Parkinsonism with excessive daytime sleepiness

Abstract Background Parkinsonian patients with excessive daytime sleepiness (EDS), hallucinations, REM sleep behavior disorder (RBD), short mean sleep latencies, and sleep-onset REM periods (SOREMP) on multiple sleep latency tests (MSLT) have been reported. In these patients a narcolepsy-like pathophysiology of sleep-wake disturbances has been suggested. Patients and methods We studied 14 consecutive patients with Parkinsonism and EDS. Standard studies included assessment of duration and severity of Parkinsonism (Hoehn & Yahr score), Epworth sleepiness score (ESS), history of REM-symptoms (RBD/hallucinations/sleep paralysis/cataplexy-like episodes), polysomnography (PSG),MSLT, and measurement of cerebrospinal fluid (CSF) levels of hypocretin-1 (orexin A). Results There were 12 men and 2 women (mean age 69 years; range 54–82). The mean duration and the Hoehn & Yahr score were 6.3 years and 2.2, respectively. Diagnoses included idiopathic Parkinsons disease (IPD, n=10), dementia with diffuse Lewy bodies (n=3), and multisystem atrophy (n=1). The ESS was 10 in all patients (mean 12; range 10–18). REM-symptoms were reported by all but two patients (hallucinations: n=9; RBD: n=9).None of the patients reported cataplexy-like symptoms or sleep paralysis. On PSG sleep apnea (apnea hypopnea index > 10/h, n=7), periodic limb movements during sleep (PLMS-index > 10/h, n=6), and features of RBD (n=5) were found. On MSLT mean sleep latency was < 5 minutes in 10 patients, and SOREMP were found in two patients. When compared with controls (n=20, mean 497 pg/ml; range 350–603), CSF hypocretin-1 levels were normal in 8 patients and low in 2 patients (221 and 307 pg/ml, respectively). Conclusion These findings do not support the hypothesis of a final common pathway in the pathophysiology of narcolepsy and Parkinsonism with EDS. Sleep apnea and PLMS may play a so-far underestimated role in the pathogenesis of EDS in Parkinsonian patients.     

Comparison of the maintenance of wakefulness test (MWT) to a modified behavioral test (OSLER) in the evaluation of daytime sleepiness

The objectives were to evaluate the correlation between sleep onset as defined by the Oxford sleep resistance (OSLER) test and by simultaneous electroencephalography (EEG) and to determine the correlation between sleep latencies measured by the OSLER test and maintenance of wakefulness test (MWT) performed on the same day. This was a prospective, cross-sectional study carried out in a tertiary-care university-based sleep laboratory. Participants were 11 consecutive subjects presenting to the sleep center with clinical indications for nocturnal polysomnography and MWT. The interventions included MWT and OSLER test. Mean sleep latencies for the OSLER and MWT in each subject were closely correlated (ICC = 0.94, [Intra-class correlation]P < 0.05). Sleep latency by OSLER and simultaneous measurement of EEG also had excellent agreement (ICC = 0.91) with a bias of -0.97 min. The OSLER test is a practical and reliable tool for evaluating daytime sleepiness when compared with the MWT. No obvious systematic adaptation was seen during sequential OSLER test performance. Given its portability and minimal technical requirements, the OSLER test may be useful for large-scale applications in the evaluation of daytime wakefulness and vigilance.     

Excessive daytime sleepiness and 'sleep attacks' induced by entacapone

Three patients with advanced Parkinson's disease, all of whom developed excessive daytime sleepiness and 'sleep attacks' after the administration of entacapone, are described. This is another demonstration that inappropriate daytime sleep episodes are not exclusive to dopamine agonists.     

Modafinil affects mood,but not cognitive function,in healthy young volunteers

Modafinil is a selective wakefulness-promoting agent with beneficial effects in narcolepsy and conditions of sleep deprivation. In a double-blind study we examined its effects in 30 healthy, non sleep-deprived students (19 men and 11 women, aged 19-23 years), who were randomly allocated to placebo, 100 or 200 mg modafinil and 3 h later completed 100 mm visual analogue scales relating to mood and bodily symptoms, before and after an extensive battery of cognitive tests (pen and paper and CANTAB). There were no significant differences between the three treatment groups on any of the cognitive tests used in this study. There was a significant post-treatment change in the factor measuring 'somatic anxiety' and in individual ratings of 'shaking', 'palpitations', 'dizziness', 'restlessness', 'muscular tension', 'physical tiredness' and 'irritability', which was mainly due to significantly higher ratings of somatic anxiety in the 100 mg group compared with the other two groups. Further changes in mood were revealed after the stress of cognitive testing, with the 100 mg group showing greater increases in the 'psychological anxiety' and the 'aggressive mood' factors (as measured from the Bond and Lader scales).     

Initiating treatment with modafinil for control of excessive daytime sleepiness in patients switching from methylphenidate: an open-label safety study assessing three strategies

Rationale. Modafinil is a first-line wake-promoting medication and a useful therapeutic alternative to psychostimulant medications for excessive daytime sleepiness. Objective. This 5-week, randomized, open-label study evaluated three strategies for switching patients from methylphenidate, a commonly used psychostimulant, to modafinil. Methods. Patients (n=40) with excessive daytime sleepiness related to narcolepsy, who had received previous treatment with methylphenidate, were switched from methylphenidate to modafinil (200 mg/day followed by 400 mg/day) without a washout period between treatments, with a 2-day washout period between treatments, or by using a taper-down/titrate-up protocol. Adverse events were recorded throughout the study, and Epworth Sleepiness Scale scores were determined at the end of the study. Results. The majority of patients (95%) were successfully switched to modafinil. At the study end point, mean Epworth Sleepiness Scale scores were <12 for each treatment group. All three switching strategies were well tolerated, with adverse events mild or moderate in nature. Adverse events most frequently reported during modafinil treatment were among those seen previously in large-scale, placebo-controlled studies. There were no meaningful differences among the treatment groups in the frequency or severity of adverse events or in their relationship to modafinil treatment. Only one patient discontinued modafinil treatment because of a treatment-related adverse event (i.e. moderate headache); another patient discontinued due to insufficient efficacy. Conclusions. Switching from methylphenidate to modafinil was well tolerated with or without a washout period or when the methylphenidate dose is gradually tapered during initiation of modafinil therapy. Daytime wakefulness was maintained in patients who have switched from methylphenidate to modafinil. These data suggest that patients with narcolepsy may be switched from methylphenidate to modafinil with few complications and inconveniences. Electronic Publication     

A study of excessive daytime sleepiness and its clinical significance in three groups of Parkinson's disease patients taking pramipexole, cabergoline and levodopa mono and combination therapy

Summary. Objective. To determine if therapy with an ergot and a non-ergot dopamine agonist and levodopa confers an increased risk of excessive daytime sleepiness and secondary "sleep attacks" in Parkinson's disease (PD). Methods. Comparative study of three clinical groups taking, pramipexole (Group 1, n = 19, 8 monotherapy), cabergoline (Group 2, n = 22, 10 monotherapy), and levodopa monotherapy (Group 3, n = 14). Clinical and demographic characteristics, occurrence of "sleep attacks", and assessment of daytime sleepiness [using the Epworth Sleepiness Scale (ESS)], recorded. Results. No patients reported "sleep attacks". Mean ESS scores: Group 1 (pramipexole) 8.0 ± 4.5 (range 0–16), Group 2 (cabergoline) 8.1 ± 3.9 (range 0–19), Group 3 (levodopa), 8.1 ± 5.5 (range 1–18). There was no significant difference between groups (p = 0.897). Scores of ≥16 indicating excessive daytime sleepiness (EDS) were evenly distributed throughout treatment groups, particularly in older patients with more advanced disease. Conclusions. Received March 31, 2000; accepted August 3, 2000     

Sensitivity and specificity of the multiple sleep latency test (MSLT), the maintenance of wakefulness test and the epworth sleepiness scale: failure of the MSLT as a gold standard

Excessive daytime sleepiness (EDS) is an important symptom that needs to be quantified, but there is confusion over the best way to do this. Three of the most commonly used tests: the multiple sleep latency test (MSLT), the maintenance of wakefulness test (MWT) and the Epworth sleepiness scale (ESS) give results that are significantly correlated in a statistical sense, but are not closely related. The purpose of this investigation was to help clarify this problem. Previously published data from several investigations were used to calculate the reference range of normal values for each test, defined by the mean+/-2 SD or by the 2.5 and 97.5 percentiles. The 'rule of thumb' that many people rely on to interpret MSLT results is shown here to be misleading. Previously published results from each test were also available for narcoleptic patients who were drug-free at the time and who by definition had EDS. This enabled the sensitivity and specificity of the three tests to be compared for the first time, in their ability to distinguish the EDS of narcolepsy from the daytime sleepiness of normal subjects. The receiver operator characteristic curves clearly showed that the ESS is the most discriminating test, the MWT is next best and the MSLT the least discriminating test of daytime sleepiness. The MSLT can no longer be considered the gold standard for such tests.     

阻塞性睡眠呼吸暂停低通气综合征患者健康相关生命质量与多导睡眠监测结果相关性

目的评估阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者健康相关生命质量(HRQoL),并研究其与多导睡眠监测(PSG)结果、过度白天嗜睡的相关性,寻找影响OSAHS患者HRQoL的因素。方法对64例OSAHS患者和50例正常对照使用健康结局问卷(SF-36)和Epworth嗜睡问卷(ESS)评估并比较其HRQoL。研究OSAHS患者SF-36评分与PSG监测结果、ESS评分和生理指标之间的相关性,分析造成其HRQoL变化的因素。结果OSAHS患者与正常对照相比,SF-36中4个维度及总分显著下降,整体处于白天过度嗜睡状态;OSAHS患者ESS评分与SF-36中6个维度及总分呈显著负相关;SF-36总分、ESS评分与觉醒指数呈显著负相关;SF-36总分与血氧低于90%占睡眠比例(SaO290%)呈显著负相关;ESS是OSAHS患者HRQoL的独立预测因素,能解释SF-36总分变异的26.9%。结论OSAHS患者健康相关生命质量有明显的损害。过度白天嗜睡、夜间严重持续的低氧血症和睡眠结构的破坏可能是引起HRQoL损害的主要原因。     

Comparison of the antidepressants reboxetine, fluvoxamine and amitriptyline upon spontaneous pupillary fluctuations in healthy human volunteers

Rationale: Spontaneous fluctuations in the size of the pupil in darkness are a recognised index of ”sleepiness”. Objective: To evaluate the effects of single oral doses of three antidepressants: reboxetine (4 mg), a selective noradrenaline reuptake inhibitor, fluvoxamine (100 mg), a selective serotonin reuptake inhibitor, and amitriptyline (100 mg), a tricyclic antidepressant of known sedative property, upon spontaneous pupillary fluctuations in healthy male volunteers (n=16). Methods: Using the recently developed pupillographic sleepiness test (PST), resting pupil diameter was recorded and two measures of pupillary fluctuations were obtained: total power obtained from a fast Fourier transform and spectral analysis, and the pupillary unrest index (PUI), a cumulative measure of changes in pupil size. Subjects also rated themselves on a battery of visual analogue scales for ”alertness”, ”anxiety” and ”contentedness”. Results: Resting pupil diameter was enhanced by reboxetine, but remained unaffected by the other two antidepressants. Amitriptyline, consistent with its sedative property, increased the total power of pupillary fluctuations and showed a tendency to increase PUI. These pupillary effects of amitriptyline were paralleled by reduced scores on the ”alertness”, ”contentedness” and ”anxiety” self ratings. Neither fluvoxamine nor reboxetine affected pupillary fatigue waves or subjective ratings of ”alertness”. Reboxetine caused a small reduction in subjectively rated ”anxiety”. Conclusions: The mydriatic effect of reboxetine may be due to noradrenaline reuptake blockade in the iris and/or in the central nervous system. The enhancement of pupillary fatigue waves by the sedative antidepressant amitriptyline, but not by the non-sedative antidepressants fluvoxamine and reboxetine, indicates that the PST is a suitable quantitative objective test for the detection of drug-induced changes in the level of arousal. Received: 9 July 1999 / Final version: 26 October 1999     

Insomnia,Sleepiness, and Depression in Adolescents Living in Residential Care Facilities

The main objective of this study was to document sleep patterns and disturbances reported by youths temporarily living in residential care facilities. A secondary objective was to examine the relationships between sleep disturbances and mood and daytime sleepiness. A self-reported questionnaire on sleep patterns and habits assessing duration, frequency, and consequences of sleep difficulties, the Beck Depression Inventory-2, and the Epworth Sleepiness Scale were administered to a sample of 66 adolescents. Results suggest a high rate of sleep disturbances in this sample, with 41% reporting insomnia symptoms and 21% meeting diagnostic criteria for an insomnia syndrome. Those with more severe insomnia syndrome showed more severe depressive symptoms and daytime consequences.