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[Organic psychosyndrome and sleep apnea. Transdermal nicotine--a new therapy concept?].

We examined 11 patients (10 female, 1 male) of 73 to 79 years of age suffering from organic psychosyndrome (HOPS), using the apnoea screen system MESAM IV (1) and APNOE-SCREEN I. All examined patients had a sleep related disordered breathing (SBAS) with apnoea index (AI) between 10 and 52 (P/h). 3 patients (2 female, 1 male) had an increasing apnoea index under medication of theophyllin 375 mg/d. these theophyllin-nonresponsive patients received transdermal Nicotin in a concentration of 21 mg/d (during the night). The apnoea index decreased not significantly, while the tiredness was reduced significantly by 42.9%, the confusion by 40% and the nightly restlessness by 50%.

Administration, Cutaneous↗

Chorea and related disorders.

Chorea refers to irregular, flowing, non-stereotyped, random, involuntary movements that often possess a writhing quality referred to as choreoathetosis. When mild, chorea can be difficult to differentiate from restlessness. When chorea is proximal and of large amplitude, it is called ballism. Chorea is usually worsened by anxiety and stress and subsides during sleep. Most patients attempt to disguise chorea by incorporating it into a purposeful activity. Whereas ballism is most often encountered as hemiballism due to contralateral structural lesions of the subthalamic nucleus and/or its afferent or efferent projections, chorea may be the expression of a wide range of disorders, including metabolic, infectious, inflammatory, vascular, and neurodegenerative, as well as drug induced syndromes. In clinical practice, Sydenham's chorea is the most common form of childhood chorea, whereas Huntington's disease and drug induced chorea account for the majority of adult onset cases. The aim of this review is to provide an up to date discussion of this disorder, as well as a practical approach to its management.

Chorea↗

[The efficacy of ropinirole in the treatment of chronic insomnia secondary to restless legs syndrome: polysomnography data].

INTRODUCTION: Following the line of our earlier investigations, we made an open pilot study using a polysomnograph to objectively show the efficacy of Ropinirole in the treatment of chronic insomnia secondary to the restless legs syndrome (RLS). PATIENTS AND METHODS: We did polysomnograph studies on 5 patients with the characteristics of primary RLS, according to the criteria of the International Group for the study of RLS, who had had chronic insomnia for over 5 years. We used Spiegel's questionnaires to show subjective improvement. RESULTS: The following parameters were significant between the first night (without treatment) and the second night (with 0.25 mg of Ropinirole) and between night 30 without (treatment) and night 31 (with 0.25 mg of Ropinirole). The results were expressed as average values for the 5 patients with their respective standard deviations. Efficiency of sleep: 62.62% +/- 11.31 as compared with 82.82% +/- 8.80, p = 0.010. After 30 days: 64.88% +/- 17.17 against 88.75% +/- 2.09, p = 0.014. Total time asleep: 295' +/- 51.76 against 397.7 +/- 38.50, p = 0.006. After 30 days: 294.6' +/- 87.40 against 391' +/- 22.38, p = 0.025. Number of periodic movements: 91 +/- 33.59 against 30.8 +/- 35.56, p = 0.011. After 30 days: 189.8 +/- 99.79 against 36.2 +/- 21.56, p = 0.013. All patients had subjective improvement in the parameters of Spiegel's test (p = 0.0005). CONCLUSIONS: The improvement in efficiency of sleep seen on polisomnography, total time slept and reduction in periodic limb movements were statistically significant. The subjective improvement described was also confirmed by Spiegel's questionnaire.

Chronic Disease↗

Sleep disturbance in patients with juvenile neuronal ceroid lipofuscinosis: a new application of the SCSB-method.

Five patients (3 male, 2 female, mean age 20.4 years, range 14-28) with juvenile neuronal ceroid lipofuscinosis were studied using the Static Charge-Sensitive Bed method. Three distinct patterns of respiration (calm, periodic and restless) were differentiated in an automatic analysis. The amount of restless respiration was found to increase with duration of the disease. The result is discussed in terms of methodology and the clinical picture of JNCL.

Adolescent↗

Conversion of the modulatory actions of dopamine on spinal reflexes from depression to facilitation in D3 receptor knock-out mice.

Descending monoaminergic systems modulate spinal cord function, yet spinal dopaminergic actions are poorly understood. Using the in vitro lumbar cord, we studied the effects of dopamine and D2-like receptor ligands on spinal reflexes in wild-type (WT) and D3-receptor knock-out mice (D3KO). Low dopamine levels (1 microM) decreased the monosynaptic "stretch" reflex (MSR) amplitude in WT animals and increased it in D3KO animals. Higher dopamine concentrations (10-100 microM) decreased MSR amplitudes in both groups, but always more strongly in WT. Like low dopamine, the D3 receptor agonists pergolide and PD 128907 reduced MSR amplitude in WT but not D3KO mice. Conversely, D3 receptor antagonists (GR 103691 and nafadotride) increased the MSR in WT but not in D3KO mice. In comparison, D2-preferring agonists bromocriptine and quinpirole depressed the MSR in both groups. Low dopamine (1-5 microM) also depressed longer-latency (presumably polysynaptic) reflexes in WT but facilitated responses in D3KO mice. Additionally, in some experiments (e.g., during 10 microM dopamine or pergolide in WT), polysynaptic reflexes were facilitated in parallel to MSR depression, demonstrating differential modulatory control of these reflex circuits. Thus, low dopamine activates D3 receptors to limit reflex excitability. Moreover, in D3 ligand-insensitive mice, excitatory actions are unmasked, functionally converting the modulatory action of dopamine from depression to facilitation. Restless legs syndrome (RLS) is a CNS disorder involving abnormal limb sensations. Because RLS symptoms peak at night when dopamine levels are lowest, are relieved by D3 agonists, and likely involve increased reflex excitability, the D3KO mouse putatively explains how impaired D3 activity could contribute to this sleep disorder.

Animals↗

The two faces of Eve: dopamine's modulation of wakefulness and sleep.

In Parkinson's disease (PD), waking is frequently punctuated by sleep episodes, including rapid eye movement (REM) (i.e., dream) sleep, and sleep is interrupted by motor activities such as periodic limb movements and REM sleep behavior disorder. Because these pathologic behaviors are unaccounted for by contemporary models, this review summarizes the complex effects of dopamine (DA) on normal and pathological waking-sleeping. Maintenance of wakefulness is probably promoted by mesocorticolimbic DA circuits, and suppression of nocturnal movement appears to be influenced by indirect pathways linking midbrain DA neurons with pre-motor structures in the mesopontine tegmentum and ventromedial medulla. A diencephalospinal DA system may have an additional important role in mediating state-specific sensorimotor activity that is relevant to periodic limb movements and restless legs syndrome.

Arousal↗

The actions of amylobarbitone sodium, butobarbitone and quinalbarbitone sodium upon insomnia and nocturnal restlessness compared in psychiatric patients.

Amylobarbitone sodium, butobarbitone, quinalbarbitone sodium, and a placebo were compared in a controlled, double-blind trial in psychiatric patients with insomnia. An apparatus recording movement in bed is described, with sleep assessments by night nurses and patients. All three barbiturates significantly reduced movement and gave significantly longer, less broken and sounder sleep, without increased incidence of "hang-over." There was no follow-on effect from night to night. With effective doses there was no significant difference between these barbiturates in onset and duration of hypnotic action, although usually accepted as either short or intermediate acting.

Adult↗

Gastroesophageal reflux incidence and respiratory dysfunction during sleep in infants: treatment with cisapride.

We studied the effects of positional treatment and cisapride (a new prokinetic agent) on the incidence and duration of gastroesophageal reflux in 22 infants (4-26 weeks old) in asleep, awake, fasted, and postcibal periods. In addition to gastroesophageal reflux (assessed by 24-h continuous esophageal pH monitoring), all infants presented with a disrupted irregular sleep pattern ("respiratory dysfunction") (assessed by a simultaneously performed cardiopneumogram). Reflux was particularly prominent during the sleep and fasted periods. Investigations (cardiopneumogram and esophageal pH monitoring) in the study population were repeated under treatment conditions (cisapride) after 13-16 days. All pH monitoring data with regard to the total investigation time decreased significantly (p less than 0.001). The treatment-related differences were largest in the asleep and fasted periods, but treatment data were not completely within normal ranges (established in age-matched asymptomatic infants), as they were for the awake periods. Associated symptoms of gastroesophageal reflux (belching, cough, nocturnal wheezing, irritability, and restlessness at night) were evaluated before and during treatment by history. A combination of positional treatment and cisapride seemed effective (objectivated by pH monitoring data and clinical improvement); cisapride did not cause adverse reactions. The disrupted sleep pattern improved significantly or disappeared (p less than 0.001) in all infants. These data suggest that in a number of young infants, gastroesophageal reflux may be associated with a disturbed, irregular sleep of poor quality, which is characterized by a typical breathing pattern (multiple, irregularly repeated, short apneas).

Cisapride↗

Sleep and the menopause.

Sleep problems and their consequences are a serious public health issue, imposing a substantial burden on the individual and society. Although sleep occupies one-third of our lives and can be considered to be an important subject, sleep medicine is a young speciality and problems are poorly investigated. Sleeping problems are frequently reported during the menopausal transition. Subjectively women find that hormone replacement therapy (HRT) significantly improves sleep quality. Thus, HRT can be considered as a first-line therapy for insomnia. However, in some cases insomnia coincides with the menopause transition and cannot be considered to result from ovarian failure. Depressive mood, stress and behavioural factors, as well as restless legs and periodic limb movement syndromes may be the underlying cause. Thus, if no relief with HRT has been achieved after a few months, other aetiologies should be explored.

Estrogen Replacement Therapy↗

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.

Acetates↗

The restless legs syndrome.

The restless legs syndrome (RLS) is one of the commonest neurological sensorimotor disorders at least in the Western countries and is often associated with periodic limb movements (PLM) during sleep leading to severe insomnia. However, it remains largely underdiagnosed and its underlying pathogenesis is presently unknown. Women are more affected than men and early-onset disease is associated with familial cases. A genetic origin has been suggested but the mode of inheritance is unknown. Secondary causes of RLS may share a common underlying pathophysiology implicating iron deficiency or misuse. The excellent response to dopaminegic drugs points to a central role of dopamine in the pathophysiology of RLS. Iron may also represent a primary factor in the development of RLS, as suggested by recent pathological and brain imaging studies. However, the way dopamine and iron, and probably other compounds, interact to generate the circadian pattern in the occurrence of RLS and PLM symptoms remains unknown. The same is also the case for the level of interaction of the two compounds within the central nervous system (CNS). Recent electrophysiological and animals studies suggest that complex spinal mechanisms are involved in the generation of RLS and PLM symptomatology. Dopamine modulation of spinal reflexes through dopamine D3 receptors was recently highlighted in animal models. The present review suggests that RLS is a complex disorder that may result from a complex dysfunction of interacting neuronal networks at one or several levels of the CNS and involving numerous neurotransmitter systems.

Animals↗

Behavioural disturbance in people with Down's syndrome and dementia.

Behavioural disturbance associated with dementia in people with Down's syndrome has not been fully researched. This study investigated such problems in demented Down's syndrome subjects and nondemented Down's syndrome controls. Changes in mood, difficulty with communication, gait deterioration, loss of self-care skills, sleep disturbance, day-time wandering and urinary incontinence were found to be associated with dementia. Problems giving the greatest cause for concern to carers were restlessness, loss of communication skills, urinary incontinence and wandering. Care provision specifically focused on management of behavioural disturbance in individuals who develop dementia is recommended.

Activities of Daily Living↗

The influence of light therapy in depressive patients.

Our study investigated the effects of light therapy on mainly endogenously depressive patients. We applied white fluorescent light of 1500-2000 lux for a length of 4-6 hours daily. For 10 days no antidepressants or sleeping pills were given. We observed a quick and substantial improvement of depressive symptoms within 3 to 5 days. 9 patients showed a very good and 5 patients a good remission of symptoms. This corresponds to an improvement of 65% and is comparable to the effects of antidepressants. The improvement however with light is more rapid and more intensive, the main improvement is to be seen until the 5th day of treatment. No influence was found on vital signs or laboratory values. The rare side-effect was an increase in general drive and activity, which was perceived as agreeable however, and did not take the character of restlessness. Two times an increase of sexual drive was reported. The patients' self-rating concerning vital energy and concentration improved along with the values of the HDRS and CGI as with the quality of sleep. In general patients found light therapy to be agreeable. 1 patient only minimally improved (295.7). No improvement was to be seen in 5 patients (4 x 296.1, 309.1). From our findings we can conclude that light therapy in our patients had the same therapeutic efficacy as tricyclics. In our study the antidepressive effect of light could be maintained with Amitriptylin. Unlike other authors we did not observe a relapse into depression in the responders after ending light therapy.

Adult↗

Ropinirole: for the treatment of restless legs syndrome.

Ropinirole is a non-ergoline dopamine agonist that exhibits a high affinity for D(2) and D(3) receptors but little or no affinity for D(1)-like and non-dopaminergic receptors. Symptoms of restless legs syndrome (RLS) [measured using the International Restless Legs scale and Clinical Global Impression-Global Improvement Scale scores] significantly improved with ropinirole compared with placebo in large, randomised, double-blind trials. Ropinirole reduced periodic leg movements and improved sleep efficiency relative to baseline and placebo in several trials (two of which were randomised, double-blind and relatively large) in patients with RLS. Ropinirole was generally well tolerated in patients with RLS; adverse events were generally mild to moderate in nature and consistent with those expected of dopamine agonists. Few patients receiving ropinirole withdrew from therapy because of adverse events, the most predominant of which were nausea and headache.

Antiparkinson Agents↗

[Night-time premedication with Di-potassium-clorazepate, diazepam or a placebo before anaesthesia; a double-blind trial (author' transl)].

The efficacy of dipotassium clorazepate (DPCA) and of diazepam (DP) as night-time premedication was tested against a placebo in a double-blind trial in 300 patients of all ages. Examination of the patients in the morning before anaesthesia showed that tachycardia, nausea and anxiety were considerably less in patients who had been premedicated with DPCA or DP. Relief from anxiety and restlessness according to standardized self-evaluation scale was most marked in the DPCA group. There were statistically significant differences between the groups with respect to the sleep pattern: 66 per cent of patients in the DPCA group fell asleep within the normal time of 2-15 minutes compared with 53 per cent in the DP group and 48 per cent in the placebo group. Uninterrupted sleep until the morning was experienced by about 70 per cent of patients who had been premedicated with DPCA as against 47 per cent and 31 per cent who had been given DP or a placebo respectively. The total sleeping period was normal or slightly prolonged in 73 and 74 per cent of patients who had received one or the other drug but in only 38 per cent of patients in the placebo group. As regarded the quality of sleep (quiet, uninterrupted sleep and feeling rested) the DPCA group considered it to have been much sounder than did the other groups. On account of its marked ataractic and sleep-protecting properties DPCA is considered to be the most suitable agent for night-time premedication.

Adult↗

Sleep disturbances in patients with primary Sjögren's syndrome.

A standardized sleep questionnaire was used to investigate the sleeping habits of outpatients with primary Sjögren's syndrome (pSS) (n = 40) and RA (n = 42). Sleep deficit (difference between need of sleep and actual sleeping time) was significantly higher in patients with pSS when compared with healthy matched controls (P < 0.0001), and with patients suffering from RA (P < 0.001). When trying to fall asleep, patients with pSS were significantly more often disturbed by muscular tension (45%) and restless legs (24%), than patients with RA (12%, P < 0.01 and 2%, P < 0.01), and they were also significantly more troubled by nocturnal pain than patients with RA (P < 0.01). The pSS group reported significantly more disturbing by awakening during the night and was awake for longer periods than the RA group. Fatigue was a significantly more frequent complaint in patients with pSS. Polysomnography showed that all recorded patients (n = 10) had some sleep disturbances; reduced sleep efficiency (n = 8), increased number of awakenings (n = 5) and increased wakefulness surrounded by sleep (n = 9). Five patients had alpha intrusion in their sleep EEGs. The sleep disturbances seen in patients with primary Sjögren's syndrome may contribute to the fatigue associated with this disease.

Adult↗

Iron and the restless legs syndrome.

STUDY OBJECTIVES: Using blinded procedures, determine the relation between serum ferritin levels and severity of subjective and objective symptoms of the restless legs syndrome (RLS) for a representative patient sample covering the entire adult age range. DESIGN: All patient records from the past 4 years were retrospectively reviewed to obtain data from all cases with RLS. All patients were included who had ferritin levels obtained at about the same time as a polysomnogram (PSG), met diagnostic criteria for RLS, and were not on iron or medications that would reduce the RLS symptoms at the time of the PSG. SETTING: Sleep Disorders Center. PATIENTS: 27 (18 females, 9 males), aged 29-81 years. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Measurements included clinical ratings of RLS severity and PSG measures of sleep efficiency and periodic limb movements (PLMS) in sleep with and without arousal. Lower ferritin correlated significantly to greater RLS severity and decreased sleep efficiency. All but one patient with severe RLS had ferritin levels < or = 50 mcg/l. Patients with lower ferritin (< or = 50 mcg/l) also showed significantly more PLMS with arousal than did those with higher ferritin, but the PLMS/hour was not significantly related to ferritin. This last finding may be due to inclusion of two 'outliers' or because of severely disturbed sleep of the more severe RLS patients. CONCLUSIONS: These data are consistent with those from a prior unblinded study and suggest that RLS patients will have fewer symptoms if they have ferritin levels greater than 50 mcg/l.

Adult↗

Restless legs syndrome. How to provide symptom relief with drug and nondrug therapies.

Restless legs syndrome (RLS) is a perplexing, debilitating, and fairly common condition that can be challenging to manage. Hallmark symptoms include an increase in the severity of sensations during rest and an irresistible urge to move the affected limbs. RLS often occurs concomitantly with periodic limb movement disorder. There are no known causes of RLS, but likely triggers include heredity, iron and vitamin deficiencies, caffeine, and alcohol. Chronic conditions such as diabetes, peripheral neuropathy, and Parkinson's disease can worsen and prolong RLS symptoms. Symptom management begins by establishing proper nutrition intake and improved sleep hygiene. If these fail, conservative pharmacologic treatment is appropriate, with regimens chosen from dopaminergic agents, benzodiazepines, opioids, and anticonvulsants.

Diagnosis, Differential↗