Chronic agomelatine treatment corrects the abnormalities in the circadian rhythm of motor activity and sleep/wake cycle induced by prenatal restraint stress in adult rats.

Agomelatine is a novel antidepressant acting as an MT1/MT2 melatonin receptor agonist/5-HT2C serotonin receptor antagonist. Because of its peculiar pharmacological profile, this drug caters the potential to correct the abnormalities of circadian rhythms associated with mood disorders, including abnormalities of the sleep/wake cycle. Here, we examined the effect of chronic agomelatine treatment on sleep architecture and circadian rhythms of motor activity using the rat model of prenatal restraint stress (PRS) as a putative 'aetiological' model of depression. PRS was delivered to the mothers during the last 10 d of pregnancy. The adult progeny ('PRS rats') showed a reduced duration of slow wave sleep, an increased duration of rapid eye movement (REM) sleep, an increased number of REM sleep events and an increase in motor activity before the beginning of the dark phase of the light/dark cycle. In addition, adult PRS rats showed an increased expression of the transcript of the primary response gene, c-Fos, in the hippocampus just prior to the beginning of the dark phase. All these changes were reversed by a chronic oral treatment with agomelatine (2000 ppm in the diet). The effect of agomelatine on sleep was largely attenuated by treatment with the MT1/MT2 melatonin receptor antagonist, S22153, which caused PRS-like sleep disturbances on its own. These data provide the first evidence that agomelatine corrects sleep architecture and restores circadian homeostasis in a preclinical model of depression and supports the value of agomelatine as a novel antidepressant that resynchronizes circadian rhythms under pathological conditions.

A study on the efficacy of treatment with mud packs and baths with Sillene mineral water (Chianciano Spa Italy) in patients suffering from knee osteoarthritis.

Mud-bath therapy plays a primary role in the treatment and prevention of osteoarthritis that has been recognised since antiquity. Numerous studies have demonstrated its clinical benefits and its effects on inflammatory mediators (interleukins), the immune system, cenesthesic factors (endorphins), and the diencephalic­pituitary­adrenal axis. This study was conducted to assess the efficacy of mud-bath therapy with mineral water from the Sillene Spring at Italy's Chianciano Spa in patients with osteoarthritis of the knee. Patients (n = 61) were divided into two groups. Group A underwent three cycles of mud-based spa therapy over a year's time, whereas group B did not. Clinical conditions, visual analogue scale pain ratings, and Lequesne indexes of the two groups were compared. We also compared these same parameters in the patients of the two groups that were following the therapy with drugs and in the patients of the group A before and after spa treatment. The percentage of patients with no symptoms or mild symptoms was higher in group A than in group B. Within group A, this percentage was higher after treatment than before spa therapy. Even in the comparison between the patients of the two groups that were following the therapy with drug, the results was that in group A the percentage of patients with no symptoms or mild symptoms was higher than in group B. Statistical analyses based on various tests revealed that almost all these differences were highly significant. No adverse effects were observed in any of the patients in group A. In conclusion, the mud-bath therapy performed at Chianciano Spa with Sillene Spring water remarkably improved the clinical conditions of patients with knee arthritis and significantly reduces the frequency and severity of symptoms and the disability they cause.

Abnormal sexual behavior during sleep.

INTRODUCTION: Automatic, uncontrolled, and unaware sexual behaviors during sleep have occasionally been described. The clinical and polysomnographic features of nocturnal sexual behavior allow it to be considered a distinct parasomnia named "sexsomnia". Recently, abnormal sexual behaviors during sleep have been evaluated in the forensic medical context because violent behaviors can be associated with this parasomnia. AIM: To describe the clinical and polysomnographic findings in three patients who referred to our sleep laboratory for sleep disorders and who reported episodes of sleep-related sexual activation. MAIN OUTCOME MEASURES: We analyzed video-polysomnographic recordings, sleep structure, sleep microstructure, and sleep-related respiratory events. METHODS: The patients were three males aged 42, 32, and 46 years. All had unremarkable medical, neurological, and psychiatric histories. All underwent full-night polysomnography. RESULTS: Each patient presented a distinct sleep disorder: one had severe obstructive sleep apnea syndrome (OSAS), one presented clinical and polysomnographic features of non-rapid eye movement (NREM) sleep parasomnia (somnambulism), and the third presented clinical and polysomnographic features of rapid eye movement behavior disorder. CONCLUSIONS: In our patients, the clinical and polysomnographic findings suggest that abnormal nocturnal sexual behavior can occur in association with distinct sleep disorders, characterized by different pathophysiologic mechanisms and distinctive treatments. Abnormal sexual behaviors during sleep should be investigated with polysomnography in order to define their pathophysiology and to establish appropriate treatments.

Efficacy of Spa Therapy, Mud-Pack Therapy, Balneotherapy, and Mud-Bath Therapy in the Management of Knee Osteoarthritis. A Systematic Review.

BACKGROUND: Osteoarthritis (OA) is the most common musculoskeletal disease in the world. OA is the result of an inflammatory and degenerative process affecting the entire joint. Osteoarthritis, especially involving the knee, has a relevant socioeconomic impact in terms of drugs, hospital admissions, work absences, and temporary or permanent invalidity. Therapy of knee osteoarthritis is based on pharmacological and nonpharmacological measures. METHODS: We conducted a systematic review of the studies published between 2002 and 2017 on spa therapy, mud-pack therapy, balneotherapy, and mud-bath therapy in the treatment of knee osteoarthritis in order to investigate the evidence of the efficacy of such treatment on pain, functional limitation, drug use, and quality of life. Overall, 35 studies were examined among which 12 were selected and included in the review if they are trial comparative. We have been able to illustrate the main results obtained in the individual studies and to elaborate these results in order to allow as much a unitary presentation as possible and hence an overall judgment. RESULTS: Because the studies we reviewed differed markedly from one another in terms of the methods used, we were unable to conduct a quantitative analysis (meta-analysis) of pooled data from the 12 studies. For the purposes of the present review, we reevaluated the results of the different studies using the same statistical method, Student's t-test, which is used to compare the means of two frequency distributions. Among all the studies, the most relevant indexes used to measure effectiveness of spa therapy were improved including VAS, Lequesne, and WOMAC Score. CONCLUSIONS: The mud-pack therapy, balneotherapy, mud-bath therapy, and spa therapy have proved to be effective in the treatment and in the secondary prevention of knee osteoarthritis, by reducing pain, nonsteroidal anti-inflammatory drug consumption, and functional limitation and improving quality of life of affected patients.

Sleep cyclic alternating pattern in normal school-age children.

OBJECTIVES: To evaluate cyclic alternating pattern (CAP) in sleep of school-age children in order to obtain a standardized database for CAP parameters in this age range. METHODS: CAP parameters were quantified in 10 normal healthy subjects (6 males and 4 females, mean age 8.3 years; range 6-10 years). All subjects underwent polysomnography recordings for two consecutive nights in a standard laboratory setting. Sleep data were stored on computer using a 16-channel polysomnography digital system. Sleep macrostructure was visually scored according to the criteria by Rechtschaffen and Kales (Brain Information Service/Brain Research Institute, University of California, Los Angeles, 1968); CAP was visually scored following the criteria by Terzano et al. (Sleep Med 2 (2001) 537). RESULTS: CAP rate showed a progressive increase with the deepness of sleep, with high values during slow wave sleep (SWS). CAP time showed its longest duration during non-REM (NREM) sleep stage 2 (S2), followed by SWS and sleep stage 1 (S1). No differences across NREM sleep stages were found for CAP cycle and phase B mean duration; on the contrary, phase A showed longer duration during SWS than in S1 and S2. Phases A1 were the most numerous (84.45%) followed by A3 (9.14%) and by A2 (6.44%). The distribution of phases A subtypes across NREM stages showed significant differences for the A1 subtypes that occurred more frequently during SWS than in S2 and S1 (and during S2 than in S1). Subtypes A3 were more frequent during S1 than SWS while no differences were found for subtype A2. The analysis of A1 interval distribution showed a log-normal-like distribution with a peak around 25 s for the A1 phases and no clear peak for A2-A3 phases. CONCLUSIONS: The analysis of CAP in school-age children is characterized by an increase of CAP rate during SWS and a high percentage of A1 phases. The distribution of interval between consecutive A1 phases showed a peak around 25 s.

Microstructure of sleep in depressed patients according to the cyclic alternating pattern.

BACKGROUND: The aim of this study was to evaluate the microstructure of the EEG sleep of depressed subjects by cyclic alternating pattern (CAP) analysis. METHODS: 78 patients affected by major depression and 18 control subjects matched for age and sex underwent a full night polysomnographic study. RESULTS: A significant increase in CAP rate (60 versus 35%) was found in the patients group compared to controls while no significant difference was found with the traditional analysis. CONCLUSION: In depressed subjects CAP analysis is able to show a microstructural sleep impairment, which is not evident at the macrostructural level, providing an objective measure of sleep disturbance in those patients.

Clinical researches on the efficacy of spa therapy in fibromyalgia. A systematic review.

BACKGROUND: Fibromyalgia is characterized by chronic widespread pain, tenderness at muscle and tendon insertions point when digital pressure is applied, sleep disorders, chronic fatigue, depressive episodes, anxiety, and other functional somatic syndromes. OBJECTIVE: The aim of this study was to determine whether balneotherapy with mineral waters and mineral-water containing mud is effective in the management of fibromyalgia. METHODS: We conducted a systematic review of the literature regarding spa therapy in the treatment of the fibromyalgia. We searched many databases for articles published between 2000 and 2012 and we selected 7 studies among 65 articles retrieved. A total of 142 patients received balneotherapy and 129 were controls. CONCLUSION: Study data confirms that spa therapy could improve the symptoms of fibromyalgia including pain, depression and minor symptoms.

A human anti-neuronal autoantibody against GABA B receptor induces experimental autoimmune agrypnia.

In the serum and cerebrospinal fluid of a patient with recurrent acute episodes of respiratory crises, autonomic symptoms and total insomnia (agrypnia), we identified a novel anti-neural complement fixing antibody directed against GABA(B) receptor (GABA(B)R). Patient purified IgG recognized a band of approximately 110 kDa on protein extracts of mouse cerebellum, cortex and brainstem and immunolabelled cultured Chinese hamster ovary (CHO) cells, transfected with human GABA(B)R1 and rat GABA(B)R2 receptors. Western blot analysis of transfected CHO homogenates showed the same band using both patient purified IgG and anti-GABA(B)R1 antibody. In order to verify the pathogenic role of these purified antibodies, we injected patient IgG intrathecally into cisterna magna of C57BL/6 mice pre-implanted with EEG electrodes and we observed severe ataxia followed by breathing depression and total suppression of slow wave sleep, as evidenced by EEG recording, in a dose-dependent manner. Immunohistochemistry on brain sections of mice injected with patient IgG showed the simultaneous presence of bound human IgG and C5b-9 deposits on Purkinje cells and cerebellar granular layer. After incubation with anti-GABA(B)R antibody, a marked reduction of receptor immunostaining was found with relative sparing of neuronal architecture. In conclusion we recognized an anti-neuronal autoantibody directed against GABA(B)R that is associated with autoimmune agrypnia and we showed that our patient purified IgG was able to induce in mice experimental autoimmune agrypnia characterized by a complex neurological syndrome affecting several CNS functions.

Rhythmic tongue movements during sleep: a peculiar parasomnia in Costello syndrome.

We describe a peculiar parasomnia observed in four Costello infants, characterized by periodic rhythmic movements of the tongue. Ten Costello patients (4 male; age range 9 months to 29 years) underwent 1 full-night laboratory-based video polysomnography. The four youngest patients (2 male and 2 female; age range 9-31 months) presented during sleep repeated stereotyped movements of the tongue, producing a sucking-like or licking-like movement, mostly during non-rapid eye movement (NREM) sleep. Rhythmic tongue movements in Costello syndrome show the features of an NREM sleep parasomnia. Tongue movements during sleep probably originate from brainstem structures and could be facilitated by an impaired control of the oropharyngeal and tongue muscles.

Obstructive sleep apnea in Costello syndrome.

Costello syndrome (CS) was initially described by Costello in 1971; it is caused by a germline mutation in HRAS proto-oncogene. The aim of the present study was to evaluate the respiratory activity during sleep in a group of subjects with CS. We studied 10 consecutive patients, 4 males and 6 females, aged 3-29 years, affected by CS. All patients underwent clinical, neurological, otholaryngologic and radiologic evaluation, and a full-night polysomnography in the sleep laboratory. Polysomnography showed that seven patients presented a relevant number of respiratory events of obstructive type during sleep. The apnea-hypopnea index (AHI) ranged from 0 to 19.2 events per hour (mean index = 7.5 +/- 6.9 events/hr). In one patient AHI was not evaluable because of tracheostomy. Apnea induced mild or moderate hemoglobin desaturations (mean of lowest SpO2 values = 85.4 +/- 5.5%). Only sporadic respiratory pauses of central type were observed (mean number of central apnea per study: 7.2 +/- 6.8 events/hr). Sleep structure was fragmented, with a high number of awakenings (mean number of awakenings was 13.2 +/- 8.1; of these, 4.8 +/- 2.5 lasted longer than 2 min). In all patients, otolaryngologic and radiologic observations revealed one or more sites of narrowing in the upper airways. Our results suggest that Costello patients have a high prevalence of obstructive sleep-related respiratory disorders, which need to be assessed by means of polysomnography.