Rapid development of tolerance to the sleep promoting effects of alcohol : a mouse model

Alcohol promotes sleep and is widely used as a sleep aid. Tolerance to the sleep promoting effects of alcohol develops over time with its repeated use, which plays an important role in the gradual escalation of alcohol consumption, resulting in alcohol dependence. To understand the mechanism underlying alcohol tolerance and dependence, it is required to have an appropriate model mimicking human conditions of alcohol administration and development of tolerance to the sedative effects of alcohol. We propose an animal model which closely mimics human conditions of alcohol self-administration with a clear demonstration of rapid tolerance to the sedative effects of alcohol

Examination of EEG spectra to identify markers/predictors of apneic events in obstructive sleep apnea

Background: Obstructive sleep apnea (OSA)is the most common sleep disorder, affecting 13% of men and 6% of women in the U.S. The incidence of OSA has increased 300% in last 20 years. OSA not only causes excessive daytime sleepiness, decreased work productivity, and reduced quality of life, but also increases patients’ risks for hypertension, stroke, heart failure and atrial fibrillation. Currently, the gold standard for OSA diagnosis is polysomnography (PSG), which requires patients to be monitored continuously throughout a single night of sleep. Due to the length of this monitoring process, undiagnosed patients have been forced to wait for 3-4 months to undergo PSG. Shortening this monitoring process would enable patients with OSA to be identified and treated earlier. SALIENT FINDINGS: The initiation of stage N3 sleep is measurably different in OSA patients before and after treatment, with significant differences primarily appearing in left-sided leads, but not right-sided leads. Treatment with CPAP corrects these differences, so that both healthy and CPAP-treated OSA patients do not show differences in either the left-sided or the right-sided leads. In untreated OSA patients vs. healthy patients, the changes in spectral power are marked by a decrease in theta band power concomitant with an increase in delta band power. Unlike the other left-sided leads, the F3 lead did not show significant differences in OSA patients. Therefore, although differences are exclusively left-sided, they are not found in all left-sided leads. No significant differences in alpha band power were seen in any leads

Sleep disorders in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting both the central and peripheral nervous system. The median survival rate for ALS patients after symptom onset is 2.5 to 3.5 years and after diagnosis of ALS is about 1.5 to 2.5 years. Patients with ALS can have a wide spectrum of sleep disorders including but not limited to insomnia, sleep related breathing disorders, parasomnias, obstructive sleep apnea (OSA) and nocturnal hypoventilation (NH). Sleep-related breathing disorders substantially increase both morbidity and mortality in ALS patients. In this review, we have discussed the ALS motor symptoms, sleep-related breathing disorders, behavioral abnormalities and sleep disturbing factors which impair the health-related quality of life

Ischemic Stroke Disrupts Sleep Homeostasis in Middle-Aged Mice

Sleep disturbances, including insomnia and excessive daytime sleepiness, are highly prevalent in patients with ischemic stroke (IS), which severely impacts recovery and rehabilitation efforts. However, how IS induces sleep disturbances is unclear. Three experiments were performed on middle-aged C57BL/6J mice, instrumented with sleep recording electrodes and/or subjected to 1 h of middle cerebral artery (MCAO; Stroke group) or sham (Sham group) occlusion to induce IS. After 48 h of reperfusion (a) experiment 1 verified sensorimotor deficit (using Garcia scale) and infarction (using TTC staining) in this mouse model; (b) experiment 2 examined the effects of IS on the quality (sleep latency and NREM delta power) and quantity (duration) of sleep; and (c) experiment 3 determined the effects of IS on sleep homeostasis using sleep deprivation (SD) and recovery sleep (RS) paradigm. Stroke mice display (a) a significant correlation between sensorimotor deficit and cerebral infarction; (b) insomnia-like symptoms (increased sleep latency, reduced NREM duration and delta power) during the light (inactive) period and daytime sleepiness-like symptoms during the dark (active) period mimicking sleep in IS patients; and (c) impairments in the markers of sleep pressure (during SD) and sleep dissipation (during RS). Our results suggest that IS disrupts sleep homeostasis to cause sleep disturbances

The use of hi-fidelity mannequin for status epilepticus simulation to enhance medical student's performance

Status Epilepticus (SE) is one of the most commonly occurring neurologic emergencies and there are about 200,000 episodes of SE in the US with a high mortality risk of around 22% and requires rapid effective treatment for optimal response to therapy and outcome and because of necessity to act fast and accurately, it is obviously frightening for the new learners. Using a Hi-fidelity manikins for simulation of SE ensures no harm to the real patients but definitely help improving the skills of the trainees which we wanted to show with our two year data collection and analysis

Solriamfetol for Excessive Sleepiness in Obstructive Sleep Apnea (TONES 3). A Randomized Controlled Trial.

Rationale: Primary treatment of obstructive sleep apnea can be accompanied by a persistence of excessive sleepiness despite adherence. Furthermore, effectiveness of sleep apnea treatment is limited by poor adherence. Currently available pharmacologic options for the treatment of sleepiness in this population are limited. Objectives: To evaluate the efficacy and safety of solriamfetol (JZP-110), a selective dopamine and norepinephrine reuptake inhibitor with robust wake-promoting effects, for the treatment of excessive sleepiness in participants with obstructive sleep apnea with current or prior sleep apnea treatment. Methods: This was a double-blind, randomized, placebo-controlled, parallel-group, 12-week trial comparing solriamfetol, 37.5, 75, 150, and 300 mg, with placebo. Measurements and Main Results: Of 476 randomized participants, 459 were included in the prespecified efficacy analyses. Coprimary endpoints (Maintenance of Wakefulness Test sleep latency and Epworth Sleepiness Scale score) were met at all solriamfetol doses (P < 0.05), with dose-dependent effects observed at Week 1 maintained over the study duration. All doses except 37.5 mg resulted in higher percentages of participants reporting improvement on Patient Global Impression of Change (key secondary endpoint; P < 0.05). Adverse events were reported in 47.9% of placebo- and 67.9% of solriamfetol-treated participants; five participants experienced serious adverse events (two [1.7%] placebo, three [0.8%] solriamfetol); none were deemed related to study drug. The most common adverse events with solriamfetol were headache (10.1%), nausea (7.9%), decreased appetite (7.6%), anxiety (7.0%), and nasopharyngitis (5.1%). Conclusions: Solriamfetol significantly increased wakefulness and reduced sleepiness in participants with obstructive sleep apnea and excessive sleepiness; most adverse events were mild or moderate in severity. Clinical trial registered with www.clinicaltrials.gov (NCT02348606) and www.eudract.ema.europa.eu (EudraCT 2014-005514-31)