Many patients with assumed idiopathic REM sleep behavior disorder (RBD) may actually represent an early clinical manifestation of an evolving neurodegenerative disorder, such as the alpha-synucleinopathies, Parkinson's disease or multiple system atrophy. Early detection of these patients is clinically relevant for long-term prospective as well as future neuroprotective studies. For this purpose, we validated a 10-item patient self-rating questionnaire (maximum total score 13 points) covering the clinical features of RBD. The RBD screening questionnaire (RBDSQ) was applied to 54 patients with polysomnographically confirmed RBD (29 men; mean age 53.7 +/- 15.8 years), 160 control subjects (81 men; mean age 50.8 +/- 15.5 years) in whom RBD was excluded by history and polysomnography (PSG, control group 1) and 133 unselected healthy subjects (58 men; mean age 46.9 +/- 12.3 years; no PSG, control group 2). In most subjects (n = 153) of control group 1, other sleep-wake disturbances were present. The mean RBDSQ score in the RBD group was 9.5 +/- 2.8 points compared with 4.6 +/- 3.0 points in control group 1 (P < 0.0001). Considering an RBDSQ score of five points as a positive test result, we found a sensitivity of 0.96 and a specificity of 0.56. The RBDSQ poorly discriminated patients with the most challenging differential diagnoses such as sleepwalking or epilepsy. In control group 2, the mean RBDSQ score (2.02 +/- 1.78) was significantly lower than in the RBD group (P < 0.0005), revealing a specificity of 0.92. Due to its high sensitivity, the RBDSQ appears to be particularly useful as a screening tool.

Restless legs syndrome (RLS) is a frequent neurological disorder characterized by an imperative urge to move the legs during night, unpleasant sensation in the lower limbs, disturbed sleep and increased cardiovascular morbidity. In a genome-wide association study we found highly significant associations between RLS and intronic variants in the homeobox gene MEIS1, the BTBD9 gene encoding a BTB(POZ) domain as well as variants in a third locus containing the genes encoding mitogen-activated protein kinase MAP2K5 and the transcription factor LBXCOR1 on chromosomes 2p, 6p and 15q, respectively. Two independent replications confirmed these association signals. Each genetic variant was associated with a more than 50% increase in risk for RLS, with the combined allelic variants conferring more than half of the risk. MEIS1 has been implicated in limb development, raising the possibility that RLS has components of a developmental disorder.

Background Idiopathic REM sleep behavior disorder (RBD) is a parasomnia that is an important risk factor for PD and Lewy body dementia. Its prevalence is unknown. One barrier to determining prevalence is that current screening tools are too long for large-scale epidemiologic surveys. Therefore, we designed the REM Sleep Behavior Disorder Single-Question Screen (RBD1Q), a screening question for dream enactment with a simple yes/no response. Methods Four hundred and eighty-four sleep-clinic– based participants (242 idiopathic RBD patients and 242 controls) completed the screen during a multicenter case-control study. All participants underwent a polysomnogram to define gold-standard diagnosis according to standard criteria. Results We found a sensitivity of 93.8% and a specificity of 87.2%. Sensitivity and specificity were similar in healthy volunteers, compared to controls or patients, with other sleep diagnoses. Conclusions A single-question screen for RBD may reliably detect disease, with psychometric properties favorably comparable to those reported for longer questionnaires.

REM sleep behaviour disorder (RBD) and olfactory dysfunction are common and very early features of alpha-synucleinopathies, in particular Parkinson's disease. To investigate the hypothesis that these two clinical features in combination are an indicator of evolving alpha-synucleinopathy, olfactory function was assessed in RBD. We studied 30 patients (18 male, 12 female; mean age 48 +/- 14 years, range 19-78 years) with clinical (idiopathic, n = 6; symptomatic, n = 13, mostly associated with narcolepsy) or subclinical (n = 11, associated with narcolepsy) RBD according to standard criteria and 30 age- and gender-matched healthy control subjects using standardized 'Sniffin' Sticks'. RBD patients had a significantly higher olfactory threshold (P = 0.0001), lower discrimination score (P = 0.003), and lower identification score (P = 0.001). Compared with normative data, 97% of the RBD patients had a pathologically increased olfactory threshold, 63% an impaired odour discrimination score, and 63% a decreased identification score. On neurological examination, signs of parkinsonism were newly found in five patients with clinical RBD (not associated with narcolepsy), who usually had a long history of 'idiopathic' RBD. Four of the five patients fulfilled the UK Brain Bank criteria for the clinical diagnosis of Parkinson's disease. The underlying nigrostriatal degeneration of clinical Parkinson's disease was confirmed by I-123-FP-CIT SPECT in one patient and early nigrostriatal degeneration was identified by SPECT in a further two patients with 'idiopathic' clinical RBD out of 11 RBD patients who agreed to undergo SPECT studies. Our study shows that RBD patients have a profound impairment of olfactory function. Five patients with clinical RBD not associated with narcolepsy had clinical or imaging signs of nigrostriatal degeneration. This new clinical finding correlates with the neuropathological staging of Parkinson's disease (stages 1-3) as proposed by Braak. In stage 1, the anterior olfactory nucleus or the olfactory bulb is affected (along with the dorsal motor nucleus of the glossopharyngeal and vagal nerves). In stage 2, additional lesions consistently remain confined to the medulla oblongata and pontine tegmentum, which are critical areas for RBD. Midbrain lesions are found only in stage 3, in particular degeneration of dopaminergic neurons in the substantia nigra pars compacta. Thus, 'idiopathic' RBD patients with olfactory impairment might present with stage 2 preclinical alpha-synucleinopathy. Since narcoleptic patients are not known to have an increased risk of developing parkinsonism, the pathophysiology and clinical relevance of hyposmia in RBD/narcolepsy patients requires further research.

Only in the last three decades, the restless legs syndrome (RLS) has been examined in randomized controlled trials. The Movement Disorder Society (MDS) commissioned a task force to perform an evidence-based review of the medical literature on treatment modalities used to manage patients with RLS. The task force performed a search of the published literature using electronic databases. The therapeutic efficacy of each drug was classified as being either efficacious, likely efficacious, investigational, nonefficacious, or lacking sufficient evidence to classify. Implications for clinical practice were generated based on the levels of evidence and particular features of each modality, such as adverse Produced by a task force commissioned by The Movement Disorder Society.Additional Supporting Information may be found in the online version of this article. y Chairperson RLS EBM task force. { RLS EBM task force member.