Heart rate variability in patients with idiopathic Parkinson's disease with and without obstructive sleep apnea syndrome

BackgroundObstructive sleep apnea syndrome (OSAS) is associated with repeated apnea-induced sympathetic surges leading to specific alterations of the power spectrum of heart rate variability (HRV). Sympathetic dysfunction evolves early in idiopathic Parkinson’s disease (PD), but the consequences on cardiac autonomic response to OSAS have not been studied so far in PD patients.MethodsSixty-two patients with PD (35 without OSAS (PD-wo), 27 with OSAS (PD-OSAS)) and 62 age-matched control subjects (25 without OSAS (Co-wo), 37 with OSAS (Co-OSAS)) were included. HRV variables – including mean R–R interval, standard deviation of all normal-to-normal R–R intervals (SDNN), both low frequency (LF) and high frequency (HF) power bands, and the LF/HF ratio – were computed automatically from full-night polysomnography and calculated separately for each sleep stage.ResultsHRV variables were similar in PD-wo and PD-OSAS. In contrast, Co-OSAS showed significantly higher LF power in NREM1 and NREM2 sleep and higher LF/HF ratio in NREM1, NREM2 and slow wave sleep than Co-wo. Similarly, correlations between HRV variables and parameters of OSAS severity were found only in controls but not in PD patients.ConclusionOur results suggest that the sympathetic response to OSAS is blunted in PD, giving further clinical evidence of the sympathetic denervation commonly observed in this neurodegenerative disorder.     

Reproducibility of heart rate and blood pressure variability in patients with chronic obstructive pulmonary disease

Abstract. Wide variations in respiratory rate and hypoxic stimulation of chemoreceptors may produce unreliable autonomic results in patients with COPD. We studied the reproducibility of two consecutive measurements of heart rate variability (HRV) and blood pressure variability (BPV) by time frequency analysis in patients with COPD while controlling respiratory rate and oxygen hemoglobin saturation (SaO₂). Reproducibility was assessed by paired t-tests and correlation analyses between repeated measures. Correlation analyses of the log transformed low (LF) and high frequency (HF) HRV were 11.5 ± 1.1 in measurement A and 11.5 ± 1.0 in measurement B (r = 0.89, p < 0.0001), and 10.5 ± 1.1 in measurement A and 10.6 ± 1.1 in measurement B (r = 0.89, p < 0.0001) respectively. The log transformed LF and HF BPV were 4.9 ± 1.3 in measurement A and 5.3 ± 0.9 in measurement B (r = 0.70, p < 0.0002), and 6.4 ± 1.3 in measurement A and 6.6 ± 1.2 in measurement B (R = 0.71 p < 0.0001) respectively. In conclusion, time frequency analysis of HRV and BPV is reproducible and reliable in patients with COPD while controlling their respiratory rate and oxygen hemoglobin saturation. Reproducibility of these measurements may allow for a non-invasive evaluation of autonomic tone in response to treatments in COPD patients.     

Volume reduction in cerebral blood flow in patients with Alzheimer's disease: a sonographic study

Neuroimaging techniques such as PET and SPECT demonstrated a consistent reduction of cerebral blood flow (CBF) in Alzheimer's disease (AD). The aim of the study was to assess the potential role of ultrasonography for CBF measurement in AD patients and whether the CBF volume correlates positively with disease severity. Fifty patients who met the diagnostic criteria of probable AD (NINDS-ADRDA) were compared to 50 age-matched healthy elderly volunteers. The extracranial internal carotid arteries (ICAs) and the vertebral arteries (VAs) of the patients and controls were examined. Angle-corrected time-averaged flow velocity (TAV) and the diameter of the vessel were measured. Intravascular flow volumes were calculated as the product of TAV and the cross-sectional area of the circular vessel. CBF volume was calculated as the sum of flow volumes in the ICAs and VAs of both sides. All subjects underwent the MMSE. The mean global CBF (474.87 +/- 94.085 vs. 744.26 +/- 94.082 ml/min; p < 0.0001) was lower in AD patients than in healthy volunteers. A significant decline in global flow volumes (r = 0.48; p < 0.0007) with the degree of cognitive impairment was also present. The ability of ultrasonography to characterize flow decreases makes such a technique an attractive tool for the study of AD, for the evaluation of pharmacological therapies and, possibly, for early diagnosis.     

Tissue wasting in patients with chronic obstructive pulmonary disease

Malnutrition is common among individuals suffering from hypoxemic chronic obstructive pulmonary disease (COPD), advanced HIV disease, and in patients with chronic, severe congestive heart failure. Although increased morbidity and mortality has been associated with weight loss in these conditions, the pathophysiology of malnutrition remains somewhat unclear for each. In COPD, the primary postulated mechanism is hypermetabolism resulting in elevated total caloric expenditure arising from increased airway resistance, increased O2 cost of ventilation, increased dietary induced thermogenesis, inefficient substrate use and perhaps, increased levels of proinflammatory cytokines. In AIDS, postulated mechanisms include hypermetabolism arising from increased activation of proinflammatory cytokines, along with futile cycling of fatty acids and de novo lipogenesis early in the course of HIV infection; intestinal malabsorption and anorexia also play a role in many inflicted individuals. In cardiac cachexia, dietary and metabolic factors, and levels and activity of cytokines, thyroid hormone, catecholamines and cortisol have been suggested as being responsible for causing weight loss in a most cases.     

Quadriceps muscle endurance in patients with chronic obstructive pulmonary disease

The purpose of this study was to compare quadriceps muscle strength (maximal voluntary contraction, MVC), endurance (T(LIM)), and dynamic work capacity (W(LIM)) in 89 patients (57 men and 32 women) with chronic obstructive pulmonary disease (COPD) to 31 healthy controls (20 men and 11 women). Compared with the healthy subjects, COPD patients demonstrated statistically significant (P < 0.05) lower values for MVC, T(LIM) and W(LIM). The MVC was 20-30% lower, whereas T(LIM) and W(LIM) were 70-80% lower in the patients. Stepwise multiple regression analysis revealed that pulmonary function variables contributed only partially to the explanation of variance in MVC, T(LIM), and W(LIM). Our results indicate that in patients with COPD, quadriceps muscle endurance and dynamic work capacity are impaired to a greater extent than is quadriceps muscle strength. For rehabilitation purposes, the findings may lead to more specific exercise programs, further enhancing rehabilitation outcomes in terms of functional abilities and social participation.     

Restless legs syndrome in patients with chronic obstructive pulmonary disease

OBJECTIVE: To evaluate the prevalence of restless legs syndrome (RLS) in patients with chronic obstructive pulmonary disease (COPD) and the relationship between RLS and clinical/laboratory findings of COPD. METHODS: One hundred and thirty-four COPD patients without secondary causes of RLS were included. Thirty-nine (29.1%) patients were diagnosed with RLS and classified as Group 1. The control group consisted of 65 age-matched COPD patients without RLS. Group 1 was divided into subgroups according to the Johns Hopkins Severity (JHS) scale. Patients with a score of 0, 1, or 2 were classified as JHS 0-2 and those with a score of 3 as JHS 3. Group 1 and the control group and subgroups were compared for clinical and laboratory characteristics. RESULTS: We found that the duration of COPD was longer and that airway obstruction, hypercapnia, and hypoxia were more evident in patients with RLS than those without. Similar differences were also detected between JHS subgroups 3 (more severe) and 0-2. Polyneuropathy frequency was significantly higher in Group 1 compared to controls. However, Group 1 subgroups showed a similar frequency of polyneuropathy. In a multivariate analysis, hypercapnia made a significant independent contribution to both JHS 0-2 and JHS 3 patients when RLS severity was set as the dependent variable. Polyneuropathy and the duration of COPD were significant independent variables for patients in the JHS 3 subgroup. Polyneuropathy was the strongest predictor for the JHS 3 patients. CONCLUSIONS: We conclude that RLS is frequent in COPD, particularly in patients with severe hypoxemia/hypercapnia and in late stages of the disease.     

Plasma lipids and coagulation in patients with arteriosclerotic dementia

Plasma lipids and lipoproteins, glucose, uric acid, and haemocoagulative parameters were studied in a group of 22 elderly hospitalized patients with arteriosclerotic dementia, and compared with those of a control group of a similar age. No significant differences were found in lipids, lipoproteins, glucose, or uric acid but the fibrinogen level was significantly raised in the group with arteriosclerotic dementia. A comparison of the metabolic parameters of the dementia patients with those of a group of subjects with peripheral occlusive arteriosclerosis showed, on the other hand, that this latter group had significantly raised plasma triglycerides as well as a significantly higher incidence of the Fredrickson phenotypes of hyperlipoproteinaemia. These findings indicate that the common laboratory parameters used to evaluate arteriosclerosis are not adequate to point out any pathogenic mechanism for arteriosclerotic dementia, and research should therefore be focused in other directions.     

Heart rate variability in patients with untreated Parkinson's disease

The aim of this study was to evaluate cardiovascular responses as a marker of autonomic nervous system (ANS) disturbances in patients with untreated Parkinson's disease (PD) and to assess the relationship between them and the clinical characteristics of PD. The ANS functions were investigated in 50 patients with PD and 55 healthy subjects by measuring standard cardiovascular autonomic reflexes and heart rate variability (HRV) at rest using spectral analysis (the autoregressive model and the fast Fourier transformation), the percentage of the counts of beat-to-beat variation greater than 50 ms and the fractal dimension. Significantly attenuated HRV and deficient blood pressure reaction to tilting were found in the PD patient group. The patients with hypokinesia/rigidity as the initial symptom of PD had a more pronounced HRV deficit than those with tremor onset. Untreated PD patients suffer significant failure in cardiovascular nervous system regulation, and in patients with hypokinesia/rigidity as their initial disease manifestation the risk of this ANS dysfunction is high. However, in the early stages of PD these changes did not reach significance at individual level.     

Phrenic nerve conduction studies in patients with chronic obstructive pulmonary disease

Introduction: The most common etiology of hypercapnic respiratory failure is chronic obstructive pulmonary disease (COPD). However, the differential diagnosis also includes neuromuscular disorders. We studied the specificity of reduced amplitude phrenic nerve compound motor action potential (CMAP) to diagnose neuromuscular disorders. Methods: A group of patients with advanced COPD were recruited prospectively and compared with controls. Phrenic nerve CMAPs were measured bilaterally using supraclavicular surface stimulation and bipolar recording (G1: 5 cm above the xiphoid; G2: 16 cm from G1). Results: A group of 20 patients (15 men) and a group of 29 controls (15 men) were included. Phrenic nerve CMAPs of patients with COPD had significantly longer latency and higher amplitude. Conclusion: Our study demonstrates that patients with hypercapnic respiratory failure and reduced phrenic nerve CMAP amplitude most probably have a neuromuscular disorder affecting the diaphragm and not COPD or another lung disorder. Muscle Nerve 47: 504–509, 2013     

The evaluation of cognitive functions with P300 test for chronic obstructive pulmonary disease patients in attack and stable period

OBJECTIVES: Hypoxia, in chronic obstructive pulmonary disease (COPD), leads to a decrease in cerebral perfusion and an impairment of some cognitive abilities. We aimed to investigate the relation between arterial blood gas analysis (ABA) and pulmonary function test (PFT) parameters with cognitive function of COPD patients during attack and stable period. PATIENTS AND METHODS: ABA, PFT, P300 tests of 30 patients in stabilized period and 30 patients in attack, and 17 healthy controls were evaluated. RESULTS: When both COPD groups and controls were compared, it was seen that latency of P300 was shorter in the control group (p<0.001), but there was no difference between COPD groups (p>0.05). P300 amplitude measures were lower in both COPD groups than control group, but it was not statistically significant (p>0.05). When we compared the measures of attack group, we saw that arterial oxygen tension (PaO(2)), arterial oxygen saturation (SaO(2)), forced expiratory volume in 1s (FEV(1)), FEV(1)/forced vital capacity (FVC) values increased (p<0.001), and P300 latency shortened (p<0.05) in attack group during stable period. P300 latency correlated significantly with PaO(2) (r=-0.557, p<0.001), SaO(2) (r=-0.424, p<0.001), FEV(1) (r=-0.441, p<0.001), FEV(1)/FVC (r=-0.477, p<0.001) values, and age (r=0.329, p<0.05). P300 amplitude is only correlated with PaO(2) (r=0.236, p<0.05). CONCLUSION: Longer latency of P300 appears to be an expected sequel of COPD. P300 test can be considered as a potential objective marker of cognitive impairment.     

Heart rate variability in Parkinson's disease patients treated with tolcapone

Following the introduction of tolcapone, a potent, reversible Catechol-O-methyltransferase (COMT) inhibitor, it has been possible to optimise the management of Parkinson's disease (PD) patients in chronic Levodopa (L-dopa) therapy. The interaction between tolcapone and the endogenous metabolism of catecholamines points to a possible influence on autonomic cardiovascular function.Cardiovascular reflexes have been analysed in a group of seven PD patients (four males, three females; mean age 69.7years, mean disease duration 14.1years) by means of the heart rate variability (HRV) method using a continuous 24-h ECG (ECGD), before and after six months of treatment with tolcapone (in addition to L-dopa).We have observed no statistically significant differences in HRV parameters, nor any changes in the incidence of hyperkinetic and hypokinetic arrhythmias, which suggest that autonomic cardiovascular function in PD patients is not influenced by six months of treatment with tolcapone.     

Prevalence of sub-threshold depression in elderly patients with chronic obstructive pulmonary disease

OBJECTIVES: We hypothesized that COPD patients with sub-threshold depression would have levels of disability and impaired quality of life approaching that for major depression and significantly greater than for non-depressed COPD patients. SETTING: A university teaching hospital METHOD: 137 outpatients (69 men), with a mean age of 73 years (range 60-89 years) with symptomatic irreversible, moderate to severe COPD were recruited. Subjects were interviewed using the Geriatric Mental State Schedule (GMS), a structured psychiatric interview schedule, along with its diagnostic algorithm AGECAT. A GMS/AGECAT score of 3 or more is indicative of a case-level of depression, a GMS/AGECAT score of 1-2 indicates sub-threshold depression and GMS/AGECAT of 0, no depression. Physical disability was measured by the Manchester Respiratory Activities of Daily Living questionnaire (MRADL) and quality of life was assessed by the Breathing Problems Questionnaire (BPQ). RESULTS: Mean (SD) one second forced expiratory volume was 0.89 (0.33) litres. The prevalence of GMS/AGECAT case-level depression (>or= 3) was 57 cases (42%); of GMS/AGECAT sub-threshold depression (1-2) 34 (25%); and GMS/AGECAT non-depression (0) 46 (33%). Comparison of MRADL score in the three groups (mean, 95% confidence intervals) revealed [GMS >or= 3 = 9.9 (8.4 to 11.3) vs GMS = 1-2, 12.9 (11.2 to 14.4) vs GMS = 0, 15.6 (14 to 16.6) p < 0.0001]. BPQ scores (mean, 95% confidence intervals) showed [GMS >or= 3 = 54 (50 to 57) vs GMS = 1-2, 40 (36.3 to 44) GMS = 0, 33 (30.6 to 36.7) p < 0.0001]. There was no significant difference in FEV(1) between the three groups. CONCLUSION: Sub-threshold depression accounted for 25% of the sample. In this study disability associated with sub-threshold depression in patients with COPD was intermediate to that associated with case-level depression and no with depression and significantly worse than in the latter group. Sub-threshold depression is associated with substantial morbidity in COPD.     

The prevalence of anxiety disorders in patients with chronic obstructive pulmonary disease

Fifty consecutive outpatients with stable chronic obstructive pulmonary disease were evaluated for lifetime prevalence of psychiatric morbidity. Eight percent had a diagnosis of panic disorder. This finding suggests that this patient population should be monitored for panic disorder.     

Long-term mortality in ischemic stroke patients with concomitant chronic obstructive pulmonary disease

BackgroundLong-term mortality in ischemic stroke patients with concomitant COPD has been largely unexplored. This study aimed to compare long-term all-cause mortality in ischemic stroke patients with and without COPD.MethodsThis was a retrospective cohort study of ischemic stroke patients with and without COPD in the Geisinger Neuroscience Ischemic Stroke database to examine all-cause mortality up to 3 years using Kaplan-Meier estimator and Cox proportional hazards model.ResultsOf the 6,589 ischemic stroke patients included in this study, 5,525 (83.9%) did not have COPD (group A). Group B (n=1,006) consisted of patients with COPD diagnosis by ICD-9/10-CM codes. COPD patients in Group C (n=233) were diagnosed by spirometry, and in Group D (n=175) by both ICD-9/10-CM codes and spirometry confirmation. The survival probabilities at three years in Group B, C, and D were significantly lower than in Group A. Group B (HR=1.262, 95% CI 1.122–1.42, p<0.001) and group C (HR=1.251, 95% CI 1.01–1.55, p=0.041) had significantly lower hazard of mortality compared to group A. There was no significant difference in survival between COPD subtypes of chronic bronchitis and emphysema. Patients in Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 stage had an increased mortality hazard compared to the GOLD 1 stage.ConclusionsWhile ischemic stroke patients with preexisting COPD have worse long-term survival than those without COPD, the results largely depended on the definition of COPD used. These results suggest that ischemic stroke patients with COPD need more personalized medical care to decrease long-term mortality.     

Electrophysiologic changes during exercise testing in patients with chronic obstructive pulmonary disease

To determine whether skeletal muscle is involved in the exercise limitation of chronic obstructive pulmonary disease (COPD), we investigated electrical adaptations in muscle during incremental cycling exercise testing. Changes in quadriceps activity were compared using surface electromyography (SEMG) and motor point stimulation in ten COPD patients and ten healthy subjects. Patients showed significantly lower exercise capacity, and M-wave duration was increased from exercise onset (P < 0.05) with a parallel decrease in amplitude (P < 0.05). The SEMG power spectrum median frequency was always higher (P < 0.04) in patients and its decline was earlier (P < 0.01). The ratio of the root mean square of the SEMG to oxygen uptake was decreased (P < 0.001) during exercise in patients, although it remained constant in controls. Electromyographic parameters were significantly more involved in the exercise limitation than ventilatory factors. Thus, modified electrical activity in muscle appeared in COPD patients from exercise onset, indicating that skeletal muscle function is clearly implicated in the exercise intolerance of these patients.     

Polyneuropathy associated with chronic hypoxaemia: prevalence in patients with chronic obstructive pulmonary disease

Summary The prevalence of clinical and electrophysiological signs of peripheral nerve disease was evaluated in 151 patients with chronic obstructive pulmonary disease. Patients with concomitant disorders affecting the peripheral nervous system were excluded. Thirty patients had clinical signs of a mild sensorimotor and distal neuropathy and 13 additional patients had only electrophysiological abnormalities. The rate and the severity of the neuropathy correlated with the severity of chronic hypoxaemia. Three out of 20 patients with mild hypoxaemia (PaO₂ less than 15 mm Hg below normal) had polyneuropathy as compared with 15 out of 36 with severe hypoxaemia (PaO₂ more than 30 mm Hg below normal (rates different at the 10% level)). PaO₂ and age were the only variables discriminating between patients with and without peripheral neuropathy.Supported by the Insitut de Recherches Internationales Servier 92202 Neuilly, France. Presented in part at the inaugural meeting of the European Neurological Society, Nice, France, June 1988     

Subcortical arteriosclerotic encephalopathy (Binswanger''s disease): a report of five patients

Five patients with variable clinical symptoms were diagnosed as having--subcortical arteriosclerotic encephalopathy (Binswanger disease) based on the presence of lacunar infarcts in basal ganglia, various abnormalities of subcortical white matter and severe thickening and hyalinization of penetrating arteries and arterioles. One case had a classical clinical picture while in the others the course of the disease was short and was associated with severe systemic abnormalities. The variability of the clinical features, the identify of "classical" clinical symptoms with other forms of cerebral arteriosclerosis, the similarity between "atypical" cases and other entities, and the high frequency of associated conditions makes it difficult to characterize the clinical pathological entity called subcortical arteriosclerotic encephalopathy.     

Regional cerebral blood flow in patients with Parkinson's disease.

Regional cerebral blood flow (rCBF) was measured by the xenon 133 inhalation method in 60 patients with Parkinson's disease and compared with flow data obtained in 51 age-matched normal control subjects. Mean brain rCBF was significantly reduced in patients with parkinsonism (9.5%, P less than .001). The most marked and significant rCBF decreases were observed in the older patients (18.8%, P less than .001). There was no correlation between degree of rCBF reduction and duration of parkinsonism. Decreases in hemispheric mean rCBF values were similar in both hemispheres even in patients with unilateral signs. The present study provides additional evidence for involvement of the cerebral cortex in Parkinson's disease. The rCBF decline may be associated in part with high prevalence of mental impairment and cortical atrophy and with diminished cerebral metabolic rate due to brain dopamine deficiency in patients with parkinsonism.