MM2-type sporadic Creutzfeldt–Jakob disease (sCJD) in a Chinese cohort, describe the clinical features of MM2-cortical (MM2C) and MM2-thalamic (MM2T) type sCJD to improve the early detection of MM2-type sCJD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 209 patients with sCJD admitted to the Xuanwu Hospital between February 2012 and August 2022 were reviewed. The patients were classified into probable MM2C, MM2T-type sCJD, and other types of sCJD according to current clinical diagnostic criteria. Clinical and ancillary data were compared between the groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifty-one (24.4%) patients were clinically diagnosed with MM2-type sCJD, of which 44 were diagnosed with MM2C-type sCJD and 7 with MM2T-type sCJD. In the absence of RT-QuIC, 27 (61.3%) patients of MM2C-type sCJD did not meet the US CDC sCJD criteria for possible sCJD on admission, even though the mean period from onset to admission was 6.0 months. However, all of these patients had cortical hyperintensity on DWI. Compared to the other types of sCJD, MM2C-type sCJD was associated with slower disease progression and the absence of the typical clinical features of sCJD; the MM2T-type sCJD group had a higher proportion of males, earlier age of onset, longer duration of disease, and a higher incidence of bilateral thalamic hypometabolism/hypoperfusion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>In the absence of multiple typical sCJD symptoms within 6 months, the presence of cortical hyperintensity on DWI should raise concerns for MM2C-type sCJD after excluding other etiologies. Bilateral thalamic hypometabolism/hypoperfusion may be more helpful in the clinical diagnosis of MM2T-type sCJD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 7","pages":"1209-1218"},"PeriodicalIF":5.3,"publicationDate":"2023-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.51802","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6096392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}