Italian Association of Sleep Medicine (AIMS) position statement and guideline on the treatment of menopausal sleep disorders.

Insomnia, vasomotor symptoms (VMS) and depression often co-occur after the menopause, with consequent health problems and reductions in quality of life. The aim of this position statement is to provide evidence-based advice on the management of postmenopausal sleep disorders derived from a systematic review of the literature. The latter yielded results on VMS, insomnia, circadian rhythm disorders, obstructive sleep apnea (OSA) and restless leg syndrome (RLS). Overall, the studies show that menopausal hormone therapy (MHT) improves VMS, insomnia, and mood. Several antidepressants can improve insomnia, either on their own or in association with MHT; these include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. Long-term benefits for postmenopausal insomnia may also be achieved with non-drug strategies such as cognitive behavioral therapy (CBT) and aerobic exercise. Continuous positive airway pressure (CPAP) and mandibular advancement devices (MADs) both reduce blood pressure and cortisol levels in postmenopausal women suffering from OSA. However, the data regarding MHT on postmenopausal restless legs syndrome are conflicting.

Site and type of craniopharyngiomas impact differently on 24-hour circadian rhythms and surgical outcome. A neurophysiological evaluation.

This study aimed to quantify 24h body core temperature (BcT°) and sleep-wake cycle rhythm alterations in craniopharyngioma (CP) patients and to identify markers related to the postsurgical outcomes. Ten consecutive CP patients underwent neuroradiological, endocrinological and ophthalmological evaluations, 24h BcT° and sleep-wake cycle recordings before and after endoscopic endonasal surgery. The sample included four women and six men. Nocturnal sleep efficiency was pathologically reduced in eight patients before surgery. Seven out of ten patients presented one to three daytime naps. 24h BcT° rhythm was pathological in six out of ten cases. Post-surgery sleep efficiency normalized in four out of eight patients, whereas nine out of ten patients presented with two to six longer daytime naps. Diurnal naps were mainly present in patients showing pre-operative involvement of the third ventricle floor. 24h BcT° remained pathological in only one out of six cases, returned to normal in two and improved in three. 24h BcT° rhythm improved more in papillary CPs than in adamantomatous CPs. Our data confirmed that both CP and surgery frequently disrupt the sleep-wake cycle and BcT° rhythms. Tumour location and histotype may be related to a worse postsurgical outcome. Therefore, in-depth investigation including circadian monitoring is crucial for surgical outcome.

Association between restless legs syndrome and hypertension: a preliminary population-based study in South Tyrol, Italy.

BACKGROUND AND PURPOSE: Restless legs syndrome (RLS) is a sleep-related movement disorder characterized by an irresistible urge to move the legs accompanied by paresthesia and/or dysesthesia that begins or worsens in the evening and night and that is partially or totally relieved by movement. Many studies have investigated the association between RLS and cardiovascular risk factors, particularly hypertension, leading to conflicting results. The aim of this study was to assess the association between RLS and hypertension considering also other cardiovascular risk factors that could act as confounders. METHODS: In all, 1709 participants of an on-going adult population-based study performed in South Tyrol, northern Italy, were enrolled. RLS was assessed through face-to-face interviews according to current International Restless Legs Syndrome Study Group diagnostic criteria. The presence of hypertension was self-reported and determined by questionnaires administered by trained study nurses. RESULTS: The association between RLS and hypertension was not significant after adjustment for age, sex, diabetes mellitus, history of myocardial infarction, raised blood lipids and body mass index (odds ratio 1.24, 95% CI 0.85-1.80, P = 0.271). CONCLUSION: Despite the small sample size of this study, RLS and hypertension were not associated in our adult population after adjustment for possible confounding factors. The presence of other cardiovascular risk factors could play a role as a confounder of this association.

Combined brain voxel-based morphometry and diffusion tensor imaging study in idiopathic restless legs syndrome patients.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate the presence of abnormalities in the brain of patients with restless legs syndrome (RLS) using voxel-based morphometry and diffusion tensor imaging (DTI). METHODS: Twenty patients and twenty controls were studied. Voxel-based morphometry analysis was performed using statistical parametric mapping (SPM8) and FSL-VBM software tools. For voxel-wise analysis of DTI, tract-based spatial statistics (TBSS) and SPM8 were used. RESULTS: Applying an appropriate threshold of probability, no significant results were found either in comparison or in correlation analyses. CONCLUSIONS: Our data argue against clear structural or microstructural abnormalities in the brain of patients with idiopathic RLS, suggesting a prevalent role of functional or metabolic impairment.

Increased prevalence of nocturnal smoking in restless legs syndrome (RLS).

OBJECTIVE: We investigated the prevalence of nocturnal smoking (NS) in patients with RLS. METHODS: One hundred RLS patients living in Emilia-Romagna (Northern Italy) and 100 matched controls, randomly selected from the general population, underwent interviews for the presence of nocturnal smoking and for obsessive-compulsive traits, depression, excessive daytime sleepiness (EDS) and subjective sleep quality. RESULTS: NS was more prevalent in RLS patients than controls (lifetime prevalence: 12% vs. 2%, P=0.012). Patients with NS had more frequently Sleep-Related Eating Disorders (SRED) than patients without NS (83.3% vs. 26.1%, P=0.0002). Pathological and borderline Maudsley Obsessive-Compulsive Inventory (MOCI) values as well as pathological values at the Beck Depression Inventory (BDI) increased from controls to RLS patients without NS to RLS patients with NS (P=0.005 and P=0.01, respectively). CONCLUSIONS: We demonstrate an increased prevalence of NS in patients with RLS, in many cases associated with increased SRED. NS may be associated with psychopathological traits in RLS and may be relevant in the management of RLS patients.

Fatal insomnia and agrypnia excitata: sleep and the limbic system.

Fatal familial insomnia, a human prion disease, Morvan's chorea, an autoimmune limbic encephalopathy, and delirium tremens, the well-known alcohol (or benzodiazepine [BDZ]) withdrawal syndrome, share a clinical phenotype largely consisting in an inability to sleep associated with motor and autonomic activation. Agrypnia excitata is the term which aptly defines this clinical condition, whose pathogenetic mechanism consists in an intralimbic disconnection releasing the hypothalamus and brainstem reticular formation from corticolimbic inhibitory control. Severance of cortical-subcortical limbic structures is due to visceral thalamus degeneration in fatal familial insomnia, and may depend on autoantibodies blocking voltage-gated potassium channels within the limbic system in Morvan's chorea, and the sudden changes in gabaergic synapses down-regulated by chronic alcohol abuse within the limbic system in delirium tremens. On the basis of these findings, we suggest that a neuronal network, extending from the medulla to the limbic cortex, controls the sleep-wake cycle, operating in an integrated fashion following a caudorostral organization.

Sleep-related smoking syndrome.

OBJECTIVE: We describe six patients affected by frequent episodes from sleep associated with compulsive smoking and/or eating. Patients woke up with a desire to smoke and/or eat because of an "inner" drive. METHOD: Video-polysomnography (VPSG) was performed in three patients. RESULTS: VPSG documented a normal sleep structure with an increased arousal index. CONCLUSION: Compulsive eating during sleep has been classified as sleep-related eating syndrome or Nocturnal eating syndrome, but its association with compulsive smoking has not been previously reported.

Catathrenia (nocturnal groaning): an abnormal respiratory pattern during sleep.

Catathrenia (nocturnal groaning) is a rare condition characterized by monotonous irregular groans occurring during sleep. Ten patients (five women; mean age: 27 +/- 7.4 years, range: 15-41) with sleep-related groaning persisting for years or decades and normal daytime fibreoptic laryngoscopy and respiratory function tests underwent videopolysomnographic recording (VPSG) analysing their respiratory patterns during sleep. After the VPSG, all patients were clinically followed up for a mean period of 4.9 +/- 3.5 years. On VPSG, all patients showed nocturnal groaning during NREM sleep and particularly during REM sleep stages. Groaning was associated with disproportionate prolonged expiration causing reduced breathing rate without oxygen desaturation. The breathing pattern with prolonged expiration and sound production alternated with a normal respiratory pattern without groaning. Endoesophageal pressure during groaning showed mildly positive swings at the initial phase of expiration suggesting a partial mild expiratory upper airway obstruction. At the end of the follow-up period, all patients reported persistent nocturnal groaning but no other clinical manifestations. Groaning confined to sleep alternating with normal breathing and the absence of long-term clinical consequences suggest that catathrenia is because of an abnormality of the internal respiratory drive system, possibly related to persistence of a neonatal (vestigial) type of breathing pattern.

Visual and computer-based detection of slow eye movements in overnight and 24-h EOG recordings.

OBJECTIVE: The present work aimed to evaluate the performance of an automatic slow eye movement (SEM) detector in overnight and 24-h electro-oculograms (EOG) including all sleep stages (1, 2, 3, 4, REM) and wakefulness. METHODS: Ten overnight and five 24-h EOG recordings acquired in healthy subjects were inspected by three experts to score SEMs. Computerized EOG analysis to detect SEMs was performed on 30-s epochs using an algorithm based on EOG wavelet transform, recently developed by our group and initially validated by considering only pre-sleep wakefulness, stages 1 and 2. RESULTS: The validation procedure showed the algorithm could identify epochs containing SEM activity (concordance index k=0.62, 80.7% sensitivity, 63% selectivity). In particular, the experts and the algorithm identified SEM epochs mainly in pre-sleep wakefulness, stage 1, stage 2 and REM sleep. In addition, the algorithm yielded consistent indications as to the duration and position of SEM events within the epoch. CONCLUSIONS: The study confirmed SEM activity at physiological sleep onset (pre-sleep wakefulness, stage 1 and stage 2), and also identified SEMs in REM sleep. The algorithm proved reliable even in the stages not used for its training. SIGNIFICANCE: The study may enhance our understanding of SEM meaning and function. The algorithm is a reliable tool for automatic SEM detection, overcoming the inconsistency of manual scoring and reducing the time taken by experts.

Sleep--wake and body core temperature rhythms in multiple sclerosis with fatigue.

OBJECTIVE: To study sleep-wake and body core temperature (BCT) circadian rhythms in patients with multiple sclerosis (MS)-associated with chronic fatigue. METHODS: Six relapsing-remitting MS patients with chronic fatigue underwent 48 consecutive hours polysomnography (PSG) with BCT measurement, followed by a Multiple Sleep Latency Test (MSLT). All patients were relapse- and drug-free. Mood depression, brain and cervical cord enhanced MRI, dynamic spirometry and Fatigue Severity Scale (FSS) were assessed just before PSG. RESULTS: In all patients mood depression was absent and dynamic spirometry normal, but FSS confirmed fatigue. MRI showed non-enhancing lesions. Nocturnal sleep was characterized by normal architecture and mean sleep efficiency was only slightly reduced. Arousal index was normal and periodic limb movements during sleep (PLMS) were present in four patients, with an increased index (PLMS-I) in only two of them. Upon MSLT, mean sleep latency was normal in all patients with one sleep onset REM period in one patient. All patients displayed a normal BCT 24-h rhythm. Mesor, amplitude and acrophase of BCT rhythm did not show significant differences between MS and controls. CONCLUSIONS: We found substantially normal sleep-wake and BCT rhythmicity in six patients with MS and fatigue. Non-restorative sleep and abnormal BCT regulation were unlikely mechanisms of chronic fatigue in our MS patients. SIGNIFICANCE: Subjective fatigue and abnormal sleep and BCT can be independent manifestation in MS patients. The findings support the notion that objective measures of fatigue comparable to the MSLT for sleepiness do not exist.

Sleep-related breathing disorders and headache.

Obtructive sleep apnoea syndrome (OSAS) is a common disorder in the general population with an estimated prevalence in an adult population of 2% in women and 4% in men. Although several studies have suggested that headaches, particularly morning headaches, are more common in patients with OSAS than in normal subjects, others have yielded contradictory findings. When the sleep-related breathing disorder was treated with success, the headache generally disappeared, supporting a causal role of the sleep disorder for headache. Several hypotheses have been proposed to explain the relationship between OSAS and the occurrence of headache, particularly on awakening. Night-time fluctuations of oxygen saturation during the night with hypercapnia, vasodilatation, increased intracranial pressure and impaired sleep quality are all considered contributing factors. However the exact mechanisms of headache pathogenesis and the relationship between OSAS, headache and morning headaches in particular remain controversial.

Propriospinal myoclonus at sleep onset.

AIMS: To describe the clinical and polygraphic features of propriospinal myoclonus (PSM) at sleep onset. MATERIAL AND METHODS: PSM was first described in 1997 in patients with jerks occurring in the relaxation period preceding sleep. EMG showed jerks to arise in spinally innervated muscles, propagating thereafter to rostral and caudal muscles at a low speed, typical of propriospinal pathways. RESULTS: PSM arose when EEG alpha activity spread over the scalp and disappeared during either active wakefulness or actual sleep. In some patients EMG activity could sometimes remain localized to the abdominal muscles, propagating to other segments only in fully developed jerks. Neurological examination, brain and spinal MRI were usually normal and clonazepam afforded partial improvement. PSM has been recently observed also in restless legs syndrome, during relaxed wakefulness preceding falling asleep, coexisting with motor restlessness and sensory discomfort. PSM disappeared when spindles and K-complexes and typical Periodic Limb Movements appeared with EMG activity limited to leg muscles, without propriospinal propagation. CONCLUSIONS: Conceivably, PSM arises in axial muscles due to some spinal generator set into motion by facilitating influences characteristic of the wake-sleep transition and then undergoes multimeric propriospinal propagation. In the International Classification of Sleep Disorders (ICSD-2), PSM is listed in chapter VII, among the "Isolated symptoms, apparently normal variants and unresolved issues".

Sleep and movement disorders.

Polygraphic monitoring of abnormal movements during sleep started in the 1960s in the wake of the interest in sleep and sleep disorders triggered by the discovery of REM sleep. This paper reviews the contribution of the Bologna school to the identification and understanding of motor disorders in sleep.

Sleep-related non-epileptic motor phenomena.

We describe the clinical, neurophysiological and polysomnographic characteristics of some involuntary motor nocturnal events occurring during sleep or at the transition from wakefulness to sleep.

Sleepwalking and other ambulatory behaviours during sleep.

Different pathological conditions may lead to somnambulic automatisms arising from nocturnal sleep. Video polysomnography represents the diagnostic tool but, due to the difficulty of capturing complex episodes in the sleep laboratory, audio-video recordings at home of the episodes may help in the differential diagnosis also. Sleepwalking is a disorder of arousal in which the subject arises from deep sleep, even displaying long complex behaviour, including leaving the bed and walking, with memory impairment of the event. Disordered arousal mechanisms with an inability of the brain to fully awaken from slow-wave sleep are thought to lead to these motor automatisms. REM sleep behaviour disorders begin during REM sleep and are accompanied by features of REM sleep. The motor behaviour may be violent and injurious to the patient and/or bed partner. In some patients, however, the behaviour may be similar to that observed in sleepwalking and some patients have an overlap syndrome. In nocturnal frontal lobe epilepsy in particular, and in complex partial seizures in general, stereotypic and repetitive motor attacks may recur, at any time, on the same night and on different nights, with a continuum between minimal or minor attacks and major or prolonged episodes up to agitated epileptic nocturnal wanderings.

Hyperkinetic manifestations in nocturnal frontal lobe epilepsy. Semeiological features and physiopathological hypothesis.

Nocturnal frontal lobe epilepsy is a syndromic entity that includes paroxysmal episodes with variable semeiology, intensity and duration, representing different aspects of the same epileptic condition. In a large series studied by videopolysomnographic recording at the Department of Neurological Sciences in Bologna, we disclosed four main semeiological patterns: the paroxysmal arousals, brief simple motor phenomena, similar to a sudden arousal, recurring several times per night; the hypermotor seizures, more complex motor episodes with violent motor behaviour, vocalisation, screaming, fearful and repetitive movements of the trunk and limbs; asymmetric, bilateral tonic seizures, which can evoke the seizures from the frontal mesial area; and epileptic nocturnal wanderings, which can mimic sleepwalking episodes.

A pilot double-blind placebo-controlled trial of low-dose pramipexole in sleep-related eating disorder.

Sleep-related eating disorder (SRED) is characterized by recurrent arousals from sleep associated with compulsive ingestion of food. No controlled therapeutic trials are available for SRED. We assessed the safety, tolerability and efficacy of pramipexole, a dopamine D3-receptor agonist, in the treatment of SRED. Eleven consecutive patients with SRED in the absence of concurrent daytime eating disorders underwent actigraphic recording and subjective sleep diary evaluation for a week before and every week for 2 weeks of treatment with pramipexole 0.18-0.36 mg or placebo, administered in a double-blind crossover randomized sequence. The primary outcomes of the trial were actigraphic measures of night sleep parameters (sleep efficiency, motor activity mean and median, number and duration of wake episodes), secondary outcomes were the number of good sleep nights/weekly, number and duration of nocturnal awakenings/night, and visual analogue preference score. Pramipexole was well tolerated without any patient withdrawing from the study. Pramipexole reduced night-time activity median (P = 0.02) and increased the number of nights of good sleep/week (P = 0.02). All other measurements remained unaffected. Pramipexole at low doses was well tolerated, improving some measures of sleep quality and reducing median night activity in SRED. Further studies with higher dosages and for longer time-periods are warranted.

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

The aim of the study was to determine the clinical frequency and features of REM sleep behaviour disorder (RBD) in a large population of Parkinson's 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.