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PubMed1998

Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart).

BACKGROUND: Patients with chronic heart failure (CHF) have a continuing high mortality. Autonomic dysfunction may play an important role in the pathophysiology of cardiac death in CHF. UK-HEART examined the value of heart rate variability (HRV) measures as independent predictors of death in CHF. METHODS AND RESULTS: In a prospective study powered for mortality, we recruited 433 outpatients 62+/-9.6 years old with CHF (NYHA functional class I to III; mean ejection fraction, 0.41+/-0.17). Time-domain HRV indices and conventional prognostic indicators were related to death by multivariate analysis. During 482+/-161 days of follow-up, cardiothoracic ratio, SDNN, left ventricular end-systolic diameter, and serum sodium were significant predictors of all-cause mortality. The risk ratio for a 41.2-ms decrease in SDNN was 1.62 (95% CI, 1.16 to 2.44). The annual mortality rate for the study population in SDNN subgroups was 5.5% for >100 ms, 12.7% for 50 to 100 ms, and 51.4% for <50 ms. SDNN, creatinine, and serum sodium were related to progressive heart failure death. Cardiothoracic ratio, left ventricular end-diastolic diameter, the presence of nonsustained ventricular tachycardia, and serum potassium were related to sudden cardiac death. A reduction in SDNN was the most powerful predictor of the risk of death due to progressive heart failure. CONCLUSIONS: CHF is associated with autonomic dysfunction, which can be quantified by measuring HRV. A reduction in SDNN identifies patients at high risk of death and is a better predictor of death due to progressive heart failure than other conventional clinical measurements. High-risk subgroups identified by this measurement are candidates for additional therapy after prescription of an ACE inhibitor.

Aged↗
PubMed2004

Contrasting effects of carbohydrate and water on blood pressure responses to postural maneuvers in patients with posturally related (vasovagal) syncope.

Crouching then standing induces large changes in arterial blood pressure. Ingestion of carbohydrate and water are known to have contrasting effects on cardiovascular control in patients with various forms of autonomic dysfunction. We tested the hypothesis that, in patients with attacks of posturally related (neurogenic or vasovagal) syncope, postural maneuvers would cause greater changes in blood pressure than in normal controls and that they would be affected differently by carbohydrate and water. We studied 7 patients with histories indicating posturally related syncope and who we had shown to have abnormal responses to an orthostatic stress test, and 7 healthy volunteers with normal orthostatic responses. Responses of blood pressure (Portapres finger photoplethysmography) were determined to crouching and subsequent standing, before and after ingestion of a high carbohydrate "meal" (2.5MJ) and (on a different day) water (500 ml). Before the "meal" or water there were no differences between groups in baseline blood pressures or in the responses to crouching and standing. In controls, neither carbohydrate nor water had any significant effect on baseline blood pressure or on the responses to the maneuvers. In the patients, the standing pressures were also unaffected by carbohydrate but they did increase after water. In the patients the increases in pressure during the crouch were larger after carbohydrate, but smaller after water. These results show that, in patients with posturally related syncope, unlike in control subjects, carbohydrate ingestion and water result in opposite effects on blood pressure during postural maneuvers. These results raise the possibility that these patients might have a mild form of autonomic dysfunction.

Adolescent↗
PubMed2004

Penetrance of the fragile X-associated tremor/ataxia syndrome in a premutation carrier population.

CONTEXT: Premutation expansions (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene are frequent in the general population, with estimated prevalences of 1 per 259 females and 1 per 813 males. Several articles have recently described the presence of late-onset neurological symptoms in male carriers of premutation (FMR1) alleles. The main clinical features described in this newly identified syndrome are cerebellar ataxia and intention tremor. Additional documented symptoms include short-term memory loss, executive functional deficits, cognitive decline, parkinsonism, peripheral neuropathy, lower-limb proximal muscle weakness, and autonomic dysfunction. OBJECTIVE: To study the penetrance of the fragile X-associated tremor/ataxia syndrome (FXTAS) among premutation carriers. DESIGN, SETTING, AND PARTICIPANTS: Family-based study of 192 individuals (premutation carriers and controls) whose families belong to the Northern or Southern California Fragile X Associations. Data were collected (March 2002-April 2003) through a survey and a standardized neurological examination, which was videotaped and subsequently scored in a blinded fashion. MAIN OUTCOME MEASURES: Penetrance of intention tremor and ataxia among adult carriers (aged > or =50 years) of premutation expansions of the FMR1 gene. RESULTS: Data from the survey of 192 individuals demonstrated an age-related penetrance of the combination of reported intention tremor and gait ataxia in male carriers (17%, 38%, 47%, and 75% [lower-bound estimates] for participants aged 50-59, 60-69, 70-79, and > or =80 years, respectively). The male carrier group had an age-adjusted 13-fold increased risk (95% confidence interval, 3.9-25.4; P =.003) of combined intention tremor and gait ataxia when compared with male controls. The clinical examination data from 93 individuals demonstrated that male carriers experienced more difficulties on each of 3 standardized neurological rating scales compared with controls (P<.05). Female carrier scores were also higher than those of female controls (P<.05) on 2 of the 3 neurological rating scales, but no participant was identified with probable or definite FXTAS. CONCLUSIONS: The study demonstrates that older male carriers of premutation alleles of the FMR1 gene are at high risk of developing FXTAS. Since male premutation carriers are relatively common in the general population, older men with ataxia and intention tremor should be screened for the FMR1 mutation, especially if these signs are accompanied by parkinsonism, autonomic dysfunction, or cognitive decline, regardless of family history.

Aged↗
PubMed1988

Effects of blood pressure change upon brain-stem pO2 in rabbits with surgically removed baroreceptor nerve. Possible mechanisms for vertigo due to autonomic nerve dysfunction.

The effect of denervation of carotid sinus nerve (CSD) on the brain-stem tissue pO2 tension was studied in the awake rabbit. Tissue pO2 around the vestibular nuclei was measured in two groups of rabbits, normal and CSD, under two experimental conditions, viz. blood pressure (BP) modulation and tilt stimulation. BP was either depressed by hemorrhage (up to 50 mmHg) or elevated by intravenous injection of phenylephrine (up to 160 mmHg). In the normal rabbit, tissue pO2 showed minimum change during BP modulation (ranging between 70 and 160 mmHg. In contrast, CSD surgery resulted in the failure to maintain pO2 at a constant level when BP was elevated. However, tissue pO2 did not change when BP decreased. Head-up tilt stimulation (up to 40 degrees) also induced a transient decrease in BP and pO2 in the CSD rabbit; however, these were maintained at a constant level in the normal rabbit. These conditions were assumed to be due to the decrease in autoregulation of cerebral blood flow (CBF), which resulted in CSD. In these experiments, tissue pO2 recovered first, even when BP still remained low. Therefore, it can be proposed that the carotid baroreceptor reflex works for CBF autoregulation of brain stem primarily during an early phase of BP change. Therefore a disturbed carotid sinus reflex, as shown in the present experiment, may be a possible explanation for the mechanism of stress-related vertigo and/or orthostatic vertigo.

Animals↗
PubMed1991

The natural history of somatosensory and autonomic nerve dysfunction in relation to glycaemic control during the first 5 years after diagnosis of type 1 (insulin-dependent) diabetes mellitus.

The natural evolution of neural dysfunction was studied prospectively over 5 years following diagnosis of Type 1 (insulin-dependent) diabetes in 32 patients aged 12-36 years. Motor and sensory nerve conduction velocities, heart rate variation at rest and during deep breathing, and pupillary function were measured at diagnosis and after 3, 12, 24, 48, and 60 months. Thermal and vibration sensation thresholds were determined after 24, 48, and 60 months of diabetes. Mean HbA1 levels of months 3-60 within the normal range of less than 8.3% (7.3 +/- 0.2%) were observed in 13 patients (Group 1), while a mean HbA1 of months 3-60 greater than or equal to 8.3% (10.0 +/- 0.3%) was found in 19 patients (Group 2). Mean nerve conduction was significantly diminished in Group 2 as compared with Group 1 in at least 4 out of 6 nerves tested during months 12-60 (p less than 0.05). Both tests of heart rate variation were significantly impaired in Group 2 as compared with Group 1 after 24 and 60 months (p less than 0.05), but no differences in pupillary function were observed between the groups. Thermal discrimination but not vibration perception thresholds on the foot were significantly higher in Group 2 than in Group 1 at 40 and 60 months (p less than 0.05). Abnormalities in nerve conduction, thermal discrimination, and heart rate variation, but not vibration perception threshold and the pupillary function tests were significantly more frequent in Group 2 than in Group 1 at 60 months (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Clinical evidence that the vestibular system participates in autonomic control.

The vestibular system, including both the peripheral vestibular system, that is, the labyrinth, and the central vestibular system, is known to influence autonomic function in several ways that have clinical implications. This paper discusses evidence for vestibular influences on autonomic control from normal human subjects, evidence for vestibular influences on autonomic control from patients, clinical implications of vestibulo-autonomic regulation, and speculations regarding possible clinical implications of vestibulo-autonomic control. Situations that provoke vestibular-induced autonomic responses in normal subjects include vestibular laboratory testing, vehicular motion, simulators, and, possibly, exposure to microgravity. Patients with peripheral and central vestibular abnormalities manifest both symptoms and signs of autonomic dysfunction presumably via vestibulo-autonomic connections. Vestibulo-autonomic regulation impacts vestibular diagnostic testing, clinical diagnosis of balance disorders, and treatment of balance disorders. In addition to well-recognized peripheral and central vestibular disorders, anxiety disorders have recently been linked to vestibular dysfunction in a subset of patients. In particular, vestibular dysfunction has been linked to panic disorder and agoraphobia. Vestibular-autonomic connections may form a basis for an association between vestibular dysfunction and panic attacks. The importance of vestibulo-autonomic regulation in the clinical arena is not fully known. Two speculative areas discussed in this paper include vestibular-induced orthostatic intolerance and the role of vestibular-respiratory pathways on sleep apnea.

Autonomic Nervous System↗
PubMed1987

Parasympathetic assessment in Parkinson's disease.

There is little evidence of autonomic dysfunction in PD, although autonomic disturbance was included in the original description by J. Parkinson. In addition, there are no data for de novo PD patients. We selected 14 de novo parkinsonians (seven men and seven women), aged 62.7 +/- 8.2 years, with mild disease (stage 1 through 2 on the Hoehn and Yahr's scale), without history of diabetes, heart disease, or alcoholism, and without neuropathy or orthostatic hypotension. Fourteen age- and sex-matched normal persons were controls. We found a highly significant difference in the respiratory sinus arrhythmias during deep breathing (p less than 0.01); the basal heart rate, the respiratory sinus arrhythmias during quiet breathing, and the Valsalva ratios did not differ statistically, however. In the absence of neuropathy and orthostatic hypotension and in the presence of normal Valsalva ratios, we believe that the abnormality found by us may apply only to parasympathetic dysfunction, perhaps at a central level. In addition, the abnormality seems to be independent of stage and therapy.

Aged↗
PubMed2001

Pupillary autonomic denervation with increasing duration of diabetes mellitus.

BACKGROUND/AIMS: The autonomic pupillary changes in type I and II diabetic patients without clinical evidence of diabetic autonomic neuropathy (DAN) were compared with age matched controls. The relation between pupillary and cardiovascular autonomic function was assessed in the diabetic patients. METHODS: A case-control study was performed with diabetics grouped according to type and duration of diabetes. Static infrared pupillography was used to compare mean dark adapted pupil size and mean percentage changes in pupil size with pilocarpine 0.1% and cocaine 4% in the diabetic and control groups. All diabetic patients underwent cardiovascular autonomic function assessment using the Valsalva ratio, the 30:15 ratio, and testing for orthostatic hypotension. RESULTS: In total, 72 type I and 69 type II diabetic patients were compared with 120 controls. Mean dark adapted pupil size was significantly smaller in diabetic groups than controls. Except for type I diabetics with disease for less than 5 years, all patient groups had significantly greater mean percentage constriction in pupil size in response to dilute pilocarpine than controls. There was no significant difference between the mean percentage dilatation in response to cocaine 4% in diabetics and controls. A high proportion of patients had normal cardiovascular autonomic function particularly when this was assessed with the Valsalva ratio. CONCLUSIONS: Denervation hypersensitivity to dilute pilocarpine is a result of damage to the pupillary parasympathetic supply of diabetic patients. This occurs before the pupillary sympathetic pathway is affected, it can be detected early in the disease, and it may be a possible explanation for the small pupil size seen in diabetic patients. Pupillary autonomic dysfunction occurs before cardiovascular autonomic changes and detection of pupil denervation hypersensitivity to dilute pilocarpine is an inexpensive way to detect early DAN.

Adolescent↗
PubMed2004

Leucoencephalopathy with neuroaxonal spheroids (LENAS) presenting as the cerebellar subtype of multiple system atrophy.

Leucoencephalopathy with neuroaxonal spheroids (LENAS) is a rare disease of cerebral and cerebellar white matter. LENAS usually presents as a disorder of cognition and behaviour, or with gait dysfunction and ataxia. This report describes a patient who had a 14 year course of progressive neurological decline consistent with a clinical diagnosis of probable multiple system atrophy, with prominent cerebellar dysfunction and dysautonomia. Formal autonomic laboratory testing was consistent with global autonomic dysfunction of central origin. However, magnetic resonance imaging showed extensive white matter signal abnormalities, in addition to moderate cerebral and cerebellar atrophy. On postmortem microscopic examination, there were numerous axonal spheroids throughout the white matter of both regions. This case of LENAS presented unique clinical characteristics, and typical pathological findings.

Aged↗
PubMedDate not supplied

[Pure primitive dysautonomia or Bradbury-Eggleston syndrome. Report of 3 cases].

The primary autonomic failure (Bradbury-Eggleston syndrome) is rare. We report three cases (two females and one male) who are 55 year old with orthostatic hypotension, tachycardia, and other signs of dysautonomia. They hadn't a pyramidal, extrapyramidal or cerebellar syndromes. The other causes of postural hypotension are excluded. The autonomic dysfunction was confirmed by autonomic reflex tests and by evaluating of cardiac reflex function; these included heart rate responses to deep breathing and to the valsalva maneuver. Hypotension occurs in a variety of clinical setting; ascertainment of the cause is by non means easy. Primary autonomic failure remains a diagnostic category based on exclusion; its pathophysiology isn't well know and its treatment is only symptomatic.

Autonomic Nervous System Diseases↗
PubMed2001

Autonomic abnormalities in children with functional abdominal pain: coincidence or etiology?

BACKGROUND: There is increasing evidence that autonomic neuropathies may adversely affect gastrointestinal motility by involving the extrinsic nerves of the gut. The authors' hypothesize that functional abdominal pain in children is associated with generalized autonomic dysfunction. METHODS: The authors performed detailed autonomic testing in eight patients with functional abdominal pain, including deep breathing, Valsalva, tilting (to assess parasympathetic and sympathetic adrenergic function), and axon-reflex function and thermoregulatory sweat testing to assess sympathetic cholinergic function. Patients also completed a questionnaire regarding other autonomic symptoms. RESULTS: Results of autonomic testing were abnormal in seven patients. Parasympathetic function was normal in all, and the abnormalities were restricted to sympathetic cardiac, vasomotor, and sudomotor function. Abnormal results of axon-reflex testing in six were consistent with peripheral nervous system dysfunction. Five had decreased sweating over the abdomen, determined by thermoregulatory sweat testing. Five eight had nongastrointestinal autonomic symptoms, primarily palpitations and flushing. CONCLUSIONS: Functional abdominal pain in the current patients is associated with generalized dysfunction of the autonomic nervous system. This dysfunction can be peripheral or central in different individuals but seems to be restricted to the sympathetic branch. The known function of the sympathetic nervous system as the motility "brake" suggests that pain could be a manifestation of unmodulated peristalsis, resulting in abdominal cramps.

Abdominal Pain↗
PubMed1992

Autonomic nervous system dysfunction alters drug effects: implications for testing drugs for the treatment of heart failure.

Blunted cardiac responses to sympathetic and vagal activation are key features of heart failure. Since the modulation of drug effects by a selective autonomic dysfunction is little known, we developed an acute rabbit model imitating these defects. Anesthetized rabbits were subject to cervical vagotomy and propranolol (1 mg/kg i.v.) pretreatment, thus eliminating vagally and sympathetically mediated cardiac responses, while maintaining the responsiveness of the peripheral circulation to these reflexes ("V-B" animals). Responses to drugs were altered in V-B compared with normal animals: Ouabain (5-50 micrograms/kg) increased myocardial contractile force more and milrinone (30-300 micrograms/kg) less, yet it increased the heart rate more; the reflex tachycardia to nitroprusside (1-10 micrograms/kg/min) was blunted and spirapril (0.1 and 1 mg/kg, all i.v.) decreased the central venous pressure only in V-B animals. Several drug effects were thus strongly modulated by autonomic dysfunction and responses of V-B animals were closer to those of heart failure patients than the responses of the normal animals, especially for milrinone.

Animals↗
PubMed1991

Orthostatic hypotension in human immunodeficiency virus infection may be the result of generalized autonomic nervous system dysfunction.

We used an autonomic nervous system (ANS) testing battery to determine if generalized ANS dysfunction was present in five human immunodeficiency virus-positive (HIV+) patients presenting with severe orthostatic hypotension (OH). All five patients had abnormal ANS testing, which demonstrated both sympathetic and parasympathetic defects, i.e., generalized ANS dysfunction. Treatment with fludrocortisone effectively reversed the OH in four of the five patients. The OH was transient in these four patients. We believe it is important to recognize that OH may be the result of generalized ANS dysfunction in HIV-positive patients and that it can be effectively treated.

Autonomic Nervous System↗
PubMed1992

[Gallbladder motility in diabetic patients with and without cardiovascular neuropathy].

In 50 diabetic patients without gallstones, including 26 patients with cardiovascular autonomic dysfunction, and 60 normal volunteers the fasting volume and volume reduction of the gallbladder after a liquid fatty meal were determined ultrasonically in intervals of ten minutes up to one hour. Simultaneously the gastric emptying of the liquid meal was followed by ultrasound imaging. Despite an association of other complications of diabetic disease (peripheral neuropathy, retinopathy) with autonomic cardiovascular dysfunction, an altered gallbladder resting volume or impaired fat-induced volume reduction was not evident in this group of patients when compared the diabetics without cardiovascular dysfunction or controls. The time to reach the minimal residual gallbladder volume was only tendentiously prolonged in diabetics with autonomic cardiovascular dysfunction. The residual volume of the stomach showed no significant difference between the three study groups using a liquid test meal. In conclusion neuropathic dysfunction of the gallbladder is unlikely to play a major pathogenetic role in the development of gallstones in diabetic patients.

Adult↗
PubMed2007

Normal cardiovascular reflex testing in patients with parkin disease.

The objective of this study was to investigate cardiovascular autonomic function in patients with parkin disease. Ten patients with a genetically confirmed diagnosis were compared to 11 healthy controls. Symptoms related to autonomic dysfunction were collected by structured interviews. Cardiovascular autonomic reflex function was evaluated using a standard battery of eight tests. Autonomic tests included the study of sympathetic function through the analysis of blood pressure responses to head-up tilt, standing, isometric hand grip, cold pressor, mental arithmetic, Valsalva maneuver (Valsalva overshoot), and the study of parasympathetic function through the analysis of heart rate responses to deep breathing, hyperventilation, and Valsalva ratio. Seven out of 10 patients reported symptoms involving different aspects of autonomic function, while 5 out of 11 controls reported symptoms related exclusively to orthostatic dizziness and constipation. Symptoms related to bladder dysfunction were the most frequent autonomic abnormality occurring in six patients, followed by orthostatic dizziness and dry mouth (in four patients each). Constipation occurred in three patients, sialorrhea in two, and erectile dysfunction, dry eye, and warm intolerance in one each. Cardiovascular reflex testing revealed no difference between patients and controls in quantitative assessment of both sympathetic and parasympathetic functions, except for diastolic blood pressure after isometric hand grip that did not increase normally in parkin patients compared to controls (P = 0.007). These data show that cardiovascular dysautonomia is not associated to the parkin phenotype, whereas urinary complaints are more frequently reported by parkin patients than by controls. Urinary dysautonomia warrants further investigation in patients with parkin disease.

Adult↗