Effects of sleep disruption on stress, nigrostriatal markers, and behavior in a chronic/progressive MPTP male mouse model of parkinsonism.

Sleep complaints are an early clinical symptom of neurodegenerative disorders. Patients with Parkinson's disease (PD) experience sleep disruption (SD). The objective of this study was to determine if preexisting, chronic SD leads to a greater loss of tyrosine hydroxylase (TH) within the striatum and the substantia nigra following chronic/progressive exposure with the neurotoxin, 1-methyl-2-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Male mice underwent chronic SD for 4 weeks, then injected with vehicle (VEH) or increasing doses of MPTP for 4 weeks. There was a significant decrease in the plasma corticosterone levels in the MPTP group, an increase in the SD group, and a return to the VEH levels in the SD+MPTP group. Protein expression levels for TH in the striatum (terminals) and substantia nigra pars compacta (dopamine [DA] cell counts) revealed up to a 78% and 38% decrease, respectively, in the MPTP and SD+MPTP groups compared to their relevant VEH and SD groups. DA transporter protein expression increased in the striatum in the MPTP versus VEH group and in the SN/midbrain between the SD+MPTP and the VEH group. There was a main effect of MPTP on various gait measures (e.g., braking) relative to the SD or VEH groups. In the SD+MPTP group, there were no differences compared to the VEH group. Thus, SD, prior to administration of MPTP, has effects on serum corticosterone and gait but more importantly does not potentiate greater loss of TH within the nigrostriatal pathway compared to the MPTP group, suggesting that in PD patients with SD, there is no exacerbation of the DA cell loss.

Abnormal nocturnal behavior due to hypoglycemia: A case report.

RATIONALE: Hypoglycemia, which is characterized mainly by palpitations, dizziness, and sweating, is common and easy to identify. However, some other symptoms, such as mental disorder or abnormal behavior, are atypical, which may lead to a misdiagnosis of epilepsy, sleepwalking, infarction, or mental disorder, among others. PATIENT CONCERNS: We report a case of a patient with type 2 diabetes who presented with abnormal nocturnal behavior due to hypoglycemia. DIAGNOSIS: Hypoglycemia was diagnosed based on a blood glucose level of 2.1 mmol/L when the patient turned up disoriented unresponsive, unable to understand what was said to him, and producing nonsensical speech. After the patient ate a piece of chocolate, his consciousness returned to normal and all mental symptoms disappeared. Polysomnography (PSG) was synchronously performed. The results of the PSG did not show any signs of abnormality during nonrapid eye movement (NREM) or rapid eye movement (REM) sleep. INTERVENTIONS: We regulated his dose of insulin. OUTCOMES: No additional episodes occurred during the 3-month follow-up. Therefore, the abnormal nocturnal behavior of this patient was determined to be due to hypoglycemia, while the cause of the hypoglycemia was insulin overuse. LESSONS: For physicians, if the cause of abnormal behavior cannot be detected, hypoglycemia should be suspected. Long-term persistent hypoglycemia may cause brain dysfunction and even result in permanent brain damage.

Sleep disturbance as a clinical sign for severe hypogonadism: efficacy of testosterone replacement therapy on sleep disturbance among hypogonadal men without obstructive sleep apnea.

OBJECTIVE: The present subanalysis of the EARTH study investigates the effects of one year testosterone replacement therapy (TRT) on sleep disturbance among hypogonadal men without obstructive sleep apnea. METHODS: Sleep disturbance was defined as three or more points in question 4 of the aging males symptoms (AMS) questionnaire. All participants completed the AMS scale, International Prostatic Symptoms Score (IPSS), Sexual Health Inventory for Men (SHIM) and Short Form 36 (SF-36) health survey at baseline and after 12 months. Sexual symptoms were also evaluated based on three AMS subscores (Q15, 16 and 17). RESULTS: We identified 100 patients with sleep disturbance, of whom 48 (24 each in the TRT and control groups) were ultimately included for analysis. All SF-36 categories , AMS scale, IPSS and SHIM score subdomains were significantly worse in patients with sleep disturbance than in those without disturbance. Statistically significant differences in sleep disturbance, erectile symptoms, sexual desire and some domains of the SF-36 were observed between the TRT and control groups after 12 months. CONCLUSION: Sleep disturbance may be one of the clinical signs for severe hypogonadism. Moreover, TRT improved sleep conditions, sexual function and quality of life among hypogonadal men with sleep disturbance.

Sex Hormones and Sleep in Men and Women From the General Population: A Cross-Sectional Observational Study.

CONTEXT AND OBJECTIVES: Associations between sex hormones and sleep habits originate mainly from small and selected patient-based samples. We examined data from a population-based sample with various sleep characteristics and the major part of sex hormones measured by mass spectrometry. DESIGN, SETTING, AND PARTICIPANTS: We used data from 204 men and 213 women of the cross-sectional Study of Health in Pomerania-TREND. MAIN OUTCOME AND MEASURES: Associations of total T (TT) and free T, androstenedione (ASD), estrone, estradiol (E2), dehydroepiandrosterone-sulphate, SHBG, and E2 to TT ratio with sleep measures (including total sleep time, sleep efficiency, wake after sleep onset, apnea-hypopnea index [AHI], Insomnia Severity Index, Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index) were assessed by sex-specific multivariable regression models. RESULTS: In men, age-adjusted associations of TT (odds ratio 0.62; 95% confidence interval (CI) 0.46-0.83), free T, and SHBG with AHI were rendered nonsignificant after multivariable adjustment. In multivariable analyses, ASD was associated with Epworth Sleepiness Scale (ß-coefficient per SD increase in ASD: -0.71; 95% CI: -1.18 to -0.25). In women, multivariable analyses showed positive associations of dehydroepiandrosterone-sulphate with wake after sleep onset (ß-coefficient: .16; 95% CI 0.03-0.28) and of E2 and E2 to TT ratio with Epworth Sleepiness Scale. Additionally, free T and SHBG were associated with AHI in multivariable models among premenopausal women. CONCLUSIONS: The present cross-sectional, population-based study observed sex-specific associations of androgens, E2, and SHBG with sleep apnea and daytime sleepiness. However, multivariable-adjusted analyses confirmed the impact of body composition and health-related lifestyle on the association between sex hormones and sleep.

Methylphenidate ameliorates depressive comorbidity in ADHD children without any modification on differences in serum melatonin concentration between ADHD subtypes.

UNLABELLED: The vast majority of Attention-deficit/hyperactivity disorder (ADHD) patients have other associated pathologies, with depressive symptoms as one of the most prevalent. Among the mediators that may participate in ADHD, melatonin is thought to regulate circadian rhythms, neurological function and stress response. To determine (1) the serum baseline daily variations and nocturnal excretion of melatonin in ADHD subtypes and (2) the effect of chronic administration of methylphenidate, as well as the effects on symptomatology, 136 children with ADHD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision: DSM-IV-TR criteria) were divided into subgroups using the "Children's Depression Inventory" (CDI). Blood samples were drawn at 20:00 and 09:00 h, and urine was collected between 21:00 and 09:00 h, at inclusion and after 4.61 ± 2.29 months of treatment. Melatonin and its urine metabolite were measured by radioimmunoassay RIA. Factorial analysis was performed using STATA 12.0. Melatonin was higher predominantly in hyperactive-impulsive/conduct disordered children (PHI/CD) of the ADHD subtype, without the influence of comorbid depressive symptoms. Methylphenidate ameliorated this comorbidity without induction of any changes in the serum melatonin profile, but treatment with it was associated with a decrease in 6-s-melatonin excretion in both ADHD subtypes. CONCLUSIONS: In untreated children, partial homeostatic restoration of disrupted neuroendocrine equilibrium most likely led to an increased serum melatonin in PHI/CD children. A differential cerebral melatonin metabolization after methylphenidate may underlie some of the clinical benefit.

A randomized trial of temazepam versus acetazolamide in high altitude sleep disturbance.

This study is the first comparative trial of sleep medications at high altitude. We performed a randomized, double-blind trial of temazepam and acetazolamide at an altitude of 3540 meters. 34 healthy trekkers with self-reports of high-altitude sleep disturbance were randomized to temazepam 7.5 mg or acetazolamide 125 mg taken at bedtime for one night. The primary outcome was sleep quality on a 100 mm visual analog scale. Additional measurements were obtained with actigraphy; pulse oximetry; and questionnaire evaluation of sleep, daytime drowsiness, daytime sleepiness, and acute mountain sickness. Sixteen subjects were randomized to temazepam and 18 to acetazolamide. Sleep quality on the 100 mm visual analog scale was higher for temazepam (59.6, SD 20.1) than acetazolamide (46.2, SD 20.2; p=0.048). Temazepam also demonstrated higher subjective sleep quality on the Groningen Sleep Quality Scale (3.5 vs. 6.8, p=0.009) and sleep depth visual analog scale (60.3 vs. 41.4, p=0.028). The acetazolamide group reported significantly more awakenings to urinate (1.8 vs. 0.5, p=0.007). No difference was found with regards to mean nocturnal oxygen saturation (84.1 vs. 84.4, p=0.57), proportion of the night spent in periodic breathing, relative desaturations, sleep onset latency, awakenings, wake after sleep onset, sleep efficiency, Stanford Sleepiness Scale scores, daytime drowsiness, or change in self-reported Lake Louise Acute Mountain Sickness scores. We conclude that, at current recommended dosing, treatment of high-altitude sleep disturbance with temazepam is associated with increased subjective sleep quality compared to acetazolamide.