[Sleep-related movement and behavioural disorders in adults]. / Trastornos del movimiento y de la conducta durante el sueño en el adulto.

Sleep-related movement and behaviour disorders may have an impact on sleep quality and lead to daytime symptoms. These groups of conditions include diseases such as restless legs syndrome, periodic leg movements, and REM and NREM parasomnias. The knowledge of their clinical features and management is of utmost importance for the neurologist and sleep specialist. Frequently, these patients are referred to such specialists and it is relevant to know that certain sleep disorders may be associated with other neurological conditions.

TITLE: Trastornos del movimiento y de la conducta durante el sueño en el adulto.Los trastornos del movimiento y de la conducta durante el sueño pueden tener un impacto en la calidad del sueño del paciente y dar lugar a síntomas diurnos. En estos grupos de enfermedades se incluyen entidades como el síndrome de piernas inquietas, los movimientos periódicos de las piernas y las parasomnias del sueño de movimientos oculares rápidos (REM) y no REM. El conocimiento de sus características clínicas y nociones sobre su manejo es de gran importancia para el neurólogo y especialista en sueño por su frecuencia e impacto en la calidad del sujeto. Con frecuencia, estos pacientes son referidos a dichos especialistas, y es relevante conocer que ciertos trastornos del sueño pueden asociarse a otras enfermedades neurológicas.

Breakthrough symptoms during the daytime in patients with restless legs syndrome (Willis-Ekbom disease).

BACKGROUND: It is often assumed that most patients with restless legs syndrome (RLS) only experience symptoms at night. However, previous studies have estimated the prevalence of daytime symptoms to be 10-60%. This study sought to investigate the prevalence and pattern of daytime symptoms in patients with moderate-to-severe RLS. METHODS: Observational, cross-sectional investigation. A self-administered questionnaire was sent out, on a random basis, to 310 patients with RLS by the Spanish RLS patient support group. Only individuals with a confirmed diagnosis of RLS were included in the final survey. RESULTS: In total, 224 individuals were included in the survey (response rate 72%). Over 55% of patients reported daytime crises on most (>3) days of the week, and 41% suffered daytime symptoms on a daily basis. These breakthrough crises were characterized by unexpected and sudden symptoms and were frequently precipitated by a reduction in daytime activity. The mean severity of these crises on a visual analogue scale (range 0-10) was 6.8 (standard deviation 2.1), and they had a major impact on quality of life. The prevalence of breakthrough crises was related to duration of illness but not to duration of treatment. CONCLUSION: This study suggests that breakthrough crises are common in moderate-to-severe RLS and have a negative effect on quality of life. More studies are needed to investigate whether breakthrough crises reflect disease progression or, at least for those patients undergoing dopaminergic treatment, whether they represent an early indication of RLS augmentation.

Treatment of restless legs syndrome with pregabalin: a double-blind, placebo-controlled study.

OBJECTIVES: To assess the therapeutic efficacy, required dose, and tolerability of pregabalin in patients with idiopathic restless legs syndrome (RLS). METHODS: This was a double-blind, placebo-controlled trial with polysomnographic control, providing Class II evidence. Ninety-eight patients underwent a 2-week single-blind period with placebo; 58 were randomized to receive pregabalin or placebo for 12 weeks under a flexible-dose schedule. Endpoints were mean change from baseline in the International Restless Legs Scale (IRLS) total score, Clinical Global Impression (CGI), and RLS-6 scales, as well as changes in periodic limb movements (PLMs) and sleep architecture. RESULTS: Patients under treatment with pregabalin had a greater improvement in IRLS score than under placebo (63% vs 38.2%; p < 0.05). The mean effective dose of pregabalin at the end of treatment was 322.50 mg/day (+/-98.77), although therapeutic effects were already seen at a mean dose of 139 mg/day. Similarly, improvements were observed on the CGI, RLS-6 scale, and the Medical Outcomes Study sleep scale (all p < 0.01) when compared to placebo. Treatment with pregabalin also resulted in a reduction of the mean (+/-SD) PLM index (p < 0.001). Furthermore, there was a marked improvement in sleep architecture with an increase in slow wave sleep (p < 0.01), and decreases in wake after sleep onset and stages 1 and 2 (p < 0.05). Pregabalin was generally well-tolerated. Adverse events were mild but common, and included unsteadiness, daytime sleepiness, and headache. CONCLUSIONS: This study shows significant therapeutic effects of pregabalin on both sensorial and motor symptoms in restless legs syndrome. Treatment with pregabalin was associated with an improvement of sleep architecture and periodic limb movements. Adverse events included unsteadiness and sleepiness and should be screened carefully in the working population, particularly when pregabalin is administered in the afternoon. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that pregabalin is effective for the treatment of restless legs syndrome and improves sleep architecture and periodic limb movements in placebo-unresponsive patients.

Supresión del sueño REM y efecto antidepresivo / Suppression of REM sleep and antidepressant effect

La necesidad de establecer marcadores biológicos que permitan anticipar los efectos terapéuticos de los fármacos antidepresivos ha llevado a centrar los esfuerzos en estudiar la fiabilidad de estos fármacos para suprimir el sueño REM y su posible valor predictivo de la respuesta terapéutica. El análisis de la bibliografía sobre los efectos supresores de los antidepresivos sobre el sueño REM, en voluntarios sanos, muestra una supresión media del 34%, cuando se administran en dosis única, y del 29%, cuando se hace en dosis múltiple. No obstante, en ambos tipos de diseño el grado de variabilidad en la respuesta es grande, aun cuando se normalizan los resultados en función de las dosis terapéuticas. No se aprecia relación entre el perfil neuroquímico del fármaco y sus efectos sobre el REM, aunque éstos son mayores cuando el mecanismo de acción es predominantemente monoaminérgico. Con la excepción de la trazodona, los efectos supresores sobre el sueño REM disminuyen con el tiempo. Los estudios que se realicen en el futuro sobre esta cuestión deberán utilizar modelos que permitan contemplar las oscilaciones propias del sueño REM durante la noche, en función de las variaciones farmacocinéticas de cada sustancia (AU)

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L-DOPA-induced excessive daytime sleepiness in PD: a placebo-controlled case with MSLT assessment.

A 74-year-old patient with idiopathic Parkinson's disease was evaluated for unintended sleep episodes that occurred after long-term treatment with 400 mg/day of L-dopa. Overnight sleep studies and multiple sleep latency testing were carried out under double-blind administration of either L-dopa or placebo. Mean sleep latency with L-dopa was 7 minutes, in contrast to a normal value of 19 minutes, 25 seconds with placebo. The authors' results suggest that L-dopa may cause daytime somnolence in some patients with Parkinson's disease.

Treatment of restless legs syndrome with gabapentin: a double-blind, cross-over study.

OBJECTIVE: To assess the effects of gabapentin on sensory and motor symptoms in patients with restless legs syndrome (RLS). METHODS: Patients with RLS (22 idiopathic, 2 secondary to iron deficiency) were randomized and treated for 6 weeks with either gabapentin or placebo. After a 1-week washout they crossed over to the alternative treatment for 6 weeks. Patients were rated at baseline and at scheduled intervals by the RLS Rating Scale, Clinical Global Impression, pain analogue scale, and Pittsburgh Sleep Quality Index. At the end of each treatment period, all-night polysomnography was performed. RESULTS: Compared to placebo, gabapentin was associated with reduced symptoms on all rating scales. In addition, sleep studies showed a significantly reduced periodic leg movements during sleep (PLMS) index and improved sleep architecture (increased total sleep time, sleep efficiency, and slow wave sleep, and decreased stage 1 sleep). Patients whose symptoms included pain benefited most from gabapentin. The mean effective dosage at the end of the 6-week treatment period was 1,855 mg, although therapeutic effects were already observed at the end of week 4 (1,391 mg). CONCLUSIONS: Gabapentin improves sensory and motor symptoms in RLS and also improves sleep architecture and PLMS.

Circadian aspects in the pathophysiology of the restless legs syndrome.

Several pieces of evidence suggest that a dopaminergic dysfunction might play a key role in the pathophysiology of restless legs syndrome (RLS), including the therapeutic effects of dopaminergic drugs and the results of several positron emission tomography and single photon emission computed tomography studies. However, RLS symptoms display a distinct circadian pattern, with an increase of both sensorial and motor symptoms in the evening and at night. Although the latter could also be caused by homeostatic mechanisms such as a linkage to the previous amount of wakefulness, several studies performed over the last few years under semiconstant, routine conditions have suggested the existence of a 'true' circadian mechanism modulating the severity of RLS symptoms across the day-night cycle. Thus, both periodic leg movements of sleep and restlessness show a maximal severity in timely coincidence with the falling phase of the core temperature circadian cycle. The present article reviews the evidence showing circadian oscillation of dopaminergic function and postulates that the amplitude of circadian rhythm of dopaminergic function is increased in RLS, with a hypofunction at night.

Stimulant and anticataplectic effects of reboxetine in patients with narcolepsy: a pilot study.

STUDY OBJECTIVES: To investigate potential stimulant and anticataplectic effects of 10 mg reboxetine in patients diagnosed with narcolepsy. DESIGN: 12 patients were treated for a 2-week period with 10 mg reboxetine under open conditions. The dosage of reboxetine was gradually increased between Day 1 and Day 9. Outcome parameters consisted of nightime polysomnography (PSG), Multiple Sleep Latency Test (MSLT), Epworth Sleepiness Scale (ESS), Visual Analog Scale for Sleepiness (VAS), Ullanlinna Narcolepsy Scale (UNS), and the Beck Depression Inventory (BDI). SETTING: Sleep Disorders Clinic at a University Hospital. PATIENTS: 12 patients meeting ICSD-criteria for narcolepsy. INTERVENTIONS: Pharmacological treatment with reboxetine. RESULTS: Following treatment for two-weeks, a significant improvement in daytime sleepiness could be observed, as reflected by a mean decrease of 48.6% on the Epworth Sleepiness Scale and a mean increase of 54.7% in sleep latency on the MSLT. Furthermore, a significant reduction in the cataplexy subscore of the Ullanlinna Narcolepsy Scale and in REM-sleep was found. CONCLUSIONS: Our results suggest that reboxetine exerts stimulant and anticataplectic effects in narcolepsy. Contrary to previous thinking, by which stimulant action would require dopaminergic facilitation, noradrenergic mechanisms might be relevant to the control of wakefulness.

Glucocorticoid replacement is permissive for rapid eye movement sleep and sleep consolidation in patients with adrenal insufficiency.

There is a well described temporal relation between hormonal secretion and sleep phase, with hormones of the hypothalamic-pituitary-adrenal (HPA) axis possibly playing a role in determining entry into and duration of different sleep stages. In this study sleep features were studied in primary Addison's patients with undetectable levels of cortisol treated in a double blind, randomized, cross-over fashion with either hydrocortisone or placebo supplementation. We found that REM latency was significantly decreased in Addison's patients when receiving hydrocortisone at bedtime, whereas REM sleep time was increased. There was a trend toward an increase in the percentage of time in REM sleep and the number of REM sleep episodes. Waking time after sleep onset was increased, whereas no differences were observed between the two conditions when total sleep time or specific non-REM sleep parameters were evaluated. Our results suggest that in Addison's patients, cortisol plays a positive, permissive role in REM sleep regulation and may help to consolidate sleep. These effects may be mediated either directly by the central effects of glucocorticoids and/or indirectly through CRH and/or ACTH.