Hemidystonia with polymicrogyria is part of ATP1A3-related disorders

IntroductionPathogenic variants in ATP1A3 cause various phenotypes of neurological disorders, including alternating hemiplegia of childhood 2, CAPOS syndrome (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss) and rapid-onset dystonia-parkinsonism (RDP). Early developmental and epileptic encephalopathy has also been reported. Polymicrogyria has recently been added to the phenotypic spectrum of ATP1A3-related disorders.Case report.We report here a male patient with early developmental delay who at 12 months presented dystonia of the right arm which evolved into hemidystonia at the age of 2. A cerebral MRI showed bilateral perisylvian polymicrogyria with intact basal ganglia. Whole-exome and whole-genome sequencing analyses identified a de novo new ATP1A3 missense variant (p.Arg914Lys) predicted pathogenic. Hemidystonia was thought not to be due to polymicrogyria, but rather a consequence of this variant.ConclusionThis case expands the phenotypic spectrum of ATP1A3-related disorders with a new variant associated with hemidystonia and polymicrogyria and thereby, suggests a clinical continuum between the different phenotypes of this condition.     

FreeSurfer-based segmentation of hippocampal subfields: A review of methods and applications,with a novel quality control procedure for ENIGMA studies and other collaborative efforts

Structural hippocampal abnormalities are common in many neurological and psychiatric disorders, and variation in hippocampal measures is related to cognitive performance and other complex phenotypes such as stress sensitivity. Hippocampal subregions are increasingly studied, as automated algorithms have become available for mapping and volume quantification. In the context of the Enhancing Neuro Imaging Genetics through Meta Analysis Consortium, several Disease Working Groups are using the FreeSurfer software to analyze hippocampal subregion (subfield) volumes in patients with neurological and psychiatric conditions along with data from matched controls. In this overview, we explain the algorithm's principles, summarize measurement reliability studies, and demonstrate two additional aspects (subfield autocorrelation and volume/reliability correlation) with illustrative data. We then explain the rationale for a standardized hippocampal subfield segmentation quality control (QC) procedure for improved pipeline harmonization. To guide researchers to make optimal use of the algorithm, we discuss how global size and age effects can be modeled, how QC steps can be incorporated and how subfields may be aggregated into composite volumes. This discussion is based on a synopsis of 162 published neuroimaging studies (01/2013–12/2019) that applied the FreeSurfer hippocampal subfield segmentation in a broad range of domains including cognition and healthy aging, brain development and neurodegeneration, affective disorders, psychosis, stress regulation, neurotoxicity, epilepsy, inflammatory disease, childhood adversity and posttraumatic stress disorder, and candidate and whole genome (epi-)genetics. Finally, we highlight points where FreeSurfer-based hippocampal subfield studies may be optimized.     

Ten years of enhancing neuro-imaging genetics through meta-analysis: An overview from the ENIGMA Genetics Working Group

Here we review the motivation for creating the enhancing neuroimaging genetics through meta-analysis (ENIGMA) Consortium and the genetic analyses undertaken by the consortium so far. We discuss the methodological challenges, findings, and future directions of the genetics working group. A major goal of the working group is tackling the reproducibility crisis affecting “candidate gene” and genome-wide association analyses in neuroimaging. To address this, we developed harmonized analytic methods, and support their use in coordinated analyses across sites worldwide, which also makes it possible to understand heterogeneity in results across sites. These efforts have resulted in the identification of hundreds of common genomic loci robustly associated with brain structure. We have found both pleiotropic and specific genetic effects associated with brain structures, as well as genetic correlations with psychiatric and neurological diseases.     

Predicting alcohol dependence from multi-site brain structural measures

To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, it may be useful to develop classification models that are explicitly generalizable to unseen sites and populations. This problem was explored in a mega-analysis of previously published datasets from 2,034 AD and comparison participants spanning 27 sites curated by the ENIGMA Addiction Working Group. Data were grouped into a training set used for internal validation including 1,652 participants (692 AD, 24 sites), and a test set used for external validation with 382 participants (146 AD, 3 sites). An exploratory data analysis was first conducted, followed by an evolutionary search based feature selection to site generalizable and high performing subsets of brain measurements. Exploratory data analysis revealed that inclusion of case- and control-only sites led to the inadvertent learning of site-effects. Cross validation methods that do not properly account for site can drastically overestimate results. Evolutionary-based feature selection leveraging leave-one-site-out cross-validation, to combat unintentional learning, identified cortical thickness in the left superior frontal gyrus and right lateral orbitofrontal cortex, cortical surface area in the right transverse temporal gyrus, and left putamen volume as final features. Ridge regression restricted to these features yielded a test-set area under the receiver operating characteristic curve of 0.768. These findings evaluate strategies for handling multi-site data with varied underlying class distributions and identify potential biomarkers for individuals with current AD.     

MRI and ultrasonography for detection of early interphalangeal osteoarthritis

ObjectivesTo assess the interest of MRI and ultrasonography (US) in identifying early and advanced interphalangeal (IP) OA.MethodsWe conducted a case-control study including patients with symptomatic hand OA (n = 33) and young healthy volunteers (n = 26). Proximal and distal IP joints were graded according to Kellgren and Lawrence (KL) grades. In OA patients, we separated IP joints into 2 groups: “at risk of OA” joints (potential early pre-radiographic OA joints, KL = 0) and OA joints (KL = 2–4). All IP joints from healthy participants were KL = 0 and were considered strictly normal IP joints. Concurrently, synovitis, effusion, erosions, osteophytes, bone marrow lesions, cysts and cartilage space loss were graded by MRI and/or US. We assessed their prevalence, severity and diagnostic performance in hand OA and then compared normal IP joints from healthy participants and “at risk of OA” IP joints from OA patients as well as “at risk of OA” and OA IP joints from OA patients.ResultsThe prevalence and grade of most MRI/US-detected lesions were higher in IP joints from OA patients than healthy participants. Except for osteophyte assessment, MRI seemed more sensitive than US. We found more MRI/US-detected lesions in “at risk of OA” IP joints than normal joints but also in OA than “at risk of OA” joints from OA patients. US appeared both sensitive and specific for detecting osteophytes in joints without radiographic abnormalities.ConclusionsMRI and US give good performance for detecting radiographic and pre-radiographic OA lesions and could be interesting tools to identify early hand OA.     

世界MRI的市场现状及技术发展动态

一、前言磁共振成像系统(MRI)诞生以后的短短几年中,经过稳定的发展,其作用已为越来越多的人所认识。全世界在1988年底MRI的总装机量已超过3000台,美国占其中的将近一半,达到1430台,日本也超过了350台。在我国,虽然比一些发达国家起步稍晚一点,至今已装机近20台。安科公司开发成功并开始生产我国自己的MRI系统之后,为我国医学界在MRI的装备和应用方面开辟了新的前景。二、MRI的市场现状     

颅内畸胎瘤破裂的MRI表现(附5例报告)

目的　总结分析颅内畸胎瘤破裂的MRI表现。方法　共 5例 ,均经手术病理证实。均行MRI及CT检查 ,其中 2例做了MRI增强扫描。结果　MRI显示颅内微小脂肪滴及脂肪 脑脊液平面优于CT ,CT显示畸胎瘤的钙化优于MRI。结论　颅内畸胎瘤破裂具有典型的MRI表现 ,MRI检查中改变病人体位的方法和脂肪抑制技术对该病的定性诊断有很大帮助。