Brain : a journal of neurology最新文献

{"title":"Seronegative autoimmune encephalitis: exploring the unknown.","authors":"Robin W van Steenhoven, Maarten J Titulaer","doi":"10.1093/brain/awac338","DOIUrl":"https://doi.org/10.1093/brain/awac338","url":null,"abstract":"This scientific commentary refers to ‘Seronegative autoimmune encephalitis: clinical characteristics and factors associated with outcomes’ by Lee et al. (https://doi.org/10.1093/brain/awac166).","PeriodicalId":121505,"journal":{"name":"Brain : a journal of neurology","volume":" ","pages":"3339-3340"},"PeriodicalIF":14.5,"publicationDate":"2022-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2c/c5/awac338.PMC9586533.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40362893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contribution of B cells to cortical damage in multiple sclerosis.","authors":"Pavan Bhargava,&nbsp;Hans-Peter Hartung,&nbsp;Peter A Calabresi","doi":"10.1093/brain/awac233","DOIUrl":"https://doi.org/10.1093/brain/awac233","url":null,"abstract":"<p><p>Multiple sclerosis is associated with lesions not just in the white matter, but also involving the cortex. Cortical involvement has been linked to greater disease severity and hence understanding the factor underlying cortical pathology could help identify new therapeutic strategies for multiple sclerosis. The critical role of B cells in multiple sclerosis has been clarified by multiple pivotal trials of B-cell depletion in people with multiple sclerosis. The presence of B-cell rich areas of meningeal inflammation in multiple sclerosis has been identified at all stages of multiple sclerosis. Leptomeningeal inflammation is associated with greater extent of cortical demyelination and neuronal loss and with greater disease severity. Recent studies have identified several potential mechanisms by which B cells may mediate cortical injury including antibody production, extracellular vesicles containing neurotoxic substances and production of pro-inflammatory cytokines. Additionally, B cells may indirectly mediate cortical damage through effects on T cells, macrophages or microglia. Several animal models replicate the meningeal inflammation and cortical injury noted in people with multiple sclerosis. Studies in these models have identified Bruton's tyrosine kinase inhibition and type II anti-CD20 antibodies as potential agents that can impact meningeal inflammation. Trials of anti-CD20 monoclonal antibodies in people with multiple sclerosis have unsuccessfully attempted to eliminate B cells in the leptomeninges. New strategies to target B cells in multiple sclerosis include Bruton's tyrosine kinase inhibition and cell-based therapies aimed at B cells infected with Epstein-Barr virus. Future studies will clarify the mechanisms by which B cells mediate cortical injury and treatment strategies that can target B cells in the leptomeninges and CNS parenchyma.</p>","PeriodicalId":121505,"journal":{"name":"Brain : a journal of neurology","volume":" ","pages":"3363-3373"},"PeriodicalIF":14.5,"publicationDate":"2022-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40562703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bi-allelic FRA10AC1 variants in a multisystem human syndrome.","authors":"Siddharth Banka,&nbsp;Stavit Shalev,&nbsp;Soo-Mi Park,&nbsp;Katherine A Wood,&nbsp;Huw B Thomas,&nbsp;Helen L Wright,&nbsp;Mohammed Alyahya,&nbsp;Sean Bankier,&nbsp;Ola Alimi,&nbsp;Elena Chervinsky,&nbsp;Leo A H Zeef,&nbsp;Raymond T O'Keefe","doi":"10.1093/brain/awac262","DOIUrl":"https://doi.org/10.1093/brain/awac262","url":null,"abstract":"","PeriodicalId":121505,"journal":{"name":"Brain : a journal of neurology","volume":" ","pages":"e86-e89"},"PeriodicalIF":14.5,"publicationDate":"2022-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40533010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biallelic variants in SLC35B2 cause a novel chondrodysplasia with hypomyelinating leukodystrophy.","authors":"Alessandra Guasto,&nbsp;Johanne Dubail,&nbsp;Sergio Aguilera-Albesa,&nbsp;Chiara Paganini,&nbsp;Catherine Vanhulle,&nbsp;Walid Haouari,&nbsp;Nerea Gorría-Redondo,&nbsp;Elena Aznal-Sainz,&nbsp;Nathalie Boddaert,&nbsp;Laura Planas-Serra,&nbsp;Agatha Schlüter,&nbsp;Valentina Vélez-Santamaría,&nbsp;Edgard Verdura,&nbsp;Arnaud Bruneel,&nbsp;Antonio Rossi,&nbsp;Céline Huber,&nbsp;Aurora Pujol,&nbsp;Valérie Cormier-Daire","doi":"10.1093/brain/awac110","DOIUrl":"https://doi.org/10.1093/brain/awac110","url":null,"abstract":"<p><p>Sulphated proteoglycans are essential in skeletal and brain development. Recently, pathogenic variants in genes encoding proteins involved in the proteoglycan biosynthesis have been identified in a range of chondrodysplasia associated with intellectual disability. Nevertheless, several patients remain with unidentified molecular basis. This study aimed to contribute to the deciphering of new molecular bases in patients with chondrodysplasia and neurodevelopmental disease. Exome sequencing was performed to identify pathogenic variants in patients presenting with chondrodysplasia and intellectual disability. The pathogenic effects of the potentially causative variants were analysed by functional studies. We identified homozygous variants (c.1218_1220del and c.1224_1225del) in SLC35B2 in two patients with pre- and postnatal growth retardation, scoliosis, severe motor and intellectual disabilities and hypomyelinating leukodystrophy. By functional analyses, we showed that the variants affect SLC35B2 mRNA expression and protein subcellular localization leading to a functional impairment of the protein. Consistent with those results, we detected proteoglycan sulphation impairment in SLC35B2 patient fibroblasts and serum. Our data support that SLC35B2 functional impairment causes a novel syndromic chondrodysplasia with hypomyelinating leukodystrophy, most likely through a proteoglycan sulphation defect. This is the first time that SLC35B2 variants are associated with bone and brain development in human.</p>","PeriodicalId":121505,"journal":{"name":"Brain : a journal of neurology","volume":" ","pages":"3711-3722"},"PeriodicalIF":14.5,"publicationDate":"2022-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40317672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in Alzheimer's disease risk: are immune responses the key?","authors":"Rachel F Buckley","doi":"10.1093/brain/awac316","DOIUrl":"https://doi.org/10.1093/brain/awac316","url":null,"abstract":"","PeriodicalId":121505,"journal":{"name":"Brain : a journal of neurology","volume":" ","pages":"3341-3342"},"PeriodicalIF":14.5,"publicationDate":"2022-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40343419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetically identical twins show comparable tau PET load and spatial distribution.","authors":"Emma M Coomans,&nbsp;Jori Tomassen,&nbsp;Rik Ossenkoppele,&nbsp;Sandeep S V Golla,&nbsp;Marijke den Hollander,&nbsp;Lyduine E Collij,&nbsp;Emma Weltings,&nbsp;Sophie M van der Landen,&nbsp;Emma E Wolters,&nbsp;Albert D Windhorst,&nbsp;Frederik Barkhof,&nbsp;Eco J C de Geus,&nbsp;Philip Scheltens,&nbsp;Pieter Jelle Visser,&nbsp;Bart N M van Berckel,&nbsp;Anouk den Braber","doi":"10.1093/brain/awac004","DOIUrl":"https://doi.org/10.1093/brain/awac004","url":null,"abstract":"<p><p>Tau accumulation starts during the preclinical phase of Alzheimer's disease and is closely associated with cognitive decline. For preventive purposes, it is important to identify factors associated with tau accumulation and spread. Studying genetically identical twin-pairs may give insight into genetic and environmental contributions to tau pathology, as similarities in identical twin-pairs largely result from genetic factors, while differences in identical twin-pairs can largely be attributed to non-shared, environmental factors. This study aimed to examine similarities and dissimilarities in a cohort of genetically identical older twin-pairs in (i) tau load; and (ii) spatial distribution of tau, measured with 18F-flortaucipir PET. We selected 78 genetically identical twins (39 pairs; average age 73 ± 6 years), enriched for amyloid-β pathology and APOE ε4 carriership, who underwent dynamic 18F-flortaucipir PET. We extracted binding potentials (BPND) in entorhinal, temporal, widespread neocortical and global regions, and examined within-pair similarities in BPND using age and sex corrected intra-class correlations. Furthermore, we tested whether twin-pairs showed a more similar spatial 18F-flortaucipir distribution compared to non-twin pairs, and whether the participant's co-twin could be identified solely based on the spatial 18F-flortaucipir distribution. Last, we explored whether environmental (e.g. physical activity, obesity) factors could explain observed differences in twins of a pair in 18F-flortaucipir BPND. On visual inspection, Alzheimer's disease-like 18F-flortaucipir PET patterns were observed, and although we mainly identified similarities in twin-pairs, some pairs showed strong dissimilarities. 18F-flortaucipir BPND was correlated in twins in the entorhinal (r = 0.40; P = 0.01), neocortical (r = 0.59; P < 0.01) and global (r = 0.56; P < 0.01) regions, but not in the temporal region (r = 0.20; P = 0.10). The 18F-flortaucipir distribution pattern was significantly more similar between twins of the same pair [mean r = 0.27; standard deviation (SD) = 0.09] than between non-twin pairings of participants (mean r = 0.01; SD = 0.10) (P < 0.01), also after correcting for proxies of off-target binding. Based on the spatial 18F-flortaucipir distribution, we could identify with an accuracy of 86% which twins belonged to the same pair. Finally, within-pair differences in 18F-flortaucipir BPND were associated with within-pair differences in depressive symptoms (0.37 < β < 0.56), physical activity (-0.41 < β < -0.42) and social activity (-0.32 < β < -0.36) (all P < 0.05). Overall, identical twin-pairs were comparable in tau load and spatial distribution, highlighting the important role of genetic factors in the accumulation and spreading of tau pathology. Considering also the presence of dissimilarities in tau pathology in identical twin-pairs, our results additionally support a role for (potentially modifiable) environmental factors in the ","PeriodicalId":121505,"journal":{"name":"Brain : a journal of neurology","volume":" ","pages":"3571-3581"},"PeriodicalIF":14.5,"publicationDate":"2022-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/63/a5/awac004.PMC9586544.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39817280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cranial trepanation in pre-Columbian Peruvian cultures: was it an option to treat epilepsy?","authors":"Poul H Espino,&nbsp;Juan E Toro-Perez,&nbsp;Stephanie Shkrum,&nbsp;Jorge G Burneo","doi":"10.1093/brain/awac277","DOIUrl":"https://doi.org/10.1093/brain/awac277","url":null,"abstract":"","PeriodicalId":121505,"journal":{"name":"Brain : a journal of neurology","volume":" ","pages":"3335-3338"},"PeriodicalIF":14.5,"publicationDate":"2022-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40550896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is it time to rename hereditary cases of cerebral palsy?","authors":"Anamarija Kavčič","doi":"10.1093/brain/awac230","DOIUrl":"https://doi.org/10.1093/brain/awac230","url":null,"abstract":"","PeriodicalId":121505,"journal":{"name":"Brain : a journal of neurology","volume":" ","pages":"e82-e83"},"PeriodicalIF":14.5,"publicationDate":"2022-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40554286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Double administration of self-complementary AAV9NDUFS4 prevents Leigh disease in Ndufs4-/- mice.","authors":"Samantha Corrà,&nbsp;Raffaele Cerutti,&nbsp;Valeria Balmaceda,&nbsp;Carlo Viscomi,&nbsp;Massimo Zeviani","doi":"10.1093/brain/awac182","DOIUrl":"https://doi.org/10.1093/brain/awac182","url":null,"abstract":"<p><p>Leigh disease, or subacute necrotizing encephalomyelopathy, a genetically heterogeneous condition consistently characterized by defective mitochondrial bioenergetics, is the most common oxidative-phosphorylation related disease in infancy. Both neurological signs and pathological lesions of Leigh disease are mimicked by the ablation of the mouse mitochondrial respiratory chain subunit Ndufs4-/-, which is part of, and crucial for, normal Complex I activity and assembly, particularly in the brains of both children and mice. We previously conveyed the human NDUFS4 gene to the mouse brain using either single-stranded adeno-associated viral 9 recombinant vectors or the PHP.B adeno-associated viral vector. Both these approaches significantly prolonged the lifespan of the Ndufs4-/- mouse model but the extension of the survival was limited to a few weeks by the former approach, whereas the latter was applicable to a limited number of mouse strains, but not to primates. Here, we exploited the recent development of new, self-complementary adeno-associated viral 9 vectors, in which the transcription rate of the recombinant gene is markedly increased compared with the single-stranded adeno-associated viral 9 and can be applied to all mammals, including humans. Either single intra-vascular or double intra-vascular and intra-cerebro-ventricular injections were performed at post-natal Day 1. The first strategy ubiquitously conveyed the human NDUFS4 gene product in Ndufs4-/- mice, doubling the lifespan from 45 to ≈100 days after birth, when the mice developed rapidly progressive neurological failure. However, the double, contemporary intra-vascular and intra-cerebroventricular administration of self-complementary-adeno-associated viral NDUFS4 prolonged healthy lifespan up to 9 months of age. These mice were well and active at euthanization, at 6, 7, 8 and 9 months of age, to investigate the brain and other organs post-mortem. Robust expression of hNDUFS4 was detected in different cerebral areas preserving normal morphology and restoring Complex I activity and assembly. Our results warrant further investigation on the translatability of self-complementary-adeno-associated viral 9 NDUFS4-based therapy in the prodromal phase of the disease in mice and eventually humans.</p>","PeriodicalId":121505,"journal":{"name":"Brain : a journal of neurology","volume":" ","pages":"3405-3414"},"PeriodicalIF":14.5,"publicationDate":"2022-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f1/75/awac182.PMC9586549.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40563305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics, surgical outcomes, and influential factors of epilepsy in Sturge-Weber syndrome.","authors":"Shu Wang,&nbsp;Junhong Pan,&nbsp;Meng Zhao,&nbsp;Xiongfei Wang,&nbsp;Chunsheng Zhang,&nbsp;Tianfu Li,&nbsp;Mengyang Wang,&nbsp;Jing Wang,&nbsp;Jian Zhou,&nbsp;Changqing Liu,&nbsp;Yongxing Sun,&nbsp;Mingwang Zhu,&nbsp;Xueling Qi,&nbsp;Guoming Luan,&nbsp;Yuguang Guan","doi":"10.1093/brain/awab470","DOIUrl":"https://doi.org/10.1093/brain/awab470","url":null,"abstract":"<p><p>Few studies have reported the clinical presentation, surgical treatment, outcomes and influential factors for patients with epilepsy and Sturge-Weber syndrome. This large-scale retrospective study continuously enrolled 132 patients with Sturge-Weber syndrome and epilepsy from January 2008 to December 2018 at our hospital to analyse their characteristics. Among these patients, 90 underwent epilepsy surgery, and their postoperative 2-year follow-up seizure, cognitive and motor functional outcomes were assessed and analysed. Univariable and multivariable logistic analyses were conducted to explore the influential factors. Among the patients with Sturge-Weber syndrome for whom characteristics were analysed (n = 132), 76.52% of patients had their first epileptic seizures within their first year of life. The risk factors for cognitive decline were seizure history ≥ 2 years [adjusted odds ratio (aOR) = 3.829, 95% confidence interval (CI): 1.810-9.021, P = 0.008)], bilateral leptomeningeal angiomas (aOR = 3.173, 95% CI: 1.970-48.194, P = 0.013), age at onset <1 year (aOR = 2.903, 95% CI: 1.230-6.514, P = 0.013), brain calcification (aOR = 2.375, 95% CI: 1.396-5.201, P = 0.021) and left leptomeningeal angiomas (aOR = 2.228, 95% CI: 1.351-32.571, P = 0.030). Of the patients who underwent epilepsy surgery (n = 90), 44 were subject to focal resection, and 46 underwent hemisphere surgery (19 anatomical hemispherectomies and 27 modified hemispherotomies). A postoperative seizure-free status, favourable cognitive outcomes, and favourable motor outcomes were achieved in 83.33%, 44.44% and 43.33% of surgical patients, respectively. The modified hemispherotomy group had similar surgical outcomes, less intraoperative blood loss and shorter postoperative hospital stays than the anatomical hemispherectomy group. Regarding seizure outcomes, full resection (aOR = 11.115, 95% CI: 1.260-98.067, P = 0.020) and age at surgery < 2 years (aOR = 6.040, 95% CI: 1.444-73.367, P = 0.031) were positive influential factors for focal resection. Age at surgery < 2 years (aOR = 15.053, 95% CI: 1.050-215.899, P = 0.036) and infrequent seizures (aOR = 8.426, 95% CI: 1.086-87.442, P = 0.042; monthly versus weekly) were positive influential factors for hemisphere surgery. In conclusion, epilepsy surgery resulted in a good postoperative seizure-free rate and favourable cognitive and motor functional outcomes and showed acceptable safety for patients with epilepsy and Sturge-Weber syndrome. Modified hemispherotomy is a less invasive and safer type of hemisphere surgery than traditional anatomic hemispherectomy with similar surgical outcomes. Early surgery may be helpful to achieve better seizure outcomes and cognitive protection, while the risk of surgery for young children should also be considered.</p>","PeriodicalId":121505,"journal":{"name":"Brain : a journal of neurology","volume":" ","pages":"3431-3443"},"PeriodicalIF":14.5,"publicationDate":"2022-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39746022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}