Sudden withdrawal of carbamazepine increases cardiac sympathetic activity in sleep.

OBJECTIVE: To evaluate the cardiac autonomic effects of abrupt withdrawal of carbamazepine (CBZ) during sleep in patients with epilepsy. BACKGROUND: The pathophysiology of sudden unexpected death in epilepsy (SUDEP) is uncertain, with ictal or peri-ictal cardiorespiratory compromise appearing probable. Risk factors for SUDEP include multiple antiepileptic drugs (AED), poor compliance, and abrupt AED withdrawal. The spectral analysis of the beat-to-beat heart rate variability (HRV) displays two main components: low frequency (LF), representing sympathetic and parasympathetic influence and high frequency (HF), representing parasympathetic influence. The LF/HF ratio is commonly regarded as an indicator of sympathovagal balance. METHOD: Twelve patients with medically intractable seizures underwent abrupt withdrawal of CBZ to facilitate seizure recording during controlled circuit TV-EEG monitoring. Continuous EKG recording was begun 24 hours before CBZ reduction. Spectral analysis of the HRV was performed during selected samples of non-REM sleep before and after CBZ reduction. Analyses were made at least 6 hours after from (complex) partial and 12 hours from generalized seizures. RESULTS: The mean LF/HF ratio before withdrawal of CBZ was 2.15 compared with a ratio of 2.65 on day 4 after withdrawal, an increase of 19% (geometric mean; 95% CI, 2% to 34%; Wilcoxon test, z = 2.36; p = 0.018). The ratio increased in 10 patients compared with a decrease in only one patient. CONCLUSION: Abrupt withdrawal of CBZ leads to enhanced sympathetic activity in sleep as evidenced by increased LF/HF ratios. Increased sympathetic activity in the setting of seizure-induced hypoxia could predispose to SUDEP.     

A systematic review and meta-analysis of heart rate variability in epilepsy and antiepileptic drugs

Purpose: Epilepsy is associated with near‐fatal and fatal arrhythmias, and sudden unexpected death in epilepsy (SUDEP) is partly related to cardiac events. Dysfunction of the autonomous nervous system causes arrhythmias and, although previous studies have investigated the effects of epilepsy on the autonomic control of the heart, the results are still mixed regarding whether imbalance of sympathetic, vagal, or both systems is present in epilepsy, and also the importance of anticonvulsant treatment on the autonomic system. Therefore, we aimed to investigate epilepsy and its treatment impact on heart rate variability (HRV), assessed by sympathetic and parasympathetic activity expressed as low‐frequency (LF) and high‐frequency (HF) power spectrum, respectively. Method: We performed a systematic review from the first date available to July 2011 in Medline and other databases; key search terms were “epilepsy”; “anticonvulsants”; “heart rate variability”; “vagal”; and “autonomous nervous system.” Original studies that reported data and/or statistics of at least one HRV value were included, with data being extracted by two independent authors. We used a random‐effects model with Hedges’s g as the measurement of effect size to perform two main meta‐analyses comparing LF and HF HRV values in (1) epilepsy patients versus controls; (2) patients receiving versus not receiving treatment; and (3) well‐controlled versus refractory patients. Secondary analyses assessed other time‐ and frequency‐domain measurements (nonlinear methods were not analyzed due to lack of sufficient data sets). Quality assessment of each study was verified and also meta‐analytic techniques to identify and control bias. Meta‐regression for age and gender was performed. Key Findings: Initially, 366 references were identified. According to our eligibility criteria, 30 references (39 studies) were included in our analysis. Regarding HF, epilepsy patients presented lower values (g ?0.69) than controls, with the 95% confidence interval (CI) ranging from ?1.05 to ?0.33. No significant differences were observed for LF (g ?0.18; 95% CI ?0.71 to 0.35). Patients receiving treatment presented HF values to those not receiving treatment (g ?0.05; 95% CI ?0.37 to 0.27), with a trend for having higher LF values (g 0.1; 95% CI ?0.13 to 0.33), which was more pronounced in those receiving antiepileptic drugs (vs. vagus nerve stimulation). No differences were observed for well‐controlled versus refractory patients, possibly due to the low number of studies. Regression for age and gender did not influence the results. Finally, secondary time‐domain analyses also showed lower HRV and lower vagal activity in patients with epilepsy, as shown by the standard deviation of normal‐to‐normal interval (SDNN) and the root mean square of successive differences (RMSSD) indexes, respectively. Significance: We confirmed and extended the hypothesis of sympathovagal imbalance in epilepsy, as showed by lower HF, SDNN, and RMSSD values when compared to controls. In addition, there was a trend for higher LF values in patients receiving pharmacotherapy. As lower vagal (HF) and higher sympathetic (LF) tone are predictors of morbidity and mortality in cardiovascular samples, our findings highlight the importance of investigating autonomic function in patients with epilepsy in clinical practice. Assessing HRV might also be useful when planning therapeutic interventions, as some antiepileptic drugs can show hazardous effects in cardiac excitability, potentially leading to cardiac arrhythmia.     

Heart rate variability in patients with untreated epilepsy.

BACKGROUND: Several studies have reported reduced heart rate variability (HRV) in patients with chronic epilepsy under treatment with antiepileptic drugs. This impairment in cardiac autonomic control might be of relevance in relation to the risk of sudden unexpected death in patients with chronic refractory epilepsy. Little information is, however, available on HRV in untreated patients with newly diagnosed epilepsy. METHODS: We used spectral analysis to assess HRV based on 24h ambulatory EKG recordings in 22 consecutive untreated patients with epilepsy (15 with localization-related, 4 with generalized idiopathic and 3 with undetermined epilepsy). The HRV in these patients was compared with 22 age and sex matched healthy controls. RESULTS: When analysing the full 24h recordings, there were no significant difference between the patients and the controls in any of the analyzed measures of HRV: standard deviation of RR-intervals (P=0.191), total power (P=0.170), very low frequency power (P=0.329), low frequency power (LF) (P=0.161), high frequency power (HF) (P=0.186) and the LF/HF ratio (P=0.472). The results were very similar for daytime and nighttime recordings. CONCLUSION: Our results suggest that there is no major effect of epilepsy as such on HRV in patients with untreated epilepsy. It should be emphasized that this study assessed newly diagnosed patients and that the results may not be applicable to patients with chronic epilepsy.     

Carbamazepine affects autonomic cardiac control in patients with newly diagnosed epilepsy

Previous studies indicate that epilepsy patients may have impaired autonomic cardiovascular control in the interictal state although it is unclear whether the observed reduction in cardiovascular responses is due to the epilepsy and the interictal epileptogenic discharges, or to the treatment with antiepileptic drugs. Spectral analysis of heart rate variability makes it possible to partly separate the sympathetic components, low frequency (LF), from the vagal components, high frequency (HF) of autonomic cardiac control. We used spectral analysis of heart rate variability to assess the effect of carbamazepine (CBZ) on autonomic cardiac control in patients with newly diagnosed epilepsy. Fifteen adult outpatients with newly diagnosed seizures/epilepsy underwent 24 h ambulatory EKG recordings before and after commencement of CBZ treatment. Total power as well as low frequency (LF), very low frequency (VLF) and high frequency (HF) power in heart rate variability was calculated. When analysing the full 24 h recordings, patients had significantly lower standard deviation of RR-intervals (P=0.0015), total power (P=0.0010), LF (P=0.0002), VLF (P=0.0025) and HF (P=0.0139) during treatment with CBZ than before. The results were very similar for daytime and night time recordings. Our observations demonstrate that CBZ may suppress both parasympathetic and sympathetic functions in newly diagnosed patients with epilepsy. The possible implications of our results for sudden unexpected death in epilepsy are discussed.     

Relationship between ischemic stroke location and autonomic cardiac function

Autonomic cardiac dysfunction is a common complication after acute ischemic stroke (IS). We recruited 75 patients with acute IS with measurements of autonomic cardiac function, including heart rate variability (HRV) and associated parameters, and compared them with 81controls. Of the 75 patients, 28 had right hemispheric infarctions (RH), 29 had left hemispheric infarctions (LH), and 18 had brainstem infarctions (BS). A comparison of HRV in all patients with stroke and in control subjects showed significant differences between IS subgroups and controls in low frequency (LF), high frequency (HF), normalized LF, normalized HF, and LF/HF ranges. A post-hoc comparison identified significant differences between patients with IS with BS infarctions and the control group in LF, HF, and LF/HF ranges. BS infarction may cause a much greater increase in sympathetic modulation and reduced vagal activity compared to RH or LH infarction. Our findings provide evidence that acute IS causes significant damage to the cardiovascular autonomic system, manifesting as abnormalities of HRV. BS stroke might correlate with a significant reduction in parasympathetic and an increase in sympathetic influence on HRV.     

Heart rate variability in children with refractory generalized epilepsy.

OBJECTIVE: Repetitive seizures can alter the regulation of cardiac activity by the autonomic nervous system (ANS), and ANS dysregulation is thought to be associated with higher morbidity and mortality in epileptic patients, especially from sudden unexpected death. Few studies of interictal dysregulation of cardiac activity in children with epilepsy have been performed. In this study we characterize heart rate variability (HRV) in children with refractory generalized epilepsy. METHODS: Fifteen male and 15 female children, average age = 10.9+/-0.6 years, all with refractory generalized epilepsy were enrolled into the study group. A control group consisted of 15 males and 15 females with average age = 10.6+/-0.6 years. A lead I ECG was recorded for 5 min in the interictal period during daylight hours from each subject while awake. Frequency-domain analysis of HRV was performed using a non-parametric method of fast Fourier transformation. Changes of HRV were categorized into high frequency power (HF; 0.15-0.45 Hz), which represented vagal regulation, and low frequency power (LF; 0.04-0.15 Hz). LF/(HF+LF) expressed in normalized units (LF%) was considered to mirror sympathetic regulation. RESULTS: There were significant reductions in RR, LF, and HF in the study group when compared to controls. There was no significant difference in LF% between the two groups. CONCLUSIONS: We postulate that the lower HRV in our patients results from parasympathetic or vagal reduction. This suggests that decreased HRV in epileptic children occurs by a different mechanism than in adults with epilepsy.     

Effect of parathormone on heart rate variability in hemodialysis patients

INTRODUCTION: Parathormone (PTH) is a very potent uraemic toxin, which affects heart structure and function. PTH also plays the role in uraemic autonomic neuropathy (AN). The aim of the study was to investigate the relationship between high PTH level and AN assessed with frequency domain measures of heart rate variability (HRV). MATERIALS AND METHODS: A 24-h ECG was performed in 40 HD (F=19, M=21) patients aged 49+/-11 years, duration of HD therapy 37+/-30 months. Frequency domain measures of HRV were obtained according to European Society of Cardiology recommendations. Total spectral power (TP), high frequency band (HF) and low frequency band (LF) were computed as indexes of: total autonomic nervous system (ANS) activity, parasympathetic and sympathetic activities, respectively. LF/HF ratio was calculated. TP, HF, LF and LF/HF were expressed as natural logarithm. Patients were divided into two groups due to PTH level: PTH+ (PTH> or =275 pg/ml) and PTH- (PTH<275 pg/ml). RESULTS: The values of lnTP and lnLF were lower in patients PTH+ than in patients PTH- (6,58+/-0,76 vs. 6,99+/-0,44 ms2, p<0,05, and 4,91+/-0,99 vs. 5,33+/-0,65 ms2, respectively, p=0,06). We also found negative correlation between lnPTH and lnTP (r=-0,47; p<0,005), lnPTH and lnLF (r=-0,35; p<0,05), lnPTH and lnHF (r=-0,34; p<0,05). On multiple regression analysis, lnTP, lnLF and lnHF were independently related to lnPTH. CONCLUSIONS: Parathormone exerts effect on activity of both parts of autonomic nervous system: sympathetic and parasympathetic. High PTH level deteriorates total autonomic activity.     

Heart rate variability remains reduced and sympathetic tone elevated after temporal lobe epilepsy surgery

PurposeThere is evidence of autonomic dysregulation in temporal lobe epilepsy. The structures removed during temporal lobectomy are important centers of central cardiovascular control; therefore surgery may conceivably alter the cardiovascular autonomic function. The effects of temporal lobectomy on autonomic cardiac control are controversial. We investigated the effects of temporal lobectomy on heart rate variability (HRV) in the early and late postoperative periods.MethodsWe used 1-h ECG recordings to assess heart rate variability by spectral analysis in 24 consecutive patients who underwent temporal lobectomy due to intractable temporal lobe epilepsy. ECG recordings were performed before and twice (early and late) after surgery. The results were compared with age and sex matched controls.ResultsWhen compared with controls, all the time and frequency domain indices (SDRR, RMSSD, TP, LF and HF) were significantly lower in the patient group before surgery. Findings were similar in the early and late post-operative periods except that the LF/HF ratio increased in the patient group after the late post-operative period. Within the patient group, compared to pre-operative results, normalized HF was increased in the early post-operative period; however in the late post-operative period, LF/HF ratio was increased.ConclusionsThese findings show that in patients with intractable temporal lobe epilepsy, HRV is decreased globally in both sympathetic and parasympathetic domains. While the total HRV remains reduced throughout the postoperative periods, the LF/HF ratio, i.e., sympathovagal balance is altered, in favor of parasympathetic side early after surgery, but towards the sympathetic side after the first postoperative month.     

Sympathetic and parasympathetic activities evaluated by heart-rate variability in head injury of various severities.

OBJECTIVE: To investigate the autonomic function in patients with brain damage of various extents. The purposes were to correlate the parameters derived from spectral analysis of the heart-rate variability (HRV) with the classic Glasgow coma scale (GCS), and to evaluate the possible clinical application of HRV in the autonomic functions in patients with various severities of brain-stem injury. METHODS: A total of 90 patients was divided into 5 groups based on the GCS: I: 15, II: 9-14, III: 4-8, no pupil dilatation, IV: 4-8, pupil dilatation, and V: 3, brain death. Electrocardiogram was recorded for frequency-domain analysis of RR intervals. HRV were categorized into the low-frequency (LF, 0.04-0.15Hz) and high-frequency power (HF, 0.15-0.40Hz), LF to HF power ratio (LF/HF), normalized powers (LF and HF%). These HRV parameters were correlated with the severity of brain damage. RESULTS: The LF, HF, LF%, and LF/HF in Group I were essentially similar to those in the normal subjects. LF and HF decreased from Group I to IV. All parameters were nearly absent in Group V. CONCLUSIONS: The increases in LF% and LF/HF with the decrease in HF indicate augmented sympathetic and attenuated parasympathetic drive. These changes were related to the severity of brain-stem damage. Both LF and HF were nearly abolished in brain death. SIGNIFICANCE: Our analysis indicates that HRV may be an useful tool for evaluating the autonomic functions in patients with brain damage of various degrees.     

Time and frequency domain analyses of heart rate variability in patients with epilepsy

Heart rate variability (HRV) is a useful tool for the detection of sympathetic-parasympathetic balance of autonomic nervous system in patients at risk of sudden death (SD). SD is more common in patients with epilepsy and the exact mechanisms of SD are unknown. Autonomic nervous system involvement in patients with epilepsy has rarely been studied and has shown conflicting results. Our purpose was to determine if HRV showed any changes in patients with epilepsy in comparison with normal population. A short period analysis of HRV was performed for both the frequency and time domain in 43 epilepsy patients who had generalized tonic-clonic seizures (GTCS) and who were not taking any medications and also in 43 age and sex matched controls. In the time domain analysis, patients displayed higher SDNN (standard deviation of all R-R intervals), SDANN (standard deviation of mean NN intervals in 5 min recordings) and HRV triangular index than did healthy subjects (p < 0.0001). Patients tended to display higher pNN50 (number of R-R intervals differed by > 50 ms from adjacent interval divided by the total number of all R-R intervals) and RMSSD (root-mean-square of successive differences) values than did healthy subjects, but the differences were not statistically significant (p > 0.05). In the frequency domain analysis, the spectral measures of HRV showed a reduction of high frequency (HF) values (is a marker of parasympathetic activity) and an increase of low frequency (LF) values (is a measure of sympathetic activity); as a result, the ratio between low and high frequencies (LF/HF) was significantly increased (p < 0.0001, p < 0.0001 and p < 0.001, respectively). Our data suggests an increase in the sympathetic control of the heart rate in epilepsy patients who have GTCS. This increased sympathetic activity could play a key role in the development of ventricular tachyarrhythmias in patients with epilepsy and may be related to the higher incidence of sudden death in this disorder as compared to controls.     

Cardiac autonomic dysfunction in drug naïve hot water epilepsy

PurposeThis study aimed to characterize the role of autonomic nervous system dysfunction in hot water epilepsy (HWE). Heart rate variability (HRV) has been established as a good index of cardio-autonomic regulation.MethodologyForty-five patients with HWE (age: 24.6 ± 10.1 years; M:F = 37:8) and 45 age and gender matched controls (age: 24.17 ± 10.37 years; M:F = 37:8) were studied. Five minutes resting lead II electrocardiogram (ECG) was obtained (AD instruments) under standard conditions and analyzed for time and frequency domain HRV parameters using LabChart software.ResultPatients with hot water epilepsy showed significant increase in LF nu (Low frequency normalized unit) and LF/HF denoting an interictal increase in sympathetic activity. In addition, reductions were noted in parasympathetic function [RMSSD (root mean square successive difference of RR intervals), HF (High frequency) nu and LF/HF].ConclusionThis study has demonstrated an impaired sympatho-vagal balance characterized by increased sympathetic activity and reduced parasympathetic activity in patients with HWE. The present study supports the notion that the hypothalamus is involved in both, the pathogenesis of HWE and autonomic regulation.     

Interictal autonomic abnormalities in idiopathic Rolandic epilepsy

We investigated 50 young patients with a diagnosis of Rolandic Epilepsy (RE) for the presence of abnormalities in autonomic tone compared with 50 young patients with idiopathic generalized epilepsy with absences and 50 typically developing children of comparable age. We analyzed time domain (N-N interval, pNN50) and frequency domain (High Frequency (HF), Low Frequency (LF) and LF/HF ratio) indices from ten-minute resting EKG activity. Patients with RE showed significantly higher HF and lower LF power and lower LF/HF ratio than controls, independent of the epilepsy group, and did not show significant differences in any other autonomic index with respect to the two control groups. In RE, we found a negative relationship between both seizure load and frequency of sleep interictal EEG abnormalities with parasympathetic drive levels. These changes might be the expression of adaptive mechanisms to prevent the excessive sympathetic drive seen in patients with refractory epilepsies.     

Heart rate variability measures as biomarkers in patients with psychogenic nonepileptic seizures: potential and limitations

Heart rate variability (HRV) metrics provide reliable information about the functioning of the autonomic nervous system (ANS) and have been discussed as biomarkers in anxiety and personality disorders. We wanted to explore the potential of various HRV metrics (VLF, LF, HF, SDNN, RMSSD, cardiovagal index, cardiosympathetic index, approximate entropy) as biomarkers in patients with psychogenic nonepileptic seizures (PNES). HRV parameters were extracted from 3-minute resting single-lead ECGs of 129 subjects (52 with PNES, 42 with refractory epilepsy and 35 age-matched healthy controls). Compared with healthy controls, both patient groups had reduced HRV (all measures P < 0.03). Binary logistic regression analyses yielded significant models differentiating between healthy controls and patients with PNES or patients with epilepsy (correctly classifying 86.2 and 93.5% of cases, respectively), but not between patients with PNES and those with epilepsy. Interictal resting parasympathetic activity and sympathetic activity differ between healthy controls and patients with PNES or those with epilepsy. However, resting HRV measures do not differentiate between patients with PNES and those with epilepsy.     

Specific acupuncture sensation correlates with EEGs and autonomic changes in human subjects

Sympathetic overactivation is suggested to be associated with chronic pain syndrome, and acupuncture is frequently applied in therapy for this syndrome. Furthermore, the forebrain including the various cerebral cortices has been implicated in inhibitory and facilitatory control of pain as well as autonomic functions. We investigated relationships among specific sensations induced by acupuncture manipulation, effects on sympathetic and parasympathetic autonomic functions, and EEG changes. An acupuncture needle was inserted into the right trapezius muscle of the subjects, and acupuncture manipulation was repeated to induce specific acupuncture sensation repeatedly while the needle was left in the muscle. Acupuncture manipulation significantly decreased heart rate (HR), and increased systolic blood pressure (SBP). Spectral analysis indicated that acupuncture manipulation significantly decreased low frequency components (LF) of both HR variability (HRV) and SBP variability (SBPV), and significantly reduced ratio of LF to high frequency component (HF) of HRV (LF/HF, index of sympathetic activity). Furthermore, there was a significant negative correlation between changes in LF/HF ratio of HRV and the number of specific acupuncture sensations reported, and a significant positive correlation between HF of HRV and the number of acupuncture sensations. Analyses of EEG data indicated that acupuncture manipulation non-specifically increased power of all spectral bands except the gamma band. Furthermore, changes in HF (index of parasympathetic activity) and total power (overall activity of the autonomic nervous system) of HRV were positively correlated with changes in theta, alpha, and gamma power, while changes in LF of SBPV and LF/HF of HRV were negatively correlated with changes in power of all spectral bands. These results are consistent with the suggestion that autonomic changes induced by manipulation inducing specific acupuncture sensations might be mediated through the central nervous system, especially through the forebrain as shown in EEG changes, and are beneficial to relieve chronic pain by inhibiting sympathetic nervous activity.     

Heart rate variability measures as biomarkers in patients with psychogenic nonepileptic seizures: Potential and limitations

Heart rate variability (HRV) metrics provide reliable information about the functioning of the autonomic nervous system (ANS) and have been discussed as biomarkers in anxiety and personality disorders. We wanted to explore the potential of various HRV metrics (VLF, LF, HF, SDNN, RMSSD, cardiovagal index, cardiosympathetic index, approximate entropy) as biomarkers in patients with psychogenic nonepileptic seizures (PNES). HRV parameters were extracted from 3-minute resting single-lead ECGs of 129 subjects (52 with PNES, 42 with refractory epilepsy and 35 age-matched healthy controls). Compared with healthy controls, both patient groups had reduced HRV (all measures P < 0.03). Binary logistic regression analyses yielded significant models differentiating between healthy controls and patients with PNES or patients with epilepsy (correctly classifying 86.2 and 93.5% of cases, respectively), but not between patients with PNES and those with epilepsy. Interictal resting parasympathetic activity and sympathetic activity differ between healthy controls and patients with PNES or those with epilepsy. However, resting HRV measures do not differentiate between patients with PNES and those with epilepsy.     

Comparison of heart rate variability parameters during complex partial seizures and psychogenic nonepileptic seizures

Purpose: Psychogenic nonepileptic seizures (PNES) superficially resemble epileptic seizures. Little is known about ictal autonomic nervous system (ANS) activity changes in epilepsy and PNES. This study compares ictal heart rate variability (HRV) parameters as a reflection of ANS tone in epileptic seizures and PNES, and explores differences between interictal and ictal ANS tone in both patient groups. Methods: Ictal HRV parameters were extracted from single‐lead electrocardiography (ECG) data collected during video–electroencephalography (EEG) recordings of 26 patients with medically refractory temporal lobe epilepsy and 24 age‐ and sex‐matched patients with PNES. One seizure per patient in a resting, wake, supine state was analyzed. Interictal ECG data were available for comparison from 14 patients in both groups. HRV parameters in time and frequency domains were analyzed (low frequency [LF], high frequency [HF], standard deviation of all consecutive normal R wave intervals [SDNN], square root of the mean of the sum of the squares of differences between adjacent normal R wave intervals [RMSSD]). CVI (cardiovagal index), CSI (cardiosympathetic index), and ApEn (approximate entropy) were calculated from Lorenz plots. Key Findings: There were significant differences between ictal HRV measures during epileptic and nonepileptic seizures in the time and frequency domains. CSI (p < 0.001) was higher in epileptic seizures. Time interval between two consecutive R waves in the ECG (RR interval) (p = 0.002), LF (p = 0.02), HF (p = 0.003), and RMSSD (p = 0.003) were significantly lower during epileptic seizures. Binary logistic regression yielded a significant model based on the differences in CSI classifying 88% of patients with epilepsy and 73% of patients with PNES correctly. The comparison between resting and ictal states in both seizure disorders revealed significant differences in RR interval (epilepsy p < 0.001, PNES p = 0.01), CSI (epilepsy p < 0.001, PNES p = 0.02), HF (epilepsy p = 0.002, PNES p = 0.03), and RMSSD (epilepsy p = 0.004, PNES p = 0.04). In patients with epilepsy there were also significant differences in ictal versus interictal mean values of ApEn (p = 0.03) and LF (p = 0.04). Although CSI was significantly higher, the other parameters were lower during the seizures. Stepwise binary regression in the 14 patients with epilepsy produced a significant model differentiating resting state from seizures in 100% of cases. The same statistical approach did not yield a significant model in the PNES group. Significance: Our results show greater ANS activation in epileptic seizures than in PNES. The biggest ictal HRV changes associated with epileptic seizures (CSI, HF, and RMSSD) reflect high sympathetic system activation and reduced vagal tone. The reduced ApEn also reflects a high sympathetic tone. The observed ictal alterations of HRV patterns may be a more specific marker of epileptic seizures than heart rate changes alone. These altered HRV patterns could be used to detect seizures and also to differentiate epileptic seizures from PNES. Larger studies are justified with intergroup and intragroup comparisons between ictal and resting states.     

Suppressing cardiac vagal modulation and changing sleep patterns in rats after chronic ischemic stroke injury

Chronic autonomic function and sleep architecture changes in patients post-stroke are not well understood. Using wireless polysomnographic recordings, this study aimed to investigate the long-term effects on sleep patterns and autonomic function in free moving rats after middle cerebral artery occlusion (MCAO). The sleep pattern and heart rate variability (HRV) of Wistar-Kyoto rats (WKY) were analyzed. After 7-10days, the rats were divided into two groups: an MCAO group (n=8) and a sham surgery group (n=8). Compared with shams, MCAO rats showed decreased accumulated quiet sleep (QS) time over 24h during the 3rd week. The time percentage, duration and delta power of QS were also significantly decreased in the MCAO group during the dark period. Compared with baseline, there were significant increases in the parasympathetic-associated HRV measures in the sham group, including the total power (TP), high frequency power (HF) and lower frequency power (LF), throughout the post-operative weeks (primarily the 2nd and 3rd weeks), reflecting a developmental increase of parasympathetic modulation; the normalized LF and the LF-HF ratio were unaffected. In great contrast, however, most of the HRV measures in the MCAO group were not significantly changed. Therefore, this study showed that the long-term effects of ischemic stroke injury involve retardation of the establishment of parasympathetic enhancement and disturbance of the normal sleep-wake cycle.     

Heart rate variability in patients with different manifestations of gastroesophageal reflux disease

BACKGROUND: Autonomic nervous dysfunction has frequently been observed in patients with gastroesophageal reflux diseases (GERD) and impacts the pathogenesis of GERD. However, the characteristics that distinguish between GERD patients with different manifestations remain unknown. AIM: To investigate the autonomic nervous function in subgroups of GERD patients. PATIENTS: Of the 164 participants in this study, 57 were healthy controls, 34 had non-erosive reflux disease (NERD), 40 had symptomatic esophagitis (SE), and 33 asymptomatic esophagitis (AE). METHODS: Resting autonomic activity was assessed by measuring the 5-min heart rate variability (HRV) and HRV indices including time-domain parameters (standard deviation of normal-to-normal intervals [SDNN] and root mean square of successive differences [RMSSD]) and frequency-domain parameters (low-frequency power [LF; 0.04-0.15 Hz], high-frequency power [HF; 0.15-0.4 Hz], and LF/HF power ratio). Mental stress was assessed by use of a self-reported questionnaire (Brief Symptom Rating Scale [BSRS]). RESULTS: HF power was (ANOVA, p=0.041) but time-domain parameters, LF power, LF/HF power ratio, and BSRS parameters were not significantly different between the four groups. A higher HF power was found in examinees with NERD than in those with SE and AE (LSD methods: both p=0.02). When split into two groups (erosive vs. non-erosive), nearly all measures of autonomic tonus were significantly lower in the erosive than non-erosive group. Age and the presence of endoscopic esophagitis influenced the RMSSD and HF power results in the regression analysis. Mental stress or gender did not correlate with any HRV index. CONCLUSION: In comparison with NERD subjects, autonomic tonus in patients with endoscopically confirmed esophagitis (even without symptom) is lower. This finding may suggest that the structural state of esophagus but not symptomatology dictates autonomic function status.     

Autonomic function in the early stage of panic disorder: power spectral analysis of heart rate variability

Previous studies of autonomic nervous system (ANS) function in panic disorder (PD) patients have yielded conflicting results. We speculate that these differences might result from the variety of clinical stages of PD. In order to investigate this, we compared ANS activity in untreated patients in the early stage of PD with control subjects using power spectral analysis of electrocardiogram R-R intervals (PSR-R) in supine rest and during head-up tilt, which was performed according to the maximum entropy method (MEM). It recognizes two main components: high-frequency power (HF), which mainly reflects cardiac parasympathetic activity, and low-frequency power (LF), which reflects both cardiac sympathetic and parasympathetic activity. The patients with PD had significantly higher values for all components of PSR-R only in tilt position total power (TP), LF, and HF than did the control subjects (P<0.01, <0.01, <0.02, respectively). However, the LF/HF ratio which indicated sympathovagal balance did not differ significantly between the two groups in tilt position. Our findings suggest that patients with PD in the early stage of illness have co-activation of sympathetic and parasympathetic nervous systems, which might act to maintain a balance between the two autonomic systems.     

Parasympathetic activity correlates with early outcome in patients with large artery atherosclerotic stroke

To evaluate the associations between autonomic function and early stroke outcome in different subtypes of cerebral infarct, 24 patients with acute large artery atherosclerotic infarction (LAA), 26 patients with acute lacunar infarction (LAC), and 19 control subjects were prospectively recruited. Stroke outcome by the National Institute of Health Stroke Score (NIHSS) and heart rate variability (HRV) by power spectral analysis were recorded. The LAA group had lower high-frequency power (HF, P=0.017), lower normalized HF (P=0.002), higher normalized low-frequency power (LF%, P=0.016), and higher ratio of LF to HF (P=0.003) than both the LAC and control groups. Multivariate regression analysis in the LAA group showed that HF significantly correlated with early outcome (standardized coefficient=-0.486, P=0.016), and HF less than 3.9 [ln(ms(2))] was an independent risk factor for NIHSS≥4 at seventh day after admission (odd ratio=6.00, 95% confidence interval 1.02-35.37, P=0.048). There was no significant correlation between any HRV parameter and early stroke outcome in the LAC group. There were different autonomic function properties between LAA and LAC groups, and depressed parasympathetic modulation was associated with worse early outcome in patients with LAA.