Sleepwalking in Parkinson's disease: a questionnaire-based survey

Sleepwalking (SW) corresponds to a complex sleep-associated behavior that includes locomotion, mental confusion, and amnesia. SW is present in about 10% of children and 2-3% of adults. In a retrospective series of 165 patients with Parkinson's disease (PD), we found adult-onset ("de novo”) SW "de novo” in six (4%) of them. The aim of this study was to assess prospectively and systematically the frequency and characteristics of SW in PD patients. A questionnaire including items on sleep quality, sleep disorders, and specifically also SW and REM sleep behavior disorder (RBD), PD characteristics and severity, was sent to the members of the national PD patients organization in Switzerland. In the study, 36/417 patients (9%) reported SW, of which 22 (5%) had adult-onset SW. Patients with SW had significantly longer disease duration (p=0.035), they reported more often hallucinations (p=0.004) and nightmares (p=0.003), and they had higher scores, suggestive for RBD in a validated questionnaire (p=0.001). Patients with SW were also sleepier (trend to a higher Epworth Sleepiness Scale score, p=0.055). Our data suggest that SW in PD patients is (1) more common than in the general population, and (2) is associated with RBD, nightmares, and hallucinations. Further studies including polysomnographic recordings are needed to confirm the results of this questionnaire-based analysis, to understand the relationship between SW and other nighttime wandering behaviors in PD, and to clarify the underlying mechanism

EXPRESSION OF p53 AND Ki67 IN TYPE 1 AND TYPE 2 ENDOMETRIAL CARCINOMAS AND IN LOW AND HIGH GRADE SEROUS OVARIAN CARCINOMAS

Ovarian cancer is the deadliest of gynecological malignancies, and despite the efforts to improve existing treatment methods and early diagnosis, no progress has been made. Endometrial carcinoma (EC) is the fourth most common malignancy in women. The p53 gene has a leading role in the control of the cell cycle and the initiation of carcinogenesis. The p53 protein induces apoptosis, or cell cycle arrest, which allows the cell to repair genomic damage. Loss of p53 function plays a central role in the development of malignant tumors. P53 is a tumor suppressor gene whose expression in tumors is associated with progression and poor prognosis. Ki67 protein is a cell proliferation marker. Immunohistochemical staining with Ki-67 provides reliable data on the growth fraction of tumors. The Ki67 marker reflects cell proliferation in the tissue being examined. By reading the immunohistochemical expression of Ki67, we can obtain information about the proliferative index and about the growth fraction of tumors. The number of Ki67 positive tumor cells often correlates with the clinical course

Abnormal activity in hypothalamus and amygdala during humour processing in human narcolepsy with cataplexy

Narcolepsy with cataplexy (NC) is a complex sleep-wake disorder, which was recently found to be associated with a reduction or loss of hypocretin (HCRT, also called orexin). HCRT is a hypothalamic peptide implicated in the regulation of sleep/wake, motor and feeding functions. Cataplexy refers to episodes of sudden and transient loss of muscle tone triggered by strong, mostly positive emotions, such as hearing or telling jokes. Cataplexy is thought to reflect the recruitment of ponto-medullary mechanisms that normally underlie muscle atonia during REM-sleep. In contrast, the suprapontine brain mechanisms associated with the cataplectic effects of emotions in human narcolepsy with cataplexy remain essentially unknown. Here, we used event-related functional MRI to assess brain activity in 12 NC patients and 12 controls while they watched sequences of humourous pictures. Patients and controls were similar in humour appreciation and activated regions known to contribute to humour processing, including limbic and striatal regions. A direct statistical comparison between patients and controls revealed that humourous pictures elicited reduced hypothalamic response together with enhanced amygdala response in the patients. These results suggest (i) that hypothalamic HCRT activity physiologically modulates the processing of emotional inputs within the amygdala, and (ii) that suprapontine mechanisms of cataplexy involve a dysfunction of hypothalamic-amygdala interactions triggered by positive emotion

Individual spindle detection and analysis in high-density recordings across the night and in thalamic stroke

Sleep spindles are thalamocortical oscillations associated with several behavioural and clinical phenomena. In clinical populations, spindle activity has been shown to be reduced in schizophrenia, as well as after thalamic stroke. Automatic spindle detection algorithms present the only feasible way to systematically examine individual spindle characteristics. We took an established algorithm for spindle detection, and adapted it to high-density EEG sleep recordings. To illustrate the detection and analysis procedure, we examined how spindle characteristics changed across the night and introduced a linear mixed model approach applied to individual spindles in adults (n = 9). Next we examined spindle characteristics between a group of paramedian thalamic stroke patients (n = 9) and matched controls. We found a high spindle incidence rate and that, from early to late in the night, individual spindle power increased with the duration and globality of spindles; despite decreases in spindle incidence and peak-to-peak amplitude. In stroke patients, we found that only left-sided damage reduced individual spindle power. Furthermore, reduction was specific to posterior/fast spindles. Altogether, we demonstrate how state-of-the-art spindle detection techniques, applied to high-density recordings, and analysed using advanced statistical approaches can yield novel insights into how both normal and pathological circumstances affect sleep

Migraine, arousal and sleep deprivation: comment on: "sleep quality, arousal and pain thresholds in migraineurs: a blinded controlled polysomnographic study"

We discuss the hypothesis proposed by Engstrom and coworkers that Migraineurs have a relative sleep deprivation, which lowers the pain threshold and predispose to attacks. Previous data indicate that Migraineurs have a reduction of Cyclic Alternating Pattern (CAP), an essential mechanism of NREM sleep regulation which allows to dump the effect of incoming disruptive stimuli, and to protect sleep. The modifications of CAP observed in Migraineurs are similar to those observed in patients with impaired arousal (narcolepsy) and after sleep deprivation. The impairment of this mechanism makes Migraineurs more vulnerable to stimuli triggering attacks during sleep, and represents part of a more general vulnerability to incoming stimuli

Sodium oxybate in narcolepsy with cataplexy: Zurich sleep center experience

Sodium oxybate (SO; Xyrem®) has been approved in most countries for treatment of narcolepsy and cataplexy. In this study, we present a single-center experience of a series of 18 patients with narcolepsy with cataplexy (18/18 DQB1*0602 positive, 17/17 with low/absent cerebrospinal fluid hypocretin) in whom SO was prescribed. After 26 ± 13 months, 13/18 patients were still on SO at a mean dosage of 6.1 ± 1.2 g (in 8 of them in combination with stimulants). The following significant effects were observed: improved subjective sleepiness (12/13), cataplexy (13/13; median number of attacks from 20 to 1/month), hallucinations (8/10) and sleep paralysis (8/8); increase in mean sleep latency on the Maintenance of Wakefulness Test (from 5.5 to 17.4 min) and sleep/rest efficiency on actigraphy (from 61 to 76%); decrease in Epworth Sleepiness Scale score (from 18 to 14), sleep onset REM periods on the Multiple Sleep Latency Test (from 3.6 to 2.4) and errors in the Steer-Clear Test (from 11 to 2%). Five patients discontinued SO because of insufficient compliance (n = 2), lack of efficiency (n = 1) and side effects (n = 1). These data confirm and expand previous reports on the good effects and tolerability of SO as a treatment for narcolepsy with cataplexy