[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.

[Nicotine. Influence on sleep and its relevance for psychiatry and psychotherapy]. / Nikotin. Einfluss auf den Schlaf und Relevanz für Psychiatrie und Psychotherapie.

BACKGROUND: Nicotine, by its impact on several neurotransmitter systems, influences sleep. Sleep disturbance is a common symptom in different psychiatric disorders and there is a high prevalence of smoking in psychiatric patients. METHODS: Systematic literature search. RESULTS: Symptoms of insomnia are observed during nicotine consumption and its withdrawal. The effects of therapeutic nicotine substitution after smoking cessation on sleep are often masked by withdrawal symptoms. Depressive non-smokers experience an improvement of mood under nicotine administration and in turn, depressive symptoms and sleep impairment during nicotine withdrawal have a negative impact on abstinence rates. CONCLUSION: Sleep disturbance is a comorbid risk factor influencing abstinence during smoking cessation. In depressive patients the complex relationship between affect, sleep, nicotine consumption and its withdrawal should be carefully monitored. In such subgroups of smokers willing to quit this has to be taken care of in therapeutic interventions.

[Depression in restless legs syndrome. Pathogenesis, assessment, and implications for treatment]. / Depressive Erkrankungen beim Restless-legs-Syndrom. Pathogenese, Diagnose und Implikationen für die Therapie.

Depressive disorders are a prevalent comorbidity in restless legs syndrome (RLS). Although similar prevalence rates of comorbid depression can be found in other diseases, the association between RLS and depression is particularly complex due to the RLS-related sleep disorders. It is also clinically important that according to findings derived mainly from case studies many antidepressant agents can aggravate RLS symptoms. The presence of comorbid depression influences therapy outcome in general and should therefore be taken into account. So far, there is no evidence-based systematic research concerning diagnosis and treatment process, and no recommendations exist for the treatment of affective disorders in RLS. In the present work, the clinical relevance of depression in RLS and antidepressive treatment in RLS symptoms is discussed and a therapeutic algorithm (evidence level C) for the treatment of depression in RLS is provided.

[Restless legs syndrome, periodic limb movements, and psychopharmacology]. / Restless-legs-Syndrom, periodische Gliedmassenbewegungen im Schlaf und Psychopharmakologie.

Restless legs syndrome (RLS) and the often associated periodic limb movement disorder in sleep (PLMD) frequently occur in the general population as a primary disorder. In addition to organic disease, secondary forms are caused by psychotropic medication. Several antidepressants, antipsychotics, lithium, and opioid withdrawal have been shown to induce or exacerbate RLS and PLMD, while several antiepileptics used as mood stabilizers and some benzodiazepines demonstrate therapeutic potential for treating RLS/PLMD. Systematic or controlled studies for evaluating these side effects still do not exist. Among the antidepressants at higher risk of inducing this disorder are selective serotonin reuptake inhibitors, venlafaxine, and some tetracyclic antidepressants. Under medication with some tricyclic substances, periodic limb movements were observed more often. For some antidepressants with differing transmitter profiles such as bupropion RLS/PLMD ameliorating effects or at least neutral effects (Trazodon, Nortriptylin) have been described in small studies. In case of continued of or newly occurring insomnia a thorough history should be taken to identify a possible RLS/PLMD as an intolerable side effect of treatment. A change in medications should be considered if clinically feasible. In case of RLS/PLMD occurring in psychotic patients switching the antipsychotic and additionally using a second line medication such as antiepileptics or a benzodiazepine should be considered.

Are adolescents chronically sleep-deprived? An investigation of sleep habits of adolescents in the Southwest of Germany.

BACKGROUND: Adolescent sleep receives increasing attention. Several studies have shown that adolescents generally do not sleep enough. This survey assessed adolescents' sleep patterns, and results were compared with sleep logs. METHODS: A total of 818 students aged 12-18 attending three different school types were asked to complete a questionnaire, adapted from the 'School Sleep Habits Survey', and filled in a sleep protocol over 2 weeks. Information on sleep patterns and demographic data were obtained additionally. RESULTS: A total of 601 students completed the questionnaire (i.e. 73.5% return rate), 55.1% female and 44.9% male. Average sleep duration during the week amounted to 8.04+/-0.89 h and 9.51+/-1.65 h on weekends. Sleep duration times on school days decreased from an average 8.64+/-0.83 h for the age category 12-13 years to 7.83+/-0.72 h for students above 16 years. 91.6% of all students slept less than 9.2 h per night during the week. Data from the 153 returned sleep logs showed even lower sleep times (7.75+/-0.82 h for school nights). CONCLUSIONS: The main hypothesis that students sleep on average considerably less than the recommended 9 h during weekdays was confirmed. Bedtimes changed throughout the week with the latest on Friday and Saturday nights and the least sleep around midweek. There were no significant group differences regarding school type and environment (rural vs. urban). Interestingly, the majority reported only little daytime sleepiness and no impaired performance. Results regarding the consequences of chronic sleep deprivation in the literature are inconclusive. The impact on physiological parameters, especially metabolic functions, requires further investigations.

Low-dose hydrocortisone in the evening modulates symptom severity in restless legs syndrome.

BACKGROUND: Circadian symptom manifestation in the evening and night is one of the main characteristics of restless legs syndrome (RLS). Although the inverse temporal course of corticosteroid rhythm and RLS symptom severity is obvious, this relationship has yet to be studied. We investigated the effect of late-evening application of exogenous cortisol (hydrocortisone) on sensory leg discomfort (SLD), one of the main complaints of patients with RLS. METHODS: Ten untreated patients with idiopathic RLS participated in the study. Change of SLD was rated on a visual analogue scale during the 60 minutes resting period of the so-called Suggested Immobilization Test. Patients received either hydrocortisone 40 mg or placebo (saline) IV in random order in a double-blind crossover design, with 1 week between the experiments. RESULTS: Severity of SLD was lower during hydrocortisone infusion than during placebo (p = 0.032). Though blind to the experimental condition, 5 of the 10 patients experienced improvement in symptoms during hydrocortisone administration, but no patient felt an amelioration during the placebo condition. CONCLUSIONS: Our data indicate a probable physiologic relationship between evening and early night hour restless legs syndrome symptom increase and low cortisol level.

Cognitive behavioural group therapy to improve patients' strategies for coping with restless legs syndrome: a proof-of-concept trial.

BACKGROUND: Restless legs syndrome (RLS) is a usually chronic disorder accompanied by clinically relevant psychosocial impairment. To date, no psychologically based approach is available to improve the coping strategies and quality of life of RLS sufferers. OBJECTIVE: To develop cognitive behavioural therapy tailored to this disorder (the RELEGS coping therapy programme) and present the results of this proof-of-concept study. METHODS: Twenty-five patients (five men, 20 women; 15 medicated, 10 unmedicated; mean (SD) age 56.1 (12.3) years) with subjective psychosocial impairment due to RLS participated in one of three consecutive therapy groups. The severity scales (IRLS and RLS-6) indicated moderate to severe RLS symptoms at baseline. Exclusion criteria were secondary RLS, foreseeable change of RLS medication during the study period, serious physical or psychiatric comorbidity, and severe cognitive deficits. Each group took part in eight group sessions (90 min each with a break). RESULTS: At the end of the treatment, both the RLS-related quality of life and the mental health status of the subjects had improved significantly (QoL-RLS scale: from 28.6 (12.8) to 23.4 (13.1); SCL-90-R: from 51.3 (37.0) to 45.9 (32.9)). The improvement remained at follow-up 3 months later. Subjective ratings of RLS severity had improved at the end of therapy and at follow-up. Psychometric scales not specific for RLS-related impairment remained unaffected by the treatment. CONCLUSIONS: The study establishes the feasibility and high acceptance of the newly devised therapy programme. The application of RLS-oriented specific psychological strategies is a step toward an integrated treatment approach in RLS.

Hypertrophic olivary degeneration after surgical removal of cavernous malformations of the brain stem: report of four cases and review of the literature.

BACKGROUND: Hypertrophic olivary degeneration (HOD) is a pathological phenomenon that occurs after injury to the dentato-olivary pathway. Its hallmarks include hypertrophy of the olive with increased T2 signal intensity on magnetic resonance imaging, and it often manifests with palatal tremor and oscillopsia clinically. METHOD: We report the cases of four patients who developed delayed HOD after surgical resection of pontine lesions. FINDINGS: We discuss the anatomical and pathological details of this disease and review the few other reported cases of HOD after resection of lesions within the brainstem. CONCLUSIONS: HOD should be recognized as a possible complication of surgery within the brainstem and must be diagnosed promptly so that patients can be appropriately counseled and symptoms can be treated.

Investigation of 1,3-dipolar cycloaddition reactions of unsaturated nitrones in ionic liquids.

The effect of the media (achiral and chiral ionic liquids) on the stereochemistry of intramolecular 1,3-dipolar cycloaddition reactions of D-galactose-derived omega-unsaturated nitrones, leading to bicyclic isoxazolidines, has been investigated.

[Generalized anxiety disorder with comorbidity. Treatment with pregabalin]. / Generalisierte Angststörung mit Komorbidität. Behandlung mit Pregabalin.

The efficacy of pregabalin in treating generalized anxiety disorder (GAD) has been shown in recent studies. Our experience and case reports in the present publication indicate that pregabalin can be an effective therapeutic option for patients with GAD and comorbid psychiatric disorders. Treatment with pregabalin should also be considered in patients with partial remission of GAD or intolerability of SSRI or SNRI.

Effective cabergoline treatment in idiopathic restless legs syndrome.

OBJECTIVE: To assess the efficacy and safety of the dopamine agonist cabergoline (CAB) in patients with restless legs syndrome (RLS). METHODS: Patients with moderate to severe RLS were randomized into four groups receiving placebo, 0.5 mg, 1 mg, or 2 mg CAB once daily in a double-blind, placebo-controlled, multicenter dose-finding trial followed by an open long-term extension trial of 47 weeks. Efficacy was assessed with the RLS-6 scales and International RLS Study Group severity scale (IRLS). RESULTS: A total of 85 patients (age 56 +/- 10 years, 71% females) were treated. Severity of RLS-6 scale symptoms during the night (the primary endpoint) was markedly improved by all CAB doses compared to placebo (placebo: -1.4 +/- 3.1, 0.5 mg CAB: -4.2 +/- 3.0 [p = 0.0082], 1.0 mg CAB: -4.0 +/- 2.9 [p = 0.0040], 2.0 mg CAB: -4.8 +/- 3.7 [p = 0.0026]). Similar results were found for the RLS severity at bedtime and during the day, IRLS, and satisfaction with sleep. A stable, clinically relevant improvement was achieved in all efficacy measures (severity during the night: change between last assessment and baseline: -5.6 +/- 2.5, rate of remission: 71.2%) throughout 1 year with a mean CAB dose of 2.2 mg per day. During long-term treatment, 6 of 66 treated patients were affected (n = 2) or possibly affected (n = 4) by mild augmentation. Under CAB therapy up to 1 year, 11 of 85 patients discontinued treatment due to a drug-related adverse event. CONCLUSIONS: Cabergoline is an efficacious and well-tolerated option for the treatment of restless legs symptoms during the night and the day.

[Restless legs syndrome in childhood]. / Das Restless-legs-Syndrom im Kindesalter.

The diagnostic criteria of restless legs syndrome were defined in 1995 by the International Restless Legs Syndrome Study Group (IRLSSG). In light of the latest scientific evidence and increasing clinical experience, the diagnostic criteria were revised in a consensus workshop. Participants of the workshop considered the development of new diagnostic criteria especially important for the following subgroups: (1) for children and (2) for the cognitively impaired elderly. The common characteristic of both groups lies in their difficulty in expressing subjective symptoms adequately. This considerably impedes the diagnosis of restless legs syndrome. In 2002, a proposal for diagnostic criteria of restless legs syndrome in childhood was formulated by members of the study groups "Movement Disorders and Sleep" and "Paediatrics" of the German Sleep Society. The proposal was partially incorporated into the diagnostic criteria for restless legs syndrome in childhood suggested by the IRLSSG. The current criteria are recommendations to enhance further research and must be validated by clinical studies. The following article gives an overview of published studies on restless legs syndrome in childhood, reviews the proposals for diagnostic criteria, and summarizes the peculiarities to be considered in diagnosing restless legs syndrome in children.

Ruptured intrasellar superior hypophyseal artery aneurysm presenting with pure subdural haematoma. Case report.

SUMMARY: Subdural haemorrhage from a ruptured intracranial aneurysm is a well-known entity when associated with subarachnoid haemorrhage. However, haemorrhage confined only to the subdural space is rare because there are limited anatomical sites where extravasation can be purely subdural. We report the rare case of a patient who suffered pure subdural haematoma after the rupture of a left superior hypophyseal artery aneurysm located within the sella turcica. The patient was treated with endovascular coil embolization of the aneurysm. Angiography immediately after treatment and one month later revealed complete obliteration of the aneurysm. Six months after treatment, the patient remained symptom free.

[Algorithms for diagnosis and therapy of sleep disorders in general practice]. / Algorithmus zur Diagnostik und Therapie von Schlafstörungen. Schritt für Schritt auf dem Weg zum erholsamen Schlaf.

Complaints of insomnia, i.e. problems to fall asleep or maintain asleep and/or non-restorative sleep are very common in general practice. This article presents the clinical algorithm non-restorative sleep which was devised by the German Society for Sleep Research and Sleep Medicine. This algorithm presents a guideline for the diagnosis and the treatment of insomnia.

A double-blind, randomized and placebo-controlled study on the polysomnographic withdrawal effects of zopiclone, zolpidem and triazolam in healthy subjects.

Rebound effects after withdrawal from hypnotics are believed to trigger their chronic use and to enhance the risk of tolerance and dependence. It was the purpose of this study to investigate the acute polysomnographic withdrawal effects after a 4 week treatment with standard doses of the non-benzodiazepine hypnotics zopiclone and zolpidem compared with triazolam and placebo. Healthy male subjects between 22 and 35 years of age participated in a parallel study design. They received either zopiclone 7.5 mg (n=11), zolpidem 10 mg (n=11), triazolam 0.25 mg (n=10) or placebo (n=7) over 4 weeks in randomized and double-blind order. Sleep EEG was registered during 2 nights before treatment under placebo, on days 1, 27 and 28 of treatment and on days 29,30,41 and 42 under placebo. Total sleep time and sleep efficiency were lower in the 1st night after discontinuation of triazolam (p < 0.05, t-test). After withdrawal from zopiclone or zolpidem slight but not significant rebound effects concerning sleep continuity were observed. Self-rating scales showed minimal rebound insomnia after discontinuation of all three hypnotics. In the placebo group no changes of sleep parameters were observed. Assuming that rebound insomnia is part of a withdrawal reaction, this study indicates that the risks of tolerance and dependency are low when administering zopiclone or zolpidem at the recommended doses.

Irving S. Cooper and the early surgical management of movement disorders. Video history.

Irving S. Cooper was a pioneer in the field of functional neurosurgery. During his very productive and controversial career, he proposed the surgical treatment of Parkinson disease (PD) by ligating the anterior choroidal artery to control tremor and rigidity. Subsequently, he developed seminal techniques for chemopallidectomy and cryothalamectomy for PD. He also attempted to use electrical stimulation of the cerebellum or the thalamus to treat spasticity. Cooper continued his work on brain stimulation until his death in 1985. He made video recordings of nearly all of his patients during his tenure (1977-1985) at New York Medical College. Cooper's clinical video recordings were reviewed, and selected footage was compiled into a video history of Cooper's surgical management of various movement disorders. Included are pre-, post-, and some intraoperative recordings that Cooper made to document his treatment of patients with PD, tremor, Wilson disease, cerebral palsy, chorea, dystonia musculorum deformans, and some rarer entities.

Beta-lactam antibiotics functionalized with gem-bisphosphonates.

Acylation of amoxycillin and cephalexin with acids III, V and VII, and with isocyanate VIII furnished the corresponding beta-lactam antibiotics (X and XIII-XV, respectively). The antibacterial activity of these new antibiotic analogues against Helicobacter pylori was found to be identical with those of amoxycillin, Augmentin, erythromycin and ciprofloxacin.

Magnesium therapy for periodic leg movements-related insomnia and restless legs syndrome: an open pilot study.

Periodic limb movements during sleep (PLMS), with or without symptoms of a restless legs syndrome (RLS), may cause sleep disturbances. The pharmacologic treatments of choice are dopaminergic drugs. Their use, however, may be limited due to tolerance development or rebound phenomena. Anecdotal observations have shown that oral magnesium therapy may ameliorate symptoms in patients with moderate RLS. We report on an open clinical and polysomnographic study in 10 patients (mean age 57 +/- 9 years; 6 men, 4 women) suffering from insomnia related to PLMS (n = 4) or mild-to-moderate RLS (n = 6). Magnesium was administered orally at a dose of 12.4 mmol in the evening over a period of 4-6 weeks. Following magnesium treatment, PLMS associated with arousals (PLMS-A) decreased significantly (17 +/- 7 vs 7 +/- 7 events per hour of total sleep time, p < 0.05). PLMS without arousal were also moderately reduced (PLMS per hour of total sleep time 33 +/- 16 vs 21 +/- 23, p = 0.07). Sleep efficiency improved from 75 +/- 12% to 85 +/- 8% (p < 0.01). In the group of patients estimating their sleep and/or symptoms of RLS as improved after therapy (n = 7), the effects of magnesium on PLMS and PLMS-A were even more pronounced. Our study indicates that magnesium treatment may be a useful alternative therapy in patients with mild or moderate RLS-or PLMS-related insomnia. Further investigations regarding the role of magnesium in the pathophysiology of RLS and placebo-controlled studies need to be performed.

A 19-h spontaneous sleep period in idiopathic central nervous system hypersomnia.

Reports of prolonged sleep periods in idiopathic central nervous system hypersomnia, as shown by ad libitum sleep recordings, are rare. A patient with idiopathic hypersomnia with extremely long sleep periods and sleep drunkenness after awakening is described. Polysomnographic recordings showed a spontaneous sleep period of 19.4 h and a normal Multiple Sleep Latency Test. These polysomnographic findings are clearly abnormal but essentially different form those of narcolepsy. Unlike narcolepsy, 'idiopathic hypersomnia' does not seem to be a distinct clinical entity but a category for different heterogenous subtypes.