Martin Häusler

Background: Young children requiring neurosurgical care frequently undergo repeated neuroimaging. Whereas CT involves exposure to ionizing radiation, conventional MRI is time-consuming and often necessitates sedation in non-cooperative children. To address these limitations, ultrafast cranial MRI (UF-MRI) based on T2-HASTE sequences was implemented at our institution in 2019 for selected indications. The aim of this study was to evaluate the real-world implementation of UF-MRI in children younger than six years of age. Methods: We retrospectively analyzed cranial MRI examinations consisting exclusively of ultrafast sequences performed between July 2019 and December 2024 in children younger than six years. Clinical settings, diagnostic adequacy, immediate consequences for patient management, and the impact on MRI and CT utilization were systematically assessed. Results: A total of 404 UF-MRI examinations were performed in 198 inpatients and outpatients (mean age: 2 years 2 months) without the need for dedicated anesthesia team support solely for imaging. Only one examination (0.2%) required same-day repetition after mild oral sedation. In 20 patients (5.0%), UF-MRI was supplemented by conventional MRI under anesthesia, most commonly for preoperative planning. Immediate clinical consequences included no change in management in 54.5% of examinations, early follow-up in 22.8%, shunt valve adjustment in 11.6%, neurosurgical intervention in 7.7%, and other measures in 5.0%. UF-MRI accounted for 24.5% of all cranial MRI examinations in this age group and was associated with a 41% reduction in CT utilization compared with the corresponding period prior to UF-MRI implementation. Conclusions: In routine clinical practice, UF-MRI provides rapid, clinically sufficient neuroimaging in young children without the need for sedation or exposure to ionizing radiation. Its implementation significantly streamlines imaging workflows, optimizes resources utilization, reduces the need for CT, and supports timely clinical decision-making, underscoring its value as a complementary imaging modality in pediatric neuroimaging.

Pathogenic variants in voltage-gated sodium channels (VGSCs) may cause disturbed sensory function, including small fiber neuropathy (SFN) in adults, but little is known about their role in children and adolescents.A total of 39 prospectively enrolled children (age 12.03 ± 4.61 years) with abnormal pain sensation underwent detailed diagnostics including quantitative sensory testing (QST, if >5 years old), quality of life assessment, and genetic studies for VGSC variants and further etiologies.QST results were consistent with Aẟ- und C-fiber damage, including increased cold, warmth, and mechanical detection thresholds, higher thermal sensory limen, and allodynia. Intraepidermal nerve fiber densities were low in 9/18 children. This resulted in a great impact on physical quality of life and pain scales but not on social life. Five children showed heterozygous variants of unknown significance (VUS) in genes encoding VGSC (SCN9A, n = 2; SCN10A, n = 3) with maternal or paternal inheritance in two and one patients, respectively. Three further patients showed likely disease-associated variants in the HUWE1, TRIO, and PYGM genes.Despite a high disease burden and small fiber damage indicated by QST and skin histology, only VUS in VGSC and additional monogenic causes of pain symptoms outside of VGSC genes were identified. Genetic studies in affected children should therefore be comprehensive, not restricted to VGSC variants and be supplemented by a detailed clinical workup. In silico modeling and future functional studies might help to identify VUS that play a role in altered pain perception.

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.”

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 (* These authors contributed equally to this work. Location where the work was performed: Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel University (CAU), Kiel, Germany Received: 18 May 2023 Accepted: 14 July 2023 Article published online: 05 October 2023 © 2023. 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/) Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Objectives Data on the prevalence, clinical features and risk factors associated with paediatric diabetic neuropathy (DN) are scarce. Methods We retrospectively analysed data from the DPV registry, including patients under 20 years of age, treated for type 1 diabetes mellitus (T1D) between 2005 and 2021. Patients with non-diabetic neuropathy were excluded. Data came from centres in Austria, Germany, Luxembourg and Switzerland. Results 1,121 of the 84,390 patients included had been diagnosed with DN. Univariate analysis showed patients with DN to be older and predominantly female, with a longer duration of T1D, higher insulin dosages per kg and day, lower rates of insulin pump therapy, higher postprandial glucose-, higher HbA_1c-and higher cholesterol levels, and higher diastolic and systolic blood pressure values. There was also a larger proportion of smokers and higher prevalence of diabetic retinopathy. Median duration of diabetes at diagnosis of DN was 8.3 years. Multivariable analysis, adjusted for demographics revealed an increased risk for DN among female patients and those who were older, underweight (BMI-SDS), smoked cigarettes or had a longer duration of T1D or higher levels of HbA_1c and postprandial blood glucose. The presence of retinopathy and higher cholesterol levels were also linked to increased risk while not-using insulin pump therapy was not. Conclusions DN can develop after just a short duration of T1D. Prevention may be achieved by a lowering of HbA_1c-and postprandial glucose levels through improved glycaemic control. This warrants further investigation. The slight female predominance suggests further hormonal and genetic etiological factors.

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.