Etablierung eines Studiendesigns zur Untersuchung des Einflusses von Topiramat auf das Körpergewicht und den Insulin- und Fettstoffwechsel in tierexperimentellen Modellen der humanen Adipositas

Im Rahmen dieser Dissertation wurde ein Studiendesign etabliert, um den Einfluss von Topiramat auf die Zielparameter Körpergewicht sowie Futter- und Wasseraufnahme und den Insulin- und Fettstoffwechsel unter kohlenhydratreicher Ernährung zu evaluieren. Es wurden insgesamt 4 Versuchsreihen im Paarfütterungsdesign durchgeführt. Homozygote Zuckerratten und db/db Mäuse erhielten über 1 bis 4 Wochen eine Hochdosis-Topiramattherapie (100 mg/kg/d) über eine orogastrale Sonde. Die db/db Maus erwies sich als nicht robust genug für das zu etablierende Studiendesign. Bei den Zuckerratten zeigte Topiramat den bekannten akuten anorektischen Effekt. Im Verlauf wurde bei den behandelten Tieren eine Verlangsamung der Wachstumsgeschwindigkeit gegenüber den Placebotieren trotz höherer oder gleicher Futteraufnahme deutlich. Dies lässt auf Wirkmechanismen des Topiramats schliessen, die das Energiegleichgewicht der Tiere auf metabolischer Ebene beeinflussen. Als ein wichtiger metabolische Effekt konnte die bereits vorbeschriebene antidiabetische Wirkung beobachtet werden. Daneben konnte erstmals eine Verminderung der de novo Lipogeneserate im weißen Fettgewebe nachgewiesen werden. Dieser Befund lässt der Carboanhydrasehemmung durch Topiramat eine zentrale Bedeutung für die gewichtsreduzierende Wirkung zukommen und gibt Anlass zur Erforschung weiterer Hemmstoffe, die nach Möglichkeit eine höhere Spezifität für das weiße Fettgewebe aufweisen sollten

Childhood haemorrhagic stroke: a 7-year single-centre experience

Background In recent years, there has been increasing research interest in improving diagnostic and management protocols in childhood arterial ischaemic stroke (AIS). However, childhood stroke comprises, in approximately equal parts, both arterial ischaemic and haemorrhagic stroke (HS). Objective The aim of this study was to focus on the aetiology, clinical presentation, treatment and short-term outcome of children with spontaneous intracranial bleeding in a university hospital and elucidate differences to childhood AIS. Design We performed a retrospective analysis of electronic medical records of children (28 days-18 years) diagnosed with HS between 2010 and 2016. Results We included 25 children (male child, n=11) with a median age of 8 years 1 month. The most common clinical presentations were vomiting (48%), headache (40%) and altered level of consciousness (32%). In more than half of the patients, HS was caused by vascular malformations. Other risk factors were brain tumour, coagulopathy and miscellaneous severe underlying diseases. Aetiology remained unclear in one child. Therapy was neurosurgical in most children (68%). Two patients died, 5 patients needed further (rehabilitation) treatment and 18 children could be discharged home. Conclusions HS differs from AIS in aetiology (vascular malformations as number one risk factor), number of risk factors ('mono-risk' disease), clinical presentation (vomiting, headache and altered level of consciousness) and (emergency) therapy

Checklist on the quality of the repetitive peripheral magnetic stimulation (rPMS) methods in research: An international Delphi study

An increasing number of clinical research studies have used repetitive peripheral magnetic stimulation (rPMS) in recent years to alleviate pain or improve motor function. rPMS is non-invasive, painless, and administrated over peripheral nerve, spinal cord roots, or a muscle using a coil affixed to the skin and connected to a rapid-rate magnetic stimulator. Despite the clinical impact and scientific interest, the methodological inconsistencies or incomplete details and findings between studies could make the rPMS demonstration difficult to replicate. Given the lack of guidelines in rPMS literature, the present study aimed at developing a checklist to improve the quality of rPMS methods in research. An international panel of experts identified among those who had previously published on the topic were enrolled in a two-round web-based Delphi study with the aim of reaching a consensus on the items that should be reported or controlled in any rPMS study. The consensual rPMS checklist obtained comprises 8 subject-related items (e.g., age, sex), 16 methodological items (e.g., coil type, pulse duration), and 11 stimulation protocol items (e.g., paradigm of stimulation, number of pulses). This checklist will contribute to new interventional or exploratory rPMS research to guide researchers or clinicians on the methods to use to test and publish rPMS after-effects. Overall, the checklist will guide the peer-review process on the quality of rPMS methods reported in a publication. Given the dynamic nature of a consensus between international experts, it is expected that future research will affine the checklist

Cognitive performance and behavior across idiopathic/genetic epilepsies in children and adolescents

We investigated the cognitive and behavioral profile of three distinct groups of epilepsies with a genetic Background: for intergroup differences: (1) idiopathic/genetic generalized epilepsies (IGE/GGE group);(2) idiopathic focal epilepsies (IFE group);and (3) epilepsies with proven or strongly suggested monogenic or structural/numeric chromosomal etiology (genetic epilepsies, GE group). Cognitive (total IQ and subcategories) and behavioral parameters (CBCL) were assessed at the tertiary epilepsy center of the University of Munich (Germany). We used ANOVA with post-hoc Bonferroni-correction to explore significant mean differences and Fisher's exact test for significant proportional differences of intelligence impairment and behavioral problems. 126 (56 IGE/GGE, 26 IFE, 44 GE) patients were available. Total IQ was 89.0 +/- 15.9 (95% CI 84.5-93.4) for IGE/GGE, 94.8 +/- 18.1 (95% CI 87.3-102.3) for IFE and 76.4 +/- 22.4 (95% CI 67.6-85.3) for GE (p=0.001). The same trend was significant for all but one IQ subcategory. The rate of patients with an intelligence impairment (total IQ<70) was higher for GE (40%) than for IGE/GGE (14%) and for IFE (7%) patients (p=0.033). There were no significant differences between groups for behavior scores and behavioral problems. This study shows that the current ILAE classification of epilepsies with genetic etiology creates a heterogeneous group of patients with respect to cognitive performance but not behavior. These findings may help in further delineating epilepsies as regards cognitive performance, notwithstanding their closely related etiological classification

Alleviation of migraine symptoms by application of repetitive peripheral magnetic stimulation to myofascial trigger points of neck and shoulder muscles - A randomized trial

Migraine is a burdensome disease with an especially high prevalence in women between the age of 15 and 49 years. Non-pharmacological, non-invasive therapeutic methods to control symptoms are increasingly in demand to complement a multimodal intervention approach in migraine. Thirty-seven subjects (age: 25.0 +/- 4.1 years;36 females) diagnosed with high-frequency episodic migraine who presented at least one active myofascial trigger point (mTrP) in the trapezius muscles and at least one latent mTrP in the deltoid muscles bilaterally prospectively underwent six sessions of repetitive peripheral magnetic stimulation (rPMS) over two weeks. Patients were randomly assigned to receive rPMS applied to the mTrPs of the trapezius (n = 19) or deltoid muscles (n = 18). Whereas the trapezius muscle is supposed to be part of the trigemino-cervical complex (TCC) and, thus, involved in the pathophysiology of migraine, the deltoid muscle was not expected to interfere with the TCC and was therefore chosen as a control stimulation site. The headache calendar of the German Migraine and Headache Society (DMKG) as well as the Migraine Disability Assessment (MIDAS) questionnaire were used to evaluate stimulation-related effects. Frequency of headache days decreased significantly in both the trapezius and the deltoid group after six sessions of rPMS (trapezius group: p = 0.005;deltoid group: p = 0.003). The MIDAS score decreased significantly from 29 to 13 points (p = 0.0004) in the trapezius and from 31 to 15 points (p = 0.002) in the deltoid group. Thus, rPMS applied to mTrPs of neck and shoulder muscles offers a promising approach to alleviate headache frequency and symptom burden. Future clinical trials are needed to examine more profoundly these effects, preferably using a sham-controlled setting

Recanalization strategies in childhood stroke in Germany

Childhood arterial ischemic stroke (CAIS) is a rare event. Diverse etiologies, risk factors, symptoms and stroke mimics hamper obtaining a fast diagnosis and implementing immediate recanalization strategies. Over a period of 3~years (2015-2017), the data of 164 pediatric patients (> 28~days of life-18~years) with a first episode of AIS were submitted to a hospital-based nationwide surveillance system for rare disorders (ESPED). We report a subgroup analysis of patients who have undergone recanalization therapy and compare these data with those of the whole group. Twenty-eight patients (17%) with a median age of 12.2~years (range 3.3-16.9) received recanalization therapy. Hemiparesis, facial weakness and speech disturbance were the main presenting symptoms. The time from onset of symptoms to confirmation of diagnosis was significantly shorter in the intervention group (4.1~h vs. 20.4~h, p ≤ 0.0001). Only in one patient occurred a minor bleed. Cardiac disease as predisposing risk factor was more common in the recanalization group. Recanalization therapies are feasible and increasingly applied in children with AIS. High awareness, timely diagnosis and a large amount of expertise may improve time to treatment and make hyperacute therapy an option for more patients

Migraine and the development of additional psychiatric and pain disorders in the transition from adolescence to adulthood

Introduction: The transition from childhood to adolescence and from adolescence to adulthood are vulnerable phases in life. In these phases, late or insufficient treatment of diseases may lead to chronification and favor development of additional disorders. In adolescents, migraine often has a highly negative impact on school performance and everyday life. The hypothesis of the present study was that adolescents with migraine have a higher risk for developing additional disorders such as psychiatric disorders or other pain syndromes in the course of the disease. Materials and methods: In this study, we analyzed health insurance data of 56,597 German adolescents at the age of 15 years in the year 2006. By using the International Classification of Diseases (ICD 10), we determined a group with migraine diagnosis in the year 2006 and a control group without any headache diagnosis in 2006. We then compared both groups regarding the development of additional disorders (based on the ICD 10) during the following 10 years (2007 to 2016). Results: Adolescents with migraine had a 2.1 fold higher risk than persons without migraine diagnosis to develop an additional affective or mood disorder, a 1.8 fold higher risk to obtain neurotic, stress-related and somatoform disorders, a 1.8 fold higher risk to subsequently suffer from behavioral syndromes, a 1.6 higher risk to get back pain and a 1.5 fold higher risk for irritable bowel syndrome during the next 10 years. Conclusion: Adolescents with migraine are at risk for developing additional disorders later. Considering and addressing the patient’s risks and potential medical and psychosocial problems might improve the long-term outcome significantly

Quality of life after brain injury in children and adolescents (QOLIBRI-KID/ADO)-The first disease-specific self-report questionnaire after traumatic brain injury

The subjective impact of the consequences of pediatric traumatic brain injury (pTBI) on different life dimensions should be assessed multidimensionally and as sensitively as possible using a disease-specific health-related quality of life (HRQoL) instrument. The development and psychometrics of the first such self-report questionnaire for children and adolescents after TBI are reported here. Focus group interviews with children, adolescents, and their parents, cognitive debriefing, item pool generation and reduction using Delphi expert panels were performed. The resulting version was psychometrically tested on 300 individuals aged 8–17 years. After item reduction based on factor analyses, differential item functioning, reliability, and validity were investigated. The final 35 items were associated with six scales (Cognition, Self, Daily Life and Autonomy, Social Relationships, Emotions, Physical Problems). Internal consistency and construct validity were satisfactory. Health-related Quality of life (HRQoL) was significantly lower in older and in female participants, as well as those with cognitive disabilities, anxiety, depression and post-concussion symptoms, than in comparative groups. The new QOLIBRI-KID/ADO is a comprehensive, multidimensional, reliable, and valid instrument, comparable in content and items to the QOLIBRI adult version. Therefore, disease-specific HRQoL can now be measured across the lifespan and may support the amelioration of treatment, care, rehabilitation, and daily life of children and adolescents after TBI.This research was funded by Dr. Senckenbergische Stiftung/Clementine Kinderhospital Dr. Christ‘sche Stiftungen (Germany), and Uniscientia Stiftung (Switzerland)

Migräne im Kindes- und Jugendalter — Ausblick auf innovative Behandlungsansätze im Rahmen multimodaler Therapiekonzepte

Although migraine is a~relevant health issue in children and adolescents, clinical care and research are still underrepresented and underfunded in this field. Quality of life can be significantly reduced when living with frequent episodes of pain. Due to the high level of vulnerability of the developing brain during adolescence, the risk of chronification and persistence into adulthood is high. In this narrative review, we describe the corner stones of a~patient-centered, multimodular treatment regimen. Further, an update on the pathophysiology of migraine is given considering the concept of a~periodically oscillating functional state of the brain in migraine patients (\textquotedblmigraine is a~brain state\textquotedbl). Besides central mechanisms, muscular structures with the symptoms of muscular pain, tenderness, or myofascial trigger points play an important role. Against this background, the currently available nonpharmacological and innovative neuromodulating approaches are presented focusing on the method of repetitive peripheral magnetic stimulation.Die Migräne ist auch im Kindes- und Jugendalter ein häufiges, aber in klinischer Versorgung und Wissenschaft oft unterrepräsentiertes Krankheitsbild. Gerade im Kindes- und Jugendalter bestehen relevante Einschränkungen der Lebensqualität durch das (häufige) Schmerzerfahren. Bedingt durch die entwicklungsspezifisch hohe Vulnerabilität des adoleszenten Gehirns besteht ein hohes Chronifizierungs- und Persistenzrisiko bis ins Erwachsenenalter hinein. In diesem Beitrag werden die Bestandteile eines patientenzentrierten, multimodalen Therapiekonzepts dargestellt. Darüber hinaus werden die aktuellsten Erkenntnisse zu den pathophysiologischen Grundlagen der Migräneerkrankung beleuchtet, nach denen Migräne durch einen sich phasenweise verändernden Funktionszustand des Gehirns entsteht (Stichwort: „migraine is a brain state“). Auch periphere Komponenten wie Muskelschmerzen, -verspannungen und -triggerpunkte spielen eine wichtige Rolle. Vor diesem Hintergrund werden nichtpharmakologische innovative Therapieansätze vorgestellt, die auf dem Prinzip der Neuromodulation beruhen, mit Fokus auf der repetitiven peripheren Magnetstimulation

Childhood Stroke: Awareness, Interest, and Knowledge Among the Pediatric Community

Objective: Acute childhood stroke is an emergency requiring a high level of awareness among first-line healthcare providers. This survey serves as an indicator of the awareness of, the interest in, and knowledge of childhood stroke of German pediatricians.Methods: Thousand six hundred and ninety-seven physicians of pediatric in- and outpatient facilities in Bavaria, Germany, were invited via email to an online-survey about childhood stroke.Results: The overall participation rate was 14%. Forty-six percent of participants considered a diagnosis of childhood stroke at least once during the past year, and 47% provide care for patients who have suffered childhood stroke. The acronym FAST (Face-Arm-Speech-Time-Test) was correctly cited in 27% of the questionnaires. Most commonly quoted symptoms of childhood stroke were hemiparesis (90%), speech disorder (58%), seizure (44%), headache (40%), and impaired consciousness (33%). Migraine (63%), seizure (39%), and infections of the brain (31%) were most frequently named as stroke mimics. Main diagnostic measures indicated were magnetic resonance imaging (MRI) (96%) and computer tomography (CT) (55%). Main therapeutic strategies were thrombolysis (80%), anticoagulation (41%), neuroprotective measures, and thrombectomies (15% each). Thirty-nine percent of participants had taken part in training sessions, 61% studied literature, 37% discussed with colleagues, and 25% performed internet research on childhood stroke. Ninety-three percent of participants approve skill enhancement, favoring training sessions (80%), publications (43%), and web based offers (35%). Consent for offering a flyer on the topic to caregivers in facilities was given in 49%.Conclusion: Childhood stroke constitutes a topic of clinical importance to pediatricians. Participants demonstrate a considerable level of comprehension concerning the subject, but room for improvement remains. A multi-modal approach encompassing an elaborate training program, regular educational publications in professional journals, and web based offers could reach a broad range of health care providers. Paired with a public adult and childhood stroke awareness campaign, these efforts could contribute to optimize the care for children suffering from stroke