Hephata Klinik

Schwalmstadt, Germany

Hephata Klinik

Schwalmstadt, Germany

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Mayer G.,Hephata Klinik | Mayer G.,University of Marburg | Benes H.,University of Rostock | Young P.,University of Munster | And 2 more authors.
Journal of Sleep Research | Year: 2015

Summary: In 2010 the European Medicines Agency withdrew the indication of modafinil for the treatment of obstructive sleep apnea, shift work sleep disorder and for idiopathic hypersomnia (IH). In uncontrolled studies, modafinil has been reported to be efficacious in the treatment of sleep disorders. We therefore performed a randomized, placebo-controlled study with the aim of proving the efficacy of modafinil treatment in these patients. Drug-free IH patients without long sleep according to ICSD2 criteria, age >18 years and disease duration >2 years were included. After a washout phase, patients at baseline received placebo or 100 mg modafinil in the morning and at noon over 3 weeks, followed by 1 week without medication. At each visit the Epworth Sleepiness Scale (ESS) and Clinical Global Impression (CGI) rating scale were performed. At baseline and on days 8 and 21 four Maintenance of Wakefulness Tests (MWTs)/day or per day were performed. Patients kept a sleep-wake diary throughout the study. Between 2009 and 2011 three sleep centres recruited 33 participants. Compared to placebo, modafinil decreased sleepiness significantly and improved mean sleep latency in the MWT non-significantly. The CGI improved significantly from baseline to the last visit on treatment. The most frequent adverse events were headaches and gastrointestinal disorders; skin and psychiatric reactions were not reported. The number of reported naps and duration of daytime sleepiness decreased significantly. Total sleep time of nocturnal sleep was slightly reduced. The sleep diaries showed increases in feeling refreshed in the morning; the diurnal diaries showed significant improvement of performance and of exhaustion. Modafinil is an effective and safe medication in the treatment of IH. Adverse events are mild to moderate. © 2014 European Sleep Research Society.


Oberle D.,Paul Ehrlich Institute | Drechsel-Bauerle U.,Paul Ehrlich Institute | Schmidtmann I.,Johannes Gutenberg University Mainz | Mayer G.,Hephata Klinik | Keller-Stanislawski B.,Paul Ehrlich Institute
Sleep | Year: 2015

Study Objectives: Following the 2009 pandemic, reports of an association between an AS03 adjuvanted H1N1 pandemic influenza vaccine and narcolepsy were published. Besides determining background incidence rates for narcolepsy in Germany this study aimed at investigating whether there was a change in incidence rates of narcolepsy between the pre-pandemic, pandemic, and the post-pandemic period on the population level. Design: Retrospective epidemiological study on the incidence of narcolepsy with additional capture-recapture analysis. Setting: German sleep centers. Patients or Participants: Eligible were patients with an initial diagnosis of narcolepsy (ICD10 Code G47.4) within the period from January 1, 2007 to December 31, 2011. Interventions: None; observational study. Measurements and Results: A total of 342 sleep centers were invited to participate in the study. Adequate and suitable data were provided by 233 sleep centers (68.1%). A total of 1,198 patients with an initial diagnosis of narcolepsy within the observed period were included, of whom 106 (8.8%) were children and adolescents under the age of 18 years and 1,092 (91.2%) were adults. In children and adolescents, the age-standardized adjusted incidence rate significantly increased from 0.14/100,000 person-years in the pre-pandemic period to 0.50/100,000 person-years in the post-pandemic period (incidence density ratio, IDR 3.57; 95% CI 1.94-7.00). In adults, no significant change was detectable. This increase started in spring 2009. Conclusions: For the years 2007-2011, valid estimates for the incidence of narcolepsy in Germany were provided. In individuals under 18, the incidence rates continuously increased from spring 2009.


Mayer G.,Hephata Klinik | Jennum P.,Copenhagen University | Riemann D.,Albert Ludwigs University of Freiburg | Dauvilliers Y.,French Institute of Health and Medical Research
Sleep Medicine Reviews | Year: 2011

The objective of this review is to highlight the impact of insomnia in central neurological disorders by providing information on its prevalence and give recommendations for diagnosis and treatment. Insomnia in neurological disorders is a frequent, but underestimated symptom. Its occurrence may be a direct consequence of the disease itself or may be secondary to pain, depression, other sleep disorders or the effects of medications. Insomnia can have a significant impact on the patient's cognitive and physical function and may be associated with psychological distress and depression. Diagnosis of insomnia is primarily based on medical history and validated questionnaires. Actigraphy is a helpful diagnostic tool for assessing the circadian sleep-wake rhythm. For differential diagnosis and to measure the duration of sleep full polysomnography may be recommended. Prior to initiating treatment the cause of insomnia must be clearly identified. First line treatment aims at the underlying neurologic disease. The few high quality treatment studies show that short term treatment with hypnotics may be recommended in most disorders after having ruled out high risk for adverse effects. Sedating antidepressants may be an effective treatment for insomnia in stroke and Parkinson's disease (PD) patients. Melatonin and light treatment can stabilize the sleep-wake circadian rhythm and shorten sleep latency in dementias and PD. Cognitive behavioral therapy (CBT) can be effective in treating insomnia symptoms associated with most of the central neurological diseases. The prevalence and treatment of insomnia in neurological diseases still need to be studied in larger patient groups with randomized clinical trials to a) better understand their impact and causal relationship and b) to develop and improve specific evidence-based treatment strategies. © 2011 Elsevier Ltd.


Jennum P.,Copenhagen University | Mayer G.,Hephata Klinik | Mayer G.,University of Marburg | Ju Y.-E.,University of Washington | Postuma R.,McGill University
Sleep Medicine | Year: 2013

Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD, RBD without any obvious comorbid major neurological disease), is strongly associated with numerous comorbid conditions. The most prominent is that with neurodegenerative disorders, especially synuclein-mediated disorders, above all Parkinson disease (PD). Idiopathic RBD is an important risk factor for the development of synucleinopathies. Comorbidity studies suggest that iRBD is associated with a number of other potential pre-motor manifestations of synucleinopathies such as, cognitive and olfactory impairment, reduced autonomic function, neuropsychiatric manifestations and sleep complaints. Furthermore, patients with PD and RBD may have worse prognosis in terms of impaired cognitive function and overall morbidity/mortality; in dementia, the presence of RBD is strongly associated with clinical hallmarks and pathological findings of dementia with Lewy bodies. These findings underline the progressive disease process, suggesting involvement of more brain regions in patients with a more advanced disease stage. RBD is also associated with narcolepsy, and it is likely that RBD associated with narcolepsy is a distinct subtype associated with different comorbidities. RBD is also associated with antidepressant medications, autoimmune conditions, and, in rare cases, brainstem lesions. © 2012 Elsevier B.V.


Mayer G.,Hephata Klinik
Nervenarzt | Year: 2016

Knowledge of the physiology of sleep-wake regulation can contribute to an understanding of the pathophysiology and symptoms of neurological diseases and is helpful for initiating specific therapies for sleep-wake cycle stabilization. Based on historically important observations on the close relationship between sleep and neurological diseases, new insights and developments in selected neurological entities are presented in this review article. © 2016, Springer-Verlag Berlin Heidelberg.


Mayer G.,Hephata Klinik
Tagliche Praxis | Year: 2016

Narcolepsy is a rare sleep wake disorder. The main symptoms (cataplexy, excessive daytime sleepiness) are the result of a disorder of stage transition of wake, NREM and REM sleep. Narcolepsy therefore is considered to be a model disease for many other sleep wake disorders. The symptoms are multi-facetted and dis- play phenotypes which differ between children/ youngsters from adults, which cause difficulties in establishing the correct diagnosis. The psy-chosocial consequences differ according to the degree of the disorder and frequently cause in-capacity to work or early retirement if the diagnosis is not established early. Unfortunately latency to diagnosis is still very long and presently lasts up to 10 years in Europe. The reason for this long latency is the latency between the two main symptoms excessive daytime sleepiness and cataplexy or the very discrete presentation of symptoms, which can only revealed by carefully taking medical history. Early diagnosis of narcolepsy is al hallmark to avoid the costly psychosocial consequences and the impairment of quality of life of patients.


Mayer G.,Hephata Klinik
Expert Review of Neurotherapeutics | Year: 2012

Narcolepsy is a life-long neurodegenerative disorder that causes considerable impairment to quality of life. Until the 1970s, the treatment for one of the main symptoms, excessive daytime sleepiness, was restricted to stimulants, whereas the second core symptom, cataplexy, was treated with antidepressants, and the resultant fragmented night-time sleep with hypnotics. Sodium oxybate (Xyrem®, UCB Pharma, Brussels, Belgium) is an efficacious drug for all three symptoms which improves the quality of life of narcoleptic patients. Owing to its metabolic pathway, there is very little pharmacokinetic interaction with other drugs. In combination with modafinil, some of its therapeutic benefits are enhanced. Adverse events and side effects are moderate when taken according to indication and as recommended. Essential limitations have to be considered before starting the treatment (sleep-related breathing disorders, alcohol intake, hypnotic and sedative comedication, and epilepsy). This article gives an overview of sodium oxybate, which has been US FDA approved for the treatment of cataplexy and excessive daytime sleepiness in patients with narcolepsy, and EMA approved for the treatment of narcolepsy-cataplexy. © 2012 Expert Reviews Ltd.


Mayer G.,Hephata Klinik
Internistische Praxis | Year: 2016

Narcolepsy is a rare sleep wake disorder. The main symptoms (cataplexy, excessive daytime sleepiness) are the result of a disorder of stage transition of wake, NREM and REM sleep. Narcolepsy therefore is considered to be a model disease for many other sleep wake disorders. The symptoms are multi-facetted and display phenotypes which differ between children/ youngsters from adults, which cause difficulties in establishing the correct diagnosis. The psy-chosocial consequences differ according to the degree of the disorder and frequently cause in-capacity to work or early retirement if the diagnosis is not established early. Unfortunately latency to diagnosis is still very long and presently lasts up to 10 years in Europe. The reason for this long latency is the latency between the two main symptoms excessive daytime sleepiness and cataplexy or the very discrete presentation of symptoms, which can only revealed by carefully taking medical history. Early diagnosis of narcolepsy is al hallmark to avoid the costly psychosocial consequences and the impairment of quality of life of patients.


The Kleine-Levin syndrome (KLS) is a rare disease which can occur one to several times per year. The KLS belongs to the group of hypersomnia of central origin occurring mainly during the second decade of life after infections, sleep deprivation, alcohol consumption or minor trauma. Early manifestation combined with hypersexuality during symptomatic phases can be a predictor for a long course of the disease, which lasts a mean of 1-27 years. Due to the lack of biological markers diagnosis at first manifestation is difficult. The classical trias of hypersomnia, hyperphagia and hypersexuality can only be found in 45% of patients. The dominant clinical symptoms are hypersomnia with changes in perception and behavior. Subtraction of perfusion studies performed during symptomatic and asymptomatic phases showed decreased perfusion of the left hypothalamus, thalamus, basal ganglia, medial and dorsolateral frontal and temporal regions. In the few patients who had lumbar punctures in both symptomatic and asymptomatic phases hypocretin-1 was moderately to slightly lowered during symptomatic phases. Meta-analyses showed good therapeutic effects of stimulants on the symptom sleepiness. Lithium reduces the frequency and duration of symptomatic phases. Assuming that KLS is underdiagnosed it should be considered as a differential diagnosis in young patients with recurrent hypersomnia. © Springer-Verlag Berlin Heidelberg 2013.


Mayer G.,Hephata Klinik
Somnologie | Year: 2013

Kleine-Levin syndrome (KLS) is a rare sleep disorder. Most of the published studies have included only small numbers of patients. Therapeutic and diagnostic studies have the lowest evidence level. This study is a retrospective study including 15 KLS patients of the past 19 years. The patients had first symptoms in their early teens triggered by sleep deprivation, infections, and alcohol intake. Frequency ranged from 2-16/year, duration from 1-6 weeks. Liver enzymes, blood count, inflammatory markers, and magnetic resonance images were normal in all patients. Cerebral spinal fluid (CSF) hypocretin-1 was assessed in 6 patients. It was at the lower normal range in 2 patients and < 130 pg/ml in 2 other patients during an asymptomatic phase, while it was low in 2 patients (96-123 pg/ml) and normal in another patient during a symptomatic phase. Treatment with lithium was established in almost all patients and resulted in marked reduction or cessation of symptomatic episodes. The longest observation was 19 years with a relapse after cessation of lithium. Assessment of CSF hypocretin-1 during and outside of a symptomatic phase is recommended in the diagnostic workup of KLS; however, so far only the clinical course is helpful in establishing the diagnosis. Early treatment is recommended and has been found to be effective in the long course of the disease. © 2013 Springer-Verlag Berlin Heidelberg.

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