ABSTRACT
Epilepsy's impact on cardiovascular function and autonomic regulation, including heart-rate variability, is complex and may contribute to sudden unexpected death in epilepsy (SUDEP). Lateralization of autonomic control in the brain remains the subject of debate; nevertheless, ultra-short-term heart-rate variability (HRV) analysis is a useful tool for understanding the pathophysiology of autonomic dysfunction in epilepsy patients. A retrospective study reviewed medical records of patients with temporal lobe epilepsy who underwent presurgical evaluations. Data from 75 patients were analyzed and HRV indices were extracted from electrocardiogram recordings of preictal, ictal, and postictal intervals. Various HRV indices were calculated, including time domain, frequency domain, and nonlinear indices, to assess autonomic function during different seizure intervals. The study found significant differences in HRV indices based on hemispheric laterality, language dominancy, hippocampal atrophy, amygdala enlargement, sustained theta activity, and seizure frequency. HRV indices such as the root mean square of successive differences between heartbeats, pNN50, normalized low-frequency, normalized high-frequency, and the low-frequency/high-frequency ratio exhibited significant differences during the ictal period. Language dominancy, hippocampal atrophy, amygdala enlargement, and sustained theta activity were also found to affect HRV. Seizure frequency was correlated with HRV indices, suggesting a potential relationship with the risk of SUDEP.
ABSTRACT
Background and Objectives: Abnormal epileptic discharges in the brain can affect the central brain regions that regulate autonomic activity and produce cardiac symptoms, either at onset or during propagation of a seizure. These autonomic alterations are related to cardiorespiratory disturbances, such as sudden unexpected death in epilepsy. This study aims to investigate the differences in cardiac autonomic function between patients with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE) using ultra-short-term heart rate variability (HRV) analysis around seizures. Materials and Methods: We analyzed electrocardiogram (ECG) data recorded during 309 seizures in 58 patients with epilepsy. Twelve patients with FLE and 46 patients with TLE were included in this study. We extracted the HRV parameters from the ECG signal before, during and after the ictal interval with ultra-short-term HRV analysis. We statistically compared the HRV parameters using an independent t-test in each interval to compare the differences between groups, and repeated measures analysis of variance was used to test the group differences in longitudinal changes in the HRV parameters. We performed the Tukey-Kramer multiple comparisons procedure as the post hoc test. Results: Among the HRV parameters, the mean interval between heartbeats (RRi), normalized low-frequency band power (LF) and LF/HF ratio were statistically different between the interval and epilepsy types in the t-test. Repeated measures ANOVA showed that the mean RRi and RMSSD were significantly different by epilepsy type, and the normalized LF and LF/HF ratio significantly interacted with the epilepsy type and interval. Conclusions: During the pre-ictal interval, TLE patients showed an elevation in sympathetic activity, while the FLE patients showed an apparent increase and decrease in sympathetic activity when entering and ending the ictal period, respectively. The TLE patients showed a maintained elevation of sympathetic and vagal activity in the pos-ictal interval. These differences in autonomic cardiac characteristics between FLE and TLE might be relevant to the ictal symptoms which eventually result in SUDEP.
Subject(s)
Epilepsy, Frontal Lobe , Epilepsy, Temporal Lobe , Autonomic Nervous System , Electroencephalography , Epilepsy, Temporal Lobe/complications , Heart Rate , Humans , SeizuresABSTRACT
CONTEXT: The relative contribution of central adiposity vs. weight on GH response to stimulation testing in obesity is not known. OBJECTIVE: We aimed to assess the contribution of weight and specific measures of central and peripheral adiposity to GH response to GHRH-arginine testing in lean, overweight, and obese men. DESIGN: A total of 75 men [mean age, 44.3+/-1.1 yr; body mass index (BMI), 28.8+/-0.7 kg/m2] were investigated. Subjects were classified as lean (BMI<25 kg/m2; n=23), overweight (BMI>or=25 and <30 kg/m2; n=28), or obese (BMI>or=30 kg/m2; n=24). Subjects were also stratified by waist circumference (WC) (<102 cm, n=47; >or=102 cm, n=28). Body composition and regional adiposity were assessed by anthropometrics, dual-energy x-ray absorptiometry (DEXA), and abdominal computed tomography (CT) scans. RESULTS: Peak stimulated GH was 36.4+/-5.4, 16.6+/-2.9, and 7.6+/-0.9 microg/liter among lean, overweight, and obese subjects, respectively (P<0.001 for all comparisons). Peak stimulated GH was 26.9+/-3.4 microg/liter among subjects with WC less than 102 cm compared to 7.9+/-0.9 microg/liter among subjects with WC of 102 cm or greater (P<0.0001). Separate multivariate models using anthropometric, DEXA, and CT-derived measures of central adiposity demonstrated strong associations between peak stimulated GH and measures of central adiposity including WC, trunk fat by DEXA, and visceral adiposity by CT, controlling for age, BMI, and more general measures of adiposity. WC was independently associated with peak GH response to GHRH-arginine in a model including age, BMI, and hip circumference. In this model, BMI was no longer significant, and peak GH was reduced 1.02 microg/liter for each 1 cm increase in WC (P=0.02). CONCLUSIONS: GH response to GHRH-arginine testing is reduced in both overweight and obese subjects and negatively associated with indices of central abdominal obesity including WC, trunk fat, and visceral adipose tissue. The use of waist circumference, as a surrogate for central adiposity, adds predictive information to the determination of GH response, independent of BMI.
Subject(s)
Adiposity , Growth Hormone-Releasing Hormone/pharmacology , Growth Hormone/blood , Adipose Tissue/anatomy & histology , Adult , Arginine/pharmacology , Aspartate Aminotransferases/blood , Body Composition , Body Height , Body Mass Index , Body Weight , Humans , Male , Middle Aged , Obesity/blood , Thinness/blood , Young AdultABSTRACT
CONTEXT: Antiretroviral therapy can be associated with visceral adiposity and metabolic complications, increasing cardiovascular risk, and reduced growth hormone (GH) secretion may be a contributing factor. OBJECTIVE: To investigate the effects of low-dose physiological GH administration on body composition, glucose, and cardiovascular parameters in patients with human immunodeficiency virus (HIV) having abdominal fat accumulation and relative GH deficiency. DESIGN, SETTING, AND PATIENTS: A randomized, double-blind, placebo-controlled trial of 56 patients with HIV, abdominal fat accumulation, and reduced GH secretion (peak GH <7.5 ng/mL) conducted at a US academic medical center between November 2003 and October 2007. INTERVENTION: Patients were randomly assigned to receive either subcutaneous GH or matching placebo titrated to the upper quartile of normal insulinlike growth factor 1 (IGF-1) range for 18 months. Starting dose was 2 microg/kg/d and increased to maximum dose of 6 microg/kg/d (average dose, 0.33 mg/d). MAIN OUTCOME MEASURES: Change in body composition assessed by computed tomographic scan and dual-energy x-ray absorptiometry. Secondary outcomes included glucose, IGF-1, blood pressure (BP), and lipids. Treatment effect was the difference in the change between GH and placebo groups, using all available data. RESULTS: Fifty-five patients (26 with GH and 29 with placebo) were included in the safety analyses and 52 patients (25 with GH and 27 with placebo) were included in the efficacy analyses. Visceral adipose tissue area (treatment effect [last-value-carried-forward analysis {n = 56}, -19 cm(2); 95% confidence interval {CI}, -37 to -0.3 cm(2)], -19 cm(2); 95% CI, -38 to -0.5 cm(2); P = .049); trunk fat (-0.8 kg; 95% CI, -1.5 to -0.04 kg; P = .04); diastolic BP (-7 mm Hg; 95% CI, -11 to -2 mm Hg; P = .006); and triglycerides (-7 mg/dL, P = .002) improved but 2-hour glucose levels on glucose tolerance testing increased in the GH group vs the placebo group (treatment effect, 22 mg/dL; 95% CI, 6-37 mg/dL; P = .009). The IGF-1 levels increased (treatment effect, 129 ng/mL; 95% CI, 95-164 ng/mL; P < .001). Adverse events were not increased for GH vs placebo (23%; 95% CI, 9%-44% vs 28%; 95% CI, 13%-47%; P = .70). CONCLUSIONS: In HIV-associated abdominal fat accumulation and relative GH deficiency, low-dose GH received for 18 months resulted in significantly reduced visceral fat and truncal obesity, triglycerides, and diastolic BP, but 2-hour glucose levels on glucose tolerance testing were increased. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00100698.
Subject(s)
Growth Hormone/deficiency , HIV-Associated Lipodystrophy Syndrome/drug therapy , HIV-Associated Lipodystrophy Syndrome/metabolism , Human Growth Hormone/therapeutic use , Abdominal Fat , Adiponectin/blood , Adult , Blood Glucose/metabolism , Blood Pressure/drug effects , Body Composition/drug effects , Carotid Arteries/diagnostic imaging , Double-Blind Method , Female , Growth Hormone/metabolism , Humans , Insulin/blood , Insulin-Like Growth Factor I/metabolism , Lipids/blood , Male , Middle Aged , Quality of Life , Recombinant Proteins , UltrasonographyABSTRACT
OBJECTIVE: To determine the effects of gender, race, and fat redistribution on growth hormone (GH) secretory patterns in HIV-infected patients. DESIGN: We investigated GH responses to growth hormone releasing hormone (GHRH) + arginine stimulation testing in HIV-infected subjects with fat redistribution, comparing HIV-infected males (n = 139) and females (n = 25) to non HIV-infected male (n = 25) and female (n = 26) control subjects similar in age, body mass index and race. METHODS: A standard GHRH + arginine stimulation test [GHRH 1 microg/kg and arginine 0.5 g/kg (maximum dose 30 g)] was performed, and fat redistribution was assessed by anthropometry. RESULTS: HIV-infected women had significantly higher peak GH in response to GHRH + arginine (36.4 +/- 7.3 versus 18.9 +/- 2.0 ng/ml; P = 0.003) and GH area under curve (AUC) (2679 +/- 593 versus 1284 +/- 133 (mg-min)/dl, P < 0.001) compared to HIV-infected men. Among men, a cutoff of 7.5 ng/ml for peak GH response on the GHRH + arginine test achieved good specificity and sensitivity and optimally separated the HIV and control groups (e.g., the failure rates were 37% versus 8%; P = 0.004, respectively). Among women, no specific cutoff could be determined to separate the HIV-infected and control subjects. Non-Caucasians demonstrated a higher GH AUC response compared to Caucasians, among the HIV-infected male subjects. In stepwise regression modeling waist-to-hip ratio was most significantly related to peak GH in response to GHRH + arginine in HIV-infected men. CONCLUSIONS: HIV-infected men with fat redistribution have significantly reduced GH peak responses and increased failure rates to standardized GH stimulation testing in comparison to healthy male control subjects and to HIV-infected women of similar age and body mass index. GH secretion is related to gender and race in HIV-infected patients.