Behandlungseffekte der repetitiven transkraniellen Magnetstimulation (rTMS) bei Patienten mit chronischem Tinnitus aurium: Erste Ergebnisse der Behandlung mit niederfrequenter rTMS

Einleitung: In der Bundesrepublik Deutschland erkranken jährlich über 350.000 Patienten behandlungsbedürftig an Tinnitus. Die repetitive transkranielle Magnetstimulation (rTMS) wird in den letzten Jahren in verschiedenen Kliniken innerhalb einer Multicenterstudie als eine innovative technische Behandlungsmethode bei chronischen Ohrgeräuschen erprobt. Methode: An einer Stichprobe von 28 ambulanten Patienten mit chronischem Tinnitus aurium wurde die Wirksamkeit der niederfrequenten Magnetstimulation (1 Hz) bei Tinnitus im Rahmen der Routineversorgung überprüft. Ergebnisse: Im Prä-Post-Vergleich zeigte sich im Stichprobendurchschnitt eine 7 Punkte umfassende Reduktion des Tinnitus-Wertes, erfasst anhand des Tinnitus-Fragebogens (TF, Göbel und Hiller) sowie eine signifikante Reduktion der depressiv gefärbten Stimmung der Patienten im Fremd- (MÅDRS) wie im Selbsturteil (BDI II). 57% der mit rTMS Behandelten konnten als Responder eingestuft werden (Response-Kriterium: Abnahme des TF-Scores um mindestens 5 Punkte). Schlussfolgerung: Die Ergebnisse erlauben mit Einschränkungen einen positiven Ausblick in die Zukunft der rTMS in der Tinnitus-Behandlung

Insomnia: Comorbidities from the Field of Sleep Medicine and Psychiatry in a Sample of an Interdisciplinary Center for Sleep Medicine

In dieser Untersuchung wurde die Komorbidität der Insomnie mit anderen schlafmedizinischen und psychiatrischen Diagnosen untersucht. Hierzu wurden die Schlaflaborbriefe von 102 Insomniepatienten eines schlafmedizinischen Zentrums (mittleres Alter: 49 Jahre; 64 Frauen, 38 Männer) nach diesbezüglich relevanten Diagnosen durchsucht. Die höchste Komorbidität zeigte sich mit depressiven Störungen (50%) gefolgt von schlafbezogenen Atmungsstörungen (17,6 – 37,3%) und schlafbezogenen Bewegungsstörungen (12,7 – 21,5%). Dieser Befund spricht bei Vorliegen einer Insomniesymptomatik für die routinemäßige Durchführung einer fundierten Diagnostik mit sowohl Polysomnographie als auch psychiatrischer Exploration.In this study comorbidity of insomnia and other relevant diagnoses from the field of sleep medicine and psychiatry was analysed. For this purpose relevant diagnoses from physician´s letters of an interdisciplinary department of sleep medicine were documented in a sample of 102 patients with insomnia. Insomnia showed the highest comorbidity with depressive disorders (50%) followed by sleep related breathing disorders (17.6 – 37.3%) and sleep related movement disorders (12.7 – 21.5%). In case of subjectively reported insomnia symptom-atology this result indicates a profound diagnostic investigation with polysomnographic sleep recording and psychiatric exploration as a matter of clinical routine

Management of Chronic Tinnitus and Insomnia with Repetitive Transcranial Magnetic Stimulation and Cognitive Behavioral Therapy – a Combined Approach

It has been estimated that up to 80% of people will experience symptoms of tinnitus over the courses of their lives, with rates of comorbid sleeping problems ranging from 50 to 77%. Because of a potential connection between tinnitus and sleep disorders as well as high rates of comorbid psychiatric disorders, interdisciplinary approaches to treatment seem to be the most efficient option. In this study, we present the case of a 53-year-old male patient, who started to experience symptoms of tinnitus at the age of 49, most likely caused by work-related stress. Over the course of his illness, the patient developed comorbid insomnia. He consulted us for treatment of both conditions and we developed a treatment plan with ten sessions of repetitive transcranial magnetic stimulation (rTMS) followed by 10 sessions of cognitive behavioral therapy (CBT). We used the Tinnitus Fragebogen (TF) to assess the severity of the tinnitus, the Beck Depression Inventory (BDI-II) for depressive symptoms, and the WHO Well-being Index (WHO-5) for subjective well-being. Improvements could be achieved with regard to both diagnoses and the patient went from severe (48) to clinically negligible (12) TF scores, from minimal (BDI-II score 10) to no (0) depressive symptoms, and from just above critical (WHO-5 percentile 52) to above average (84) well-being. The combination of technological and psychological approaches to treat tinnitus and insomnia thus proved successful in this case. One may therefore conclude that rTMS may be considered an effective first therapeutic step for tinnitus treatment prior to CBT. To our knowledge this is the first published case in which rTMS and CBT were combined for tinnitus therapy. The approach proved successful since it led to a considerable increase in well-being and everyday functioning. To gauge the effect on a more general level, large-scale studies are still needed to cancel out potential placebo effects. Likewise, the importance of the order of the two treatments, and the possibility of using other therapies in combination with CBT to address certain tinnitus subtypes and different etiologies must be studied in greater detail

Behandlungsempfehlungen Insomnie der Gruppe «Schlaf & Psychiatrie» der SGSSC

Die Insomnie ist eine häufige Störung der Schlaf-Wach-Regulation und tritt oft komorbid auf. Die nachfolgenden Behandlungsempfehlungen stellen evidenzbasierte Diagnostik- und Therapiestrategien vor und umfassen sowohl psychotherapeutische wie auch pharmakotherapeutische Interventionen. Diese Empfehlungen der Schweizerischen Gesellschaft für Schlafforschung, Schlafmedizin und Chronobiologie (SGSSC) für die Behandlung der Insomnie wurden auf Grundlage der Leitlinien der «European Sleep Research Society» (ESRS) von 2023 [1] sowie der S3-Leitlinie/Nationalen Versorgungsleitlinie «Nicht erholsamer Schlaf/Schlafstörungen» der Deutschen Gesellschaft für Schlafforschung und Schlafmedizin (DGSM) von 2017 [2] erstellt. Sie geben nicht unbedingt die Ansicht der SMF-Redaktion wieder. Der Inhalt untersteht der redaktionellen Verantwortung der unterzeichnenden Fachgesellschaft bzw. Arbeitsgruppe

Self-help for stress and burnout without therapist contact: An online randomised controlled trial

Interventions designed to reduce stress and burnout may be costly and access is limited. This study examined the effectiveness of a self-help book, using Acceptance and commitment therapy (ACT) to target stress and burnout in a randomised controlled online trial without any therapist contact. Participants were recruited through a newsletter of a health insurance company. Participants ( N = 119) who reported at least moderate levels of stress were randomly assigned to an immediate intervention ( n = 61) or a waitlist group ( n = 58). Measures before and after the intervention assessed stress, burnout (primary outcomes), depression, well-being, emotion regulation (secondary outcomes) and ACT-specific constructs. Compared to the waitlist group, participants in the immediate intervention group reported lower stress and burnout and higher psychological flexibility at post-assessment. Effects between groups were large for stress ( d = 0.9), moderate to large for burnout ( d = 0.5–0.8) and large for psychological flexibility ( d = 0.8). All primary and most secondary outcomes and ACT processes continued to improve in the 3-month-follow-up period. Results suggest that an ACT self-help book without any therapist contact is effective in reducing stress and burnout for various occupations. Thus, it may provide a cost-effective public health intervention for reducing stress and burnout

Simple deprotection of acetal type protecting groups under neutral conditions

The hallmarks of Alzheimer's disease (AD) are characterized by cognitive decline and behavioral changes. The most prominent brain region affected by the progression of AD is the hippocampal formation. The pathogenesis involves a successive loss of hippocampal neurons accompanied by a decline in learning and memory consolidation mainly attributed to an accumulation of senile plaques. The amyloid precursor protein (APP) has been identified as precursor of Aβ-peptides, the main constituents of senile plaques. Until now, little is known about the physiological function of APP within the central nervous system. The allocation of APP to the proteome of the highly dynamic presynaptic active zone (PAZ) highlights APP as a yet unknown player in neuronal communication and signaling. In this study, we analyze the impact of APP deletion on the hippocampal PAZ proteome. The native hippocampal PAZ derived from APP mouse mutants (APP-KOs and NexCreAPP/APLP2-cDKOs) was isolated by subcellular fractionation and immunopurification. Subsequently, an isobaric labeling was performed using TMT6 for protein identification and quantification by high-resolution mass spectrometry. We combine bioinformatics tools and biochemical approaches to address the proteomics dataset and to understand the role of individual proteins. The impact of APP deletion on the hippocampal PAZ proteome was visualized by creating protein-protein interaction (PPI) networks that incorporated APP into the synaptic vesicle cycle, cytoskeletal organization, and calcium-homeostasis. The combination of subcellular fractionation, immunopurification, proteomic analysis, and bioinformatics allowed us to identify APP as structural and functional regulator in a context-sensitive manner within the hippocampal active zone network

The Swiss Primary Hypersomnolence and Narcolepsy Cohort study (SPHYNCS): Study protocol for a prospective, multicentre cohort observational study.

Narcolepsy type 1 (NT1) is a disorder with well-established markers and a suspected autoimmune aetiology. Conversely, the narcoleptic borderland (NBL) disorders, including narcolepsy type 2, idiopathic hypersomnia, insufficient sleep syndrome and hypersomnia associated with a psychiatric disorder, lack well-defined markers and remain controversial in terms of aetiology, diagnosis and management. The Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (SPHYNCS) is a comprehensive multicentre cohort study, which will investigate the clinical picture, pathophysiology and long-term course of NT1 and the NBL. The primary aim is to validate new and reappraise well-known markers for the characterization of the NBL, facilitating the diagnostic process. Seven Swiss sleep centres, belonging to the Swiss Narcolepsy Network (SNaNe), joined the study and will prospectively enrol over 500 patients with recent onset of excessive daytime sleepiness (EDS), hypersomnia or a suspected central disorder of hypersomnolence (CDH) during a 3-year recruitment phase. Healthy controls and patients with EDS due to severe sleep-disordered breathing, improving after therapy, will represent two control groups of over 50 patients each. Clinical and electrophysiological (polysomnography, multiple sleep latency test, maintenance of wakefulness test) information, and information on psychomotor vigilance and a sustained attention to response task, actigraphy and wearable devices (long-term monitoring), and responses to questionnaires will be collected at baseline and after 6, 12, 24 and 36 months. Potential disease markers will be searched for in blood, cerebrospinal fluid and stool. Analyses will include quantitative hypocretin measurements, proteomics/peptidomics, and immunological, genetic and microbiota studies. SPHYNCS will increase our understanding of CDH and the relationship between NT1 and the NBL. The identification of new disease markers is expected to lead to better and earlier diagnosis, better prognosis and personalized management of CDH

The Swiss Primary Hypersomnolence and Narcolepsy Cohort study (SPHYNCS): Study protocol for a prospective, multicentre cohort observational study

Narcolepsy type 1 (NT1) is a disorder with well-established markers and a suspected autoimmune aetiology. Conversely, the narcoleptic borderland (NBL) disorders, including narcolepsy type 2, idiopathic hypersomnia, insufficient sleep syndrome and hypersomnia associated with a psychiatric disorder, lack well-defined markers and remain controversial in terms of aetiology, diagnosis and management. The Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (SPHYNCS) is a comprehensive multicentre cohort study, which will investigate the clinical picture, pathophysiology and long-term course of NT1 and the NBL. The primary aim is to validate new and reappraise well-known markers for the characterization of the NBL, facilitating the diagnostic process. Seven Swiss sleep centres, belonging to the Swiss Narcolepsy Network (SNaNe), joined the study and will prospectively enrol over 500 patients with recent onset of excessive daytime sleepiness (EDS), hypersomnia or a suspected central disorder of hypersomnolence (CDH) during a 3-year recruitment phase. Healthy controls and patients with EDS due to severe sleep-disordered breathing, improving after therapy, will represent two control groups of over 50 patients each. Clinical and electrophysiological (polysomnography, multiple sleep latency test, maintenance of wakefulness test) information, and information on psychomotor vigilance and a sustained attention to response task, actigraphy and wearable devices (long-term monitoring), and responses to questionnaires will be collected at baseline and after 6, 12, 24 and 36 months. Potential disease markers will be searched for in blood, cerebrospinal fluid and stool. Analyses will include quantitative hypocretin measurements, proteomics/peptidomics, and immunological, genetic and microbiota studies. SPHYNCS will increase our understanding of CDH and the relationship between NT1 and the NBL. The identification of new disease markers is expected to lead to better and earlier diagnosis, better prognosis and personalized management of CDH

Glioblastomas with primitive neuronal component harbor a distinct methylation and copy‑number profle with inactivation of TP53, PTEN, and RB1

Glioblastoma IDH-wildtype presents with a wide histological spectrum. Some features are so distinctive that they are considered as separate histological variants or patterns for the purpose of classification. However, these usually lack defined (epi-)genetic alterations or profiles correlating with this histology. Here, we describe a molecular subtype with overlap to the unique histological pattern of glioblastoma with primitive neuronal component. Our cohort consists of 63 IDH-wildtype glioblastomas that harbor a characteristic DNA methylation profile. Median age at diagnosis was 59.5 years. Copy-number variations and genetic sequencing revealed frequent alterations in TP53, RB1 and PTEN, with fewer gains of chromosome 7 and homozygous CDKN2A/B deletions than usually described for IDH-wildtype glioblastoma. Gains of chromosome 1 were detected in more than half of the cases. A poorly differentiated phenotype with frequent absence of GFAP expression, high proliferation index and strong staining for p53 and TTF1 often caused misleading histological classification as carcinoma metastasis or primitive neuroectodermal tumor. Clinically, many patients presented with leptomeningeal dissemination and spinal metastasis. Outcome was poor with a median overall survival of only 12 months. Overall, we describe a new molecular subtype of IDH-wildtype glioblastoma with a distinct histological appearance and genetic signature.publishedVersio

In vivo Identification and Specificity assessment of mRNA markers of hypoxia in human and mouse tumors

<p>Abstract</p> <p>Background</p> <p>Tumor hypoxia is linked to poor prognosis, but identification and quantification of tissue hypoxia remains a challenge. The hypoxia-specificity of HIF-1α target genes in vivo has been questioned due to the confounding influence of other microenvironmental abnormalities known to affect gene expression (e.g., low pH). Here we describe a new technique that by exploiting intratumoral oxygenation heterogeneity allows us to identify and objectively rank the most robust mRNA hypoxia biomarkers.</p> <p>Methods</p> <p>Mice carrying human (FaDu_dd) or murine (SCCVII) tumors were injected with the PET hypoxia tracer FAZA. Four hours post-injection tumors were removed, frozen, and crushed into milligram-sized fragments, which were transferred individually to pre-weighed tubes containing RNAlater and then weighed. For each fragment radioactivity per tissue mass and expression patterns of selected mRNA biomarkers were analyzed and compared.</p> <p>Results</p> <p>In both tumour models, fragmentation into pieces weighing 10 to 60 mg resulted in tissue fragments with highly variable relative content of hypoxic cells as evidenced by an up to 13-fold variation in FAZA radioactivity per mass of tissue. Linear regression analysis comparing FAZA retention with patterns of gene expression in individual tissue fragments revealed that CA9, GLUT1 and LOX mRNA levels were equally and strongly correlated to hypoxic extent in FaDu_dd. The same link between hypoxia and gene expression profile was observed for CA9 and GLUT1, but not LOX, in SCCVII tumors. Apparent in vivo hypoxia-specificity for other putative molecular markers of tissue hypoxia was considerably weaker.</p> <p>Conclusions</p> <p>The portrayed technique allows multiple pairwise measurements of mRNA transcript levels and extent of hypoxia in individual tumors at a smallest possible volumetric scale which (by limiting averaging effects inherent to whole-tumor analysis) strengthen the conclusiveness on true hypoxia-specificity of candidate genes while limiting the required number of tumors. Among tested genes, our study identified CA9, GLUT1 and possibly LOX as highly specific biomarkers of tumor hypoxia in vivo.</p