[Sleep medicine differential diagnostics in psychiatry and psychotherapy]. / Schlafmedizinische Differenzialdiagnostik in Psychiatrie und Psychotherapie.

Complaints about disturbed sleep or increased daytime sleepiness are among the most frequent symptoms reported to psychiatrists by patients. Such complaints can be symptoms of an underlying psychiatric disorder or indicative of a separate or comorbid sleep disorder. Hence, basic knowledge in the differential diagnosis of sleep medicine pathologies is pivotal for psychiatrists and psychotherapists. In the present overview following a description of the diagnostic methods, the diagnostic work-up according to the major symptomatic clusters, namely disturbances in initiating and maintaining sleep, abnormal nocturnal movements and excessive daytime sleepiness will be presented.

[Restless legs syndrome and nocturnal leg pain : Differential diagnosis and treatment]. / Restless-Legs-Syndrom und nächtliche Beinschmerzen. Differenzialdiagnose und Therapie.

Pain in the legs belongs to the five most frequent regional pain symptoms. Restless legs syndrome (RLS) presents a particular differential diagnosis for pain in the legs, which is characterized by a nocturnal urge to move the legs often associated with painful sensations in the legs. It is one of the most common neurological disorders and probably the leading cause of nocturnal pain in the legs. In this overview, the diagnosis and therapy of RLS as well as aspects of pain therapy of the disorder are presented. In addition, the differential diagnoses for exclusion of other specific causes of nocturnal pain in the legs are discussed.

[Sleep and its disorders in the elderly]. / Schlaf und seine Störungen im Alter.

Restorative sleep is an important factor for preservation of health and quality of life. Sleep quality is associated with age, i.e., sleep disorders occur more frequently particularly after the age of 75 years. Furthermore, sleep shows an association with female gender, inactivity, dissatisfaction with social life, depressive symptoms, pain, intake of sedatives, genetic predisposition, and increased morbidity and mortality in the elderly. Strategies for improving sleep should include (1) effective treatment of organic diseases and mental disorders, (2) elimination of social life factors that impair sleep quality, (3) light therapy and other nonpharmacological treatment options for longer periods, and (4) short-term use of sleep medication as required. For the latter, it should be kept in mind that lower doses are needed in the elderly.

Intravenous levetiracetam: a new treatment alternative for refractory status epilepticus.

The purpose of this study was to investigate the safety and efficacy of intravenous levetiracetam (LEV-iv) in refractory status epilepticus (SE). A retrospective chart review was performed on patients who received LEV-iv for treatment of SE (n = 36) and had failed at least one other antiepileptic drug. LEV-iv (median 3000 mg/day; range 1000-9000) was administered as a bolus loading (500-2000 mg per 30-60 min, n = 30) or as a continuous pump infusion (n = 6). SE was terminated in 69% ("responders"); 31% ("non-responders") remained in SE. Factors associated with failure were: dose escalation over 3000 mg/day, lack of bolus loading, treatment latency over 48 h, age over 80 years, non-convulsive SE with coma ("subtle SE"), periodic lateralised epileptiform discharges (PLEDs) on EEG, acute cerebral lesion and intubation narcosis. SE was terminated in all eight patients without brain lesion (p = 0.033), and in all seven patients with complex partial SE (p = 0.051). Outcome was favourable (ambulatory patients) in 48% (responders) compared with 0% (non-responders), and "adverse" (death or continuing coma/stupor) in 24% (responders) compared with 100% (non-responders). Mortality was 17% (responders 4%, non-responders 45%). No patient had cardiocirculatory side effects or worsening of SE. Two patients experienced nausea and vomiting during LEV-iv loading, leading to aspiration pneumonia in one. This study suggests that LEV-iv may be a safe and efficacious treatment of SE. Prospective and controlled trials are imperative to confirm these preliminary findings.

Cell-free transport to distinct Golgi cisternae is compartment specific and ARF independent.

The small GTPase ADP-ribosylation factor (ARF) is absolutely required for coatomer vesicle formation on Golgi membranes but not for anterograde transport to the medial-Golgi in a mammalian in vitro transport system. This might indicate that the in vivo mechanism of intra-Golgi transport is not faithfully reproduced in vitro, or that intra-Golgi transport occurs by a nonvesicular mechanism. As one approach to distinguishing between these possibilities, we have characterized two additional cell-free systems that reconstitute transport to the trans-Golgi (trans assay) and trans-Golgi network (TGN assay). Like in vitro transport to the medial-Golgi (medial assay), transport to the trans-Golgi and TGN requires cytosol, ATP, and N-ethylmaleimide-sensitive fusion protein (NSF). However, each assay has its own distinct characteristics of transport. The kinetics of transport to late compartments are slower, and less cytosol is needed for guanosine-5'-O-(3-thiotriphosphate) (GTPgammaS) to inhibit transport, suggesting that each assay reconstitutes a distinct transport event. Depletion of ARF from cytosol abolishes vesicle formation and inhibition by GTPgammaS, but transport in all assays is otherwise unaffected. Purified recombinant myristoylated ARF1 restores inhibition by GTPgammaS, indicating that the GTP-sensitive component in all assays is ARF. We also show that asymmetry in donor and acceptor membrane properties in the medial assay is a unique feature of this assay that is unrelated to the production of vesicles. These findings demonstrate that characteristics specific to transport between different Golgi compartments are reconstituted in the cell-free system and that vesicle formation is not required for in vitro transport at any level of the stack.

Comorbidity of restless legs syndrome and HIV infection.

BACKGROUND: The lifetime prevalence of restless legs syndrome (RLS) is about 10 % in the general population. The association of RLS with HIV infection is unknown. We aimed to investigate the prevalence of RLS in HIV positive patients and to define predictors. METHODS: A standardized questionnaire was presented to 228 HIV infected patients of the HIV outpatient clinic at the Department of Neurology,University of Münster, Germany. 129 patients (57% recall; 15% female, 44 +/- 9 years; mean CD4(+) cell count 333 +/- 274/microl, 82% under highly active antiretroviral treatment) were included in the statistical analysis. 100 age- and sex-matched controls (20 % female, 42 +/- 13 years) were recruited from waiting relatives of surgical patients. Beside demographic and disease-specific data, the questionnaire included the diagnostic questions for RLS and the RLS severity scale by the International RLS Study Group. Diagnosis of RLS was confirmed by experienced neurologists. RESULTS: 33.3% of the HIV infected patients and 7% of the controls (p <0.001) fulfilled the diagnostic criteria for RLS. The mean RLS severity score was higher in HIV infected patients (19.5 +/- 7.2) than in controls (7.3 +/- 1.5; p <0.001) and correlated inversely with the CD4(+) cell count (r = -0.381; p = 0.024) and the BMI (r = -0.548; p <0.001) but not with other disease-specific factors. CONCLUSIONS: HIV infected patients show a significantly higher prevalence rate for RLS than the general population. The HIV infection itself with its immunological changes and involvement of the central nervous system may predispose for a risk of RLS in HIV infected patients.

Intravenous levetiracetam in clinical practice--Results from an independent registry.

PURPOSE: Most common clinical studies with antiepileptic drugs do not reflect medical everyday practice due to their strict in- and exclusion criteria and specifications of treatment regimens. Here we present a large non-interventional registry with the intention to evaluate the spectrum of applications in daily use and the efficacy and tolerability of intravenously given levetiracetam (LEV-iv). METHODS: In a prospective approach of 17 neurological and neuropediatric centres in Germany LEV-iv treated patients of all ages were included over a period of 10 months. The observational period was 10 days with daily documentation of LEV-iv administration, type and frequency of seizures, currently used drugs and doses, and adverse events (AEs). In addition, treatment efficacy and tolerability were assessed by patients and physicians at study end as well as practicability of LEV-iv using a five-step scale. RESULTS: In 95 patients LEV-iv was administered, 93 were included into the analysis. The median LEV-iv dose was 1500 mg (range 110-6000 mg) per day. Median age was 66 years (range 0.7-90.3 years). The majority of patients (n=70, 75%) suffered from status epilepticus (SE, n=55, 59%) and acute seizure clusters (n=15, 16%). Of those with SE, 41 patients (75%) had SE for the first time. Acute seizure clusters and SE terminated in 83% after LEV-iv administration. A total of 29 adverse events were reported in 17 of the 95 patients from the safety set. Ten of these were at least possibly related to LEV-iv treatment. Slight decrease of blood pressure during the infusion (3 patients each) was captured most frequently. No serious side effect was observed. Physicians rated the efficacy and tolerability of LEV-iv treatment as good or very good in 78% and 82% of the cases, respectively. CONCLUSION: In this large observational study of everyday practise the use of LEV-iv exhibited a remarkable good response and tolerability in patients with acute onset seizures (mostly SE). Further randomized controlled studies, like the established status epilepticus trial (ESET) are needed to confirm these findings.

Treatment of idiopathic restless legs syndrome (RLS) with gabapentin.

Nine patients with idiopathic restless legs syndrome (RLS) were treated with 300 mg of gabapentin as an initial dose and an up-titration until relief of symptoms for 4 weeks. Subjective symptoms improved significantly. Polysomnographic data showed a reduction of periodic leg movements during sleep (PLMS) (p = 0.003) and PLMS index (p = 0.001). The authors conclude that gabapentin provides a well-tolerated and effective treatment of idiopathic RLS.

The association of dopamine agonists with daytime sleepiness, sleep problems and quality of life in patients with Parkinson's disease--a prospective study.

OBJECTIVE: Reports that dopamine agonists (DA) precipitate sudden daytime sleep episodes in Parkinson's disease (PD) patients have received widespread attention. It remains unclear if non-ergoline and ergoline DAs have differential sedating effects or if sedation rather represents a class effect of DAs. The aim of this study was the evaluation of sleep disturbances and the quality of life (QoL) in PD patients with different dopaminergic treatment strategies. PATIENTS AND METHODS: This analysis is part of the FAQT-study, a prospective German cohort study evaluating determinants of QoL in PD patients. A subgroup of 111 PD patients was evaluated twice, at baseline and after one year of follow-up, using standardised and validated questionnaires (Unified Parkinson's disease rating scale (UPDRS), Hoehn and Yahr classification, Center for Epidemiologic Studies Depression Scale (CESD), Short Form-36 (SF-36), Parkinson Disease Questionnaire (PDQ-39)). The impact of treatment strategies on sleep problems, daytime sleepiness, bad dreams and hallucinations, depression and QoL in PD patients was analysed separately for ergoline DAs, non-ergoline DAs and the patient group taking no DA. RESULTS: At baseline, sleep problems were reported by about one third of the patients with and without DA medication. Excessive daytime sleepiness (EDS) was higher in the two DA groups (ergoline 11.9%, non-ergoline 9.1%) than among patients not taking DAs (4.5 %). At follow-up, sleep problems in general had decreased among patients taking DAs continuously and among those newly taking DAs, while the sleep problems increased in patients discontinuing DAs. However, EDS had increased to 25% in patients newly taking DAs, and decreased to 15.9% in those taking them continuously. QoL scores at follow-up were slightly increased in the patient groups newly taking and discontinuing DAs (the latter except in physical functioning) while those on continuing DA-medication remained unchanged. CONCLUSION: No differential effects of ergoline or non-ergoline DAs on sleep problems were found. Different dopaminergic treatment strategies did not influence QoL. Our results support the evidence that sedation may be rather a class effect of DAs.

Normal striatal D2 receptor binding in idiopathic restless legs syndrome with periodic leg movements in sleep.

Dopaminergic treatment is very effective in restless legs syndrome (RLS) and periodic leg movements in sleep (PLMS). However, neuroreceptor imaging studies that addressed altered striatal dopaminergic function have given controversial results. In this present study, 14 patients with idiopathic RLS (iRLS) and PLMS with a good response to dopaminergic and non-dopaminergic treatment and ten healthy sex- and age-matched controls were investigated off-medication by using 123I-IBZM and SPECT. RLS symptoms and sleep disturbances were evaluated using three nights of polysomnography, the Pittsburgh Sleep Quality Index, and the International RLS Study Group (IRLSSG) rating scale. The patients presented with sleep disturbances, a high PLMS index (56.2 +/- 33.1 per h), and severe RLS symptoms during SPECT (IRLSSG rating scale 23.1 +/- 8.0), and showed no significant differences in striatal to frontal IBZM binding to D2 receptors compared to controls (ratio striatum/frontal cortex, right side 1.60 +/- 0.10 vs 1.63 +/- 0.08, P = 0.35, NS; left side 1.61 +/- 0.11 vs 1.63 +/- 0.08, P = 0.51, NS). These findings show normal function of striatal D2 receptors in successfully treated patients with iRLS and PLMS. Dopaminergic and non-dopaminergic pretreatment does not appear to change striatal D2 receptor binding as compared to healthy controls. Structures other than striatal D2 receptors are discussed as possible causes of the treatment effects in RLS.

[Sleep-related headaches]. / Schlafgebundene Kopfschmerzen.

Headaches and sleep disorders are frequent and can be associated with each other. Some headache syndromes are related to certain sleep phases or circadian rhythms. These so-called sleep-related headache syndromes include specific types of migraine, cluster headache, chronic paroxysmal hemicrania, and the hypnic headache syndrome. Except for the latter, they were included in the International Classification of Sleep Disorders and are described in this article.

Movement disorders in sleep: Parkinson's disease and restless legs syndrome.

In recent years, sleep abnormalities have increasingly been observed in patients with movement disorders. During sleep, most patients with Parkinson's disease also exhibit the movements characteristically seen during the wake period. Movement activity during sleep may impair sleep quality and lead to daytime sleepiness and reduced quality of life. Disordered REM sleep with enhanced muscle tone is common in patients with neurodegenerative disease, and may precede the clinically evident symptoms of Parkinson's disease by years. Sleep disorders in patients with Parkinson's disease are common, and require the application of individual treatment strategies. A further frequent disorder primarily classified as a sleep disorder (dyssomnia) is the restless legs syndrome (RLS), which is closely related to the nocturnal periodic limb movement disorder and affects up to 15% of the population. The present review focuses on nocturnal motor activity and sleep in Parkinson's disease and RLS.

Effects of frontal transcranial direct current stimulation on emotional state and processing in healthy humans.

The prefrontal cortex is involved in mood and emotional processing. In patients suffering from depression, the left dorsolateral prefrontal cortex (DLPFC) is hypoactive, while activity of the right DLPFC is enhanced. Counterbalancing these pathological excitability alterations by repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) improves mood in these patients. In healthy subjects, however, rTMS of the same areas has no major effect, and the effects of tDCS are mixed. We aimed to evaluate the effects of prefrontal tDCS on emotion and emotion-related cognitive processing in healthy humans. In a first study, we administered excitability-enhancing anodal, excitability-diminishing cathodal, and placebo tDCS to the left DLPFC, combined with antagonistic stimulation of the right frontopolar cortex, and tested acute emotional changes by an adjective checklist. Subjective emotions were not influenced by tDCS. Emotional face identification, however, which was explored in a second experiment, was subtly improved by a tDCS-driven excitability modulation of the prefrontal cortex, markedly by anodal tDCS of the left DLPFC for positive emotional content. We conclude that tDCS of the prefrontal cortex improves emotion processing in healthy subjects, but does not influence subjective emotional state.

Diurnal time course of heat pain perception in healthy humans.

Rapid skin heating by infrared lasers can be used to investigate the integrity of the nociceptive system by activating A-delta and C fibers. The aim of our study was to analyze if healthy humans exhibit any clinically relevant diurnal variations in their heat pain sensitivity. Circadian A-delta fiber function was analyzed by studying N2 and P2 components of laser-evoked potentials (LEP) and pain thresholds evoked by laser stimulation of the foot every 2h from 8a.m. to 10p.m. in 15 healthy subjects. Heat stimuli were generated by an infrared Tm-YAG laser and were delivered to an area of 4 cm × 4.5 cm on the dorsum of the right or left foot in 3 runs of incremental and decremental intensities. After each stimulus subjects were asked to classify the intensity of pain with a numeric rating scale (NRS). LEPs were recorded with fixed stimulus intensities that were 1.5× of the pain threshold. Data were collected with the SynAmps System (Neuroscan, El Paso, USA) and averaged across 35-40 trials. Laser-induced heat pain thresholds and circadian latencies of LEP did not significantly vary during the day. Our results correspond with previous studies that did not detect any consistent significant diurnal variations in perception of heat pain perception using contact thermodes. The intensity of pain perception did not demonstrate any correlation with mood or sleep parameters as measured with the Beck Depression Inventory (BDI), the subjective sleep scales Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS).

[Expert opinions regarding daytime sleepiness in neurological diseases and obstructive sleep apnea syndrome]. / Begutachtung der Tagesschläfrigkeit bei neurologischen Erkrankungen und dem obstruktiven Schlafapnoesyndrom (OSAS).

Patients with increased daytime sleepiness are impaired in all areas of their social environment. Expert opinions are recommended for pension proceedings, regarding driving licenses as well as for restrictions at the workplace. All possibilities should be considered in the differential diagnosis of sleep disorders, which have to be treated before an expert opinion is submitted. Statutory regulations on evaluation of sleepiness are contained in the guidelines for assessing a patient's fitness to drive. The importance of daytime sleepiness in other occupations should be assessed according to the respective workplace. The patient should be informed of the appraisal with regard to career choice and workplace design. The expert thus has the responsible task of carrying out interdisciplinary differential diagnosis of pathological sleepiness and monitoring treatment success with appropriate test methods. In the present paper the legal guidelines in Germany and available test methods are presented.