Objective: The purpose of this study was to characterize the nature of the relation between periodic leg movements during sleep (PLMS) and cortical arousals to contribute to the debate on the clinical significance and treatment of PLMS. Methods: A prospective, placebo‐controlled, single‐blind, parallel group study was carried out including 46 drug‐naive patients with idiopathic restless legs syndrome (RLS). Each patient underwent 2 consecutive full‐night polysomnographic studies. The first night was the baseline night. Prior to the second night, 1 group received a single oral dose of 0.25mg pramipexole, whereas a second group received a single oral dose of 0.5mg clonazepam, and the remaining patients received placebo. Sleep stages, cyclic alternating pattern (CAP), and leg movement activity were scored following standard criteria; symptoms of RLS were also assessed. Results: Pramipexole suppressed PLMS without affecting electroencephalographic (EEG) instability (CAP) and arousals (corresponding to CAP A3 and, partially, A2 subtypes), whereas clonazepam did the opposite, reducing non‐rapid eye movement sleep EEG instability without effects on PLMS. Both drugs were effective on sensory RLS symptoms. Interpretation: This study demonstrates that a selective pharmacological approach can disconnect PLMS from arousal events, suggesting an indirect relation between each other. These results might weaken the hypothesis of a direct pathological role of PLMS in sleep disruption and can be important for the discussion on the existence of a distinct entity called periodic limb movements disorder. Moreover, the study opens the doors to the possibility of a joint treatment for RLS targeting sensory and motor symptoms, as well as sleep instability. ANN NEUROL 2012;71:834–844

The purposes of this study were to validate the use of a single standard question for the rapid screening of restless legs syndrome (RLS) and to analyze the eventual effects of the presence of RLS on self-assessed daytime sleepiness, global clinical severity and cognitive functioning. We evaluated a group of 521 consecutive patients who accessed our neurology clinic for different reasons. Beside the answer to the single question and age, sex, and clinical diagnosis, the following items were collected from all patients and normal controls: the four criteria for RLS, the Epworth Sleepiness Scale (ESS), the Clinical Global Impression of Severity (CGI-S), and the Mini-Mental State evaluation. RLS was found in 112 patients (70 idiopathic). The single question had 100% sensitivity and 96.8% specificity for the diagnosis of RLS. ESS and CGI-S were significantly higher in both RLS patient groups than in normal controls. RLS severity was significantly higher in idiopathic than in associated/symptomatic RLS patients. RLS can be screened with high sensitivity and good reliability in large patient groups by means of the single question; however, the final diagnosis should always be confirmed by the diagnostic features of RLS and accompanied by a careful search for comorbid conditions.

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This study shows peculiar CAP modifications in children with AS and represents an attempt to correlate the quantification of sleep EEG oscillations with the degree of mental ability/disability.

Patients with RLS show significant abnormalities in sleep microstructure, represented by an excessive sleep instability/discontinuity. Acute pramipexole administration seems to exert no action on these abnormalities; the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of presleep RLS symptoms and PLMS.

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Objective The primary objective of this study was to characterize the association between cyclic alternating pattern (CAP) and neurocognitive performance in a group of normal subjects before and after two nights of experimentally-induced sleep fragmentation. Subjects and Methods Fifteen healthy subjects underwent one night of uninterrupted and two sequential nights of experimental sleep fragmentation achieved by auditory and mechanical stimuli. Eight subjects were re-examined using a similar paradigm with three nights of uninterrupted sleep. Sleep was polygraphically recorded and CAP analysis was performed for all recordings. A battery of neurocognitive tests was performed for spatial attention, inhibition of return, mental rotation, and Stroop color word test in the afternoon following the first and third night of sleep under fragmented and non-fragmented conditions. Results With sleep fragmentation, the percentage of slow-wave sleep was dramatically reduced and there was a two-fold increase in total CAP rate across all NREM sleep stages. Moreover, the number of all CAP A subtypes/hour of sleep (index) was significantly increased. Total CAP rate during the non-fragmented night correlated with reaction times. Similarly, the percentages of A1 and A3 subtypes were negatively and positively correlated with reaction times, respectively. Of the neurocognitive test battery, however, only values obtained from some subtests of the Mental Rotation test showed a significant improvement after sleep fragmentation. Conclusions The results of this study suggest that CAP A1 subtypes are associated with higher cognitive functioning, whereas CAP A3 subtypes are associated with lower cognitive functioning in young healthy subjects. The lack of cognitive functioning impairment after sleep fragmentation may be due to persistence and even enhancement of transient slow-wave activity contained in CAP A1 subtypes which also caused a significant enhancement of the EEG power spectrum in the lower frequencies.