REM sleep behavior disorder is not linked to postural instability and gait dysfunction in Parkinson

To evaluate a potential association of REM‐sleep behavior disorder (RBD) with gait and postural impairment in Parkinson's disease (PD). Gait difficulties and postural impairment are frequent in PD and are a major cause of disability. Animal studies indicate a key role of the pedunculopontine nucleus (PPN) in gait, postural control, and REM sleep, and also in the pathophysiology of RBD. In humans, such an association has not been investigated. Twenty‐six patients with mild‐to‐moderate PD (13 with polysomnography confirmed and 13 with excluded RBD), and 20 age‐matched healthy controls were prospectively investigated. Gait assessment on a treadmill, and static and dynamic posturography were performed. PD patients with RBD do not differ from those without RBD in gait and postural control. Greater severity of PD or prevalence of gait and postural disturbances in the presence of RBD were not found. RBD was not associated with any particular motor phenotype. We found no association of RBD with gait disturbances and postural impairment. Human gait and postural control and RBD appear to depend upon different neuronal circuits. © 2010 Movement Disorder Society     

Idiopathic REM sleep behavior disorder in the transition to degenerative disease

Idiopathic REM sleep behavior disorder (RBD) predicts Parkinson's disease (PD) and dementia. However, the nature of the disease that emerges from RBD has not been fully characterized. Since 2004, we have been conducting a prospective study of idiopathic RBD patients, providing an opportunity to directly observe patients as they transitioned to a defined neurodegenerative syndrome. Patients with idiopathic RBD underwent an extensive annual evaluation of motor function, olfaction, color vision, autonomic function, cognition and psychiatric symptoms. Neurodegenerative disease was defined according to standard criteria. We compared these measures in patients who had developed PD to those with dementia, all within the first year of developing disease. Of 67 patients, 6 developed PD and eleven developed dementia. Except for cognitive functioning, all tests of olfaction, color vision, autonomic function, depression, and quantitative measures of motor speed were similar in patients with PD and dementia. Of dementia patients, seven met criteria for probable Lewy body dementia (LBD) and four for Alzheimer's disease (or, possible LBD). In all probable LBD cases, the diagnosis was made because of parkinsonism, with no patient experiencing hallucinations or fluctuations. Patients with “Alzheimer's disease” seemed to have LBD, as they demonstrated typical LBD cognitive profiles on neuropsychological testing and were indistinguishable from LBD patients in ancillary measures. Therefore, among RBD patients with new‐onset LBD, hallucinations or fluctuations are absent, suggesting that RBD is a reliable early sign of LBD. The indistinguishability of dementia and PD in all ancillary measures suggests a single unitary “RBD‐then‐neurodegeneration” process, the clinical presentation of which depends upon selective neuronal vulnerability. © 2009 Movement Disorder Society     

REM behavior disorder,hallucinations and cognitive impairment in Parkinson's disease: A two‐year follow up

In Parkinson's disease (PD) the presence of REM parasonnias as REM Behaviour Disorder (RBD) or vivid dreams/nightmares, is recognized as largely associated with hallucinations, even if the risk of the development of hallucinations seem not to depend on how long the REM parasomnias had been occurring. The aim of this study was to establish if RBDs occurring earlier than hallucinations in PD are predictive of cognitive impairment development. Three groups of PD patients: i) group 1, without RBD and without hallucinations; ii) group 2, with RBD but without hallucinations; iii) group 3, with RBD and hallucinations have been prospectively investigated at baseline and after two years throughout a clinical and neuropsychological evaluation. After two years, the group 1 continued to present normal neuropsychological tests and did not present either RBDs or hallucinations. In the group 2, the frontal impairment evidenced at baseline was confirmed; the onset of newly hallucinations was reported in a subgroup of 12 patients, who proved to be older, with a more severe executive impairment at baseline and with a more severe motor symptoms progression than those RBD patients who had not manifested hallucinations. The group 3, characterized at baseline by a more severe cognitive impairment presented, after two years, a cognitive worsening and a higher mortality rate. The longitudinal but at preliminary step investigation identified a PD subgroup of patients, in whom a common background disease profile, including the presence of RBD, could represent a “red flag” in developing further cognitive impairment. © 2008 Movement Disorder Society     

Manifestations of Parkinson disease differ in association with REM sleep behavior disorder

REM sleep behavior disorder (RBD) is commonly associated with Parkinson disease (PD), but it is unclear whether this association has implications for disease manifestations. We evaluated 36 PD patients for the presence of RBD by polysomnography. Patients underwent an extensive evaluation by a movement disorders specialist blinded to polysomnography results. Severity of motor manifestations, autonomic, visual, psychiatric, and olfactory dysfunctions and quality of life (QOL) were assessed, and compared using regression analysis that adjusted for disease duration, age and sex. Severity of motor manifestations did not differ between groups. However, the presence of RBD in PD was strongly associated with symptoms and signs of orthostatic hypotension (systolic blood pressure lying to standing = ?25.7 ± 13.0 mmHg vs. ?4.9 ±14.1, P < 0.001); and orthostatic symptom prevalence = 71% vs. 27%, P = 0.0076). There was no association between RBD and other autonomic symptoms. Color vision was worse in patients with RBD, but olfactory dysfunction did not differ between groups. The prevalence of depression, hallucinations, paranoia, and impulse disorders did not differ between groups. Emotional functioning and general health QOL measures were lower in those with RBD, but there were no differences between groups on disease‐specific indices or on measures of overall physical QOL. These findings suggest that the pathophysiology of RBD and nonmotor manifestations of PD, particularly autonomic dysfunction, are linked. © 2008 Movement Disorder Society     

Altered regional homogeneity and connectivity in cerebellum and visual-motor relevant cortex in Parkinson's disease with rapid eye movement sleep behavior disorder

ObjectiveRapid eye movement sleep behavior disorder (RBD) frequently occurs in Parkinson's disease (PD), however, the exact pathophysiological mechanism underlying its occurrence is not clear. In this study, we explored whether there is abnormal spontaneous neuronal activities and connectivity maps in some brain areas under resting-state in PD patients with RBD.MethodsWe recruited 38 PD patients (19 PD with RBD and 19 PD without RBD), and 20 age- and gender-matched normal controls. We used resting-state functional magnetic resonance imaging (RS-fMRI) to analyze regional homogeneity (ReHo) and functional connectivity (FC), and further to reveal the neuronal activity in all subjects.ResultsCompared with the PD without RBD patients, the PD with RBD patients showed a significant increase in regional homogeneity in the left cerebellum, the right middle occipital region and the left middle temporal region, and decreased regional homogeneity in the left middle frontal region. The REM sleep behavioral disorders questionnaire scores were significantly positively correlated with the ReHo values of the left cerebellum. The functional connectivity analysis in which the four regions described above were used as regions of interest revealed increased functional activity between the left cerebellum and bilateral occipital regions, bilateral temporal regions and bilateral supplementary motor area.ConclusionThe pathophysiological mechanism of PD with RBD may be related to abnormal spontaneous neuronal activity patterns with strong synchronization of cerebellar and visual-motor relevant cortex, and the increased connectivity of the cerebellum with the occipital and motor regions.     

Polysomnographic diagnosis of idiopathic REM sleep behavior disorder

The presence of either excessive tonic chin EMG activity during REM sleep, or excessive phasic submental or limb EMG twitching is required to diagnose REM sleep behavior disorder (RBD). The aim was to identify cut‐off values and to assess the sensitivity and specificity of these values taken separately or combined to diagnose idiopathic RBD patients. Eighty patients presenting with a clinical diagnosis of idiopathic RBD and 80 age‐ and gender‐matched normal controls were studied in the sleep laboratory. Receiver operating characteristic curves were drawn to find optimal cut‐off values for three REM sleep EMG parameters. Tonic and phasic EMG activity were measured in the chin, but not in the limbs. Videos were examined during the recording but were not systematically reviewed by the authors. Total correct classification of 81.9% was found for tonic chin EMG density ≥30%; 83.8% for phasic chin EMG density ≥15% and 75.6% for ≥24 leg movements per hour of REM sleep. Five patients did not fulfill any of these three polysomnographic (PSG) criteria. Conversely, one subject of the control group met the PSG criteria for RBD. This study estimates the diagnostic value of a visual scoring method for the diagnosis of idiopathic RBD and establishes cut‐off values to be used in clinical and research set‐ups. For the five RBD patients who did not show chin EMG abnormalities, it cannot be excluded that they had increased phasic EMG activity in the upper limbs and presented visible motor activity. © 2010 Movement Disorder Society     

Recurrent brief depression revisited

Recurrent Brief Depressive Disorder (RBD) is a well-defined and prevalent mood disorder with an increased risk of suicidal behavior and significant clinical impairment in the community and general practice. Occurring at least monthly with depressive episodes lasting only a few days defines recurrent Brief Depressive Disorder. The lifetime co-occurrence of both RBD and Major Depressive Disorder (MDD), called Combined Depression (CD), substantially increases the risk for attempted suicide, even more than that known for ‘pure’ MDD. The diagnostic criteria for RBD found in the ICD-10 and DSM-IV are helpful in research and clinical routine as well as several methodological issues, which make clinical diagnostic and drug response evaluation of RBD very different from MDD. Formal differences in the course of RBD and MDD require different designs for drug treatment studies. Denials of disorder, specific methodological requirements, and highly selected patient samples have probably been responsible for false negative results in double blind, placebo-controlled treatment studies. Although several authors reported successful treatment of RBD with different compounds in about 60 patients, it is still not possible to deduce a treatment algorithm for RBD to date. Obviously future treatment studies without the limitations of previous studies are clearly required for RBD. Results of ongoing studies will soon provide the first data on the biological underpinnings of RBD.     

Recurrent brief depression revisited

Recurrent Brief Depressive Disorder (RBD) is a well-defined and prevalent mood disorder with an increased risk of suicidal behavior and significant clinical impairment in the community and general practice. Occurring at least monthly with depressive episodes lasting only a few days defines recurrent Brief Depressive Disorder. The lifetime co-occurrence of both RBD and Major Depressive Disorder (MDD), called Combined Depression (CD), substantially increases the risk for attempted suicide, even more than that known for 'pure' MDD. The diagnostic criteria for RBD found in the ICD-10 and DSM-IV are helpful in research and clinical routine as well as several methodological issues, which make clinical diagnostic and drug response evaluation of RBD very different from MDD. Formal differences in the course of RBD and MDD require different designs for drug treatment studies. Denials of disorder, specific methodological requirements, and highly selected patient samples have probably been responsible for false negative results in double blind, placebo-controlled treatment studies. Although several authors reported successful treatment of RBD with different compounds in about 60 patients, it is still not possible to deduce a treatment algorithm for RBD to date. Obviously future treatment studies without the limitations of previous studies are clearly required for RBD. Results of ongoing studies will soon provide the first data on the biological underpinnings of RBD.     

Decreased phasic EMG activity during rapid eye movement sleep in treatment‐naïve Parkinson's disease: Effects of treatment with levodopa and progression of illness

Rapid eye movement (REM) sleep behavior disorder (RBD) is frequently associated with Parkinson's disease (PD) and may anticipate its diagnosis by several years. We assessed the presence of motor dyscontrol during REM sleep in treatment‐naïve PD patients and investigated the putative effect of levodopa (L ‐dopa) treatment on motor activity. Overnight sleep studies were performed on 15 previously untreated PD patients and 14 controls at baseline, again after a 3‐ to 9‐month treatment period with a low dose of L ‐dopa, and 2 to 5 days after treatment discontinuation (in 8 patients). No differences in sleep parameters were observed across groups or treatment conditions. None of the patients met criteria for RBD at baseline, whereas 5 patients were symptomatic at the time of the second sleep study. A quantitative analysis of electromyographic (EMG) activity during REM sleep showed a lower phasic twitching activity in untreated PD than in controls. However, an increase in both phasic twitching and tonic activity was found after treatment with L ‐dopa. Discontinuation of treatment resulted in a return to pretreatment values of phasic but not of tonic EMG activity. Thus, the increase in phasic activity seems to depend on the effects of L ‐dopa, whereas the increase in tonic EMG activity during REM sleep might be caused by other factors such as the progression of disease. Potential implications for the understanding of the relationship between RBD and PD are discussed. © 2002 Movement Disorder Society     

快眼动睡眠调控机制及快眼动睡眠期行为障碍的神经通路相关研究

快眼动(REM)睡眠行为障碍(RBD)是一种以REM睡眠期骨骼肌弛缓能力障碍为特征的异态睡眠。患病个体因此在REM睡眠期出现不同严重程度的与梦境吻合的异常行为。至今与RBD相关的神经核团及通路尚未完全阐明,存在不同假说。文中从REM睡眠神经调控机制入手,结合猫和大鼠RBD模型发现,回顾近年来RBD相关神经通路研究的进展,并与人类RBD病例对照,综合阐述RBD产生的相关神经通路,为RBD发病机制的研究进一步提供线索。     

Rapid eye movement sleep behavior disorder and rapid eye movement sleep without atonia in narcolepsy

Narcolepsy is a rare disabling hypersomnia disorder that may include cataplexy, sleep paralysis, hypnagogic hallucinations, and sleep-onset rapid eye movement (REM) periods, but also disrupted nighttime sleep by nocturnal awakenings, and REM sleep behavior disorder (RBD). RBD is characterized by dream-enacting behavior and impaired motor inhibition during REM sleep (REM sleep without atonia, RSWA). RBD is commonly associated with neurodegenerative disorders including Parkinsonisms, but is also reported in narcolepsy in up to 60% of patients. RBD in patients with narcolepsy is, however, a distinct phenotype with respect to other RBD patients and characterized also by absence of gender predominance, elementary rather than complex movements, less violent behavior and earlier age at onset of motor events, and strong association to narcolepsy with cataplexy/hypocretin deficiency. Patients with narcolepsy often present dissociated sleep features including RSWA, increased density of phasic chin EMG and frequent shift from REM to NREM sleep, with or without associated clinical RBD. Most patients with narcolepsy with cataplexy lack the hypocretin neurons in the lateral hypothalamus. Tonic and phasic motor activities in REM sleep and dream-enacting behavior are mostly reported in presence of cataplexy. Narcolepsy without cataplexy is a condition rarely associated with hypocretin deficiency. We proposed that hypocretin neurons are centrally involved in motor control during wakefulness and sleep in humans, and that hypocretin deficiency causes a functional defect in the motor control involved in the development of cataplexy during wakefulness and RBD/RSWA/phasic motor activity during REM sleep.     

New aspects in the pathophysiology of rapid eye movement sleep behavior disorder: the potential role of glutamate,gamma-aminobutyric acid,and glycine

Rapid eye movement sleep behavior disorder (RBD) is a parasomnia characterized by the occurrence of intense movements during rapid eye movement (REM) sleep, also named paradoxical sleep. The neuronal dysfunctions at the origin of the loss of atonia in RBD patients are not known. One possibility is that RBD is due to the degeneration of neurons inducing the muscle atonia of REM sleep. Therefore, in our paper we review data on the populations of neurons responsible for the atonia of REM sleep before discussing their potential role in RBD. We first review evidence that motoneurons are tonically hyperpolarized by gamma-aminobutyric acid (GABA) and glycine and phasically excited by glutamate during REM sleep. Then, we review data indicating that the atonia of REM sleep is induced by glycinergic/GABAergic REM-on premotoneurons contained within the raphe magnus and the ventral and alpha gigantocellular reticular nuclei localized in the ventral medullary reticular formation. These neurons are excited during REM sleep by a direct projection from glutamatergic REM-on neurons localized in the pontine sublaterodorsal tegmental nucleus (SLD).From these results, we discuss the possibility that RBD is due to a specific degeneration of descending REM-on glutamatergic neurons localized in the caudal SLD or that of the REM-on GABA/glycinergic premotoneurons localized in the ventral medullary reticular formation. We then propose that movements of RBD are induced by descending projections of cortical motor neurons before discussing possible modes of action of clonazepam and melatonin.     

REM sleep behavior disorder and motor dysfunction in Parkinson's disease – A longitudinal study

ObjectivesLongitudinal assessment of a Parkinson's disease (PD) cohort, to investigate the evolution or REM sleep behavior symptoms (RBD) over time and to test the relation between RBD at onset and motor dysfunction progression.MethodsAn early stage PD cohort (n = 61) was assessed at two time points, separated by a two years interval. Diagnostic criteria for RBD were: violent behavior during sleep and body movements or vocalization indicative of dream enacting and at least six affirmative answers in the REM sleep behavior disorder screening questionnaire. Motor function assessment was performed with the Unified Parkinson's Disease Scale part II and III (total and partial scores for tremor, bradykinesia, rigidity, gait/postural instability and dysarthria).Results25 Patients had RBD at baseline, vs. 35 at follow-up. Three RBD changed to non-RBD at follow-up, while 10 non-RBD patients developed RBD at follow-up (annual incidence of 12.5%). RBD and non-RBD patients did not differ significantly at baseline or follow-up. The presence of RBD at baseline was significantly related to an increase in UPDRS total and bradykinesia scores over time.DiscussionRBD symptoms can vary over time and have a tendency to increase during the early stages of disease. The presence of RBD symptoms could be a risk factor for motor function deterioration and particularly for bradykinesia worsening.     

Nicht-epileptische motorische Phänomene im Schlaf

Paroxysmal motor phenomena during sleep are frequent and need to be differentiated from sleep-related epileptic seizures. Non-REM parasomnias are characterized by incomplete arousal from deep sleep with impaired ability to interact. They are sub-classified as confusional arousals, sleepwalking, and sleep terrors. Sleepwalking may be associated with inadequate behavior and accidents. Most cases of REM sleep behavior disorder (RBD) are associated with neurodegenerative disorders such as Parkinson’s disease. However, RBD may precede the onset of the associated disease by many years. Jerky movements during REM sleep are usually seen, which are caused by loss of REM-associated muscle atonia. After awakening, patients tend to remember an action-filled dream, often with violent content. Periodic limb movements during sleep (PLMS) are seen in most patients suffering from restless legs syndrome (RLS), but they may also occur independent of RLS. They are regarded as a disorder if they significantly disturb sleep onset or maintenance. Sleep related bruxism may lead to relevant tooth damage. The grinding sounds are usually perceived as very disturbing by room- or housemates. Rhythmic movements at the transition between wake and sleep probably originate as a form of self-stimulation with a soothing effect, but they may eventually become pathologically relevant, disturbing sleep onset of the affected person and his or her bedpartner. Hypnagogic foot tremor, alternating leg muscle activation during sleep, and sleep starts are usually of no pathological relevance.     

Investigating rapid eye movement sleep without atonia in Parkinson's disease using the rapid eye movement sleep behavior disorder screening questionnaire

Rapid eye movement (REM) sleep behavior disorder (RBD) is frequently observed in patients with Parkinson's disease (PD). Accurate diagnosis is essential for managing this condition. Furthermore, the emergence of idiopathic RBD in later life can represent a premotor feature, heralding the development of PD. Reliable, accurate methods for identifying RBD may offer a window for early intervention. This study sought to identify whether the RBD screening questionnaire (RBDSQ) and three questionnaires focused on dream enactment were able to correctly identify patients with REM without atonia (RWA), the neurophysiological hallmark of RBD. Forty‐six patients with PD underwent neurological and sleep assessment in addition to completing the RBDSQ, the RBD single question (RBD1Q), and the Mayo Sleep Questionnaire (MSQ). The REM atonia index was derived for all participants as an objective measure of RWA. Patients identified to be RBD positive on the RBDSQ did not show increased RWA on polysomnography (80% sensitivity and 55% specificity). However, patients positive for RBD on questionnaires specific to dream enactment correctly identified higher degrees of RWA and improved the diagnostic accuracy of these questionnaires. This study suggests that the RBDSQ does not accurately identify RWA, essential for diagnosing RBD in PD. Furthermore, the results suggest that self‐report measures of RBD need to focus questions on dream enactment behavior to better identify RWA and RBD. Further studies are needed to develop accurate determination and quantification of RWA in RBD to improve management of patients with PD in the future. © 2014 International Parkinson and Movement Disorder Society     

伴快速眼球运动睡眠行为障碍的帕金森病患者临床特征

目的 评价快速眼球运动睡眠行为障碍(RBD)在帕金森病(PD)患者中的患病率以及伴发RBD的PD患者临床特征.方法 2007年连续入组124例PD患者,采用非运动症状问卷(NMSquest)第25项问答结果调查PD患者中RBD患病率;将入选患者分为RBD组(78例)和非RBD组(13例),采用统一PD评分量表(UPDRS)、Hoehn-Yahr(H-Y)分级比较2组运动症状严重程度和运动并发症发生情况;选用NMSquest量表比较2组非运动症状发生情况,选用MMSE、汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)、帕金森病睡眠量表(PDSS)和Epworth嗜睡量表(ESS)比较2组认知功能、焦虑和抑郁、夜间睡眠障碍和日间思睡程度.结果 (1)RBD的患病率为62.9%(78/124);(2)RBD组患者的病程[(3.8±2.8)年]显著短于非RBD组[(5.0±2.5)年,t=-1.972,P=0.048],但在性别、年龄、起病年龄、发病类型、左旋多巴等效剂量(LDE)和用药种类上2组差异没有统计学意义;(3)在运动症状中RBD与非RBD组在H-Y分级、UPDRS-Ⅱ、Ⅲ、Ⅳ评分以及运动并发症发生率方面差异无统计学意义;(4)在非运动症状中胃肠道功能、自主神经系统功能、精神和睡眠活动等方面的不良症状在RBD组的发生率显著高于非RBD组,但是认知、焦虑和抑郁、夜间睡眠障碍和日间思睡的严重程度在2组间差异没有统计学意义.结论 RBD在PD患者中的患病率较高,伴发RBD的PD患者病程较短且非运动系统受累更加广泛.     

REM sleep behaviour disorder in Parkinson’s disease: a questionnaire-based study

Abstract The aim of the study was to determine the clinical frequency and features of REM sleep behaviour disorder (RBD) in a large population of Parkinsons disease (PD) patients using defined diagnostic criteria both for RBD and PD. Six trained neurologists used a semistructured questionnaire based on ICSD-R diagnostic criteria for RBD to evaluate 200 PD patients and their caregivers. Interobserver reliability for the diagnosis of RBD was substantial (Kappa 0.65). Five patients were excluded from the study because of an MMSE lower than 25. The demographic and PD clinical features were compared in the clinically defined RBD group and in those without RBD (NRBD). Then the RBD features during the last year were analysed in the affected group. Out of 195 patients, 66 fulfilled the ICSD-R criteria for RBD; 62 patients reported RBD during the last year (frequency 31.8%). RBD features: two or more episodes per week in 35.5%; upper limb movements in 87%; lower limb movements in 79%; vocalisations during events in 85%. RBD onset was before PD in 27% of patients; 69% of the RBD group had injured themselves or their caregivers during sleep. According to multivariate analysis, RBD was associated with male gender, age and PD duration. Brief training and the use of a semistructured questionnaire may help the neurologist in dealing with sleep disturbances in PD patients. The search for RBD symptoms in PD is highly recommended, especially in patients with a long disease duration, the risk of sleep-related injuries being high.Bologna, Genova, Parma and Pisa Universities group for the study of REM Sleep Behavior Disorder (RBD) in Parkinsons Disease     

Clinical features associated with REM sleep behavior disorder symptoms in the early stages of Parkinson’s disease

We aimed to characterize the clinical features associated with REM sleep behaviour disorder (RBD) in early stage Parkinson’s disease (PD). Presence of clinical RBD was determined according to ICSD minimal clinical criteria and a validated RBD questionnaire. We registered time of appearance of RBD symptoms in relation to PD onset and the occurrence of RBD symptoms in the past in non-RBD patients. RBD and non-RBD groups were compared in terms of motor and cognitive dysfunction. The same comparisons were made between patients who reported RBD symptoms at some point in time (including those non-RBD patients that reported occurrence of RBD symptoms in the past) and those who did not (RBDS and non-RBDS, respectively). We assessed 75 patients. Forty-one (55%) patients presented with RBD, 19 beginning before PD onset. Five non-RBD patients reported having had RBD symptoms in the past. There were no significant differences between RBD and non-RBD patients. RBDS group presented a significantly higher proportion of non-tremor motor sub-type compared to non-RBDS patients. Our results suggest that RBD is very frequent in the early stages of PD. In some patients, RBD symptoms could have disappeared before or in the first years after motor disturbance onset. Non-tremor motor sub-type was related to RBD symptoms history, rather than to the presence of RBD clinical criteria at time of evaluation, suggesting that the physiopathological changes that cause the association with motor status could remain, in spite of symptom fluctuation.     

Abnormal motor behavior during sleep

Abnormal motor behaviors during sleep can be classified into four categories, ranging from myoclonic jerks to complex and integrated motor behaviors There have been recent developments in several of these conditions, in particular restless legs syndrome (RLS) and rapid-eye-movement sleep behavior disorder (RBD). RLS is one of the major causes of insomnia. Familial aggregation of RLS has been demonstrated by several groups, and molecular genetics studies have suggested the presence of susceptibility genes on chromosomes 12q and 14q. Pharmacologic and brain imaging studies suggest the involvement of dopaminergic mechanisms in RLS, but recent work has focused on brain iron metabolism. Studies indicate that RBD patients may eventually develop Parkinson's disease (PD). Conversely, RBD has been found in patients already diagnosed with PD. Single-photon emission computed tomography and positron emission tomography studies have shown a decrease in binding to presynaptic dopamine transporter in both idiopathic RBD and PD. Patients with RBD (associated or unassociated with PD) also have neuropsychological deficits. RBD may therefore represent the prodrome of a neurodegenerative disease leading to multiple system atrophy and Lewy body dementia. Understanding the underlying pathophysiology of abnormal sleep motor behaviors may prove useful in the management of insomnia.     

Screening for prodromal Parkinson's disease in the general community: a sleep-based approach

Objective/BackgroundNeuroprotective therapy for Parkinson's disease (PD) is most likely to be effective if provided in its prodromal stages. However, identifying prodromal PD is difficult because PD is relatively uncommon, and most markers are nonspecific. Rapid eye movement (REM) sleep behavior disorder (RBD) is by far the strongest clinical marker of prodromal PD, but most patients do not seek out medical attention. Developing an efficient way of diagnosing RBD from the general community may be the most practical method to detect prodromal PD.MethodsWe developed a screening strategy that began with a newspaper advertisement containing a single-question screen for RBD. All screen-positive subjects underwent an interview based on the Innsbruck RBD inventory aimed to optimize the positive predictive value. Those who passed both screens underwent confirmatory polysomnography. The proportion of screened RBD patients who met the International Parkinson and Movement Disorder Society (MDS) criteria for prodromal PD was assessed. A broad array of clinical markers of neurodegeneration was compared between newspaper-screened RBD patients and 130 RBD patients clinically referred to the sleep center.ResultsOf 111 RBD-screen-positive participants, 40 (36%) passed the secondary screen, and 29 underwent full polysomnography. Of these 29 patients, 19 were ultimately proven to have RBD (PPV = 66%), 12 (63%) of whom met the criteria for prodromal PD. Compared to patients referred to the sleep center, newspaper-screened patients had similar age, sex, olfaction, autonomic function, and color vision. However, motor and cognitive assessments were slightly better in newspaper-screened patients.ConclusionsA multistep screening approach using RBD screening questionnaires and telephone follow-up can efficiently identify prodromal PD in the general community.