Enhanced dehydroepiandrosterone levels are positively correlated with N3 sleep stage in long-term mindfulness meditation practitioners

Objectives: Meditation practices positively influence the neural, hormonal and autonomic systems. We have demonstrated that long-term practice of mindfulness meditation increases N3 and rapid eye movement (REM) sleep stages and bring efficient autonomic modulation during sleep. In the present study, the probable humoral correlation that could bring about these changes is evaluated. Material and Methods: Long-term Vipassana meditators (n=41) and controls (n=24) (males, 30-60 years of age) underwent a two-day consecutive whole night polysomnography recording. During the second day, with exposure to 100Lux brightness, blood was sampled from the antecubital vein between 8-9 PM and in subsequent early morning. Sleep stage was scored as per American Society of Sleep Medicine (ASSM) guidelines for the second-day recording. Sleep-related hormones were estimated - melatonin by radioimmunoassay; dehydroepiandrosterone (DHEA), cortisol, growth hormone (GH) and prolactin with enzyme-linked immunosorbent assay (ELISA); DHEA/cortisol ratio was calculated. Percentage of sleep stages and hormonal levels were compared between both groups using independent ‘t’ test and Pearson’s correlation was estimated between sleep stages and hormonal levels. Results: Meditators showed increased N3, REM sleep stages. Though evening cortisol was comparable between the two groups; early morning cortisol, diurnal DHEA and melatonin were significantly higher in meditators. Diurnal DHEA correlated significantly with the N3 sleep stage in meditators. Discussion: Higher diurnal DHEA despite variations in corresponding cortisol in meditators demonstrates that long-term Vipassana meditation practice modulates the hypothalamicpituitary-adrenal (HPA) axis and thereby influences sleep. Thus, the study provides evidence to explore the mechanism most likely involved with mindfulness meditation intervention in insomnia

Study of cardiac autonomic function in drug-naive, newly diagnosed epilepsy patients

Background: Epilepsy is associated with ictal autonomic dysfunction which may extend into the inter-ictal period. Antiepileptic drugs have often been blamed for cardiac autonomic dysfunction in epilepsy patients. In this study we have investigated cardiac autonomic parameters in order to evaluate autonomic functions of drug-naive epilepsy patients. METHOD: Twenty drug-naive patients (15 males and 5 females) with epilepsy, and an equal number of age and gender matched controls, were evaluated for short-term resting heart rate variability and conventional cardiovascular autonomic measurements. Results: The mean age of patients was 29.30 +/- 9.80 yrs (17-55 yrs), mean age at seizure onset was 19.70 +/- 9.15 yrs (3-40 yrs) and mean length of time since last seizure was 5.60 +/- 7.00 days (1-30 days). While there was no difference in the resting heart rate or conventional autonomic test parameters, time domain heart rate variability measurements showed a decreased percentage of R-R intervals of less than 50 ms and root mean square of R-R intervals in patients, when compared to controls. Frequency domain parameters showed a decreased total power (patients: 1,796.58 +/- 1,052.45 ms2; controls: 2,934.23 +/- 1,767.06 ms2, p = 0.008). Parameters indicative of decreased vagal tone, i.e. decreased high frequency power and increased low to high frequency ratio (patients: 1.69 +/- 0.94; controls: 1.14 +/- 0.64, p = 0.045), were observed among patients compared to controls. CONCLUSION: Subtle but definite cardiac autonomic dysfunction, especially in vagal tone, was identified in drug-naive, new-onset epilepsy patients. Seizures can cause long-term and often progressive cardiac autonomic dysfunction which may be independent of concomitant antiepileptic drugs

Conditioned Medium Reconditions Hippocampal Neurons against Kainic Acid Induced Excitotoxicity: An In Vitro

Stem cell therapy is gaining attention as a promising treatment option for neurodegenerative diseases. The functional efficacy of grafted cells is a matter of debate and the recent consensus is that the cellular and functional recoveries might be due to “by-stander” effects of grafted cells. In the present study, we investigated the neuroprotective effect of conditioned medium (CM) derived from human embryonic kidney (HEK) cells in a kainic acid (KA) induced hippocampal degeneration model system in in vitro condition. Hippocampal cell line was exposed to KA (200 µM) for 24 hrs (lesion group) whereas, in the treatment group, hippocampal cell line was exposed to KA in combination with HEK-CM (KA + HEK-CM). We observed that KA exposure to cells resulted in significant neuronal loss. Interestingly, HEK-CM cotreatment completely attenuated the excitotoxic effects of KA. In HEK-CM cotreatment group, the cell viability was ~85–95% as opposed to 47% in KA alone group. Further investigation demonstrated that treatment with HEK-CM stimulated the endogenous cell survival factors like brain derived neurotrophic factors (BDNF) and antiapoptotic factor Bcl-2, revealing the possible mechanism of neuroprotection. Our results suggest that HEK-CM protects hippocampal neurons against excitotoxicity by stimulating the host’s endogenous cell survival mechanisms

Modulation of Cardiac Autonomic Dysfunction in Ischemic Stroke following Ayurveda (Indian System of Medicine) Treatment

Objectives. Cardiac autonomic dysfunction in stroke has implications on morbidity and mortality. Ayurveda (Indian system of medicine) describes stroke as pakshaghata. We intended to study the effect of Ayurveda therapies on the cardiac autonomic dysfunction. Methods. Fifty patients of ischemic stroke (middle cerebral artery territory) (mean age 39.26 ± 9.88 years; male 43, female 7) were recruited within one month of ictus. All patients received standard allopathic medications as advised by neurologist. In addition, patients were randomized to receive physiotherapy (Group I) or Ayurveda treatment (Group II) for 14 days. Continuous electrocardiogram and finger arterial pressure were recorded for 15 min before and after treatments and analyzed offline to obtain heart rate and blood pressure variability and baroreflex sensitivity (BRS). Results were analysed by RMANOVA. Results. Patients in Group II showed statistically significant improvement in cardiac autonomic parameters. The standard deviation of normal to normal intervals,and total and low frequency powers were significantly enhanced (F=8.16, P=0.007, F=9.73, P=0.004, F=13.51, and P=0.001, resp.). The BRS too increased following the treatment period (F=10.129, P=0.004). Conclusions. The current study is the first to report a positive modulation of cardiac autonomic activity after adjuvant Ayurveda treatment in ischemic stroke. Further long term studies are warranted

Investigation of Autonomic Dysfunction in Alzheimer’s Disease—A Computational Model-Based Approach

(1) Background and Objective: Alzheimer’s disease (AD) is commonly accompanied by autonomic dysfunction. Investigating autonomic dysfunction’s occurrence patterns and severity may aid in making a distinction between different dementia subtypes, as cardiac autonomic dysfunction and AD severity are correlated. Heart rate variability (HRV) allows for a non-invasive assessment of the autonomic nervous system (ANS). AD is characterized by cholinergic depletion. A computational model of ANS based on the kinetics of acetylcholine and norepinephrine is used to simulate HRV for various autonomic states. The model has the flexibility to suitably modulate the concentration of acetylcholine corresponding to different autonomic states. (2) Methods: Twenty clinically plausible AD patients are compared to 20 age- and gender-matched healthy controls using HRV measures. Statistical analysis is performed to identify the HRV parameters that vary significantly in AD. By modulating the acetylcholine concentration in a controlled manner, different autonomic states of Alzheimer’s disease are simulated using the ANS model. (3) Results: In patients with AD, there is a significant decrease in vagal activity, sympathovagal imbalance with a dominant sympathetic activity, and change in the time domain, frequency domain, and nonlinear HRV characteristics. Simulated HRV features corresponding to 10 progressive states of AD are presented. (4) Conclusions: There is a significant difference in the HRV features during AD. As cholinergic depletion and autonomic dysfunction have a common neurological basis, autonomic function assessment can help in diagnosis and assessment of AD. Quantitative models may help in better comprehending the pathophysiology of the disease and assessment of its progress

Prolonged reaction to mental arithmetic stress in first-degree relatives of schizophrenia patients

Objective:  Several studies have reported abnormal heart rate variability (HRV) in schizophrenia patients, suggesting a pathophysiological link between central autonomic dysfunction and symptoms of schizophrenia and that these could be heritable. This study aimed at evaluating cardiac autonomic response to mental arithmetic stress in first-degree relatives of schizophrenia patients (FDRS) employing HRV analysis. Methods: HRV measures were computed for 25 healthy FDRS and 25 age- and gender-matched controls during rest, mental arithmetic stress task and recovery period. Subtracting serial sevens from 700 for five minutes formed the stress task. Recovery period lasted five minutes starting from the termination of the stress task. Results: Both groups showed similar alterations during the stress task. After stress termination, recovery to the basal values was observed in controls but not in patients’ relatives, maintaining a pattern similar to that during the stress task. Conclusions: Poor recovery from cardiac autonomic functions (CAF) alterations induced by arithmetic stress may be a heritable trait marker of schizophrenia. Our report supports endophenotypic potential of HRV in schizophrenia research.</p

Opioid versus non-opioid analgesia for spine surgery:a systematic review and meta-analysis of randomized controlled trials

PURPOSE: Opioids are the primary analgesics used in patients undergoing spine surgery. Postoperative pain is common despite their liberal use and so are opioid-associated side effects. Non-opioid analgesics are gaining popularity as alternative to opioids in spine surgery.METHODS: This systematic review evaluated current evidence regarding opioid and non-opioid intraoperative analgesia and their influence on immediate postoperative pain and adverse events in spine surgery.RESULTS: A total of 10,459 records were obtained by searching Medline, EMBASE and Web of Science databases and six randomized controlled trials were included. Differences in postoperative pain scores between opioid and non-opioid groups were not significant at 1 h: 4 studies, mean difference (MD) = 0.65 units, 95% confidence intervals (CI) [-0.12 to 1.41], p = 0.10, but favored non-opioid at 24 h after surgery: 3 studies, MD = 0.75 units, 95%CI [0.03 to 1.46], p = 0.04. The time for first postoperative analgesic requirement was shorter (MD = -45.06 min, 95%CI [-72.50 to -17.62], p = 0.001), and morphine consumption during first 24 h after surgery was higher in opioid compared to non-opioid group (MD = 4.54 mg, 95%CI [3.26 to 5.82], p &lt; 0.00001). Adverse effects of postoperative nausea and vomiting (Relative risk (RR) = 2.15, 95%CI [1.37 to 3.38], p = 0.0009) and shivering (RR = 2.52, 95%CI [1.08 to 5.89], p = 0.03) were higher and bradycardia was lower (RR = 0.35, 95%CI [0.17 to 0.71], p = 0.004) with opioid analgesia.CONCLUSION: The certainty of evidence on GRADE assessment is low for studied outcomes. Available evidence supports intraoperative non-opioid analgesia for overall postoperative pain outcomes in spine surgery. More research is needed to find the best drug combination and dosing regimen. Prospero Registration: CRD42020209042.</p