Debora Aricò

Dissociation of periodic leg movements from arousals in restless legs syndrome

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.

A single question for the rapid screening of restless legs syndrome in the neurological clinical practice

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.

The slow-wave components of the cyclic alternating pattern (CAP) have a role in sleep-related learning processes.

Slow waves, a key feature of the EEG of NREM sleep, may be causally involved in producing a sleep-dependent, progressive downscaling of synaptic strength, which would lead to several benefits in terms of both cellular function and network performance. Also the A1 subtypes of the so-called cyclic alternating pattern (CAP) are composed mostly of slow waves and map over the frontal and prefrontal regions of the scalp. The aim of this study was to evaluate the eventual changes of CAP induced by an implicit learning paradigm which has already been shown to be able to increase locally sleep slow-wave activity (SWA). Our hypothesis was that learning is accompanied by a change in the components of CAP characterized by SWA (0.5-2.5Hz), i.e. its A1 subtypes. For this reason, in the present study we evaluated sleep recordings obtained in 10 healthy young normal subjects (mean age 25.8+/-1.8 years) who were asked to perform a motor learning task just before going to sleep. Sleep EEG was recorded for 2h and subjects were also tested after the night following the rotation task. Sleep stages and CAP (classified into three subtypes: A1, A2, and A3) were identified in the first hour of each recording. We found a significant increase in the number of CAP A1 subtypes per hour of NREM sleep on the night following the rotation test; the correlation between the change in A1 index and the post-sleep performance improvement after the rotation task was positive. These results confirm our hypothesis that CAP slow components are modified by a learning task during the day preceding sleep and support the idea that these components may play a role in sleep-related cognitive processes.

Effects of NREM sleep instability on cognitive processing.

OBJECTIVE Cyclic alternating pattern (CAP) A1 subtypes, characterized by high-voltage slow waves, are generated by the frontal cortex and are suspected to have a role in cognitive processing during NREM sleep. Conversely, CAP A2 and A3 subtypes are characterized by variable amounts of rapid EEG potentials arising from the parietal-occipital areas and often coincide with arousals. We tested the hypothesis that CAP subtypes differentially correlate with cognitive functions. SUBJECTS AND METHODS Eight healthy participants were recruited. Two nocturnal polysomnography studies and a series of neuropsychological tests were obtained in the subjects during the morning and afternoon of the first day and on the morning of the second day. RESULTS In agreement with our original hypothesis, we found that CAP A1 subtypes were correlated with better neuropsychological functioning the day after, for verbal fluency, working memory, and both delayed recall and recognition of words. These same neuropsychological test results were found to be negatively correlated with CAP A2 subtypes. CAP A3 subtypes were negatively correlated with the Trial Making test Parts A and B. CONCLUSIONS The results suggest that CAP A1 might be related to better cognitive functioning, whereas CAP A2 and A3 correlated with worse cognitive functioning. Further studies are needed to better understand how CAP influences cognitive performance, especially frontally-dependent functions and memory.

The effects of experimental sleep fragmentation on cognitive processing

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 twofold 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.

Direct comparison of cortical excitability to transcranial magnetic stimulation in obstructive sleep apnea syndrome and restless legs syndrome.

OBJECTIVE Changes to transcranial magnetic stimulation (TMS) have been reported in obstructive sleep apnea syndrome (OSAS) and restless legs syndrome (RLS), although no direct comparison study is available. The aim of this new investigation is to assess and compare cortical excitability of OSAS and RLS patients using the same methodology and under the same experimental conditions. METHODS Fourteen patients with OSAS and 12 with RLS were compared to 14 age-matched controls. All patients were untreated and had a severe degree of disease. Resting motor threshold (rMT), cortical silent period (CSP) and motor evoked potentials MEPs, as well as intracortical inhibition (ICI) and facilitation at interstimulus interval (ISI) of 3 and 10 ms, respectively, were explored from the right first dorsal interosseous muscle, during wakefulness. RESULTS rMT was higher in OSAS than in RLS and controls. CSP was shorter in RLS only when compared to apneic patients, whereas it was similar between OSAS and controls. OSAS subjects exhibited slightly prolonged central motor conductivity, whereas MEP amplitude was smaller in both patient groups. The ICI ratio at ISI of 3 ms was decreased in RLS patients only. CONCLUSIONS Distinct changes of responses at TMS were found, probably connected with the different neurophysiological substrates underlying OSAS and RLS and could not be interpreted as a mere reflection of the effects of sleep architecture alteration. TMS can be considered an additional tool for the understanding of clinical and pathophysiological aspects of sleep disorders, and possibly for the evaluation of the effect of therapy.

Absence of cardiovascular disease risk factors in restless legs syndrome.

Objective –  Restless legs syndrome (RLS) might represent a condition at risk of cardiovascular (and cerebrovascular) disease; the role of sleep periodic leg movements, sleep deprivation, and presence of common risk factors for heart disease in these patients remains to be determined. The aim of this study was to evaluate the eventual presence of risk factors for cerebrovascular disease in RLS.

Cyclic alternating pattern in sleep and its relationship to creativity

BACKGROUND/OBJECTIVES Sleep has been shown to enhance creativity, but the reason for this enhancement is not entirely known. There are several different physiologic states associated with sleep. In addition to rapid (REM) and non-rapid eye movement (NREM) sleep, NREM sleep can be broken down into Stages (1-4) that are characterized by the degree of EEG slow-wave activity. In addition, during NREM sleep the cyclic alternating pattern (CAPs) of EEG activity has been described which can also be divided into three subtypes (A1-A3) according to the frequency of the EEG waves. Differences in CAP subtype ratios have been previously linked to cognitive performances. The purpose of this study was to asses the relationship between CAP activity during sleep and creativity. METHODS The participants were eight healthy young adults (four women) who underwent three consecutive nights of polysomnographic recording and took the Abbreviated Torrance Test for Adults (ATTA) on the second and third mornings after the recordings. RESULTS There were positive correlations between Stage 1 of NREM sleep and some measures of creativity such as fluency (R=.797; p=.029) and flexibility (R=.43; p=.002), between Stage 4 of NREM sleep and originality (R=.779; p=.034) and a global measure of figural creativity (R=.758; p=.040). There was also a negative correlation between REM sleep and originality (R=-.827; p=.042). During NREM sleep the CAP rate, which in young people reflects primarily the A1 subtype, also correlated with originality (R=.765; p=.038). CONCLUSIONS NREM sleep is associated with low levels of cortical arousal, and low cortical arousal may enhance the ability of people to access to the remote associations that are critical for creative innovations. In addition, A1 CAP subtypes reflect frontal activity, and the frontal lobes are important for divergent thinking, also a critical aspect of creativity.

Impact of acute administration of sodium oxybate on nocturnal sleep polysomnography and on multiple sleep latency test in narcolepsy with cataplexy

OBJECTIVE To analyze the acute effects of sodium oxybate (SO) on polysomnographic night-time recordings (PSG) and multiple sleep latency test (MSLT) on patients with narcolepsy with cataplexy (NC). METHODS Sixteen NC adult patients were recruited, together with 16 normal controls. Two consecutive PSG followed by two MSLT sessions were carried out, before and during the first night of SO assumption, respectively. RESULTS The administration of SO was followed by a significant decrease in number of stage shifts and awakenings, wakefulness after sleep onset, and percentage of sleep stage 1. Sleep efficiency and slow wave sleep percentage increased. REM latency decreased significantly from 73 to 12 min. Cyclic alternating pattern (CAP) rate remained unchanged but the percentage of CAP A3 subtypes decreased. The number of CAP A3 subtypes per hour of NREM sleep decreased significantly, whereas that of A1 remained unchanged. The duration of A1 and A3 subtypes was slightly increased. Chin muscle tone was not modified by SO as well as periodic leg movements during sleep, but their periodicity index decreased, becoming similar to that of controls. MSLT sleep latency also significantly improved after SO intake. CONCLUSIONS The administration of SO in NC patients is followed by immediate important and complex effects on PSG parameters and MSLT, including an evident (over)increase in slow wave sleep, which does not display a physiological microstructure, a moderate decrease in periodic and isolated LMs, possibly mediated by a disinhibited dopaminergic neuronal activity, and an improvement on daytime mean sleep latency at the MSLT.

Silent Cerebral Small Vessel Disease in Restless Legs Syndrome.

STUDY OBJECTIVES Growing literature suggests that patients with restless legs syndrome (RLS) may be at increased risk for hypertension, heart disease, and stroke. Cerebral small vessel disease (SVD) is a known risk factor for clinical stroke. This study evaluated silent cerebral SVD by MRI in patients with RLS, in the absence of a history of previous clinical stroke or known stroke risk factors and taking into account disease duration. METHODS Fifty-three patients with RLS < 10 y were prospectively recruited along with 44 with RLS > 10 y and 74 normal controls. A magnetic resonance imaging study was obtained from all subjects and scans were analyzed for area and volume of SVD. RESULTS There was a significant increase in SVD area in the entire group of RLS patients compared to controls (P = 0.036); this was almost entirely driven by the group with RLS > 10 y. SVD area and volume were significantly increased in patients with RLS > 10 y with respect to both controls (P < 0.0001 and P < 0.0014, respectively) and RLS < 10 y (P < 0.00022 and P < 0.003, respectively). Age, duration of RLS, and the interaction of age and duration of RLS were independent predictors of SVD disease. Duration of RLS was an independent predictor of the burden of cerebral SVD (area P < 0.00012 and volume P < 0.0025), whereas sex and insomnia were not. CONCLUSION RLS duration should be taken into account when analyzing the association between RLS and cerebrovascular disease; our data support the hypothesis that a long-lasting RLS and its accompanying periodic limb movements in sleep are a risk factor for silent SVD and perhaps for the development of clinical stroke.