STUDY OBJECTIVES:Narcolepsy type 1 (NT1) is characterized by fragmented sleep, yet brief transitions may be concealed in traditional 30-s epochs. We therefore aimed to assess sleep fragmentation in NT1 patients and their non-narcoleptic siblings using 5-s mini-epochs. METHODS:We analyzed sleep stages from human-scored 30-s epochs and automatically (U-Sleep) scored 5-s mini-epochs in polysomnographies from 125 NT1 patients and their 100 non-narcoleptic siblings. Sleep fragmentation was quantified using transition indices and probabilities in epochs and mini-epochs, furthermore, stratified by 1st and 2nd night-half. Predictors (H1N1-vaccination, CSF hypocretin-1 deficiency severity (low [40-150 pg/mL]; undetectable [<40 pg/mL]), HLA-DQB1*06:02-positivity, narcolepsy core symptom severity) for sleep transitions were explored. RESULTS:NT1 patients had significantly higher all-stages and sleep-wake transition indices compared to siblings in epochs and mini-epochs. Both epoch and mini-epoch transition indices varied significantly from 1st to 2nd night-half. Only in mini-epochs, sleep-wake fragmentation was (a) higher in patients with severe core symptoms, and (b) increased in the 2nd night-half in NT1 patients with severe hypocretin-1 deficiency (<40 pg/mL) and/or severe core symptoms. CONCLUSIONS:Our findings suggest that sleep fragmentation, a core feature of NT1, is associated with disease severity and hypocretin deficiency severity when high-resolution sleep stages are analyzed. Five-second sleep staging and split-night analyses enhance detection of sleep instability and reveal new specific patterns and clinical associations. Automated mini-epoch analyses may improve future NT1 phenotyping and possibly its borderland by supplementing with clinically relevant high-resolution features otherwise hidden in traditional full-night 30-s epoch analyses. Statement of Significance This study demonstrates that high-resolution 5-s sleep staging provides more detailed sleep characterization than epochs and additionally uncovers clinically relevant sleep fragmentation patterns in narcolepsy type 1 which remain hidden in traditional 30-s analyses. By combining 5-s mini-epoch scoring with split-night analyses, we identified specific associations between disease severity and increased sleep-wake fragmentation. In mini-epochs, but not in epochs, sleep-wake fragmentation was significantly higher in patients with all core narcolepsy symptoms and increased significantly from the 1st to the 2nd night-half in patients with undetectable hypocretin-1 levels (<40 pg/mL) and/or all core narcolepsy symptoms. These findings highlight the clinical value of high-resolution, temporally sensitive sleep stage analyses for detailed phenotyping and detection of future disease biomarkers.
To identify and synthesize evidence from European qualitative studies on cancer-related quality of life outcomes, needs, experiences, preferences, and concerns of people undergoing cancer treatment in the last decade. Systematic review ( https://www.crd.york.ac.uk/PROSPERO , CRD42024575065) of European studies using qualitative methodology, assessing constructs related to HRQoL, and involving adults receiving cancer treatment. The search was performed in PubMed and Scopus from January 2013 to July 2024. Titles, abstracts, and full texts screening, data extraction and risk of bias assessment were conducted independently by two researchers. The main outcomes were the themes reported in each study. The thematic analysis was performed by organizing the themes of the studies into categories. Out of 18,256 articles initially identified, 36 met the inclusion criteria: 21 with generic and 15 with specific objectives. Five categories encompassing 110 themes were identified from the generic studies: Psychological Function (n = 41), Clinical Management (n = 26), Symptoms and Physical Function (n = 18), Social Function (n = 16), and Life Disruption (n = 9). Eleven studies with specific objectives focused on clinical management with all their themes fitting within the categories identified in the generic studies. Results showed the predominance of psychological function and clinical management themes. Symptoms and physical function, social function, and life disruption maintained their importance within the classical HRQoL framework. The emergence of clinical management is consistent with the growing patient-centered care approach, suggesting the need to integrate this content into the evaluation of patients undergoing cancer treatment. Limitations: most European countries were not represented, and publication bias could hide traditional domains.
Abstract Background CLN3 Batten disease is a severe pediatric neurodegenerative disorder caused by mutations in the CLN3 gene, most commonly a 1 kb deletion encompassing exons 7 and 8. CLN3 deficiency is associated with lysosomal dysfunction, impaired cellular clearance and disrupted metabolism. While neurons are particularly vulnerable in CLN3 Batten disease and have been the primary focus of research, glial cells are increasingly recognized as active contributors to disease pathology. Among them, astrocytes—the most abundant glial cell type in the brain—play critical roles in maintaining neuronal health and homeostasis. However, astrocytes remain understudied in CLN3 patient-derived models. Methods We present the first iPSC-derived astrocyte model from a skin biopsy of a CLN3 patient carrying the common 1 kb deletion. Cellular and molecular features of iPSC and astrocytes derived from both healthy controls and the CLN3 patient were characterized via qPCR, immunocytochemistry and targeted mass spectrometry. In addition, comprehensive omics-based profiling, through transcriptomic and label-free quantitative proteomics, was performed to uncover novel molecular mechanisms and generate hypotheses that can guide future mechanistic and functional studies. Results Transcriptomic and proteomic analyses during astrocyte differentiation revealed an upregulation of mitochondrial respiratory chain complexes I and IV—contrasting with the downregulation typically observed in CLN3-deficient neurons. We also identified a metabolic shift favoring the elongation of very-long-chain saturated fatty acids, accompanied by reduced lipid synthesis and enhanced fatty acid oxidation. These metabolic alterations were paralleled by an upregulation of proteins involved in oxidative stress responses, likely reflecting a compensatory adaptation to mitochondrial and lipid metabolic dysregulation. Furthermore, we observed significant changes in chromatin organization during astrocyte differentiation in CLN3 cells, suggesting epigenetic remodeling as a contributing factor to disease pathology. Conclusion Our findings prompt the hypothesis that mitochondrial dysfunction may precede lysosomal defects in CLN3-deficient astrocytes. Restoring mitochondrial health could improve brain metabolism, inflammation control, neurotransmitter regulation, and neuronal survival, highlighting mitochondria as promising therapeutic targets in CLN3 Batten disease.
To assess trends in volume and utilization of neuroimaging (CT and MR) across Europe over the last decade, within the context of evolving clinical practice on behalf of the European Society of Neuroradiology’s Choosing Wisely committee. A systematic search of PubMed was performed (following PRISMA 2020 guidelines) to identify studies reporting European neuroimaging volumes. As no eligible studies were identified, descriptive analysis of Eurostat and OECD data was performed for 29 European countries from 2015 to 2022, covering CT and MR examination volumes and scanner availability per 100,000 population across four geographic regions (Northern, Southern, Eastern, and Western Europe). Total CT/MR volumes served as neuroimaging surrogates. 316 publications were identified (with none meeting predefined inclusion criteria). Eurostat data from 29 countries revealed substantial growth in imaging from 2015 to 2022. Per capita CT exam rates increased 40.8
