Autonomic Conditions Research Articles

Cardiac and Autonomic Dysfunctions Assessed Through Recurrence Quantitative Analysis of Electrocardiogram Signals and an Application to the 6-Hydroxydopamine Parkinson's Disease Animal Model.

A classic method to evaluate autonomic dysfunction is through the evaluation of heart rate variability (HRV). HRV provides a series of coefficients, such as Standard Deviation of n-n intervals (SDNN) and Root Mean Square of Successive Differences (RMSSD), which have well-established physiological associations. However, using only electrocardiogram (ECG) signals, it is difficult to identify proper autonomic activity, and the standard techniques are not sensitive and robust enough to distinguish pure autonomic modulation in heart dynamics from cardiac dysfunctions. In this proof-of-concept study we propose the use of Poincaré mapping and Recurrence Quantification Analysis (RQA) to identify and characterize stochasticity and chaoticity dynamics in ECG recordings. By applying these non-linear techniques in the ECG signals recorded from a set of Parkinson’s disease (PD) animal model 6-hydroxydopamine (6-OHDA), we showed that they present less variability in long time epochs and more stochasticity in short-time epochs, in their autonomic dynamics, when compared with those of the sham group. These results suggest that PD animal models present more “rigid heart rate” associated with “trembling ECG” and bradycardia, which are direct expressions of Parkinsonian symptoms. We also compared the RQA factors calculated from the ECG of animal models using four computational ECG signals under different noise and autonomic modulatory conditions, emulating the main ECG features of atrial fibrillation and QT-long syndrome.

A neuro-cardiac self-regulation therapy to improve autonomic and neural function after SCI: a randomized controlled trial protocol

BackgroundSpinal cord injury (SCI) is associated with autonomic imbalance and significant secondary conditions, including cardiac and brain dysfunction that adversely impact health and wellbeing. This study will investigate the effectiveness (intention-to-treat) of a neuro-cardiac self-regulation therapy to improve autonomic and neural/brain activity in adults with SCI living in the community.MethodsA two-arm parallel, randomised controlled trial in which adults with SCI living in the community post-rehabilitation will be randomly assigned to a treatment or control group. The treatment group (N = 60) aged 18–70 years with a chronic traumatic or non-traumatic SCI, will receive intervention sessions once per week for 10 weeks, designed to regulate autonomic activity using computer-based feedback of heart rate variability and controlled breathing (called HRV-F). Comprehensive neurophysiological and psychological assessment will occur at baseline, immediate post-treatment, and 6 and 12-months post-treatment. Primary outcome measures include electrocardiography/heart rate variability (to assess autonomic nervous system function) and transcranial doppler sonography (to assess cerebral blood circulation in basal cerebral arteries). Secondary outcomes measures include continuous blood pressure, electroencephalography, functional near-infrared spectroscopy, respiration/breath rate, electrooculography, cognitive capacity, psychological status, pain, fatigue, sleep and quality of life. Controls (N = 60) will receive usual community care, reading material and a brief telephone call once per week for 10 weeks and be similarly assessed over the same time period as the HRV-F group. Linear mixed model analysis with repeated measures will determine effectiveness of HRV-F and latent class mixture modelling used to determine trajectories for primary and selected secondary outcomes of interest.DiscussionTreatments for improving autonomic function after SCI are limited. It is therefore important to establish whether a neuro-cardiac self-regulation therapy can result in improved autonomic functioning post-SCI, as well as whether HRV-F is associated with better outcomes for secondary conditions such as cardiovascular health, cognitive capacity and mental health.Trial registrationThe study has been prospectively registered with the Australian and New Zealand Clinical Trial Registry (ACTRN12621000870853.aspx).Date of Registration: 6th July 2021.Trial Sponsor: The University of Sydney, NSW 2006.Protocol version: 22/07/2021.

Emotion Analysis Using Electrodermal Signals and Spiking Deep Belief Network.

In this work, an attempt has been made to discriminate arousal and valence dimensions in Electrodermal Activity (EDA) signals using Spiking Deep Belief Network (SDBN). EDA signals having different arousal and valence dimensions are obtained from public online database. These signals are divided into equal parts and normalized using channel normalization. Later, signals are subjected to SDBN for event-related features and classification. A leave-one-out cross validation is used to investigate the classification performance. The result shows that the SDBN classifiers are able to discriminate the emotional states. The network yields better classification performance for emotional dimensions of arousal and valence. It appears that the proposed approach can be used to differentiate autonomic and pathological conditions.

An update on MSA: premotor and non-motor features open a window of opportunities for early diagnosis and intervention

In this review, we describe the wide clinical spectrum of features that can be seen in multiple system atrophy (MSA) with a focus on the premotor phase and the non-motor symptoms providing an up-to-date overview of the current understanding in this fast-growing field. First, we highlight the non-motor features at disease onset when MSA can be indistinguishable from pure autonomic failure or other chronic neurodegenerative conditions. We describe the progression of clinical features to aid the diagnosis of MSA early in the disease course. We go on to describe the levels of diagnostic certainty and we discuss MSA subtypes that do not fit into the current diagnostic criteria, highlighting the complexity of the disease as well as the need for revised diagnostic tools. Second, we describe the pathology, clinical description, and investigations of cardiovascular autonomic failure, urogenital and sexual dysfunction, orthostatic hypotension, and respiratory and REM-sleep behavior disorders, which may precede the motor presentation by months or years. Their presence at presentation, even in the absence of ataxia and parkinsonism, should be regarded as highly suggestive of the premotor phase of MSA. Finally, we discuss how the recognition of the broader spectrum of clinical features of MSA and especially the non-motor features at disease onset represent a window of opportunity for disease-modifying interventions.

Reduced Baroreflex Function in the STZ‐Induced Rat Model of Alzheimer's Disease

BackgroundAlzheimer's disease (AD) is a progressive neurodegenerative disorder causing multiple autonomic conditions including cardiovascular impairments. The inability to maintain blood pressure via baroreflex regulation is up to 5.6 times more prevalent in AD and patients present most commonly with orthostatic hypotension. This study aimed to assess the influence of AD on autonomic regulation of blood pressure using the streptozotocin (STZ)‐induced AD rat model, which mimics many hallmark symptoms of sporadic AD in humans.MethodsMale Sprague‐Dawley rats (345 ± 18 g) were randomly divided into two groups and subjected to intracerebroventricular injection of either vehicle (citrate buffer, CTL) or 2 mg/kg STZ in citrate buffer. After two weeks, memory performance (Morris water maze, MWM), baroreflex function (via femoral cannulation), and heart rate variability (HRV) were evaluated.ResultsMWM verified memory impairment in STZ‐treated rats when compared to CTL (p≤0.01). Analysis of baroreflex function in anesthetized rats revealed a significant impairment in the STZ group when compared to CTL. Particularly, STZ‐treated rats were unable to increase compensatory HR at lower blood pressures (at 50 mmHg: CTL, n=5, 369 ± 13 bpm vs. STZ, n=7, 315 ± 14 bpm; p≤0.05). STZ rats also had a lower baroreflex gain indicating reduced sensitivity to blood pressure fluctuations (p≤0.001). Additionally, recordings of splanchnic sympathetic nerve activity (SSNA) in a subset of rats identified reduced nerve activity during low blood pressure in the STZ group (∫SSNA at 50 mmHg: CTL, n=3, 0.3 ± 0.03 mV.s vs. STZ, n=3, 0.17 ± 0.02 mV.s; p≤0.05). There was no difference between groups at higher blood pressures (150 mmHg). Within the STZ group, HRV was significantly increased only during PE infusion (SDNN, p≤0.05; SD1, p≤0.05; SD2, p≤0.05). Interestingly, the change in HR following blockage of sympathetic or parasympathetic input was not different between groups. Also intrinsic HR and the blood pressure change to ganglionic blockage were similar between STZ and CTL rats.ConclusionsOur study provides the first insight into the pathological influence of AD on baroreflex function. We showed that STZ rats exhibit lower HR and reduced sympathetic output in response to low blood pressure. These results provide the basis for identifying the mechanism behind orthostatic hypotension in AD patients.Support or Funding InformationATSU biomedical grant (JCE) and seed money (TDO)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Autonomic Function and QT Interval During Night-Time Sleep in Infant Long QT Syndrome.

Sudden infant death syndrome mainly occurs during night-time sleep. Approximately 10% of cases are thought to involve infants with long QT syndrome (LQTS). Autonomic function and QT interval in night-time sleep in early infancy in LQTS infants, however, remain controversial.Methods and Results:Holter electrocardiography was performed in 11 LQTS infants before medication in early infancy, and in 11 age-matched control infants. Control infants were re-evaluated in late infancy. The power spectral density was calculated and parasympathetic activity and sympathovagal balance were obtained. Electrocardiograms of a representative hour during night-time sleep, daytime sleep, and daytime activity, were chosen and QT/RR intervals were manually measured. LQTS infants had significantly lower parasympathetic activity and higher sympathovagal balance during night-time sleep than control infants in early infancy. These autonomic conditions in early infancy were significantly depressed compared with late infancy. Corrected QT interval (QTc) during night-time sleep (490±20 ms) was significantly longer than that in daytime sleep (477±21 ms, P=0.04) or daytime activity (458±18 ms, P=0.003) in LQTS infants, and significantly longer than that during night-time sleep in controls. A combination of the longest QTc and autonomic imbalance during night-time sleep in early infancy may be responsible for development of life-threatening arrhythmia in LQTS infants. Critical cases should be included in future studies.

Improved Patient Outcomes by Normalizing Sympathovagal Balance: Differentiating Syncope-Precise Subtype Differentiation Leads to Improved Outcomes.

Syncope is difficult to definitively diagnose, even with tilt-table testing and beat-to-beat blood pressure measurements, the gold-standard. Both are qualitative, subjective assessments. There are subtypes of syncope associated with autonomic conditions for which tilt-table testing is not useful. Heart rate variability analyses also include too much ambiguity. Three subtypes of syncope are differentiated: vasovagal syncope (VVS) due to parasympathetic excess (VVS-PE), VVS with abnormal heart rate response (VVS-HR), and VVS without PE (VVS-PN). P&S monitoring (ANSAR, Inc., Philadelphia, PA) differentiates subtypes in 2727 cardiology patients (50.5% female; average age: 57 years; age range: 12–100 years), serially tested over four years (3.3 tests per patient, average). P&S monitoring noninvasively, independently, and simultaneously measures parasympathetic and sympathetic (P&S) activity, including the normal P-decrease followed by an S-increase with head-up postural change (standing). Syncope, as an S-excess (SE) with stand, is differentiated from orthostatic dysfunction (e.g., POTS) as S-withdrawal with stand. Upon standing, VVS-PE is further differentiated as SE with PE, VVS-HR as SE with abnormal HR, and VVS-PN as SE with normal P- and HR-responses. Improved understanding of the underlying pathophysiology by more accurate subtyping leads to more precise therapy and improved outcomes.

Adjustable autonomy: a systematic literature review

Developing autonomous systems that operate successfully in dynamic environments entails many challenges. Researchers introduce the concept of adjustable autonomy to mitigate some of these challenges. Adjustable autonomy enables a system to operate in different autonomic conditions and transfers control between the system’s operators. To gauge the extent to which such autonomy has been studied, this paper presents a systematic literature review of adjustable autonomy. It reviews 171 research papers and examines, in detail, 78 research papers. The review provides a fundamental understanding of adjustable autonomy and its application in multi-agent systems. The paper contributes to (1) identifying adjustable autonomy approaches and evaluating their utility, (2) specifying the requirements of formulating adjustable autonomy, (3) presenting adjustable autonomy assessment techniques, and (4) exploring the adjustable autonomy research and identify the research gaps.

Autonomic function in adults with allergic rhinitis and its association with disease severity and duration

BackgroundThe association between allergic rhinitis (AR) and the autonomic nervous system (ANS) has recently received substantial attention. However, no studies have assessed how the heart rate variability (HRV) parameters are associated with duration and disease severity in AR. ObjectiveTo compare the difference in autonomic conditions among individuals with AR of various durations and severities and healthy controls. MethodsWe divided individuals with AR into subgroups based on duration and severity of disease. Next, we measured HRV, and the results were compared among subgroups and healthy controls. ResultsHigh frequency (HF) and normalized high frequency (NHF) were significantly higher in the intermittent group than in the control group, whereas normalized low frequency (NLF) and the ratio of absolute LF to HF power (LF/HF) were significantly lower in the intermittent group than in the control group. Furthermore, NLF was significantly higher in the persistent group than in the intermittent group. HF and NHF were significantly higher in the mild group than in the control group, whereas NLF and LF/HF were significantly lower in the mild group than in the control group. The total nasal symptom and itchy nose scores were negatively correlated with NHF. ConclusionOur results indicate that patients with intermittent and mild AR have hypervagal activity and hyposympathetic activity, and the predominance lessens in patients with more persistent AR and severe symptoms. Further investigation of the mechanisms underlying the association between autonomic function and persistent and severe AR is needed.

Emerging subspecialties in neurology: autonomic disorders.

Autonomic nervous system (ANS) dysfunction as a cause of disease is an increasingly recognized health problem, not only in the field of neurology, but also in cardiology, gastroenterology, endocrinology, urology, psychiatry, and primary care medicine. Patients may present with a myriad of symptoms including orthostatic intolerance, recurrent syncope, labile blood pressure, disorders of sweating and thermoregulation, neurogenic bladder, sexual dysfunction, gastrointestinal dysmotility, pupil abnormalities, and sleep disorders. These symptoms may, in turn, be a consequence of genetic (e.g., hereditary sensory and autonomic neuropathies, transthyretin amyloidosis), neurodegenerative (e.g., Parkinson disease [PD], multiple system atrophy [MSA]), autoimmune (e.g., autoimmune ganglionopathies), or acquired disorders (e.g., spinal cord lesions, type 2 diabetes). Although autonomic symptoms may be among the most debilitating features of these progressive conditions, they are often treatable. Autonomic disorders specialists require a comprehensive knowledge of the anatomy, physiology, and pharmacology of the ANS, understanding of the pathophysiology and management of acute and chronic autonomic conditions, and expertise in the performance and interpretation of clinical and laboratory evaluation of the ANS. The authors thank Dr. Horacio Kaufmann for reviewing an earlier version of this manuscript.

알레르기 비염 환자의 변증별 자율신경계 특성 분석 연구

Objectives : We performed a clinical study to investigate autonomic conditions in persistent allergic rhinitis depending on various pattern identifications and the availability of heart rate variability (HRV) as a pattern identification diagnostic tool. Methods : 32 patients with persistent allergic rhinitis were asked to interview with doctor of Korean Medicine and perform the four pattern questionnaires (Cold–Heat Pattern, Phlegm Pattern, Yin Deficiency pattern, bloodstasis pattern). Then, they were examined their autonomic conditions with heart rate variability test.

Autonomic Conditions in Tinnitus and Implications for Korean Medicine

Tinnitus patients suffer from not only auditory sensations but also physical, mental, and social difficulties. Even though tinnitus is believed to be associated with the autonomic nervous system, changes in autonomic conditions in tinnitus patients are not receiving much research attention. The aims of this study were to investigate the autonomic condition of tinnitus patients and to consider Korean medicine in the treatment of tinnitus with an evidence-based approach. We performed a retrospective chart review and compared the heart rate variability (HRV) parameters of 40 tinnitus patients (19 acute and 21 chronic) and 40 healthy controls. In tinnitus patients, the power of the high frequency component and total power of the HRV significantly decreased (P < 0.05), and the low frequency to high frequency ratio significantly increased (P < 0.05). There was no significant difference between the acute and chronic patients. When comparing each group with the controls, there was a tendency that the longer the duration of tinnitus was, the larger the observed HRV change was. In conclusion, tinnitus patients have vagal withdrawal and sympathetic overactivity, and chronic tinnitus more strongly affects autonomic conditions than acute tinnitus. This study provides evidence for Korean medical treatments of tinnitus, such as acupuncture and Qi-training, that cause modulation of cardiac autonomic function.

Autonomic Function Tests: Some Clinical Applications

Modern autonomic function tests can non-invasively evaluate the severity and distribution of autonomic failure. They have sufficient sensitivity to detect even subclinical dysautonomia. Standard laboratory testing evaluates cardiovagal, sudomotor and adrenergic autonomic functions. Cardiovagal function is typically evaluated by testing heart rate response to deep breathing at a defined rate and to the Valsalva maneuver. Sudomotor function can be evaluated with the quantitative sudomotor axon reflex test and the thermoregulatory sweat test. Adrenergic function is evaluated by the blood pressure and heart rate responses to the Valsalva maneuver and to head-up tilt. Tests are useful in defining the presence of autonomic failure, their natural history, and response to treatment. They can also define patterns of dysautonomia that are useful in helping the clinician diagnose certain autonomic conditions. For example, the tests are useful in the diagnosis of the autonomic neuropathies and distal small fiber neuropathy. The autonomic neuropathies (such as those due to diabetes or amyloidosis) are characterized by severe generalized autonomic failure. Distal small fiber neuropathy is characterized by an absence of autonomic failure except for distal sudomotor failure. Selective autonomic failure (which only one system is affected) can be diagnosed by autonomic testing. An example is chronic idiopathic anhidrosis, where only sudomotor function is affected. Among the synucleinopathies, autonomic function tests can distinguish Parkinson's disease (PD) from multiple system atrophy (MSA). There is a gradation of autonomic failure. PD is characterized by mild autonomic failure and a length-dependent pattern of sudomotor involvement. MSA and pure autonomic failure have severe generalized autonomic failure while DLB is intermediate.

Botulinum toxin therapy: its use for neurological disorders of the autonomic nervous system

Botulinum toxin (BoNT) has gained widespread use for the treatment of overactive muscles, overactive exocrine glands and, most recently, non-muscular pain conditions. Autonomic conditions treated with BoNT include achalasia, gastroparesis, sphincter of Oddi spasms, and unspecific esophageal spasms in gastroenterology and prostate disorders in urology. BoNT's use for autonomic conditions related to neurology includes various forms of bladder dysfunction (detrusor sphincter dyssynergia, idiopathic detrusor overactivity, neurogenic detrusor overactivity, urinary retention and bladder pain syndrome), pelvic floor disorders (pelvic floor spasms and anal fissures), hyperhidrosis (axillary, palmar, and plantar hyperhidrosis, diffuse sweating, Frey's syndrome) and hypersalivation (hypersalivation in Parkinsonian syndromes, motor neuron disease, neuroleptic use, and cerebral palsy). Hyperhidrosis, hypersalivation, some forms of bladder dysfunction and pelvic floor disorders can easily be treated by neurologists. Most bladder dysfunctions require cooperation with urology departments.

Autonomic boundary conditions for ventricular fibrillation

We sought to describe conditions under which changes in autonomic activity interacted with changes in oxygen availability to cause ventricular fibrillation (VF) in rats anesthetized with urethane. Parasympathetic activation was achieved by stimulation of efferent vagus nerve segments. Sympathetic activation was accomplished by varying doses of systemic isoproterenol. Hypoxemia was induced by varying the dead space attached to an endotracheal tube. BP, ECG, pulse oximetry, and echocardiograms in M‐mode were used. Ventricular fibrillation could be induced with high‐dose isoproterenol, vagotomy, and moderate hypoxemia (O2 sat 50–60%). Lower doses of isoproterenol or non‐zero vagal tone (simulated with vagus nerve stimulation) led to bradyarrhythmia. Severe hypoxemia (O2 sat &lt;50%) also led to bradyarrhythmia. In addition, the dose of isoproterenol necessary to favor VF (≥16 mg/kg) was greater than the dose necessary to achieve maximal heart rate (≤12 mg/kg). We also examined defibrillation. Given that systemic hypoxemia can contribute to a specific set of autonomic conditions favorable for VF, and bradyarrhythmias result when hypoxemia is more severe or vagal tone is present, we conclude VF is an unlikely outcome of extreme autonomic overactivity.

Poster 441 Effective Treatment of Hyperhidrosis Secondary to Bowel Program in Spinal Cord Injury: A Case Report

Disclosures: D. Rosenblum, none. Patients or Programs: Hyperhidrosis, or significant sweating, in spinal cord injury can be precipitated by noxious stimuli. The culprit is often ambiguous. It can be associated with autonomic dysreflexia and other conditions such as syrinx. This case is of a 57-year-old woman who sustained C5 ASIA A tetraplegia secondary to trauma. She was stabilized and admitted for further medical and rehabilitative care. She has a neurogenic bladder, neurogenic bowel, and has rarely had dysreflexia episodes. However, shortly after each effective bowel program, she reported chills and excessive hyperhidrosis, with no headache and no hypertension. Her medications included baclofen and Neurontin. Physical examination did not reveal any source of noxious stimuli, such as wounds. A workup revealed normal laboratory tests, and a KUB showed no excessive stool. Magnetic resonance imaging of the spine did not show a syrinx. Different bowel medications, oral and suppositories, including lidocaine gel instillation as well as enemas with anesthetic agents, were unsuccessful in alleviating her symptoms. Scopolamine patch trials were unsuccessful. Tricyclic antidepressant medications, added at night to also help with neuropathic pain, did not impact the hyperhidrosis. Probantheline was provided, with complete resolution of her bowel program–induced hyperhidrosis. Program Description: Use of medication to control hyperhidrosis. Setting: Inpatient rehabilitation unit. Results: Probantheline successfully controlled the patient’s hyperhidrosis. Other medications, as noted, did not. Discussion: Hyperhidrosis is excessive sweating and is seen in people with both tetraplegia and paraplegia. The pathophysiology includes overactivity of the sympathetic nervous system and may be triggered by noxious stimulation. Hyperhidrosis will be reviewed, including the applicable neuroanatomy and sweat gland innervations, as well as workup and treatment approaches. The pharmacology of probantheline is reviewed. Conclusions: Probantheline effectively treated bowel program– induced hyperhidrosis. The mechanism of action of prophantheline, its pharmacology, uses, and adverse effects are reviewed. The prevalence, pathophysiology, differential diagnosis, and treatment options of hyperhidrosis in spinal cord injury are presented.

A Novel Index of Sympathovagal Balance From Independent Component Analysis of Heart Rate and Blood Pressure Variability: Performance in Patients With Carotid Stenting and in the EuroBavar Data Set

The authors applied independent component analysis to oscillations of heart rate and blood pressure and obtained a new index of sympathovagal balance. The performance of this index was tested in patients with carotid artery stenting and in the EuroBavar data set according to the following criteria: (1) the index should vary similarly among subjects in response to different autonomic conditions; (2) the variability in the index among subjects exposed to the same autonomic conditions should be small; and (3) the response of the index to various autonomic conditions should reflect the underlying changes in the physiological state and have a meaningful interpretation. The new index from independent component analysis better fulfilled the criteria than the commonly used sympathovagal index, the ratio of low-to-high frequency spectra power of heart rate variability, and had higher discrimination power in distinguishing the autonomic status of the patients who had undergone carotid artery stenting from that of the control subjects.

Comorbid health conditions in women with syncope

We determine the comorbid conditions associated with syncope in women. In addition, we hypothesize a higher proportion of autonomic comorbid conditions during the female reproductive age. We identified a cohort of patients admitted to US hospitals with the principal diagnosis of syncope. We compare patient demographics stratified by gender as well as syncope associated comorbidities. We compared these comorbidities in female of reproductive age (15-45) to men as control. From a total sample of 305,932, females constituted 56.7% (n = 173,434). Females were slightly older (mean age 70.9 +/- 17.9 vs. 66.7 +/- 17.3; P < 0.0001); with similar racial distribution (white 57.8 vs. 57.5%), and similar length of hospital stay (mean 2.66 +/- 2.63 vs. 2.68 +/- 2.72 days; P > 0.05). Females had higher proportion of migraine (1.65 vs. 1.29%; odds ratio 'OR' 1.29; 95% confidence interval 'CI' 1.21, 1.36); chronic fatigue syndrome (1.73 vs. 1.3%; OR 1.32; 95% CI 1.25, 1.4); gastroparesis (0.2 vs. 0.12%; OR 1.64; 95% CI 1.35, 1.98); interstitial cystitis (0.07 vs. 0.01%; OR 7.44; 95% CI 4.10, 13.5); and postural tachycardia syndrome (0.49 vs. 0.44%; OR 1.1; 95% CI 1.001, 1.23). Orthostatic hypotension was not different between the groups (P = 0.24). When the sample was stratified by age category, the odds ratio for gastroparesis, orthostatic hypotension, and postural tachycardia syndrome was increased (P < 0.05). A higher proportion of autonomic dysfunction was present in women compared to men. In addition, these comorbid autonomic conditions were especially prominent during the female reproductive age.

Autonomic alterations and cardiac changes in epilepsy

Studies with heart rate variability have revealed interictal autonomic alterations in patients with epilepsy. In addition, epilepsy is frequently associated with ictal tachycardia or bradycardia, which sometimes precedes the onset of seizures. Ictal tachycardia is sometimes associated with electrocardiography (ECG) morphologic changes and ictal bradycardia often progresses to asystole. Such cardiac manifestations of seizures have been hypothesized as possible causes for sudden unexplained death in epilepsy (SUPEP). The present review relates to interictal and ictal cardiac manifestations of epilepsy with focus on heart rate, heart rate variability, and ECG changes. Aspects of the supporting mechanisms are discussed and attention is drawn to the interaction between central and peripheral effects, interictal autonomic conditions, ictal autonomic discharges, and administration of antiepileptic drugs in shaping the ictal cardiac changes. Because these interactions are complex and not totally understood, closer surveillance of patients and more experimental work is necessary to elucidate the mechanistic support of autonomic and cardiac changes in epilepsy, and to design better strategies to avoid their undesirable effects. It is also suggested that some of these changes could be used as predictors or markers for the onset of seizures.

Cardiovascular variability is/is not an index of autonomic control of circulation

To the Editor : As repeatedly underlined in this debate, neural cardiovascular (CV) regulation is characterized by a complex interaction between central and reflex mechanisms, with the contribution of other important factors such as respiratory frequency and depth. It would therefore be unrealistic