Documents in Process

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder causing about two third of all dementia cases in the elderly. Although AD pathological features have been intensively examined in numerous scientific studies employing invertebrate and vertebrate model organisms, the exact underlying mechanisms remain poorly understood. [...]

Cytoplasmic TDP-43 pathology is a pathological sign of ALS/ALS-FTD and a converging disease event across different genotypes, phenotypes and CNS areas. To understand this process and target it therapeutically, we need to define which cell types are affected and which cell-type specific effects make them particularly vulnerable. [...]

When planning longitudinal magnetic resonance imaging (MRI) studies, it is advisable to consider various (confounding) factors that could influence brain structural changes over time. The goal of this study was to identify factors that contribute to intraindividual variability of brain structure within a short period of time. [...]

Combining genetic data from different genotyping arrays (mega-analysis) increases statistical power but introduces array-specific batch effects that may bias results. This project developed a two-step genotype imputation workflow addressing this bias in studies using multiple genotyping platforms.Genotype data of 10 647 individuals generated using five different arrays were included. [...]

Impaired speech due to dysarthria significantly impacts quality of life. Patient-reported outcomes (PROs) offer critical insight into the lived experience of communication disability and are central to regulatory frameworks for patient-focused drug development.To develop and validate the Dysarthria Impact Scale (DIS), a brief PRO designed to assess the impact of motor speech disorders on quality of life across neurological conditions.A multi-site, cross-sectional study was conducted with 244 participants, including individuals with Huntington's disease, Parkinson's disease, hereditary ataxias, and head and neck cancer, and healthy controls. [...]

Background Friedreich ataxia (FRDA) is an inherited, progressive neurodegenerative disease. Interindividual heterogeneity in the rate and phenotypic profile of disease progression indicates a biologic variability in the pattern and spatial evolution of underlying changes, but the occurrence of possible FRDA subgroups, which could aid in clinical trial design and treatment, are still unknown. [...]

Patients with severe prestroke disability (PSD) remain underrepresented in mechanical thrombectomy studies, despite their growing relevance in aging populations. This study used data from the German Stroke Registry-Endovascular Treatment to evaluate functional recovery, mortality, and poststroke care outcomes in this high-risk population.We analyzed 9456 mechanical thrombectomy-treated patients with stroke from the German Stroke Registry-Endovascular Treatment (2015-2021), categorized by premorbid modified Rankin Scale (mRS): no PSD (mRS score, 0-1), moderate PSD (mPSD; mRS score, 2-3), and severe PSD (sPSD; mRS score, 4-5). [...]

The hypothalamus as one of the core structures in metabolic control is increasingly recognized to be morphologically altered in various neurodegenerative diseases.The purpose of this study was to quantitatively investigate the hypothalamic volumes in patients with progressive supranuclear palsy (PSP) and to compare them with controls and Parkinson disease (PD) patients.An automatic hypothalamic volume quantification method based on the use of convolutional neural networks (CNN) of U-Net architecture was applied to the automatic segmentation of the hypothalamus and intracranial volumes (ICV). This CNN-based volumetric analysis was performed in high resolution T1 weighted MRI in two PSP cohorts: cohort A with 78 PSP patients and 63 controls was recorded at 3.0 T at multiple sites; the single site cohort B consisted of 66 PSP patients, 66 PD patients, and 44 controls, recorded at 1.5 T.In cohort A, significant hypothalamic volume reduction was observed in PSP (774 ± 83 mm3) when compared to controls (817 ± 74 mm3). [...]

Incomplete genotype-phenotype correlations challenge the management of non-SCID FOXN1 immunodeficiency. We describe the detailed clinical course of three distinct newborns with four novel FOXN1 mutations identified by TRECNBS. [...]