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This article, published in the journal Neuropediatrics, examines the outcome and brain volume changes over time in children with MOG-encephalitis (MOG-E), a rare clinical phenotype of MOGAD. The study included 21 children with MOG-E, who presented with symptoms such as encephalopathy, headache, focal neurological signs, seizures, or CSF pleocytosis. The results showed that the majority of children had a good clinical outcome, with resolution of MRI changes and decreasing MOG antibodies over time. However, brain volumetry measurements indicated a decrease in whole brain volume, particularly in gray matter, after onset. [Extracted from the article]

This article, published in the journal Neuropediatrics, explores the differences between prepubertal and (post)pubertal children with multiple sclerosis (MS) in terms of clinical, laboratory, and imaging features. The study included 248 MS patients from various European pediatric hospitals who were diagnosed before the age of 18. The results showed that prepubertal children had an equal distribution of MS between sexes, while postpubertal children had a higher prevalence in females. Prepubertal children also had more relapses in the first two years and a different range of MRI features compared to (post)pubertal children. Overall, the findings suggest both similarities and differences between the two age groups in terms of MS characteristics. [Extracted from the article]

Highlights from the article: Combined levodopa/decarboxylase inhibitor treatment was initiated and proved to be effective in both sisters leading to a reduction of chorea, hyperkinesia and motor restlessness (Video - segment 2). In the older sister therapy was started with 0,67/0,17 mg/kg/day levodopa/benserazide divided into two doses and augmented to 1/0,25 mg/kg/day levodopa/benserazide divided into three doses within three weeks. For patients with benign hereditary chorea levodopa therapy has been shown to effectively reduce hyperkinetic movements [[11]] but to our knowledge has not been tested in patients with a hyperkinetic movement disorder due to mutations in phosphodiesterases. Combined levodopa/decarboxylase inhibitor therapy also showed effectiveness in both here reported children leading to a reduction of hyperkinetic symptoms.

Malformations of the brain are common and vary in severity, from negligible to potentially fatal. Their causes have not been fully elucidated. Here, we report pathogenic variants in the core protein-folding machinery TRiC/CCT in individuals with brain malformations, intellectual disability, and seizures. The chaperonin TRiC is an obligate hetero-oligomer, and we identify variants in seven of its eight subunits, all of which impair function or assembly through different mechanisms. Transcriptome and proteome analyses of patient-derived fibroblasts demonstrate the various consequences of TRiC impairment. The results reveal an unexpected and potentially widespread role for protein folding in the development of the central nervous system and define a disease spectrum of "TRiCopathies."

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance. Genes encoding ion channels show strong association with multiple epilepsy subtypes, including epileptic encephalopathies, generalized and focal epilepsies, while most other gene discoveries are subtype-specific, highlighting distinct genetic contributions to different epilepsies. Combining results from rare single nucleotide/short indel-, copy number-, and common variants, we offer an expanded view of the genetic architecture of epilepsy, with growing evidence of convergence among different genetic risk loci on the same genes. Top candidate genes are enriched for roles in synaptic transmission and neuronal excitability, particularly postnatally and in the neocortex. We also identify shared rare variant risk between epilepsy and other neurodevelopmental disorders. Our data can be accessed via an interactive browser, hopefully facilitating diagnostic efforts and accelerating the development of follow-up studies., Competing Interests: Competing Interests B.M.N is a member of the scientific advisory board at Deep Genomics and Neumora. No other authors have competing interests to declare

Objective: Describing spectrum, evolution, and clinical relationship of brain magnetic resonance imaging (MRI) findings in a large case series of children with febrile infection-related epilepsy syndrome (FIRES)., Methods: This retrospective study included 31 children with FIRES. Clinical data and MRI findings of the brain were evaluated. Poor clinical outcome was defined as severe disability, persistent vegetative state or stupor, very low intelligence quotient (<80), or death (modified Rankin scale 4-6 and Glasgow Outcome Score 1-3)., Results: Seventeen (54.8%) children with FIRES showed no abnormalities in the initial MRI, whereas 28 (90.3%) children showed MRI abnormalities at follow-up. The most frequent abnormalities were brain atrophy (74.2%) and T2/fluid-attenuated inversion recovery changes (64.5%), mostly hippocampal (45.2%). Generalized brain atrophy was the most frequent type of atrophy (58%). The earliest atrophy was recorded 9 days after the onset of disease. It progressed even beyond the acute phase in most children (51.6%). The exploratory data analysis revealed nominal significance between all MRI abnormalities considered together and poor outcome ( p  = 0.049) and between generalized brain atrophy and anesthesia ( p  = 0.024). After adjustment for multiple testing, the p- values were not significant. The outcome in four (12.9%) children was not poor despite generalized brain atrophy., Conclusion: In contrast to the uniform clinical course, MRI demonstrated a broad spectrum of findings. Initially, these were mostly normal and therefore indicative of FIRES but then changed rapidly and were mostly progressive despite the stable chronic course. The cause may be ongoing disease, treatment intensity, or both. Future studies should focus on what process underlies the onset and the progression of brain atrophy. However, brain atrophy was not always related to poor outcomes in children despite FIRES., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

HNRNPA1 variants are known to cause degenerative motoneuron and muscle diseases which manifests in middle age or later. We report on a girl with early childhood onset, rapidly progressive generalized myopathy including ultrastructural findings in line with a proteinopathy. Proteomics of patient-derived muscle and combined screening of genomic data for copy number variations identified a HNRNPA1 de novo intragenic deletion as causative for the phenotype. Our report expands the spectrum of HNRNPA1-related diseases towards early-childhood onset and adds HNRNPA1 to the growing list of ALS and myopathy genes for which certain mutations may cause severe pediatric phenotypes.

Here we present a deep learning-based image analysis platform (DLAP), tailored to autonomously quantify cell numbers, and fluorescence signals within cellular compartments, derived from RNAscope or immunohistochemistry. We utilised DLAP to analyse subtypes of tyrosine hydroxylase (TH)-positive dopaminergic midbrain neurons in mouse and human brain-sections. These neurons modulate complex behaviour, and are differentially affected in Parkinson's and other diseases. DLAP allows the analysis of large cell numbers, and facilitates the identification of small cellular subpopulations. Using DLAP, we identified a small subpopulation of TH-positive neurons (~5%), mainly located in the very lateral Substantia nigra (SN), that was immunofluorescence-negative for the plasmalemmal dopamine transporter (DAT), with ~40% smaller cell bodies. These neurons were negative for aldehyde dehydrogenase 1A1, with a lower co-expression rate for dopamine-D2-autoreceptors, but a ~7-fold higher likelihood of calbindin-d28k co-expression (~70%). These results have important implications, as DAT is crucial for dopamine signalling, and is commonly used as a marker for dopaminergic SN neurons., (© 2023. The Author(s).)

Background: Evidence-based practice (EBP) is the integration of best research evidence with clinical expertise and patients' values and preferences. Little is known about knowledge, attitudes, and application of EBP among chiropractic students and trainees. Our aims were to (1) examine the feasibility of implementing a new journal club format within a Swiss university chiropractic healthcare education setting, and (2) assess the associations between the new journal club implementation and EBP characteristics among chiropractic students., Methods: A before-and-after study was conducted through a newly implemented journal club with 5th and 6th year chiropractic students and postgraduate trainees between 1 and 2021 and 31 July 2021. The journal club was developed based on the "community of practice" and "team-based learning" conceptual frameworks. EBP knowledge, attitudes, personal application, and future use, were assessed with a validated questionnaire. We summarised participant characteristics using descriptive statistics, estimated before-and-after EBP total and subscale scores (i.e., knowledge, attitudes, personal application, and future use), and conducted an exploratory subgroup analysis based on journal club attendance (Group A: 3-5 sessions attended; Group B: ≤ 2 sessions attended)., Results: Among 32 eligible students and trainees, 29 participants (mean age 26 years; 79% women) were enrolled: 25 (78%) responded to the pre- and 29 (91%) to the post-assessment surveys. Most (80%) were chiropractic students and 20% were postgraduate trainees. Group A consisted of 12 (41%) and Group B of 17 (59%) participants, respectively. We found reasonable feasibility for the new journal club format and our findings were compatible with no difference in before-and-after EBP scores (median EBP total score before: 72.6 [IQR, 63.7-77.4], and after: 73.4 [IQR, 61.3-78.2]). Exploratory subgroup analyses based on journal club attendance were consistent with our overall findings., Conclusion: Our study suggests that the newly implemented journal club and embedding chiropractic educational research within the journal club were feasible and acceptable. Small before-and-after differences in the EBP subscale scores for knowledge, attitudes, personal application, and future use were observed in chiropractic students and postgraduate trainees. The small study size and short timeframe during a single semester limit potential inferences., (© 2023. The Author(s).)

Background: Aplasia cutis congenita (ACC) is a rare congenital anomaly characterized by localized or widespread absence of skin at birth, mainly affecting the scalp. Most information about ACC exists as individual case reports and medium-sized studies., Objectives: This study aimed to investigate the epidemiology of ACC, using data from a large European network of population-based registries for congenital anomalies (EUROCAT)., Methods: Twenty-eight EUROCAT population-based registries in 16 European countries were involved. Poisson regression models were exploited to estimate the overall and live birth prevalence, to test time trends in prevalence between four 5-year periods and to evaluate the impact of the change of coding for ACC from the unspecific ICD9-BPA code to the specific ICD10 code. Proportions of ACC cases associated with other anomalies were reported., Results: Five hundred cases were identified in the period 1998-2017 (prevalence: 5.10 per 100,000 births). Prevalence across 5-year periods did not differ significantly and no significant differences were evident due to the change from ICD9 to ICD10 in ACC coding. Heterogeneity in prevalence was observed across registries. The scalp was the most common site for ACC (96.4%) and associated congenital anomalies were present in 33.8% of cases. Patau and Adams-Oliver syndromes were the most frequent among the associated chromosomal anomalies (88.3%) and the associated genetic syndromes (57.7%), respectively. 16% of cases were associated with limb anomalies and 15.4% with congenital heart defects. A family history of ACC was found in 2% of cases., Conclusion: To our knowledge, this is the only population-based study on ACC. The EUROCAT methodologies provide reliable prevalence estimates and proportions of associated anomalies., (© 2022 European Academy of Dermatology and Venereology.)

INTRODUCTION: Neck pain and injury are common problems in military high-performance aircraft and helicopter aircrews. A contributing factor may be the reclined sitting position in cockpits. This study aimed to determine the effect of typical cockpit ergonomics on cervical proprioception, assessed by using the cervical joint position error (cJPE). METHODS: A total of 49 healthy male military employees (mean age 19.9 ± 2.2 yr) were examined. Measurements of the cJPE were obtained in the flexion, extension, and rotation directions in an upright and in a 30°-reclined sitting position. Each condition comprised three trials, with an additional 3-kg head load to mimic real world working conditions. RESULTS: A smaller cJPE was noted in the 30°-reclined sitting position (mean cJPE = 3.9 cm) than in the upright sitting position (mean cJPE = 4.6 cm) in the flexion direction. The cJPE decreased significantly in all movement directions across the three trials; for example, in the flexion direction in the 30°-reclined sitting position: Trial 1/2/3 mean cJPE = 5.0/3.8/3.1 cm. CONCLUSION: It seems that a reclined seating position has a positive influence on cJPE. However, the result is weak. In both sitting positions and all three directions, the first tests of the cJPE showed the highest values. Already after one or two further measurement runs, a significantly reduced cJPE was observed. This rapid improvement might indicate that an exercise similar to the cJPE test may improve the pilots' cervical proprioception and possibly reduce the risk of injury or pain. Heggli U, Swanenburg J, Hofstetter L, Häusler M, Schweinhardt P, Bron D. Typical cockpit ergonomics influence on cervical motor control in healthy young male adults . Aerosp Med Hum Perform. 2023; 94(3):107-112.

Herpes simplex virus (HSV) type 1 is a frequent pathogen causing infectious encephalitis (HSVE). Early treatment with intravenous acyclovir has led to a significant decrease in mortality. However, especially in children, deterioration during or after HSVE may occur without any evidence of HSV reactivation or improvement following repeated antiviral therapy. Here, we report 15 patients (age range 3 months to 15 years) who suffered from autoimmune encephalitis with autoantibodies to NMDAR1 following Herpes encephalitis, presenting with movement abnormalities (young children) or neuropsychiatric symptoms (older children) as major complaints, respectively. The diagnosis was based on positive cerebrospinal fluid (CSF) and/or serum anti-NMDAR-antibodies with two children showing only positive CSF antibody findings. The time lag between first symptoms and diagnosis of autoimmune encephalitis was significantly longer than between first symptoms and diagnosis of HSVE ( p <0.01). All patients improved during immunosuppressive treatment, during which plasmapheresis or rituximab treatments were applied in 11 patients, irrespective of their age. Despite immunotherapy, no patients relapsed with HSVE. Early diagnosis and treatment of autoimmune encephalitis after HSVE may be associated with a better outcome so that high clinical awareness and routine testing for anti-NMDAR-antibodies after HSVE seems advisable. If autoimmune encephalitis is suspected, antibody testing should also be performed on CSF if negative in serum., Competing Interests: None declared., (Thieme. All rights reserved.)