Camila Andrade Mendes Medeiros

Effect of exogenous melatonin on sleep and motor dysfunction in Parkinson's disease. A randomized, double blind, placebo-controlled study.

Insomnia, sleep fragmentation and excessive daytime sleepiness are common in Parkinsons disease (PD) and may contribute to the reduction of cognition and alertness in those patients. Melatonin has been shown to improve sleep in several conditions. In experimental models of PD, melatonin can ameliorate motor symptoms. To evaluate the effect of melatonin on sleep and motor dysfuntion in PD, we studied 18 patients (Hoehn & Yahr I to III) from a PD clinic. Prior to treatment, motor dysfunction was assessed by UPDRS II, III and IV. Subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and daytime somnolence by the Epworth Sleepiness Scale (ESS). Full polysomnography (PSG) was performed in all subjects. Patients were then randomized to receive melatonin (3mg) or placebo one hour before bedtime for four weeks. All measures were repeated at the end of treatment. On initial assessment, 14 patients (70%) showed poor quality sleep (PSQI > 6) and eight (40%) excessive daytime sleepiness (ESS > 10). Increased sleep latency (50%), REM sleep without atonia (66%), and reduced sleep efficiency (72%) were found on PSG. Eight patients had an apnea/ hipopnea index greater than 15 but no severe oxygen desaturation was observed. Sleep fragmentation tended to be more severe in patients on lower doses of levodopa (p = 0.07). Although melatonin significantly improved subjective quality of sleep (p = 0.03) as evaluated by the PSQI index, PSG abnormalities were not changed. Motor dysfunction was not improved by the use of melatonin. Undetected differences in motor scores and PSG findings may have been due to a small sample size and a type II error.

Obstructive sleep apnea and biomarkers of inflammation in ischemic stroke

Medeiros CAM, de Bruin VMS, Andrade GM, Coutinho WM, de Castro‐Silva C, de Bruin PFC. Obstructive sleep apnea and biomarkers of inflammation in ischemic stroke.
Acta Neurol Scand: 2012: 126: 17–22.
© 2011 John Wiley & Sons A/S.

Quality of sleep and day-time sleepiness in chronic hemodialysis: A study of 400 patients

Abstract Objective. Impaired sleep has potential health consequences in chronic hemodialysis patients. To date, this issue has not been examined in studies involving a large number of subjects. This study aimed to identify factors associated with poor sleep quality and excessive day-time sleepiness (EDS) in dialysis patients. Material and methods. This cross-sectional observational study involved 400 patients (59% male) from three hemodialysis centers (SD-HEMOFOR). Quality of sleep was evaluated by the Pittsburgh Sleep Quality Index (PSQI), EDS by the Epworth Sleepiness Scale (ESS), risk of obstructive sleep apnea (OSA) by the Berlin questionnaire and comorbidity severity by the Charlson Comorbidity Index (CCI). Results. Poor sleep quality (PSQI >5) was found in 227 individuals (57%) and was associated with older age (p = 0.001), diabetes (p = 0.03), heart failure (p < 0.005), hypoalbuminemia (p = 0.01), low transferrin saturation (TSAT) (p = 0.009), higher CCI score (p = 0.01) and depression (p < 0.005). Independent factors were older age, heart failure, low TSAT and depressive symptoms. Day-time somnolence was present in 108 patients (27%) and was independently associated with stroke [odds ratio (OR) = 2.84, CI 1.03–7.76), lower hemoglobin concentration (OR = 2.45, CI 0.95–3.03) and high risk of OSA (OR = 1.65, CI 1.03–2.63). High risk of OSA (n = 120; 30%), was associated with hypertension (p < 0.001), overweight/obesity (p = 0.001), older age (p = 0.003) and symptoms of depression (p = 0.01). Conclusions. Poor sleep quality and EDS were prevalent on chronic hemodialysis. Heart failure, low TSAT and depressive symptoms were independently associated with poor sleep quality. Stroke, anemia and high risk of OSA were independently associated with EDS. These results provide new insight into possible treatment strategies.

Melatonin improves sleep and reduces nitrite in the exhaled breath condensate in cystic fibrosis--a randomized, double-blind placebo-controlled study.

Abstract:  Cystic fibrosis (CF) is a chronic progressive disorder characterized by repeated episodes of respiratory infection. Impaired sleep is common in CF leading to reduced quality of life. Melatonin, a secretory product of the pineal gland, has an important function in the synchronization of circadian rhythms, including the sleep–wake cycle, and has been shown to possess significant anti‐oxidant properties. To evaluate the effects of exogenous melatonin on sleep and inflammation and oxidative stress markers in CF, a randomized double‐blind, placebo‐controlled study initially involving 20 patients with CF was conducted. One individual failed to conclude the study. All subjects were clinically stable when studied and without recent infectious exacerbation or hospitalization in the last 30 days. Groups were randomized for placebo (n = 10; mean age 12.1 ± 6.0) or 3 mg melatonin (n = 9; mean age 16.6 ± 8.26) for 21 days. Actigraphy was performed for 6 days before the start of medication and in the third week (days 14–20) of treatment. Isoprostane and nitrite levels were determined in exhaled breath condensate (EBC) at baseline (day 0) and after treatment (day 21). Melatonin improved sleep efficiency (P = 0.01) and tended to improve sleep latency (P = 0.08). Melatonin reduced EBC nitrite (P = 0.01) but not isoprostane. In summary, melatonin administration reduces nitrite levels in EBC and improves sleep measures in clinically stable CF patients. The failure of melatonin to reduce isoprostane levels may have been a result of the low dose of melatonin used as a treatment.

Neck circumference, a bedside clinical feature related to mortality of acute ischemic stroke

OBJECTIVE The aim of this study was to evaluate clinical/demographic factors, sleep alterations and one year mortality in acute ischemic stroke. METHODS This was a prospective study of 89 consecutive patients (mean age 64.39 ± 8.51 years) with acute ischemic stroke. High risk of obstructive sleep apnea (OSA) was evaluated by the Berlin questionnaire, daytime somnolence by the Epworth Sleepiness Scale (> 10) and subjective sleep quality by the Pittsburgh Sleep Quality Index (> 5). Clinical and anthropometric data including body mass index, hip-waist ratio, neck circumference (NC) were obtained. Increased NC was defined if > 43 cm in men and > 38 cm in women. Stroke severity was estimated by the Barthel Index and the modified Rankin Scale. The end-point was death after 12 months follow-up. RESULT One-year mortality was 8.9%. Non-survivors were older (p = 0.006) and had larger NC (p = 0.02). Among all cases, large NC was related to high risk of OSA, diabetes and hypertension (Fishers exact test). Compared to men, women showed relatively larger NC. Overall, family history of stroke (74.2 %), diabetes (33.7%) and hypertension (78.6%) were frequent; obesity (11.2%) was uncommon. Daytime sleepiness (34.8 %), poor sleep quality (65.2%) and risk of OSA (58.42%) were frequently found. CONCLUSION Poor sleep quality, excessive daytime sleepiness and high risk of OSA are frequent in this sample with acute ischemic stroke. One-year mortality was related to older age and large NC. As obesity is uncommon in acute stroke patients, a large NC should be taken as a significant clinical sign related to mortality.

Clinical outcome after acute ischaemic stroke: the influence of restless legs syndrome

Background and purpose:  The objective was to evaluate the presence of Restless Legs Syndrome (RLS) in acute stroke, its association with sleep disturbances and clinical outcome during long‐term follow‐up.

Melatonin in Parkinson’s disease

JO N 2788 advanced and speculates that the beneficial effects of melatonin administration might have been associated to correction of this hypothetical circadian abnormality in our subjects. Although we agree that Dr. Fertl’s explanation for our findings deserves further investigation, there are some aspects related to this hypothesis that we would like to address. Phase advance in PD can be influenced by drug therapy but also by age [3], disease severity, pattern of daily activities [4] and associated comorbidities, such as depressive symptoms and daytime sleepiness [5]. Thus, a clear demonstration of an association between levodopa therapy and phase advance in these patients must take into careful consideration all these variables, which, to our knowledge, has not yet been done. We disagree from Dr. Fertl when she states that our patients were on “relatively high mean daily dose of levodopa”. On the contrary, we believe that 600 mg/d is a modest dose, in view of the current recommendations encouraging levodopa therapy to reduce motor disability [6]. Interestingly, patients without fluctuations and on lower doses of levodopa showed a trend for more sleep fragmentation in our study. Finally, given the evidence that melatonin is associated with nigrostriatal protection, reduced Camila Andrade Mendes Medeiros Pedro Felipe Carvalhedo de Bruin Livia Ariane Lopes Maria Cecilia Magalhaes Maria de Lourdes Seabra Veralice Meireles Sales de Bruin

PROFILE OF DEPRESSIVE SYMPTOMS IN SLEEP APNEA- GENDER DIFFERENCES AND THE ROLE OF OBESITY

Objective: The objective was to evaluate depressive symptoms, sleep alterations and the role of gender and obesity in obstructive sleep apnea (OSA) patients. Methods: Patients (N=140; 92 males and 48 female; age 54.6±8.2 years), submitted to polysomnography for suspected OSA, were assessed by the 17-item Hamilton Rating Scale for Depression (HRSD), Charlson comorbidity index (CCI) and Epworth Sleepiness Scale (ESS). All patients were divided in two groups: snorers/mild OSA group (apnea hypopnea index (AHI) ≤15, N=54) and moderate/severe OSA group (AHI>15, N=86). Results: The most affected components of the HDRS in both genders were anxiety, somatic and psychological, followed by work and activities complaints and depressed mood. Late insomnia predominated over early and middle night insomnia. Snorers/mild OSA women showed higher HDRS scores (p=0.002). Obese patients showed higher HDRS scores vs non-obese (BMI>30, N=96) (8.52±5.0 vs 6.38±5.0, p=0.02). The profile of depressive symptoms was similar for obese vs non-obese. Excessive daytime sleepiness (ESS>10) was present in 57 cases (40.7%). ESS scores were negatively correlated with minimum SpO 2 values (r=-0.18, p=0.03) and positively correlated with arousal frequency (r=0.24, p=0.02). Sedatives (12.1%) or antidepressants (5.7%) were seldom used. Conclusion: Depressive symptoms in OSA, in both genders, are characterized by somatic and psychological anxiety, work complaints, depressed mood and late insomnia; obese patients are more affected.

Interleukin‐6 in ischemic stroke associated with obstructive sleep apnea

We thank Dr. Gao and co-workers for their interest in our article, which describes the increased levels of Interleukin-6 (IL-6), an inflammatory marker, in stroke patients commensurate with severity of obstructive sleep apnea (OSA). According to our data, IL-6 is also correlated with oxyhemoglobin desaturation and with desaturation index (1). In their letter, Dr. Gao and co-workers raise concerns about the possibility of a confounding effect of obesity and metabolic syndrome on the relationship between OSA and inflammation described in our patients. Although we partially agree with their observations, there are some aspects that need to be addressed. Dr. Gao and co-workers are correct to point out that OSA, obesity, and metabolic syndrome are considered risk factors for cardiovascular mortality including coronary artery disease and stroke. While this may be true, it has also been demonstrated that OSA has an independent role in the development of metabolic dysfunction (2). Furthermore, oxygen desaturation is an independent risk factor for insulin resistance (3), and sleep loss is associated with increased IL-6 and TNF-alpha (4). Of interest, intermittent hypoxia without high-cholesterol diet showed proatherogenic effects; unfortunately, inflammatory markers were not evaluated in the previous study (5). Crucial to this discussion, an independent correlation between oxygen desaturation and inflammation has been recently described (6). Finally, it has been argued that underlying chronic intermittent hypoxia caused by OSA could explain the paradoxical protective effect of obesity on morbidity/ mortality (7). In our study, we found that obesity is rare in acute ischemic stroke patients, confirming a previous report (8). Additionally, neck circumference and body mass index were not determinants for increased IL-6. It has been previously shown that neck circumference is associated with the severity of OSA independently of visceral obesity, particularly in non-obese patient (9). This is in agreement with a recent report associating neck circumference with mortality in acute ischemic stroke patients (10). Based on these findings, neck circumference may be a better measure than hipwaist or the body mass index in the detection of OSA and increased morbidity and mortality. The atherosclerotic process is definitely linked to inflammation and it has been shown that OSA-related hypoxia and systemic inflammation might be associated with the progression of atherosclerosis and thus increase the risks of cardiovascular and cerebrovascular complications in patients with OSA (11). Presently, it may be difficult to discriminate between the effects of atherosclerosis and OSA. However, future studies designed to compare the effects of endothelial dysfunction and oxygen desaturation on inflammatory markers may clarify the differential role of atherosclerosis and OSA on inflammation. It should also be mentioned that prospective epidemiological studies demonstrating an association between increased circulating inflammatory markers and mortality rates (12) and the lack of association with recurrent vascular events (13) have not taken into consideration the presence of OSA. Interestingly, a metanalysis showing the association between C-reactive protein (CRP) and risk of coronary heart disease, ischemic stroke, vascular mortality, and death from several cancers and lung disease has suggested that the relevance of CRP to such a range of disorders is unclear: consequently, the association of CRP with ischemic vascular disease probably depends considerably on other conventional risk factors and other markers of inflammation (14). In summary, there is enough evidence to support a key role for IL-6 as an inflammatory marker in ischemic stroke associated with OSA, as described in our study.