Decreased sympathetic inhibition in gastroesophageal reflux disease

This study was undertaken to evaluate autonomic nervous system function in patients with gastroesophageal reflux disease. Based on clinical criteria, 28 consecutive patients with no history of heart, metabolic, or neurologic disease (mean age 41 y, range 20–62 y) reporting with upper gastrointestinal symptoms typical of gastroesophageal reflux underwent esophageal manometry, ambulatory 24-hour pH study with electrocardiographic monitoring, power spectral analysis of heart rate variability, and cardiovascular tests. Twelve healthy subjects served as controls. A positive result of prolonged esophageal pH study (pH in the distal esophagus less than 4, lasting more than 4.2% of recording time) was observed in 21 patients (reflux group); seven patients were categorized in the nonreflux group. No patient showed arrhythmias or any correlation between heart rate variability changes during electrocardiographic monitoring and episodes of reflux (pH less than 4, lasting more than 5 minutes). A decrease of sympathetic function occurred only in the reflux group (p<0.05) supported by the lower increase of systolic/diastolic blood pressure at sustained handgrip. No other cardiovascular tests showed statistically significant differences in the control or nonreflux groups. Total time reflux showed an inverse correlation with sympathetic function in the reflux group (r=-0.415, p<0.028). We concluded that there is some evidence for a slightly decreased sympathetic function in patients with gastroesophaged reflux disease that is inversely correlated with total time reflux. In these patients, decreased sympathetic function may cause dysfunction of intrinsic inhibitory control with increased transient spontaneous lower-esophageal sphincter relaxations, thus resulting in gastroesophageal reflux disease.     

Autonomic dysfunction in Alzheimer's disease

Twenty-nine patients fitting the NINCDS-ADRDA criteria of Alzheimer's disease participated in a study of autonomic functions. A number of tests on parasympathetic and sympathetic functions were made. Eighteen of the patients were tested a second time one year later. Fifteen healthy subjects with no family history of dementia disorders served as controls. Compared to the controls, the patients showed signs suggesting autonomic dysfunction affecting parasympathetic, as well as vasomotor sympathetic, functions.     

Autonomic control of cardiovascular dynamics during weightlessness

Measuring cardiovascular dynamics is a new method of assessing the autonomic regulation of the cardiovascular system, it provides an easily-implemented non-invasive way of monitoring the effects of weightlessness on this regulatory function. The major findings of studies on cardiovascular dynamics during actual or simulated weightlessness are presented, taking into account the recent consensus on this approach. Future improvements of these studies are discussed.     

Diversity of sympathetic vasoconstrictor pathways and their plasticity after spinal cord injury

Sympathetic vasoconstrictor pathways pass through paravertebral ganglia carrying ongoing and reflex activity arising within the central nervous system to their vascular targets. The pattern of reflex activity is selective for particular vascular beds and appropriate for the physiological outcome (vasoconstriction or vasodilation). The preganglionic signals are distributed to most postganglionic neurones in ganglia via synapses that are always suprathreshold for action potential initiation (like skeletal neuromuscular junctions). Most postganglionic neurones receive only one of these “strong” inputs, other preganglionic connections being ineffective. Pre- and postganglionic neurones discharge normally at frequencies of 0.5–1 Hz and maximally in short bursts at <10 Hz. Animal experiments have revealed unexpected changes in these pathways following spinal cord injury. (1) After destruction of preganglionic neurones or axons, surviving terminals in ganglia sprout and rapidly re-establish strong connections, probably even to inappropriate postganglionic neurones. This could explain aberrant reflexes after spinal cord injury. (2) Cutaneous (tail) and splanchnic (mesenteric) arteries taken from below a spinal transection show dramatically enhanced responses in vitro to norepinephrine released from perivascular nerves. However the mechanisms that are modified differ between the two vessels, being mostly postjunctional in the tail artery and mostly prejunctional in the mesenteric artery. The changes are mimicked when postganglionic neurones are silenced by removal of their preganglionic input. Whether or not other arteries are also hyperresponsive to reflex activation, these observations suggest that the greatest contribution to raised peripheral resistance in autonomic dysreflexia follows the modifications of neurovascular transmission.     

Autonomic dysfunction in different subtypes of multiple system atrophy

Multiple system atrophy (MSA) can clinically be divided into the cerebellar (MSA‐C) and the parkinsonian (MSA‐P) variant. However, till now, it is unknown whether autonomic dysfunction in these two entities differs regarding severity and profile. We compared the pattern of autonomic dysfunction in 12 patients with MSA‐C and 26 with MSA‐P in comparison with 27 age‐ and sex‐matched healthy controls using a standard battery of autonomic function tests and a structured anamnesis of the autonomic nervous system. MSA‐P patients complained significantly more often about the symptoms of autonomic dysfunctions than MSA‐C patients, especially regarding vasomotor, secretomotor, and gastrointestinal subsystems. However, regarding cardiovascular, sudomotor pupil, urogenital, and sleep subsystems, there were no significant quantitative or qualitative differences as analyzed by autonomic anamnesis and testing. Our results suggest that there are only minor differences in the pattern of autonomic dysfunction between the two clinical MSA phenotypes. © 2008 Movement Disorder Society     

Baroreceptor sensitivity response to phase IV of the Valsalva maneuver in spinal cord injury

Due to the increased prevalence of ischemic heart disease and hypertension reported in individuals with chronic spinal cord injury (SCI), we investigated whether subjects with low level SCI (paraplegia), without apparent evidence of coronary artery disease, exhibit normal baroreceptor and autonomic function. Eighteen males participated in this study: seven normotensive with paraplegia, five hypertensive with paraplegia and six normotensive non-SCI controls. The Valsalva maneuver was performed by maintaining a pressure of 40 mmHg over 15s and R-R intervals (RRI) and arterial blood pressure were measured continuously. Phase IV of the Valsalva maneuver was determined by linear regression analysis between RRI and systolic pressure, with a final slope calculated. The power spectra for RRI and blood pressure variability parameters were also analyzed, in addition to the index , a frequency domain estimate of the overall gain in baroreceptor control of the RRI-arterial blood pressure. The normotensive subjects with paraplegia were found to have an impaired baroreceptor response when compared with agematched, non-SCI controls. In addition, the levels of both the low frequency and high frequency spectral components of RRI and the index were reduced in these individuals at rest. These cumulative findings strongly suggest that the integrity of the sinoaortic baroreceptors, as well as efferent parasympathetic function, may be compromised in otherwise apparently healthy individuals with chronic paraplegia.     

Autonomic nervous system disorders in stroke

Disturbances of the autonomic nervous system are common in patients with various cerebrovascular diseases. They are attributed to damage of the central autonomic network, particularly in the frontoparietal cortical areas and in the brain stem, or to a disruption of the autonomic pathways descending from the hypothalamus via the mesencephalon, pons, and medulla to the spinal cord. The most common clinical problems include abnormalities in heart rate and blood pressure regulation, reflecting cardiovascular autonomic dysfunction, and asymmetric sweating with cold hemiplegic limbs, reflecting changes in the sudomotor and vasomotor regulatory systems. Bladder and bowel dysfunction and impotence are also frequent complaints after stroke, but the present knowledge concerning their prevalence and clinical significance is still limited. Cardiovascular autonomic dysfunction, which is mainly related to increased sympathetic activity, is most evident in the acute phase of stroke, whereas other autonomic disorders, such as abnormal sweating, are long-standing or even irreversible. In addition to the well-established sympathetic hyperfunction, abnormalities of the parasympathetic nervous system may also contribute to the autonomic imbalance after stroke. Reliable recognition of autonomic dysfunction using quantitative analysis methods is important, because these disturbances are not only subjectively disabling and uncomfortable, but they may also be prognostically unfavorable. Moreover, quantitative measurements also form the ground for successive treatment of various stroke-related autonomic disorders.     

Autonomic function in patients with chronic fatigue syndrome

Subtle signs of autonomic dysfunction and orthostatic intolerance have been reported in patients with chronic fatigue syndrome (CFS). To assess cardiovascular autonomic function noninvasively in an unselected group of patients with CFS, we examined responsiveness to several cardiovascular reflex tests in 37 CFS patients and 38 healthy control subjects. Blood pressure and heart rate (HR) were recorded continuously by a Finapres device before and during forced breathing, standing up, Valsalva maneuver, and sustained handgrip exercise (HG). In addition, a mental arithmetic test was carried out and questionnaires to assess the severity of CFS symptoms were completed. At rest, there were no significant differences in blood pressure or in HR between the two groups. The in- and expiratory difference in HR tended to be lower in CFS patients (28.4±10.5 beats) than in healthy controls (32.2±9.5) (p=0.11). The maximal increase in HR during standing up was not significantly different between the CFS group (37.6±8.9 beats) and the control group (40.2±8.9 beats). There were no significant differences between both groups with regard to the Valsalva ratio, but the systolic and diastolic blood pressure responses were significantly larger in CFS patients, despite the fact that many CFS patients were not able to sustain the Valsalva maneuver. The HR response to MA was significantly less in the CFS group (22.6±9.9) than in the control group (29.5±16.7) (p<0.05), suggesting impaired cardiac sympathetic responsiveness to mental stress. The lower HR responses could not be explained by the level of concentration in the CFS group. During HG exercise, the hemodynamic responses were lower in the CFS group than in the control group, but this might be attributed to the lower level of muscle exertion in CFS patients. There were no significant differences between CFS patients with and without symptoms of autonomic dysfunction regarding the hemodynamic responses to the cardiovascular reflex tests. The findings of the study suggest that there are no gross alterations in cardiovascular autonomic function in patients with CFS.     

Transmitter diversity in ganglion cells of the guinea pig gallbladder: an immunohistochemical study.

Several neurotransmitters have been reported to exist in the ganglionated plexus of the guinea pig gallbladder. These include substance P, neuropeptide Y (NPY), calcitonin gene-related peptide, vasoactive intestinal peptide (VIP), acetylcholine, norepinephrine, serotonin, and dopamine. To determine which neuropeptides are intrinsic to gallbladder ganglia, we performed immunohistochemistry on colchicine-treated preparations. In separate, single-labeled preparations, a majority of neurons contained substance P-, NPY-, or somatostatin-like immunoreactivity. In double-labeled preparations, a large majority of the neurons that contained substance P-like immunoreactivity also contained NPY-like immunoreactivity and somatostatin-like immunoreactivity. Immunoreactivity for VIP was present in a small percentage of the gallbladder neurons which did not contain substance P-like immunoreactivity. Additional experiments were done to test for the presence of other compounds, known to exist in the neurons of the gut. Although immunoreactivity was found in control preparations of small intestine, the ganglionated plexus of the gallbladder lacked immunoreactivity for galanin, dynorphin, enkephalin, gastrin-releasing peptide, or gamma-aminobutyric acid. We conclude that ganglia of the guinea pig gallbladder contain at least two populations of neurons, based on transmitter phenotype. One of these populations appears to contain substance P, NPY, and somatostatin. Another population, which represents a small contingent of the total population of neurons, contains VIP.     

Autonomic failure: observations of a physician–patient

Here I describe the clinical symptoms of autonomic failure that I began experiencing when I turned 80, a treatment combination that has been remarkably effective, and the recent finding of high titers of antibodies against the ganglionic nicotinic receptor.     

Clinical cues for detecting ictal asystole

Objective The occurrence of asystole during an epileptic seizure is the most dramatic manifestation of ictal bradycardia. Recognition of ictal asystole is important as treatment with both antiepileptic drugs and cardiac pacing may be necessary. The purpose of this study was to identify clinical cues to aid in the detection of ictal asystole. Methods We analyzed the clinical and electrophysiologic features of all recorded seizures in consecutive patients diagnosed with ictal bradycardia and asystole on prolonged video-EEG/ECG monitoring over a 14 year period. Results Twenty-nine seizures with ictal bradycardia were identified in 13 patients. Of these, 11 seizures in seven patients were associated with asystole. Bilateral transient limb movements consisting of asymmetric posturing or jerking occurred during eight episodes of ictal asystole, and loss of muscle tone occurred during four. In contrast, neither bilateral limb movement nor loss of muscle tone was observed in any of the non-asystolic seizures, whether ictal bradycardia was present or not. All patients with ictal asystole reported a history of seizure-related falls and brief body and limb jerking. Conclusions The presence of loss of muscle tone or bilateral asymmetric jerky limb movements during a seizure suggests the possibility of ictal asystole. Video-EEG/ECG monitoring should be considered in patients with epilepsy demonstrating these clinical features to determine if ictal asystole is present.     

Cognitive functioning in orthostatic hypotension due to pure autonomic failure

Abstract Psychophysiological science proposes close interactions between cognitive processes and autonomic responses, yet the consequences of autonomic failure on cognitive functioning have not been documented. This pilot study investigates, for the first time, the cognitive profile of 14 patients with Pure Autonomic Failure (PAF). Each patient was administered a comprehensive battery of neuropsychological tests and neuroimaging investigation. A number of patients (n = 6) presented with cognitive impairment. The two most frequent types of impairment were: deficits of speed and attention, and executive functioning. Impairments of free recall memory, intellectual functioning, nominal and calculation functions were also documented, albeit in a much lower frequency. These cognitive changes were not always associated with white matter abnormalities. We speculate that the cognitive impairments associated with PAF represent consequences of systemic hypotension with cerebral underperfusion. However, a failure in integrated bodily arousal responses during cognitive behaviours may also contribute to some of the observed deficits.     

The symptoms of autonomic dysfunction in HIV-positive Africans

Background

Human immunodeficiency virus (HIV) infection is associated with autonomic neuropathy. The resultant autonomic dysfunction impairs quality of life and can have fatal consequences. Our aim was to clearly define the symptoms of autonomic dysfunction in African HIV-positive patients and determine whether these symptoms were related with (a) autonomic reflex responses (b) the degree of immunosupression.

Methods

Thirty-one HIV-positive treatment-naïve African patients (mean CD4 cell count 269.5 ± 253.4/mm³) and 12 healthy controls completed a detailed questionnaire (Autonomic System Profile, Mayo Clinic, Rochester, MN) relating to specific symptoms of autonomic dysfunction. After completion of the questionnaire, subjects underwent a standard battery of autonomic reflex tests.

Results

The autonomic symptom score was higher in the male HIV-positive patients (26.7 ± 14.7 points) and female patients with CD4 <200/mm³ (24.7 ± 18.0) than sex-matched controls (male controls, 9.9 ± 6.8, P < 0.05; female controls, 8.8 ± 10.1; P < 0.05). Six patients had scores indicative of severe autonomic dysfunction (>43.8 points). The most common autonomic symptoms were: orthostatic intolerance, secretomotor and gastrointestinal dysfunction. There was no relationship between CD4 cell counts and autonomic symptom scores. The blood pressure response to sustained handgrip was blunted, but all other cardiovascular reflex tests were within the normal range or borderline.

Conclusion

African HIV-positive patients report symptoms of autonomic dysfunction, despite normal or borderline autonomic reflex responses.

     

The effects of left and right monocular viewing on hemispheric activation

Background/Objectives: Prior research has revealed that whereas activation of the left hemisphere primarily increases the activity of the parasympathetic division of the autonomic nervous system, right-hemisphere activation increases the activity of the sympathetic division. In addition, each hemisphere primarily receives retinocollicular projections from the contralateral eye. A prior study reported that pupillary dilation was greater with left- than with right-eye monocular viewing. The goal of this study was to test the alternative hypotheses that this asymmetric pupil dilation with left-eye viewing was induced by activation of the right-hemispheric-mediated sympathetic activity, versus a reduction of left-hemisphere-mediated parasympathetic activity. Thus, this study was designed to learn whether there are changes in hemispheric activation, as measured by alteration of spontaneous alpha activity, during right versus left monocular viewing.

Method: High-density electroencephalography (EEG) was recorded from healthy participants viewing a crosshair with their right, left, or both eyes.

Results: There was a significantly less alpha power over the right hemisphere’s parietal-occipital area with left and binocular viewing than with right-eye monocular viewing.

Conclusions: The greater relative reduction of right-hemisphere alpha activity during left than during right monocular viewing provides further evidence that left-eye viewing induces greater increase in right-hemisphere activation than does right-eye viewing.     

Autonomic dysfunction and the gastrointestinal tract

Autonomic neuropathy of the gastrointestinal tract may represent a primary disorder, but much more often it is secondary due to systemic disorders like diabetes mellitus. This review gives an overview about the common clinical manifestations and the principles and limitations in diagnostic work-up of autonomic dysfunction of the gastrointestinal tract. Diagnostic evaluation usually includes a combination of screening tests for autonomic neuropathy and specialized diagnostic procedures for the detection of sequela of autonomic neuropathy in gastrointestinal motility.     

Autonomic involvement in multiple sclerosis: a pupillometric study

To study pupillary autonomic function in multiple sclerosis (MS), we examined 36 subjects with low disability, preserved visual acuity and no recent history (2 years) of optic neuritis or actual visual complaints. Compared to controls, MS patients showed a greater dilatator reaction with darkness and, for the light reflex, a lower amplitude and contraction rate and a greater recovery of pupillary diameter 5 s after the stimulus. Within the MS group, no difference was found comparing patients with or without the following characteristics: nuclear magnetic resonance imaging evidence of midbrain lesions; increased visual evoked potential P100 latency; and a previous history of optic neuritis. No correlation was found between P100 latency, duration of disease and pupillometric parameters. Our results indicate that in MS patients there is autonomic dysfunction with a reduction of parasympathetic tone and a relative increase in sympathetic dilatator tone to the pupils. We suggest that pupillary abnormalities could be due to non-specific impairment of the central pathways subserving pupil functions.     

Vagal control of heart rate variability in vasovagal syncope: Studies based on 24-h electrocardiogram recordings

The autonomic nervous system has an important role in the pathophysiology of vasovagal syncope. The purpose of this investigation was to evaluate to what extent the autonomic system is involved in the mechanism of fainting and to characterize the profile of heart rate variability of individuals who are prone to undergo a critical event. Thirty patients (mean age 41 years) with vasovagal syncope and 15 comparable controls were monitored by 24-h electrocardiography. Heart rate variability was analysed over the whole 24 h and during the daytime and night-time using time domain parameters (average of heart periods, RR; standard deviation of heart periods, SDNN; standard deviation of the average of RR intervals over all the 5-min segments of the entire recording, SDANN; percentage of the total number of all RR intervals of pairs of adjacent RR intervals differing more than 50 ms over the entire recording, pNN50; the square root of the sum of the square of differences between adjacent RR intervals, rMSSD), as indicated by the Task Force for Clinical Use of Standard Measurements of Heart Rate Variability. These parameters explore the influence of the autonomic nervous system on sinus node function and provide information about the vagal control to the heart. Among these parameters, pNN50 and rMSSD were significantly reduced in individuals with vasovagal syncope when compared with controls, over each time period considered. The two parameters are related to high-frequency oscillations in the frequency domain and to the vagal influence of the heart. These results indicate that the vagal tone to the heart is altered in subjects who suffer from vasovagal syncope. The results of this study provide an insight into the pathophysiological mechanism of fainting and may offer another means of evaluating patients with syncope.     

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.