Recommendations for optimal interdisciplinary management and healthcare settings for patients with rare neurological diseases

BackgroundIn 2017, the German Academy for Rare Neurological Diseases (Deutsche Akademie fur Seltene Neurologische Erkrankungen;DASNE) was founded to pave the way for an optimized personalized management of patients with rare neurological diseases (RND) in all age groups. Since then a dynamic national network for rare neurological disorders has been established comprising renowned experts in neurology, pediatric neurology, (neuro-) genetics and neuroradiology. DASNE has successfully implemented case presentations and multidisciplinary discussions both at yearly symposia and monthly virtual case conferences, as well as further educational activities covering a broad spectrum of interdisciplinary expertise associated with RND. Here, we present recommendation statements for optimized personalized management of patients with RND, which have been developed and reviewed in a structured Delphi process by a group of experts.MethodsAn interdisciplinary group of 37 RND experts comprising DASNE experts, patient representatives, as well as healthcare professionals and managers was involved in the Delphi process. First, an online collection was performed of topics considered relevant for optimal patient care by the expert group. Second, a two-step Delphi process was carried out to rank the importance of the selected topics. Small interdisciplinary working groups then drafted recommendations. In two consensus meetings and one online review round these recommendations were finally consented.Results38 statements were consented and grouped into 11 topics: health care structure, core neurological expertise and core mission, interdisciplinary team composition, diagnostics, continuous care and therapy development, case conferences, exchange / cooperation between Centers for Rare Diseases and other healthcare partners, patient advocacy group, databases, translation and health policy.ConclusionsThis German interdisciplinary Delphi expert panel developed consented recommendations for optimal care of patients with RND in a structured Delphi process. These represent a basis for further developments and adjustments in the health care system to improve care for patients with RND and their families

Towards an understanding of climate proxy formation in the Chew Bahir basin, southern Ethiopian Rift

Deciphering paleoclimate from lake sediments is a challenge due to the complex relationship between climate parameters and sediment composition. Here we show the links between potassium (K) concentrations in the sediments of the Chew Bahir basin in the Southern Ethiopian Rift and fluctuations in the catchment precipitation/evaporation balance. Our micro-X-ray fluorescence and X-ray diffraction results suggest that the most likely process linking climate with potassium concentrations is the authigenic illitization of smectites during episodes of higher alkalinity and salinity in the closed -basin lake, due to a drier climate. Whole-rock and clay size fraction analyses suggest that illitization of the Chew Bahir clay minerals with increasing evaporation is enhanced by octahedral Al-to-Mg substitution in the clay minerals, with the resulting layer charge increase facilitating potassium-fixation. Linking mineralogy with geochemistry shows the links between hydroclimatic control, process and formation of the Chew Bahir K patterns, in the context of well-known and widely documented eastern African climate fluctuations over the last 45,000 years. These results indicate characteristic mineral alteration patterns associated with orbitally controlled wet-dry cycles such as the African Humid Period (similar to 15-5 ka) or high-latitude controlled climate events such as the Younger Dryas (similar to 12.8-11.6 ka) chronozone. Determining the impact of authigenic mineral alteration on the Chew Bahir records enables the interpretation of the previously established pXRF-derived aridity proxy K and provides a better paleohydrological understanding of complex climate proxy formation

Outpatient behavior therapy for juveniles and young adults with alcohol problems Second year treatments outcome

UuStB Koeln(38)-8106313 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Cholesteryl ester hydrolase activity is abolished in HSL macrophages but unchanged in macrophages lacking KIAA1363[S]

Cholesteryl ester (CE) accumulation in macrophages represents a crucial event during foam cell formation, a hallmark of atherogenesis. Here we investigated the role of two previously described CE hydrolases, hormone-sensitive lipase (HSL) and KIAA1363, in macrophage CE hydrolysis. HSL and KIAA1363 exhibited marked differences in their abilities to hydrolyze CE, triacylglycerol (TG), diacylglycerol (DG), and 2-acetyl monoalkylglycerol ether (AcMAGE), a precursor for biosynthesis of platelet-activating factor (PAF). HSL efficiently cleaved all four substrates, whereas KIAA1363 hydrolyzed only AcMAGE. This contradicts previous studies suggesting that KIAA1363 is a neutral CE hydrolase. Macrophages of KIAA1363−/− and wild-type mice exhibited identical neutral CE hydrolase activity, which was almost abolished in tissues and macrophages of HSL−/− mice. Conversely, AcMAGE hydrolase activity was diminished in macrophages and some tissues of KIAA1363−/− but unchanged in HSL−/− mice. CE turnover was unaffected in macrophages lacking KIAA1363 and HSL, whereas cAMP-dependent cholesterol efflux was influenced by HSL but not by KIAA1363. Despite decreased CE hydrolase activities, HSL−/− macrophages exhibited CE accumulation similar to wild-type (WT) macrophages. We conclude that additional enzymes must exist that cooperate with HSL to regulate CE levels in macrophages. KIAA1363 affects AcMAGE hydrolase activity but is of minor importance as a direct CE hydrolase in macrophages

First epileptic seizure and epilepsies in adulthood. Abridged version ofthe S2k guideline of the German Society for Neurology in cooperationwith the German Society for Epileptology

Holtkamp M, May T, Berkenfeld R, et al. Erster epileptischer Anfall und Epilepsien im Erwachsenenalter. Kurzfassung S2k-Leitlinie der Deutschen Gesellschaft für Neurologie in Zusammenarbeit mit der Deutschen Gesellschaft für Epileptologie. Clinical Epileptology. 2024.The new S2k guideline "First epileptic seizure and epilepsies in adulthood" provides recommendations on clinically relevant issues in five major topics: management of first epileptic seizures, pharmacotherapy, epilepsy surgery, complementary and supportive treatment, and psychosocial aspects. For the topic management of first epileptic seizures, the guideline provides recommendations on identifying the two major differential diagnoses, syncope and psychogenic non-epileptic seizure. The importance of additional examinations such as EEG, MRI and cerebrospinal fluid for syndromic classification and etiological allocation is discussed. Recommendations on neuropsychological and psychiatric screening tests are also given. The topic pharmacotherapy issues recommendations on antiseizure medication in monotherapy for focal, generalized and unclassified epilepsies; patient groups with special challenges such as the aged, women of childbearing potential and people with mental retardation are emphasized. Further issues are indications for measuring serum concentrations of antiseizure medication and possible risks of switching manufacturers. In the topic epilepsy surgery, indications for presurgical assessment and the multiple therapeutic approaches, such as resection, laser ablation, and neurostimulation are presented. Recommendations on postoperative management of patients, including rehabilitation and psychosocial counselling, are given. The topic complementary and supportive therapeutic approaches comprises recommendations on the diagnostics and treatment of common psychiatric comorbidities of epilepsy, such as anxiety disorder, depression and psychosis. Another important issue is the management of psychogenic non-epileptic seizures as a neuropsychiatric differential diagnosis or comorbidity of epileptic seizures. Furthermore, recommendations on the potential role of ketogenic diet and on acupuncture, homeopathy and other complementary approaches are made. The recommendations on psychosocial aspects comprise practical issues, such as fitness to drive a car, training and occupation, medical rehabilitation, sport, transition, patients' self-help, education programs for patients and next of kin, adherence, advise on SUDEP