Svenja Happe

Gabapentin versus Ropinirole in the Treatment of Idiopathic Restless Legs Syndrome

Dopaminergic agents such as ropinirole are the drugs of first choice in treating restless legs syndrome (RLS). Recently, gabapentin, a structural analogue of γ-aminobutyric acid, has also been shown to improve sensorimotor symptoms in RLS. Therefore, the tolerability and efficacy of randomized treatment with either gabapentin or ropinirole in patients with idiopathic RLS was evaluated in this 4-week open clinical trial. Patients with idiopathic RLS were treated with either 300 mg of gabapentin (n = 8) or 0.5 mg of ropinirole (n = 8) as the initial dose, and the dose was up-titrated until relief of symptoms was achieved (gabapentin mean dosage 800 ± 397 mg, range 300–1,200 mg; ropinirole mean dosage 0.78 ± 0.47 mg, range 0.25–1.50 mg). In both groups, International Restless Legs Syndrome Study Group questionnaire scores improved significantly (p ≤ 0.018), whereas the scores of the Epworth sleepiness scale remained unchanged within normal limits. Polysomnographic data showed a reduction of periodic leg movements during sleep (PLMS; p < 0.03) and PLMS index (p < 0.02) in both groups. Side effects were only mild and mostly transient. After 6–10 months of follow-up, in most patients, RLS symptoms were still improved. We conclude that gabapentin and ropinirole provide a similarly well-tolerated and effective treatment of PLMS and sensorimotor symptoms in patients with idiopathic RLS.

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.

Sleep disorders and depression in patients with Parkinson's disease

Objectives– Sleep disorders and depression are frequent in patients with Parkinsons disease (PD). However, the exact prevalence and the causality are still unknown. Patients and methods– We interviewed 56 consecutive PD patients and 59 age‐matched healthy controls concerning sleep disorders and depression. Sleep Disorders Questionnaire (SDQ) and Zung Depression Scale (ZDS) were used as standardized valid and reliable psychometric tests. Results– Patients with PD had significantly higher values in the clinical‐diagnostic scale narcolepsy (P=0.01), correlating with the l‐dopa dose (P=0.007). Concerning sleep apnea (P=0.49), psychiatric sleep disorder (P=1.00) and periodic limb movement disorder (P=0.12), no significant difference could be identified. PD patients showed significantly higher depression scores than healthy control subjects (P=0.01), increasing with the duration of PD (P=0.04). Conclusion– The significant higher narcolepsy score in PD patients must be seen due to dopaminergic medication and PD‐specific neurodegeneration and immobility rather than due to narcolepsy. This leads to the conclusion that extreme caution is advised when carrying out the SDQ and interpreting the results in various persons and patient groups with motor problems. The strong association of depression, disease severity and sleep disorders in PD patients underlines the importance of identifying and treating both conditions in these patients.

Periodic leg movements in patients with Parkinson's disease are associated with reduced striatal dopamine transporter binding

Abstract. We used single photon emission computed tomography (SPECT) to study striatal [123I]β-CIT binding and polysomnography to study periodic leg movements during sleep (PLMS) in eleven patients with idiopathic Parkinsons disease (PD). The reduced striatal [123I]β-CIT binding was significantly correlated with the number of PLMS. We propose that striatal dopaminergic nerve cell loss is involved in the increased number of PLMS in PD patients.

Agreement of different methods for assessing sleep characteristics: a comparison of two actigraphs, wrist and hip placement, and self-report with polysomnography

OBJECTIVE To assess the agreement of sleep parameters measured by two actigraphs (SOMNOwatch plus, ActiGraph GT3X+) at two different placements (wrist, hip) and of self-reported sleep with polysomnography (PSG). METHODS We estimated agreement with PSG for total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), number of awakenings after sleep onset (NASO), and sleep efficiency (SE%) for 100 participants of the general population, aged 18-75 years by judging mean differences to PSG and intervals of agreement using Bland-Altman plots. RESULTS Mean difference to PSG for TST was 8.3 min (95% confidence intervals [CI] -7.4; 24.1) for SOMNOwatch plus (wrist), 39.8 min (95% CI 24.3; 55.3) for self-report, -79.0 min (95% CI -89.0; -68.9) for SOMNOwatch plus (hip), and -81.1 min (95% CI -91.9; -70.4) for GT3X+ (hip), respectively. The width of intervals of agreement differed with the placement of the devices. Mean differences to PSG were higher for hip-based measurements compared with wrist placement for most parameters. CONCLUSIONS Agreement of sleep parameters assessed by actigraphy with PSG differs with the placement of the device and is limited for hip-based measurements. Agreement of self-report with PSG is comparable to that of actigraphy for some parameters.

Successful treatment of excessive daytime sleepiness in Parkinson's disease with modafinil.

Sirs: More than 15 % of patients with Parkinson’s disease (PD) suffer from excessive daytime sleepiness (EDS) [1]. EDS constitutes a major health hazard, since it is associated with an increased risk of accidents and a substantially reduced quality of life. The neurodegenerative process itself, sleep disorders such as sleep apnoea syndrome and narcolepsy, mood disorders as well as various drugs can all be responsible for EDS [2]. Recently, the dopamine D2/D3receptor agonists ropinirole and pramipexole were reported to induce EDS and sudden sleep episodes in some patients with PD [3]. However, it is presently unknown whether these adverse events are specifically associated with these dopamine agonists or whether sedation is a class effect of dopaminergic drugs in general. In PD patients with complaints of EDS, diagnostic testing including polysomnography is warranted to exclude secondary causes of EDS as the basis for therapeutical interventions. We describe a 65-year-old woman with idiopathic PD whose initial complaint was EDS that improved with modafinil, a wake-promoting agent used successfully to treat EDS associated with narcolepsy. A 65-year-old right-handed former nurse presented with a 6-months history of EDS. She reported frequent yawning and falling asleep unexpectedly in the opera, while reading the newspaper, watching television, and even during conversations despite 9 to 12 hours of night-time sleep and regular daytime napping. Nighttime sleep with sleep initiation and sleep maintenance was reported to be normal but not to be recreational, and problems with wakingup were severe. She denied vivid dreaming, sleep paralysis, sudden loss of muscle tone, hypnagogic and hypnopompic hallucinations. Her partner noted rare jerky twitching of her legs and rare snoring but without pauses of breathing. The Pittsburgh sleep quality index (PSQI) was normal (score of 3). In addition to the EDS, she observed a weakness of the left leg during recent weeks. Her previous medical history was unremarkable apart from essential arterial hypertension treated successfully with carvedilole (12.5 mg/day) and hysterectomy and ovarectomy 25 years ago requiring hormonal replacement. On clinical examination the patient showed a mild hemiparkinsonian syndrome with slight facial hypomimia, bradykinesia and cogwheel rigidity in the left upper and lower extremities. Tremor was absent. No other focal signs were present and there were no signs of dementia or depression on neuropsychological testing. Routine laboratory tests revealed no abnormalities. Polymerase chain reaction for human leucocyte antigen (HLA) DR 2 was negative. In the EEG, only changes of vigilance were remarkable. Cranial MRI showed slight subcortical vascular encephalopathy but was otherwise normal. SPECT imaging using [123I]-ßCIT as a marker of dopamine transporters on dopaminergic nerve terminals showed a bilateral degeneration of nigrostriatal neurons, more pronounced on the right side, as typical for early PD [4]. Treatment with levodopa/benserazide (62.5/ 12.5 mg/day) and selegiline (5 mg/day) improved parkinsonism, but EDS remained unchanged, even after switching to amantadine (300 mg/day) and selegiline (5 mg/day). Two years later, the patient’s parkinsonism had progressed to Hoehn and Yahr stage II. A change of treatment to levodopa/benserazide (150/37.5 mg/day) and amantadine (300 mg/day) improved motor symptoms with a reduction of the UPDRS (Unified Parkinson’s Disease Rating Scale)-motor-score from 20 to 5. However, EDS still remained unchanged. Two nights of nocturnal polysomnography and multiple sleep latency test (MSLT) were performed and manually scored in accordance with published guidelines (table 1). Control data for polysomnographical findings and MSLT were obtained from Rye et al.5 and from our own laboratory. Control data for the Epworth sleepiness scale (ESS) were obtained from 10 PD patients and from 11 healthy adults out of our own sleep laboratory data. In the patient described here, more than 7.5 hours of total sleep was recorded in the second (diagnostic) night in the sleep laboratory. Polysomnography demonstrated a fragmented sleep profile, a prolonged sleep latency to stage 2, a diminished sleep efficiency in comparison with control subjects, and a slightly increased index of periodic leg movements (PLM) per hour sleep (see table 1). The respiratory disturbance-index (RDI) was < 10 per hour sleep. Analysis of nocturnal EMG documented rare intermittent enhanced LETTER TO THE EDITORS

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 Parkinsons 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 Parkinsons 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.

The Association between Disease Severity and Sleep-Related Problems in Patients with Parkinson’s Disease

Although sleep-related problems are a frequent finding in patients with Parkinson’s disease (PD), the aetiology is still unknown. We examined the associations between disease severity, sleep-related problems and social status in 116 PD patients participating in the FAQT Study, a prospective, German cohort study evaluating determinants of quality of life in PD patients. 47.4% of the patients reported sleep onset difficulties, 26.7% sleep interruptions, 14.7% had five or more sleep-related events during the night and 71.6% showed symptoms of increased daytime somnolence. The disease severity was significantly associated with sleep-related events (p = 0.01), the depression score with sleep onset difficulties (p = 0.04), sleep interruptions (p = 0.01) and the levodopa dose (p < 0.01). We conclude that depressive symptoms and increasing levodopa doses in PD patients mainly cause sleep onset difficulties and sleep interruptions, while the severity of motor symptoms contributes to sleep-related events like sleep walking, heavy sweating and nightmares.

Scalp Topography of the Spontaneous K-Complex and of Delta-Waves in Human Sleep

Objective: Together with spindles, K-complexes are well known hallmarks of stage 2 sleep (S2). However, little is known about their topographical distribution in comparison to delta-waves and to K-complexes superimposed by spindles. Patients and methods: In this study, the topographical distribution of spontaneous K-complexes and delta-waves in S2 and delta-waves in stage 4 sleep (S4) in 10 healthy young adults (aged 20 to 35 years, 7 female) was investigated. K-complexes with and without spindles in S2, delta-waves with and without spindles in S2, and delta-waves in S4 distributed all over the night were visually selected. EEG power maps and statistical parametric maps were calculated. Results: Absolute delta power of S2 K-complexes appeared to be significantly higher than of S2 delta-waves and delta power of S4 delta-waves was higher than of S2 delta-waves. In K-complexes and delta-waves, power was found to be highest over medio-frontal regions in the delta frequency band (0.5 - 4.0 Hz) with a second maximum occipitally in delta-waves, no matter whether superimposed by a spindle or not. Conclusion: K-complexes and delta-waves in S2 differ in topographical distribution. Even though in S2 delta-waves have less power, they have a similar topographical distribution in S2 and S4, supporting the hypothesis that delta-waves in S2 further develop towards delta-waves in slow wave sleep. The delta frequency components of K-complexes and delta-waves are unaffected by spindles.

Incidence of restless legs syndrome in two population-based cohort studies in Germany

OBJECTIVES Prospective data about the new-onset of restless legs syndrome (RLS) are lacking. Our aim was to assess the incidence rate of RLS in the general population. METHODS RLS, defined by the minimal diagnostic criteria, was assessed twice in two independently conducted prospective population-based cohort studies in Germany. The Dortmund Health Study (DHS) had a mean follow-up of 2.2 years, and included 1312 participants, and the Study of Health in Pomerania (SHIP) followed 4308 participants for, on average, 5.2 years. RLS was assessed during face-to-face interviews in both studies at baseline and at follow-up in SHIP, and with mailed questionnaires at follow-up in DHS. RESULTS The age-standardized incidence rate of RLS was 22/1000 person-years (p-y) (cumulative incidence over the follow-up: 9.1%) in DHS and 9/1000 p-y (cumulative incidence: 7.0%) in SHIP. Women had a higher incidence rate than men (DHS: 27/1000 p-y vs. 17/1000 p-y, p=0.28; SHIP: 12/1000 p-y vs. 7/1000 p-y, p<0.001). There was a linear increase in RLS incidence rate with age in both studies. The persistence of RLS symptoms from baseline to follow-up was 47.4% in DHS and 41.5% in SHIP. CONCLUSION The incidence rate of RLS is high, while the persistence of RLS over time is low, suggesting that RLS symptoms vary considerably. The increased RLS incidence rate among women and the elderly is consistent with previous prevalence data.