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Davide Sparasci,1 Francesco Fanfulla,2 Raffaele Ferri,3 Debora Aricò,3 Daniela Distefano,4 Emanuele Pravatà ,4 Raphael Heinzer,5 José Haba-Rubio,5 Mathieu Berger,5 Gianna Carla Riccitelli,6– 8 Claudio Gobbi,6,8 Chiara Zecca,6,8,* Mauro Manconi1,8,* 1Sleep Medicine Unit, Neurocenter of Southern Switzerland, Lugano, Switzerland; 2Sleep Medicine Unit, Istituti Clinici Scientifici Maugeri, IRCCS, Scientific Institute of Pavia, Pavia, Italy; 3Sleep Research Centre; Department of Neurology I.C., Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS), Troina, Italy; 4Neuroradiology Clinic, Ospedale Regionale di Lugano, Neurocenter of Southern Switzerland, Lugano, Switzerland; 5Center for Investigation and Research in Sleep (CIRS), Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland; 6Multiple Sclerosis Center, Neurocenter of Southern Switzerland, Lugano, Switzerland; 7Neuropsychology and Behavioural Neurology Research Unit, Neurocenter of Southern Switzerland, Lugano, Switzerland; 8Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland*These authors contributed equally to this workCorrespondence: Raffaele Ferri, Sleep Research Centre; Department of Neurology I.C., Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS), Via Conte Ruggero 73, Troina, 94018, Italy, Email rferri@oasi.en.itBackground: Multiple sclerosis (MS) represents a risk factor for sleep disorders, but there are conflicting results about the prevalence and severity of sleep-related breathing disorders (SRBD) in MS. Most available data come from self-administered questionnaires.Objective: To conduct a polysomnographic study in MS focused on SRBD, compared to a group of healthy controls (HC), also considering the neuroimaging findings. To evaluate the impact of SRBD on vigilance, fatigue and depression in MS.Methods: In this cross-sectional, observational, instrumental study, 67 MS patients (men/women: 20/47; mean age: 50.6± 8.2 years) underwent PSG and maintenance of wakefulness test. Findings were compared to 67 age-, sex-, BMI-matched HC, by using parametric (Student’s t-test) and nonparametric statistics (chi-squared test). A subgroup analysis was then performed, evaluating the influence of brainstem (mesencephalic, pontine and medullary) lesions at neuroimaging on instrumental and clinical data: MS patients with at least one brainstem lesion vs MS patients without vs HC.Results: The frequency of SRBD was comparable in MS patients and HC. No MS patient had a central apnea index ≥ 2/h. The respiratory disturbance index (RDI) did not correlate to clinical parameters such as fatigue and depression. Patients with MS were drowsier than HC (47% vs 26%, p = 0.019) and showed a worse sleep pattern, in terms of duration, efficiency and architecture.Conclusion: Our study does not provide evidence of an association between MS-specific symptoms such as fatigue, sleepiness, depression and central or obstructive apneas, even in the presence of brainstem lesions.Keywords: sleep-related breathing disorders, multiple sclerosis, sleep quality, polysomnography

Background: a reduced intracortical facilitation (ICF), a transcranial magnetic stimulation (TMS) measure largely mediated by glutamatergic neurotransmission, was observed in subjects affected by isolated REM sleep behavior disorder (iRBD). However, direct comparison between iRBD and Parkinson’s disease (PD) with RBD is currently lacking. Methods: resting motor threshold, contralateral cortical silent period, amplitude and latency of motor evoked potentials, short-interval intracortical inhibition, and intracortical facilitation (ICF) were recorded from 15 drug-naïve iRBD patients, 15 drug-naïve PD with RBD patients, and 15 healthy participants from the right First Dorsal Interosseous muscle. REM sleep atonia index (RAI), Mini Mental State Examination (MMSE), Geriatric Depression Scale (GDS), and Epworth Sleepiness Scale (ESS) were assessed. Results: Groups were similar for sex, age, education, and patients for RBD duration and RAI. Neurological examination, MMSE, ESS, and GDS were normal in iRBD patients and controls; ESS scored worse in PD patients, but with no difference between groups at post hoc analysis. Compared to controls, both patient groups exhibited a significantly decreased ICF, without difference between them. Conclusions: iRBD and PD with RBD shared a reduced ICF, thus suggesting the involvement of glutamatergic transmission both in subjects at risk for degeneration and in those with an overt α-synucleinopathy.

Introduction With this study we aimed to: 1) identify subjects with hyperprolactinemia in a clinical sample of patients; 2) compare the neurologic, psychiatric, and sleep conditions found in patients subgrouped by excessive daytime sleepiness (EDS) and hyperprolactinemia; 3) identify patients with hyperprolactinemia and EDS not supported by the presence of any other neurologic, psychiatric, or sleep disorder, or substance/medication use. Methods A retrospective chart review of inpatients was carried out in order to identify all patients in whom the prolactin (PRL) serum levels were determined. A total of 130 subjects were retrieved: 55 had increased levels of PRL while the remaining 75 participants had normal PRL levels. Results EDS was reported by 32 (58.2%) participants with increased PRL and 34 (45.3%) with normal PRL. Obstructive sleep apnea or other sleep or neurologic/psychiatric conditions could explain EDS in all participants with normal PRL. Among subjects with increased PRL, eight had no other neurologic/psychiatric or sleep disorder (or drug) potentially causing EDS; these participants, at polysomnography, had time in bed, sleep period time, and total sleep time longer than those with EDS associated to another condition. Conclusion These findings can be considered as a preliminary indication of a role of hyperprolactinemia in EDS and represent a basis for future controlled studies able to test in a reliable, objective, and methodologically more appropriate way this hypothesis. Support (If Any) This study was partially supported by a fund from the Italian Ministry of Health “Ricerca Corrente” (RC n. 2764026) (Drs. Cosentino, Aricò, Lanuzza, Lanza, Tripodi, and Ferri)

The objectives of this study were: (1) to identify subjects with hyperprolactinemia in a clinical sample of patients; (2) to compare the neurologic, psychiatric, and sleep conditions found in patients subgrouped by excessive daytime sleepiness (EDS) and hyperprolactinemia; and (3) to identify patients with hyperprolactinemia and EDS not supported by the presence of any other neurologic, psychiatric, or sleep disorder, or substance/medication use. A retrospective chart review of inpatients was carried out in order to identify all patients in whom the prolactin (PRL) serum levels were determined. A total of 130 subjects were retrieved: 55 had increased levels of PRL, while the remaining 75 participants had normal PRL levels. EDS was reported by 32 (58.2%) participants with increased PRL and 34 (45.3%) with normal PRL. Obstructive sleep apnea or other sleep or neurologic/psychiatric conditions could explain EDS in all participants with normal PRL. Among subjects with increased PRL, eight had no other neurologic/psychiatric or sleep disorder (or drug) potentially causing EDS; these participants, at polysomnography, had time in bed, sleep period time, and total sleep time longer than those with EDS associated to another condition. These findings can be considered as a preliminary indication of a role of hyperprolactinemia in EDS and represent a basis for future controlled studies able to test this hypothesis in a reliable, objective, and methodologically more appropriate way.

Study Objectives Previous studies found an early impairment of the short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) to transcranial magnetic stimulation (TMS) in Parkinson’s disease. However, very little is known on the TMS correlates of rapid eye movement (REM) sleep behavior disorder (RBD), which can precede the onset of a α-synucleinopathy. Methods The following TMS measures were obtained from 14 de novo patients with isolated RBD and 14 age-matched healthy controls: resting motor threshold, cortical silent period, latency and amplitude of the motor evoked potentials, SICI, and ICF. A cognitive screening and a quantification of subjective sleepiness (Epworth Sleepiness Scale [ESS]) and depressive symptoms were also performed. Results Neurological examination, global cognitive functioning, and mood status were normal in all participants. ESS score was higher in patients, although not suggestive of diurnal sleepiness. Compared to controls, patients exhibited a significant decrease of ICF (median 0.8, range 0.5–1.4 vs. 1.9, range 1.4–2.3; p < 0.01) and a clear trend, though not significant, towards a reduction of SICI (median 0.55, range 0.1–1.4 vs. 0.25, range 0.1–0.3), with a large effect size (Cohen’s d: −0.848). REM Sleep Atonia Index significantly correlated with SICI. Conclusions In still asymptomatic patients for a parkinsonian syndrome or neurodegenerative disorder, changes of ICF and, to a lesser extent, SICI (which are largely mediated by glutamatergic and GABAergic transmission, respectively) might precede the onset of a future neurodegeneration. SICI was correlated with the muscle tone alteration, possibly supporting the proposed RBD model of retrograde influence on the cortex from the brainstem.

Objective The aim of this study was to quantitatively analyze, with the most recent and advanced tools, the presence of periodic leg movements during sleep (PLMS) and/or rapid eye movement (REM) sleep without atonia (RSWA), in a group of patients with amyotrophic lateral sclerosis (ALS), and to assess their eventual correlation with the clinical severity of the disease. Methods Twenty-nine ALS patients were enrolled (mean age 63.6 years) along with 28 age-matched "normal" controls (mean age 63.8 years). Functional impairment due to ALS was evaluated using the ALS-Functional Rating Scale-Revised (ALS-FRS) and the ALS severity scale (ALSSS). Full video polysomnographic night recordings were obtained, and PLMS were analyzed by considering their number/hour of sleep and periodicity index, the distribution of intermovement intervals, and the distribution during the night. The characteristics of the chin electromyogram (EMG) amplitude during REM sleep were analyzed by means of the automatic atonia index and the number of chin EMG activations (movements). Results The ALS patients showed longer sleep latency than the controls, together with an increase in number of stage shifts, increased sleep stage 1, and decreased sleep stage 2. None of the leg PLMS parameters were different between the ALS patients and controls. The REM atonia index was significantly decreased in the ALS patients, and the number of chin movements/hour tended to increase. Both REM atonia index and number of chin movements/hour correlated significantly with the ALS-FRS; REM atonia was higher and chin movements were less in ALS patients with more preserved function (higher scores on the ALS-FRS). Conclusion Abnormal REM sleep atonia seemed to be a genuine effect of ALS pathology per se and correlated with the clinical severity of the disease. It is unclear if this might constitute the basis of a possible risk for the development of REM sleep behavior disorder or represent a form of isolated RSWA in ALS.

Study Objectives To assess the presence of increased REM-related motor activity during sleep, by questionnaires for REM sleep behavior disorder (RBD), in participants with "isolated" REM sleep without atonia (RWA). Participants and Methods Two hundred forty-nine patients were consecutively enrolled, with age ≥18 years, sharing bedroom with a roommate, and without a severe health, neurological, or cognitive problem. Motor activity during sleep was assessed by means of the RBD Screening Questionnaire (RBDSQ) and the RBD questionnaire-Hong Kong (RBDQ-HK). A video-polysomnographic recording was obtained and the REM Atonia Index was computed. Thirteen participants were diagnosed to have RBD while the remaining 236 were subdivided into two subgroups: 34 participants with "low" (

Background: Based on the hyperexcitability and disinhibition observed in patients with restless legs syndrome (RLS) following transcranial magnetic stimulation (TMS), we conducted a study with low-frequency repetitive TMS (rTMS) over the primary motor (M1) and somatosensory cortical areas (S1) in patients with RLS. Methods: A total of 13 right-handed patients and 10 age-matched controls were studied using clinical scales and TMS. Measurements included resting motor threshold (rMT), motor-evoked potentials (MEPs), cortical silent period (CSP), and central motor conduction time (CMCT). A single evening session of rTMS (1 Hz, 20 trains, 50 stimuli each) was administered over the left M1, left S1, and sham stimulation over M1 in a random order. Clinical and TMS measures were repeated after each stimulation modality. Results: Baseline CSP was shorter in patients than in controls and remained shorter in patients for both motor and somatosensory stimulation. The patients reported a subjective improvement of both initiating and maintaining sleep the night after the rTMS over S1. Patients exhibited a decrease in rMT after rTMS of S1 only, although the effect was smaller than in controls. MEP latency and CMCT changed only in controls after stimulation. Sham stimulation was without effect on the observed variables. Conclusions: rTMS on S1-M1 connectivity alleviated the sensory–motor complaints of RLS patients. The TMS indexes of excitation and inhibition indicate an intracortical and corticospinal imbalance, mainly involving gamma-aminobutyric acid (GABA)ergic and glutamatergic circuitries, as well as an impairment of the short-term mechanisms of cortical plasticity. The rTMS-induced activation of the dorsal striatum with the consequent increase of dopamine release may have contributed to the clinical and neurophysiological outcome.

Study objectives To define statistically the upper limit of the intermovement interval (IMI, the time interval between the onset of consecutive movements) of periodic leg movements during sleep (PLMS). Methods We computed the IMI distribution of a large sample (n = 141) of patients with restless legs syndrome (RLS) and analyzed it with two independent approaches, based on fitting either empirical functions or normal and exponential functions to the data. Results The two fitting approaches consistently pointed to an upper limit of the PLMS IMI in the range between 50 and 60 s. Decreasing the upper limit of PLMS IMI from 90 to 60 s evidently decreased the PLMS index in patients with RLS and control participants; nevertheless, the PLMS index remained significantly higher in RLS vs. control participants. Shifting the upper limit of PLMS IMI to 60 s did not significantly modify the effectiveness of discrimination of PLMS between controls and patients with RLS. Conclusion These results seem to indicate that a conservative, yet data-driven upper limit for IMI contributing to the PLMS in patients with RLS might be 60 s instead of 90 s, as recommended by the present guidelines.

Background Previous studies showed an impairment of the LTP-like plasticity to TMS in restless legs syndrome (RLS). Clinically, repetitive TMS (rTMS) was effective in alleviating the sensory-motor complaints of patients, although the effects induced by low-frequency (inhibitory) rTMS have not yet been investigated. An impaired LTD-like mechanism of cortical plasticity has been hypothesized, which we have directly assessed in this pilot study. Methods Motor evoked potentials (MEPs) from the right first dorsal interosseus muscle were recorded at the stimulus intensity of 110% of the resting motor threshold (rMT) from 13 right-handed patients and ten age-matched right-handed healthy controls. Median peak-to-peak amplitudes were calculated in all participants at baseline (T 0 ), after the first train of a single evening session of low-frequency (1 Hz) rTMS over the left primary motor cortex (T 1 ), and after the whole rTMS procedure (T 2 ), which consists of 20 trains with 50 stimuli per train and intertrain interval of 30 s (1000 stimuli in total). Results No differences were found for rMT and MEPs size between the two groups at T 0 . Smaller MEPs amplitudes at both T 1 and T 2 were observed in all subjects, although this was significantly more pronounced in controls than in patients. Conclusions Compared to normal individuals, patients exhibited an impairment of the LTD-like mechanisms induced by inhibitory rTMS, thus adding support to the involvement of GABA in RLS pathophysiology. Although future studies with a larger population are needed, TMS is confirmed to be effective in noninvasive probing of the neurophysiology and neurochemistry of RLS.

Study objectives To evaluate leg movement activity during sleep (LMS) in normal school-age children and adolescents, to eventually establish age-specific periodic LMS (PLMS) index thresholds that support the diagnosis of restless legs syndrome (RLS), and to evaluate the utility of other LMS indices. Methods Polysomnographic recordings from 61 controls, 46 children with RLS, and 44 children with narcolepsy type 1 (NT1) were analyzed for total leg movements (LMS), PLMS, and isolated leg movements (ISOLMS) duration and indices, separately for school-age children and adolescents. Moreover, intermovement interval (IMI) graphs and time-of-night distribution of LMS were analyzed, and cut-off thresholds for PLMS index and total LMS index were assessed for the separation of RLS from controls. Results All indices tended to decrease from school-age children to adolescents in normal controls and in NT1, whereas in RLS, only PLMS index increased. All school-age children had a similar IMI distribution with a single peak at IMI 2-4 s followed by gradual decline. In adolescents with RLS, a second peak at IMI 10-50 s was seen. Time-of-night distribution of most indices decreased in RLS, whereas most tended to increase in NT1. A PLMS index cutoff of 2 per hour best differentiated RLS from controls in school-age children (accuracy 70.0%) and in adolescents (accuracy 70.8%); however, most participants with NT1 also showed PLMS indices higher than this threshold. Conclusions PLMS index alone does not reliably predict the diagnosis of RLS in children and adolescents. However, analyses of IMI distribution and time-of-night distribution provide additional elements to support a diagnosis of RLS.

Objective To evaluate an alternative index for periodic leg movements during sleep (PLMS) and wakefulness (PLMW) expected to be similar to the standard index when leg movement activity is genuinely periodic, but significantly lower when periodicity is low. Subjects and methods One-hundred-and-seven subjects with restless legs syndrome (RLS) were retrospectively identified and included (47 males, 60 females, mean age 56.9 years), along with 63 controls (33 males, 30 females, 42.2 years). Night-to-night variability was analysed in a subgroup of 17 subjects with RLS. PLMW were evaluated in a subgroup of 66 RLS subjects. Two ‘alternative' PLMS/PLMW indices were calculated: one increased the lower limit of the inter-movement intervals from 5 to 10 s (‘Alt1') and another additionally considered only series not interrupted by LMs with a short inter-movement interval (‘Alt2'). Results Despite a high correlation between methods, only the Alt2 algorithm provided significantly different results, with PLMS/PLMW indices being consistently lower than those provided by the other two methods. The difference was more evident in the controls and during wakefulness, when periodicity was lower. The difference between the Alt2 and the standard PLMS index showed a significantly negative correlation with the Periodicity Index. Night-to-night variability was similar for all PLMS indices and significantly higher than the variability seen in the Periodicity Index. Conclusion This methodological study introduces an alternative to the standard PLMS/PLMW indices, initiating the validation process for a new way of computing the PLMS/PLMW index, more adherent to the parameters that allows a reliable evaluation of their periodicity.

Objective To evaluate the diagnostic accuracy of the standard periodic leg movement during sleep (PLMS) index, a recently introduced alternative one, and the periodicity index (PI) for restless legs syndrome (RLS). Subjects and methods A total of 107 patients with RLS were retrospectively identified and included (47 males and 60 females, mean age 56.9 years), along with 48 normal controls (24 males and 24 females, mean age 52.0 years). The standard PLMS index, the alternative PLMS index, and the PI were calculated from polysomnographic recordings. In order to establish the best performing threshold for the diagnosis of RLS, sensitivity and specificity were calculated with a series of threshold values ranging from 5 to 20/hour for the two PLMS indices, and from 0.2 to 0.9 for the PI. Results The optimal threshold was found to be between 15 and 16/hour for the standard PLMS index, close to 13/hour for the alternative index, and around 0.5 for the periodicity index. With these thresholds, all methods showed high values of sensitivity and specificity, with corresponding high positive and negative predictive values and accuracy; the receiver operating characteristic (ROC) curve areas were similar, and the Kappa coefficient of agreement indicated a ‘very good’ agreement between the PLMS indices. Conclusions This study assessed the cut-off values of the standard (15–16/hour) and alternative (13/hour) PLMS indices, and of the PI (0.5). The diagnostic accuracy of all indices for RLS vs controls was found to be acceptably high, with the new alternative PLMS index performing slightly higher than the other two indices.

Periodic leg movements during sleep (PLMS) are sequences of ≥4 motor events with intermovement intervals (IMI) of 10–90 s. PLMS are a supportive diagnostic criterion for restless legs syndrome (RLS) and entail cardiac activation, particularly when associated with arousal. RLS patients also over-express short-interval leg movements during sleep (SILMS), which have IMI

Objective The aim of this study was to analyze statistically the number of single leg movements (LMs) forming bilateral LMs during sleep, along with their combined duration, to eventually provide evidence-based data for the adjustment of the current scoring rules defining bilateral LMs. Methods Polysomnographic recordings of 111 untreated patients with RLS with a median age of 56.0 years, along with 42 normal controls with a mean age of 60.0 years, were included. In each recording, we identified all LMs that were considered as bilateral when two or more LMs were overlapping or the onset of the following movement was 4 individual movements, and only 0.16% and 1.90% of bilateral LMs were >15 seconds in RLS patients and healthy controls, respectively. Conclusion Our results strongly suggest that bilateral LMs during sleep should be constituted by no more than four individual LMs and should have a maximum duration of 15 seconds.

Objectives To evaluate the specific time structure of periodic leg movements during sleep (PLMS) in untreated Parkinson disease (PD) patients by means of an advanced analysis; and to evaluate the effects of treatment on this activity, in a cross-sectional comparison and in a prospective follow-up study, in a subgroup of previously untreated patients. Methods Forty-four consecutive PD patients were enrolled in the study; 19 had not yet started any drug therapy for PD (PDnother); 10 out of these patients were re-evaluated after an average time lag of 19.6months from baseline. The remaining 25 patients (PDther) were taking l-dopa and/or dopamine agonists. Eighteen age-matched normal controls were also included. All subjects underwent a polysomnographic recording and the time structure of their sleep leg movement activity was analyzed by means of the periodicity index and other advanced measures. Results Both PD groups tended to show increased PLMS and decreased isolated limb movement activity with respect to controls. PLMS index >15/h was found in 26.3% of PDnother patients, 24.0% of PDther subjects, and in 16.7% of controls; none of the three PDnother patients who had PLMS index >15/h at baseline sustained this level at follow-up, nor did the other seven patients. The intermovement interval distribution showed a clear peak at 10–40s in the PDnother group; a suppression of this peak was observed after the introduction of dopaminergic treatment in the subgroup of 10 PDnother patients. Both groups of PD patients showed a progressively decreasing number of PLMS through the night; an almost complete abolition of PLMS was seen in the first 2h of sleep after the introduction of dopaminergic drug therapy. Conclusion Our data do not seem to support the hypothesis that PLMS are particularly frequent in PD but seem to indicate an interaction between PD pathophysiology and genetic predisposition for PLMS, producing a slightly increased number of patients with this sleep motor phenomenon when compared to controls.

To evaluate whether eliciting repetitive cortical and autonomic arousals during sleep is able to induce the occurrence of periodic leg movements during sleep (PLMS).Fifteen normal subjects underwent one night of uninterrupted and two sequential nights of experimental sleep fragmentation achieved by auditory and mechanical stimuli eliciting frequent EEG arousals. Sleep was polygraphically recorded and subsequently used to determine the frequency of arousals and occurrence of leg movement (LM) activity during the first (baseline) and the second fragmentation night. Also, heart rate variability parameters were obtained to assess the autonomic changes induced by the stimulation.Sleep fragmentation was associated with an increase in the arousal index, percentage of sleep stage 1, and frequency of stage shifts. In addition, there was a decrease in sleep latency and in percentage of slow-wave sleep. Moreover, a significant increase in heart rate variability and especially of its sympathetic component, was also found. In contrast, parameters of the leg movement activity showed no significant change following experimental sleep fragmentation. The lack of an increase in leg movement activity was also observed in one subject who demonstrated PLMS at baseline.Experimental sleep fragmentation is not associated with an increase in PLMS in normal young adults.

The aim of this study was to define the time structure of leg movements during sleep occurring with an intermovement interval (onset-to-onset) shorter than 10 s in patients with restless legs syndrome and controls, and to compare it to the structure of movements with intervals of 10-90 s or >90 s. Polysomnographic recordings of 141 untreated patients and 68 age-matched normal controls were analysed. All movements were detected and classified into three categories, separated by intervals of 90 s. The number of movements included in each category was significantly higher in patients than in controls. The movements with an interval of >90 s occurred steadily during the night, whereas the hourly distribution of movements with intervals of 90 s. The time structure features of the three categories of movements considered in this study were found to be clearly different. This, together with previous observations on the differential effects of dopamine agonists on movements with different intervals, suggests that movements with intervals of 90 s are regulated by neurotransmitter mechanisms different from those modulating movements with an interval of 10-90 s.

Background: Insomnia is a common sleep disorder in patients with breast cancer and studies show a higher frequency than in the general population but it appears to be understudied and the treatment seems to be a neglected problem. There is a growing body of evidence about the efficacy of cognitive behavioral therapy for insomnia (CBT-I) in breast cancer survivors. The aim of this review is to examine the best available scientific evidence related to CBT-I and insomnia in patients with breast cancer and to assess the effect of CBT-I on their psychosocial functioning, sleep, quality of life, and mood. Methods: Empirical articles published in peer-reviewed journals from the earliest reports available until August 2015 were considered. The research on PubMed generated 18 papers, three of which did not meet the inclusion criteria. Another paper was retrieved by screening the reference list of the previously selected papers. Results: A total of 16 studies were found that evaluated the effects of CBT-I in breast cancer patients. CBT-I appears to be an effective therapy for insomnia in breast cancer survivors, improving mood, general and physical fatigue and global and cognitive dimensions of quality of life. CBT-I may also reduce menopausal symptoms, such as hot flushes and night sweat problems, frequency of medicated nights, level of depression, and anxiety. Conclusions: CBT-I seems to be an eligible intervention for improving sleep in breast cancer survivors. Improvements concerning insomnia and sleep quality are durable (usually up to 12 months) and statistically significant.

Study objectives The aim of this study was to describe and analyze the association between bilateral leg movements (LMs) during sleep in subjects with restless legs syndrome (RLS), in order to eventually support or challenge the current scoring rules defining bilateral LMs. Methods Polysomnographic recordings of 100 untreated patients with RLS (57 women and 43 males, mean age 57 y) were included. In each recording, we selected as reference all LMs that occurred during sleep and that were separated from another ipsilateral LM by at least 10 sec of EMG inactivity. For each reference LM and an evaluation interval from 5 sec before the onset to 5 sec after the offset of the reference LM, we evaluated (1) the presence or absence of contralateral leg movement activity and (2) the distribution of the onset-to-onset and (3) the offset-to-onset differences between bilateral LMs. Results We selected a mean of 368 (± 222 standard deviation [SD]) reference LMs per subject. For 42% (± 22%) of the reference LMs no contralateral leg movement activity was observed within the evaluation interval. In 55% (± 22%) exactly one and in 3% (± 2%) more than one contralateral LM was observed. A further evaluation of events where exactly one contralateral LM was observed showed that in most (1) the two LMs were overlapping (93% ± 9% SD) and (2) were classified as bilateral according to the World Association of Sleep Medicine and the International Restless Legs Syndrome Study Group (WASM/ IRLSSG) (96% ± 6% SD) and (3) the American Academy of Sleep Medicine scoring rules (99% ± 2% SD). Although there was a systematic and statistically significant difference in standard LM indices during sleep based on the two different definitions of bilateral LMs, the size of the difference was not clinically meaningful (maximum individual, absolute difference in LM indices ± 2.5). In addition, we found that the duration of LMs within bilateral LM pairs was longer compared to monolateral LMs and that the duration of the single LMs in bilateral LM pairs tended to correlate. Conclusions The results of this study indicate that the two current standard scoring rules for the definition of bilateral LMs during sleep provide largely corresponding classifications in subjects with RLS and, in a clinical context, can be considered to be equivalent.

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 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.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.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.

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. Materials &Methods – Eighty-seven consecutive patients affected by idiopathic RLS were included in this study together with 81 controls. Blood count, chemistry, and kidney function tests were obtained. We detected subjects suffering from diabetes mellitus, kidney diseases, heart diseases, disk herniation, neuropathy, blood diseases, liver diseases, artery diseases, dyslipidemia, or hypertension. Polysomnography was recorded in 66 patients, and cerebral neuroimaging was obtained in 59 patients with RLS. Results – None of the differences in blood test parameters was statistically significant; however, hypertension was found to be more frequent in controls and dyslipidemia was more frequent in patients with RLS, but this was explained by its higher frequency in patients also affected by obstructive sleep apnea. A diagnosis of cerebrovascular disease was posed for 14 patients with RLS (16.1%), but no predictive factor for its presence was found at the binomial logistic regression. Conclusion – Our findings argue against the presence of an altered lipid metabolism as a risk factor for the development of cerebrovascular disease in patients with RLS, even if they do support the idea that cerebrovascular disease might be frequent in this condition.

RESTLESS LEGS SYNDROME (RLS) IS OFTEN ASSOCIATED WITH INSOMNIA, IN TERMS OF DIFFICULTY IN FALLING ASLEEP, SLEEP MAINTENANCE, AND SLEEP duration.1 Thus, sleep disruption mainly comes from the subjective report of patients and from the clinical experience of physicians. The severity of RLS-related insomnia ranges widely, from patients who seek treatment only for insomnia and underestimate their sensory symptoms to those who have no sleep complaints at all because the sensory symptoms are mild, rare, or occur prior to bedtime. Thus, insomnia is not considered necessary for or supportive of the diagnosis of RLS.1 Only a few studies have focused on the objective polysomnographic features of RLS; they have found an increase in sleep latency and a decrease in sleep efficiency only in patients with the most severe RLS symptoms.2–6 Except for the generic amount of arousals, no extensive data are available on sleep microstructure in RLS, as compared with age-matched normal control subjects. A very recent study demonstrated that sleep microstructure analysis by means of the cyclic alternating pattern (CAP)7 is helpful in understanding the mechanisms of subjective sleep perception (and misperception) in insomniacs.8 In addition, emerging evidence is available on a possible role for CAP in sleep-related cognitive processing, and sleep loss is thought to be an important factor affecting cognitive performance of patients with RLS. Periodic leg movements during sleep (PLMS) represent a very frequent objective finding in RLS, the contribution of PLMS to sleep disruption and sleep quality is an ongoing discussion.9,10 Dopamine-receptor agonists are remarkably effective and well-tolerated agents for the treatment of RLS; low evening doses of the D3-agonists pramipexole and ropinirole have become the first-line treatment for RLS.11,12 Controlled studies that include polysomnography recordings have provided evidence that ropinirole and pramipexole are effective in reducing both subjective symptoms of RLS and PLMS, even after a first single administration, in patients with RLS. On the contrary, the effects on sleep architecture have been reported in only a few studies, which failed to find extensive modifications of objective polysomnography-derived measures, other than PLMS.2–6 Even with successful treatment of the sensory symptoms of RLS, sleep problems may persist.13,14 Response to dopaminergic medications, together with positive family history and presence of PLMS, is considered to be an important supportive criterion for the diagnosis of RLS.1 The placebo effect in RLS treatment is a major issue that can impair the clinical judgment. The primary outcome measure in most studies, the International Restless Legs Syndrome Rating Scale, has been shown to yield a large placebo effect.15 In brief, the placebo effect seems to be large for subjective parameters but much smaller for objective parameters derived from polysomnography. To our knowledge, there are no studies on CAP in RLS and on the therapeutic effect of dopamine agonists on CAP in these patients. For all of these reasons, the aim of the present investigation was to analyze, in detail, the eventual baseline differences in CAP between normal control subjects and patients with RLS and the eventual changes in sleep architecture and instability induced by the acute administration of pramipexole in patients with RLS.

Patients with Alzheimer's disease (AD) might have bilateral attentional disorders, such as a reduced spatial attentional window, due to pathological changes in regions important for mediating spatial attention. AD patients may also be highly distractible with the presentation of unilateral novel stimuli or be impaired at disengaging and reallocating their attention with imperative stimuli. This study sought to test these hypotheses by asking AD patients and normal control subjects to bisect 72 horizontal lines of 3 different lengths in three conditions: no lateral stimuli, novel right or left lateral stimuli ('bottom-up'), and imperative left or right lateral stimuli ('top-down'). Regarding the bottom-up condition, no group differences emerged, but the AD patients had a greater rightward bias with short lines and a leftward bias with long lines, independent of distracting stimuli. In the top-down condition, when the patients with AD, versus controls, were presented with imperative stimuli on their left side, they demonstrated a greater attentional bias than when presented with right-sided stimuli. Thus AD patients have a reduced spatial attentional window and while they are not highly distracted by novel stimuli, after allocating their attention to left sided stimuli, they have a reduced capacity to spatially re-allocate their attention.

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 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.

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.

We report a patient affected by restless legs syndrome as the presenting symptom of multiple myeloma, a hematologic malignancy characterized by clonal proliferation of plasma cells in the bone marrow and monoclonal immunoglobulin in the blood and/or urine.

In Parkinson's disease (PD) patients, REM sleep behavior disorder (RBD) might precede PD or develop with or after the onset of PD. No previous study has explored differences between these two groups. The aim of this study was therefore to compare clinical features and REM sleep chin electromyographic patterns between patients in whom RBD heralded PD and those in whom RBD occurrence coincided with or followed the clinical manifestations of PD.Twenty-seven consecutive PD patients (mean age 67.9 years) were enrolled. Detailed clinical, laboratory, and polysomnographic studies were obtained in all participants.Sixteen of the 27 patients were affected by RBD. These had a significantly higher stage of PD and took significantly higher doses of dopaminergic therapy; their disease duration tended to be longer, and their cognitive status tended to be lower. PD patients in whom RBD preceded PD (n = 6) did not differ from PD patients without RBD in disease parameters, while PD patients in whom RBD developed with or after PD (n = 10) showed a significantly higher disease stage, took significantly higher dopaminergic therapy, and had a longer disease duration.Our findings are compatible with the hypothesis that patients in whom RBD precedes, or does not precede, PD might constitute two possibly distinct clinical and physiopathological groups, based on different progressive neuropathological sequences of events.

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.

1389-9457/$ see front matter 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.sleep.2011.08.006 ⇑ Corresponding author. Address: Department of Neurology I.C., Oasi Institute, Via C. Ruggero 73, 94018 Troina, Italy. Tel.: +39 0935 936111; fax: +39 0935 936694. E-mail addresses: rferri@oasi.en.it, raffaele.ferri@ticali.it (R. Ferri). will be enriched by the contributions of our colleagues who wish to offer stimulating opportunities for discussion and new insights into the field of sleep.

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.

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.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.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.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.

Fredrich August von Kekule, a famous German chemist, was attempting to determine the shape of the benzene molecule, which was known to have six carbon atoms. In 1865, reflecting upon his discovery of the hexagonal-ring like structure, he asserted that the solution came to him in a dream1; however, it is not clear if he was in rapid eye movement (REM) sleep dreaming or if he was in non-REM (NREM) sleep imagery. It is possible to think of this type of discoveries as an expression of creativity, i.e. the ability to use existing pieces of information and combine them in novel patterns leading to greater understanding and new solutions. Preliminary support of the role of sleep in creative thinking comes from a recent study by Wagner et al.2; these authors asked normal participants to perform a cognitive task, the Number Reduction Task. In this task, participants are required to understand a set of stimulus-response sequences and supply a single representative numerical answer. Improvement in task performance may be gradual (i.e., by slowly increasing response speed), or abrupt (after insight into an abstract rule underlying all sequences). They found that 59% of the participants that were allowed to sleep were able to perform the task in a time that was 70% shorter than the other group that did not sleep and suggested that sleep may facilitate insight-related problem solving. Here we report the results of the first study showing a direct complex correlation between sleep architecture or microstructure and creativity in normal controls.

Fredrich August von Kekule, a famous German chemist, was attempting to determine the shape of the benzene molecule, which was known to have six carbon atoms. In 1865, reflecting upon his discovery of the hexagonal-ring like structure, he asserted that the solution came to him in a dream1; however, it is not clear if he was in rapid eye movement (REM) sleep dreaming or if he was in non-REM (NREM) sleep imagery. It is possible to think of this type of discoveries as an expression of creativity, i.e. the ability to use existing pieces of information and combine them in novel patterns leading to greater understanding and new solutions. Preliminary support of the role of sleep in creative thinking comes from a recent study by Wagner et al.2; these authors asked normal participants to perform a cognitive task, the Number Reduction Task. In this task, participants are required to understand a set of stimulus-response sequences and supply a single representative numerical answer. Improvement in task performance may be gradual (i.e., by slowly increasing response speed), or abrupt (after insight into an abstract rule underlying all sequences). They found that 59% of the participants that were allowed to sleep were able to perform the task in a time that was 70% shorter than the other group that did not sleep and suggested that sleep may facilitate insight-related problem solving. Here we report the results of the first study showing a direct complex correlation between sleep architecture or microstructure and creativity in normal controls.

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 aim of this study was to assess the presence of sleep breathing disorder and periodic leg movements during sleep (PLMS), and to evaluate NREM sleep instability in a group of children with mental retardation (MR) and epilepsy. Eleven subjects with MR and epilepsy (6 males, age range 9-17 years) were recruited for this study. A control group was formed by 11 age-matched normal children. Three children with MR and epilepsy showed an apnea-hypopnea index > 5, two of them had also a PLMS index > 5. Another subject had only a PLMS index > 5. Children with MR showed many sleep architecture differences compared to controls. They also showed higher cyclic alternating pattern (CAP) rate, increased A1 index, long and less numerous CAP sequences than controls. A detailed investigation and treatment of sleep disorders in children affected by MR and epilepsy may have a positive impact on seizure control.

To analyze in detail the frequency content of the different EEG components of the Cyclic Alternating Pattern (CAP) in the whole sleep of pre-school and school age children compared to normal young adults.Fourteen pre-school age and 18 school age children and 16 adults were included in this study. Each participant underwent a polysomnographic overnight recording, after an adaptation night; sleep stages and CAP were scored following standard criteria. Average spectra were obtained for each CAP condition from the signal recorded from C3/A2 or C4/A1, separately in sleep stage 2 and slow-wave sleep (SWS), for each subject.The analysis of the relative power density in the three groups showed that in sleep stage 2 and in SWS, CAP A1, A2, A3 subtypes had a significantly higher power in all frequency ranges in pre-school children than in adults, while school children differed mainly for the lower frequencies (7 Hz). For non-CAP, pre-school and school children differed from adults at almost all frequencies analyzed. Generally, A1, A2 and A3 showed clear spectral differences in the three different groups of subjects with pre-school age children showing slightly less evident differences.CAP subtypes are characterized by clearly different spectra at different ages and also the same subtype shows a different power spectrum, during sleep stage 2 or SWS. This study shows that pre-school children have a different structure of sleep, especially from the microstructural (CAP) point of view: the differences are evident for all the CAP components and for non-CAP in almost all the frequency bands. This finding might be associated to the age-related delta decline in the 0-3 Hz frequency reported in children of the same age.Our data seem to provide information not available before and useful for the understanding of the impact of CAP on the sleep EEG neurophysiological dynamics at different ages. This type of information is crucial for a more adequate interpretation of data provided by a growing number of studies analyzing CAP in groups of pediatric patients.

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.

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.

Study Objectives: To analyze sleep in children with Asperger syndrome (AS) by means of standard sleep questionnaires, to evaluate sleep architecture and NREM sleep alterations by means of cyclic alternating pattern (CAP) and to correlate objective sleep parameters with cognitive behavioral measures. Design: Cross-sectional study involving validated sleep questionnaires, neuropsychological scales, and PSG recording. Setting: Sleep medicine center. Participants: Eight children with AS, 10 children with autism, and 12 healthy control children. Interventions: N/A Measurements and Results: Children with AS had a higher prevalence of problems of initiating sleep and daytime sleepiness. Sleep architecture parameters showed minor differences between the 3 groups. CAP parameters showed an increased percentage of A1 and a decreased percentage of A2 subtypes in subjects with AS vs. controls. All A subtype indexes (number per hour of NREM sleep) were decreased, mostly in sleep stage 2 but not in SWS. With respect to children with autism, subjects with AS showed increased CAP rate in SWS and A1 percentage. In subjects with AS, verbal IQ had a significant positive correlation with total CAP rate and CAP rate in SWS and with global and SWS A1 index. The percentage of A2 negatively correlated with full scale IQ, verbal and performance IQ. CBCL total score correlated positively with CAP rate and A1 index while externalizing score correlated negatively with A3%. Conclusions: 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.