Comparative efficacy of prolonged-release melatonin versus clonazepam for isolated rapid eye movement sleep behavior disorder.

PURPOSE: Clonazepam and melatonin are recommended as first-line treatments for isolated rapid eye movement (REM) sleep behavior disorder (iRBD). This study aimed to compare their efficacy and safety in REM sleep without atonia (RWA) and RBD-related symptoms. METHODS: This prospective, open-label, randomized trial included patients with video-polysomnography-confirmed iRBD. The patients were randomly assigned to receive either clonazepam 0.5 mg or prolonged-release (PR) melatonin 2 mg 30 min before bedtime for 4 weeks. The primary outcome was changes in RWA on follow-up polysomnography (PSG). Secondary endpoints were changes in other PSG parameters, clinical global improvement-impression scale (CGI-I) scores, and sleep questionnaire scores. The safety endpoint was adverse events. RESULTS: Of 40 patients with probable RBD considered, 34 were enrolled in the study and randomized. Visual scoring parameters of RWA indices were reduced, and automatic scoring parameters tended to be improved after clonazepam treatment but not after PR melatonin treatment. The proportion of N2 sleep was increased, and N3 and REM sleep were decreased only in the clonazepam group. The clonazepam group tended to answer "much or very much improvement" on the CGI-I more frequently than the PR melatonin group (p = 0.068). Daytime sleepiness and insomnia symptoms were reduced after PR melatonin but not after clonazepam. Depressive symptoms increased after clonazepam. Four of the patients (13.3%) reported mild to moderate adverse events, which were similar between the two groups. CONCLUSION: Four weeks of clonazepam, but not PR melatonin, improved RWA. RBD symptom improvement tended to be better after clonazepam than PR melatonin in exchange for increased depressive symptoms and daytime sleepiness. CLINICALTRIALS: gov identifier: NCT03255642 (first submitted August 21, 2017).

Subclinical Peripheral Arterial Disease in Patients with Acute Ischemic Stroke: A Study with Ultrasonography.

BACKGROUND: Peripheral arterial disease (PAD) is an advanced form of atherosclerosis defined by an abnormal ankle-brachial index (ABI). However, the ABI provides no information about the location of atherosclerosis. We investigated the clinical implication of PAD confirmed using lower-extremity ultrasonography (LEUS), with consideration of the atherosclerosis location. METHODS: Patients with acute ischemic stroke who underwent LEUS were enrolled. Patients with PAD were further divided into those with PAD at the proximal (above-popliteal artery, PADP) and distal (below-tibialis artery, PADD) segments. The clinical outcome was compared between patients with and without PAD, and between PADP and PADD. The atherosclerosis location in the cerebral artery was also compared between groups. RESULTS: Among 289 patients, PAD was observed in 108 (37.4%) patients (43 had PADP and 65 had PADD). Patients with PAD were slightly older (P < .001) and had more significant carotid artery stenosis (30.6% versus 12.7%, P < .001) than those without. Patients with PAD had poor 3-month functional outcome than those without (modified-Rankin Scale score: 3 [interquartile range, 1-4] versus 2 [1-3], respectively, P = .003). Diabetes, high-stroke severity, and the presence of PADP (odds ratio, 3.893; 95% confidence interval, 1.454-10.425; P = .007) were independently associated with poor functional outcome at 3 months. Patients with PADP showed higher prevalence of extracranial stenosis than those with PADD (41.9% versus 23.1%; P = .038). CONCLUSIONS: Our study suggests that subclinical PAD, especially PADP, is associated with poor functional outcome at 3 months after stroke onset. Interestingly, the location of cerebral atherosclerosis differed according to the location of PAD.

Delirium caused by topical administration of cyclopentolate for cataract surgery in mild cognitive impairment due to Alzheimer's disease: A case report.

RATIONALES: Cholinergic modification by anticholinergic medication can produce adverse effects in central nervous system (CNS) and cyclopentolate is an antimuscarinic agent widely used for ophthalmologic management. We demonstrate a rare case of hyperactive delirium caused by topical administration of cyclopentolate in a patient with amnestic mild cognitive impairment (MCI) due to Alzheimer's disease (AD). PATIENT CONCERNS: A 74-year-old man showed acute confusion after preparation for cataract operation in day surgery clinic. The patient became confused and agitated after instillation of topical cyclopentolate drop into the eye and the symptoms persisted over several hours. DIAGNOSIS: Previously the patient had been diagnosed with amnestic MCI with the finding of bilateral medial temporal atrophy on brain magnetic resonance imaging. 18F-flutemetamol positron emission tomography scan demonstrated multifocal amyloid deposition in the brain. INTERVENTIONS: The patient was closely observed with the supportive management. OUTCOMES: The patient began to recover 5 h after the onset of symptoms and the cognitive function was reverted to previous state within 24 h. LESSONS: It is well known that several drugs with anticholinergic effects used in perioperative periods make the patients susceptible to delirium, but even the topical administration of cyclopentolate for cataract surgery also produce adverse CNS effects in a vulnerable patient who is diagnosed with MCI due to AD in this case.

Comparison of cardiac autonomic activity between positional and nonpositional obstructive sleep apnea using heart rate variability.

OBJECTIVES: Patients with obstructive sleep apnea (OSA) experience sympathetic hyperactivation during sleep, which is associated with increased cardiovascular risk factors. However, the difference in cardiac autonomic activity in OSA patients according to position dependency has not been evaluated. This study aimed to evaluate the differences between positional OSA (pOSA) and nonpositional OSA (npOSA) using heart rate variability (HRV) analysis. METHODS: This was a single-center cross-sectional study. Twenty-eight patients with npOSA and 28 age-, sex-, and AHI-matched patients with pOSA underwent standard polysomnography. A five-minute R-R interval from stable waking conditions before bedtime was collected from each subject and analyzed for HRV. RESULTS: Patients with pOSA had lower body-mass index (BMI, 25.8 ± 2.9 vs 28.9 ± 3.7 kg/m2, p = 0.001), shorter apnea duration (24.1 ± 7.1 vs 30.3 ± 12.7 s, p = 0.028) and higher minimum oxygen saturation (78.2 ± 7.1 vs 71.5 ± 11.4%, p = 0.011) than those with npOSA. HRV analysis showed higher parasympathetic activity in pOSA patients than in npOSA patients, including a higher square root of the mean of the sum of the squares of differences between adjacent NN intervals (RMSSD, 31.3 ± 29.0 vs 18.6 ± 9.2, p = 0.032), percentage of pairs of adjacent NN intervals that differ by more than 50 ms (pNN50%, 10.7 ± 17.1 vs 3.3 ± 6.5, p = 0.024), and high-frequency (HF) power (534.7 ± 986.8 vs 146.7 ± 150.5, p = 0.026). The group difference was insignificant after adjusting for age and BMI. The log-transformed supine/nonsupine AHI ratio was the sole independent predictor of HRV parameters. CONCLUSION: The waking HRV was higher in pOSA patients than in npOSA patients due to the lower BMI of pOSA patients. The difference was especially apparent in parasympathetic indices. Higher parasympathetic activity in pOSA may suggest a lower risk for cardiovascular morbidity and mortality.

Safety and Efficacy of Gamma-Aminobutyric Acid from Fermented Rice Germ in Patients with Insomnia Symptoms: A Randomized, Double-Blind Trial.

BACKGROUND AND PURPOSE: This study aimed to determine the subjective and objective improvements in sleep quality after treatment with gamma-aminobutyric acid (GABA; 300 mg daily) extracted from unpolished rice germ. METHODS: This study was a prospective, randomized, double-blind, and placebo-controlled trial. In total, 40 patients who complained of insomnia symptoms were enrolled and randomly assigned to the GABA treatment group (n=30) or the placebo group (n=10). Polysomnography was performed, and sleep questionnaires were administered before treatment and after 4 weeks of treatment. RESULTS: After 4 weeks of treatment the sleep latency had decreased [13.4±15.7 min at pretreatment vs. 5.7±6.2 min at posttreatment (mean±SD), p=0.001] and the sleep efficacy had increased (79.4±12.9% vs. 86.1±10.5%, p=0.018) only in the GABA treatment group. Adverse events occurred in four subjects (10%). CONCLUSIONS: This study shows that treatment with unpolished-rice-germ-derived GABA improved not only the subjective sleep quality but also the objective sleep efficacy without severe adverse events.