Auditory brainstem response (ABR) in congenital central alveolar hypoventilation

Auditory brainstem responses (ABRs) were studied in a child with congenital central alveolar hypoventilation showing marked depression of respiratory drive during sleep. During wakefulness and normoventilation no ABR abnormalities were found, either at the age of 14 months or five years. ABR recordings during sleep at 14 months of age showed marked wave V latency and wave I to wave V interpeak latency prolongation of about 0.4 ms both for periods of hypoventilation and normoxic hypercapnia. ABR findings of this and other studies carried out in sleep apneas are discussed with respect to brainstem dysfunction associated with varied sleep apnea syndromes.     

Cardio-respiratory control in an infant with Ondine's curse: a multivariate autoregressive modelling approach

We applied spectral analysis through multivariant autoregressive model fitting [1] to RR interval (RRI) and respiratory (RES) oscillation obtained during quiet sleep in an infant with congenital central hypoventilation syndrome (Ondine's curse), a child with obstructive sleep apnea, and two healthy children. Power spectra, impulse response and noise contribution ratio between RRI and RES oscillation were calculated by using a minicomputer PFU-1200 (FACOM) to determine the structure of the feedback system between RRI and RES within the central nervous system. We found that the respiratory noise contribution ratio to RRI was significantly smaller in Ondine's curse (37 ± 7.7%, at 0.23 Hz) than in obstructive sleep apnea (90 ± 6.7%, at 0.39 Hz) and healthy subjects. We postulate that the result shows disturbance of the central autonomic control of breathing and heart rate in Ondine's curse.     

A case of a child who developed Cushing reflex after a clinical diagnosis of brain death

The author presents a case of brain death caused by salmonella encephalopathy in a 1-year-old girl. The patient suffered from fever, convulsive status, and coma. On the 5th day, her respiration was arrested. At that time, we confirmed the absence of brainstem reflexes. An electroencephalogram (EEG) showed a flat pattern. Only wave I was recordable in auditory brainstem responses (ABR). On the 6th day, we obtained a flat EEG and a disappearance of all components of ABR. A simultaneous elevation of her heart rate and blood pressure was observed 14 to 18 hours after the respiratory arrest. This phenomenon was equivalent to the Cushing reflex, which represents an autoregulation against increased intracranial pressure. Our case suggested that the activity of a part of the brainstem was preserved in spite of the absence of activities in EEG, ABR and brainstem reflexes at 14 hours after the onset of apnea.     

Spectral analysis of heart rate in diabetic autonomic neuropathy. A comparison with standard tests of autonomic function

Power spectral analysis of the heart rate was compared with standard tests of autonomic function performed on 15 insulin-dependent diabetic patients with symptoms of autonomic dysfunction. The high-frequency power, low-frequency power, and total power of the heart rate power spectrum measured in the supine position--possible measures of parasympathetic nervous system function--were significant predictors of the expiratory-inspiratory ratio, the beat-to-beat heart rate difference on deep respiration, the standard deviation of the resting heart rate, the 30:15 ratio, and the Valsalva ratio. The change in low-frequency power on moving from the supine to upright position, a possible measure of sympathetic nervous system function, was a modest predictor of the systolic and diastolic blood pressure fall in response to postural change, but a poor predictor of the blood pressure response to isometric exercise and a cold stimulus. This study supports the role of heart rate power spectral analysis as a clinical test of autonomic function in patients with known or suspected autonomic failure.     

Evaluation of autonomic nervous system function with spectral analysis of heart rate variability in a case of tetanus

The autonomic nervous system is affected in a wide variety of neurological disorders. Its dysfunction may play an important role in the clinical course and may result in serious complications, such as cardiac arrest. We report a case of tetanus who presented with severe autonomic nervous system dysfunction which was detected by spectral analysis of heart rate variability monitored over 24 h. This is a semi-quantitative method for evaluation of the status of the autonomic nervous system. In the present case, the analysis revealed profoundly decreased activity of both sympathetic and parasympathetic nervous system modulation of cardiac rhythm. The parasympathetic nervous system activity was more severely impaired than that of the sympathetic nervous system. The relative predominance of the sympathetic nervous system in the present case may have resulted in unopposed sympathetic nervous system hyperactivity manifested in this patient by tachycardia and excessive sweating. We further infer that the documented diminished buffering capacity of the autonomic nervous system may have lead to a sudden cardiac arrest in our case. Thus, spectral analysis of heart rate variability is a non-invasive and sensitive method for evaluating the status of the autonomic nervous system of critically ill patients in the hospital setting.     

Cardiovascular autonomic control in myotonic dystrophy type 1: a correlative study with clinical and genetic data

The autonomic nervous system has been evaluated in myotonic dystrophy with contradictory results and its relationship with heart disturbances remains unclear. Twenty-three patients with myotonic dystrophy type 1 were investigated by a battery of six cardiovascular autonomic tests and power spectral analysis of heart rate variability. Although 15 patients (65%) revealed abnormal or borderline results in some tests, only one patient had a definite autonomic damage, as indicated by two or more abnormal tests. As a group, myotonic dystrophy type 1 patients showed a significant reduction of heart rate variability during deep breathing (P < 0.0001). The exclusive involvement of parasympathetic tests suggests that a mild vagal dysfunction occurs in some myotonic dystrophy type 1 patients. The results indicate that such autonomic abnormalities are not: (1) part of a peripheral neuropathy; (2) related to cytosine-thymine-guanine repeat size or breathing pattern. Power spectral analysis showed a reduction of supine low-frequency band, which is, but not exclusively, a marker of sympathetic activity. It was inversely correlated to disease duration (P < 0.04), suggesting a progression as the disease advances. A low-frequency power, recorded after standing, was significantly associated (P < 0.02) with presence of heart involvement. Our findings suggest that a mixed, especially parasympathetic, autonomic dysfunction may occur in myotonic dystrophy type 1, although it is not a major finding. It could play a role in the occurrence of cardiac abnormalities, or increase the risk of sudden cardiovascular events.     

Abnormal heart rate variability reflecting autonomic dysfunction in brainstem infarction

Objectives Brainstem infarctions frequently cause disturbances of cardiovascular and other autonomic functions, but the pathophysiologic mechanisms of these prognostically unfavourable complications are not well-known.
Material & methods In order to evaluate the effects of ischemic brainstem infarction on autonomic cardiac regulation, we analyzed the power spectrum of heart rate variability in 15 consecutive patients with brainstem infarction and in 15 age- and sex-matched healthy control subjects. The components of the power spectrum which reflect quantitatively both sympathetic and parasympathetic cardiovascular regulatory functions were measured from 24-hour electrocardiogram in the acute phase and at 1 month and 6 months after the infarction.
Results All the measured components of heart rate variability, i.e. total power (p < 0.01), very-low-frequency power (p < 0.001), low-frequency power (p < 0.01), and high-frequency power (p < 0.05), were significantly lower in the patients with medullary brainstem infarction than in the control subjects in the acute phase of the infarction. By 6 months, these abnormalities had been reversed. On the contrary, heart rate variability in pontine brainstem infarct patients did not differ significantly from that in the control subjects.
Conclusions These results suggest that brainstem infarction located in the medulla oblongata causes cardiovascular autonomic dysregulation manifesting as impaired heart rate variability. Medullary brainstem infarction seems to cause both sympathetic and parasympathetic dysfunction, which may contribute to the occurrence of cardiac complications in stroke.     

Disturbances in cardiorespiratory function during day and night in Rett syndrome

Rett syndrome causes severe autonomic dysregulation, probably due to brainstem dysfunction. Because the brainstem plays a decisive role in cardiorespiratory regulation during sleep, we investigated cardiorespiratory function in 12 girls with Rett syndrome, day and night, for 1 week in their home environment. Heart rate and breathing were recorded via standard three-lead electrocardiogram. Depth and frequency of respiratory movements were measured via changes in impedance. All children were scored clinically, and the association with cardiorespiratory function was examined. The total recording time for all patients was 1114 hours (535 during wakefulness; 579 during sleep), and 77 +/- 22 hours (median +/- standard error of the mean) per individual. All subjects manifested apnea, shallow breathing, or hypoventilation, when awake and during sleep. A majority had bradycardia or tachycardia. The frequencies of respiratory and heart alarms were similar during wakefulness and sleep. Bradycardia events predominated during sleep. The only significant correlation between clinical score and cardiorespiratory regulation was found for muscular-skeletal function and breathing abnormalities during wakefulness. We conclude that Rett syndrome is characterized by disturbed breathing and heart rate during sleep. The severity of cardiorespiratory dysfunction exhibited marked intra- and interindividual differences.     

Spectral analysis of heart rate variability following human heart transplantation: evidence for functional reinnervation

To determine the status of innervation in long-term human donor allografts, the power spectrum of heart rate variability was analysed in 9 post-transplant patients and 7 healthy control subjects. The mean post-transplant follow-up was 17.8 months (range: 2-37 months). Continuous ECG signals were recorded throughout a 15-min rest period. An R-R interval tachogram was generated and an autoregressive model using linear predictive coding, was applied to the heart rate variability data. In 8 transplant patients the frequency oscillations were irregular, broad based and widely dispersed from 0 to 1 Hz. The patterns resembled white noise and were consistent with dissociation of the donor allograft from the recipient's central nervous system. In contrast, one patient displayed a heart rate variability spectrum indistinguishable from that of control subjects. This pattern contained two distinct spectral bands; one corresponding to the patient's respiratory rate at 0.2 Hz and a low frequency Mayer wave at 0.1 Hz. Atropine abolished the respiratory (vagal) peak. Except for this patient's post-transplant time (33 months compared to the group mean of 17.6 months), there were no clinical characteristics which distinguished this patient from the others. While the mean heart rate for the remaining 8 allografts was significantly higher than controls (95.3 vs 64.5 bt/min; P less than 0.001) the standard deviation of heart rate variability for the 8 patients was significantly narrower than controls (0.7 vs 4.86; P less than 0.01). The variance of heart rate for the patient with the normal power spectrum was fourfold greater than the mean SD of the other transplant patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Angiotensin II-derived reactive oxygen species underpinning the processing of the cardiovascular reflexes in the medulla oblongata

The brainstem is a major site in the central nervous system involved in the processing of the cardiovascular reflexes such as the baroreflex and the peripheral chemoreflex. The nucleus tractus solitarius and the rostral ventrolateral medulla are 2 important brainstem nuclei, and they play pivotal roles in autonomic cardiovascular regulation. Angiotensin II is one of the neurotransmitters involved in the processing of the cardiovascular reflexes within the brainstem. It is well-known that one of the mechanisms by which angiotensin II exerts its effect is via the activation of pathways that generate reactive oxygen species (ROS). In the central nervous system, ROS are reported to be involved in several pathological diseases such as hypertension, heart failure and sleep apnea. However, little is known about the role of ROS in the processing of the cardiovascular reflexes within the brainstem. The present review mainly discussed some recent findings documenting a role for ROS in the processing of the baroreflex and the peripheral chemoreflex in the brainstem.     

Heart rate variability, sympathetic and vagal balance and EEG arousals in upper airway resistance and mild obstructive sleep apnea syndromes

BACKGROUND AND PURPOSE: We questioned the role of respiratory events in obstructive sleep apnea syndrome (OSAS) and of upper airway resistance syndrome (UARS) on heart rate (HR) during sleep, paying specific attention to the termination of the abnormal breathing events and examining the presence of arousals or termination with only central nervous system (CNS) activation. PATIENTS AND METHODS: Twenty patients, 10 with UARS and 10 with mild OSAS, were studied. A nocturnal polysomnogram was performed including measurement of respiratory variables and pulse transit time (PTT). According to the presence or absence of a PTT event indicative of autonomic nervous system (ANS) activation, 148 events were extracted after having been randomly chosen in each represented sleep stage, with or without an electroencephalogram (EEG) arousal >1.5s. RR interval (RRI) in electrocardiogram (ECG) recordings, as well as heart rate variability, was calculated during 60 and 120s, respectively. Period amplitude analysis (PAA) was applied for RR-interval analysis, and fast Fourier transformation (FFT) was applied to perform HR variability analysis. RESULTS: Visually scored EEG arousal was significantly associated with an increase in sympathetic index of heart rate, while PTT was associated with a drop in parasympathetic index, after the respiratory events. Patients with mild OSAS presented persistently shorter RRI when compared to patients with UARS. The latter also exhibited a significant decrease in parasympathetic index (High Frequency (HF)) at the termination of a respiratory event. CONCLUSION: The HF component was only significantly decreased in patients with UARS, which indicates a predominant involvement of the parasympathetic tone in patients with UARS in comparison to those with OSAS.     

Decreased chaos of heart rate time series in children of patients with panic disorder

This study examined the differences of heart rate variability measures between children of parents with panic disorder and children of healthy controls using linear as well as nonlinear techniques. Supine and standing heart rate variability indices were measured in all children using power spectral analysis and a measure of chaos, the largest Lyapunov exponent (LLE) of heart rate time series. No significant differences emerged between the children of panic disorder parents and children of normal controls on any of the spectral heart rate variability measures. However, children of patients with panic disorder had significantly lower LLE of heart rate time series in supine posture, suggesting a relative decrease of cardiac vagal function in this group of children. This suggests a possible heritable effect of certain measures of heart rate variability, as previous studies showed decreased heart rate variability in patients with panic disorder using spectral as well as nonlinear techniques. Recent evidence also suggests that some of these nonlinear measures are superior or of additional value to the traditional time and frequency domain measures of heart rate variability to predict serious ventricular arrhythmias and sudden death.     

Respiration during sleep in Huntington's chorea

In view of recent reports on lower brainstem dysfunction in Huntington's chorea, we studied respiration during sleep in 12 patients with Huntington's chorea (HC) and in controls. There were no statistically significant differences between patients and controls with respect to apnea periods, respiratory frequency and time elapsed between minimal and maximal value of the respiratory curve. No statistically significant differences in respiratory variability were observed between patients and controls. In the present study, no indication was found for dysfunction of lower brainstem structures involved in respiration in HC.     

A comparison of the three-dimensional auditory brainstem response and the conventional auditory brainstem response in children

For measurement of neural activity in the brainstem auditory pathway, the conventional two-dimensional (2D) auditory brainstem response (ABR) does not provide a true response, because the equivalent dipoles originate from the stereoregularity pathway. It is thus necessary to use three-dimensional (3D) ABR to estimate the true response of the brainstem. We recorded 3D ABR in a group of children and adults, and compared the results with those of the conventional 2D ABR.

The subjects were 22 children (age range 3–10 years) and 10 adults with no neurological disorders, and three patients: a boy and a girl who had experienced sudden brainstem dysfunction, and a girl who had sudden deafness. 3D ABR was recorded for all subjects, and the results were displayed on a computer screen for off-line analysis using an original 3D ABR analysis program.

Four leaf-like vector segments of 3D ABR existed during the first 8 ms after stimulation. Each vector segment corresponded to a peak of the conventional ABR, and showed the original directivity. The amplitudes of waves II and IV of the 3D ABR were significantly larger than those of the conventional ABR. 3D ABR was shown to be superior to the conventional ABR in obtaining absolute amplitude. We were able to clarify the development of brainstem function using 3D ABR. In one patient in whom only one wave was obtained, 3D ABR was able to identify the wave as wave V. These results indicate that ABR is useful both for identifying the kind of wave produced and for suggesting the wave origin.     

Spectral analysis of heart rate variability in the sepsis syndrome

Sympathetic and parasympathetic activity was evaluated on 39 occasions in 17 patients with the sepsis syndrome, by measurement of the variation in resting heart rate using frequency spectrum analysis. Heart rate was recorded by electrocardiography and respiratory rate by impedance plethysmography. The sepsis syndrome was established on the basis of established clinical and physiological criteria. Subjects were studied, whenever possible, during the period of sepsis and during recovery. Spectral density of the beat-to-beat heart rate was measured within the low frequency band 0.04 to 0.10 Hz (low frequency power, LFP) modulated by sympathetic and parasympathetic activity, and within a 0.12 Hz band width at the respiratory frequency mode (respiratory frequency power, RFP) modulated by parasympathetic activity. Results were expressed as the total variability (total area beneath the power spectrum), as the spectral components normalized to the total power (LFP_n, RFP_n) or as the ratio of LFP/RFP. During the sepsis syndrome, total heart rate variability and the sympathetically mediated component, LFP_n were significantly lower than during the following recovery phase (ANOVA,p < 0.0001,p < 0.01 respectively). Both APACHE II (Acute Physiological and Chronic Health Evaluation) and TISS (Therapeutic Intervention Scoring System) scores showed an inverse correlation with total heart rate variability, logLFP, LFP_n and the LFP/RFP ratio (p < 0.002 to 0.0001). Sympathetically mediated heart rate variability was significantly lower during the sepsis syndrome and was inversely proportional to disease severity.     

Autonomic evaluation by means of standard tests and power spectral analysis in multiple sclerosis

Standard autonomic tests [heart rate response to deep breathing (HR_DB), change in systolic blood pressure due to tilt], and spectral analysis of heart rate (HR), arterial blood pressure (ABP), and the associated transfer function analysis (gains and phases) were performed in 20 patients with multiple sclerosis to determine their diagnostic value. Transfer function analysis suggested impairment of baroreflex function in 7 patients and an alteration of cardiorespiratory coupling on a brain stem level in 4 patients. In addition, sympathetic vasomotor outflow was reduced in 2 patients (spectral ABP measures in the mid frequency band) and a decrease of vagal outflow was suggested by abnormal respiratory HR parameters in another 2 patients. An abnormal HR_DB was present in 5 patients and was probably due to a central alteration (cardiorespiratory coupling) in 2 patients and due to diminished respiratory effort in 1 patient. Spectral analysis of both HR and ABP oscillations and their transfer function may considerably improve the pathophysiological interpretation of cardiovascular autonomic dysfunction in patients with central nervous system disease. © 1997 John Wiley & Sons, Muscle Nerve 20: 809–814, 1997     

No auditory conduction abnormality in children with attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral developmental disorder characterized by lack of sustained attention and hyperactivity. It has been suggested that asymmetrical conduction of the auditory stimulus in the brainstem plays a role in the pathophysiological process of ADHD. In the present study, the functional integrity of the central auditory pathway was assessed using the auditory brainstem response (ABR), mid-latency response (MLR) and slow vertex response (SVR). Twenty ADHD children and twenty controls were recruited for the study and recordings were done on a computerized evoked potential recorder using the 10-20 system of electrode placement. There emerged no significant difference in absolute peak latencies, interpeak latencies and amplitude of ABR or latency of MLR in the ADHD children as compared with the controls. Prolongation of the SVR latency was found in the children with ADHD versus the controls, but the difference was statistically insignificant. The present study does not suggest any auditory conduction abnormality as a contributory factor in ADHD.     

Autonomic effects of refractory epilepsy on heart rate variability in children: influence of intermittent vagus nerve stimulation

Aim Vagus nerve stimulation (VNS) is a therapeutic option for individuals with refractory epilepsy. Individuals with refractory epilepsy are prone to dysfunction of the autonomic nervous system. Reduced heart rate variability is a marker of dysfunction of the autonomic nervous system. Our goal was to study heart rate variability in children with refractory epilepsy and the influence of VNS on this parameter. Methods In 17 children (13 male; four female; mean age 7y 6mo; age range 3–16y) with refractory epilepsy, electroencephalographic and electrocardiographic data were obtained before and after implantation of VNS during stage 2 and slow‐wave sleep. Time and frequency domain parameters were calculated and the results were compared with an age‐ and sex‐matched group of individuals without refractory epilepsy. Results Our results show that autonomic cardiac control is affected in individuals with refractory epilepsy. There is a striking reduction in vagal tone during slow‐wave sleep and modulation capacity is smaller than in individuals without refractory epilepsy. Implantation of VNS induces a shift in sympathovagal balance towards sympathetic predominance and an improvement in autonomic modulation. Interpretation Heart rate variability is affected in children with refractory epilepsy, and changes after implantation of VNS. The observed changes could be of importance in the cardiac complications of individuals with epilepsy and should be explored in more detail.     

Evaluation of the vagal-sympathetic interaction in diabetics with autonomic neuropathy through power spectrum density analysis of the heart rate. A critical revision of the natural history of diabetic autonomic neuropathy is possible

In this paper we apply spectral analysis methods to heart rate variability to assess the autonomic nervous system activity in normal subjects and in patients affected by different degrees of diabetic autonomic neuropathy. The current opinion, based on different clinical tests, is that parasympathetic impairment occurs earlier in autonomic dysfunctions. However, the use of power spectrum density analysis based on a single parameter (heart rate) suggests a simultaneous involvement of parasympathetic and sympathetic pathways leading to the conclusion that perhaps the natural history of diabetic autonomic neuropathy should be substantially rewritten.