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Relationship between retinal ischemia and cardiovascular autonomic damage in diabetes.

In order to investigate the relationship between ischemic diabetic retinopathy and cardiac autonomic dysfunction we studied 40 diabetic patients (mean age +/- SEM: 48 +/- 2 years). Retinopathy was evaluated by fluorescein angiography and patients were divided into three groups: a) with ischemic retinopathy (15 patients), b) with edematous retinopathy (13 patients) and c) without retinopathy (12 patients). Cardiac autonomic function was assessed by 4 tests based on cardiovascular reflexes (heart rate response to Valsalva maneuver and to deep breathing; systolic blood pressure fall after standing and diastolic blood pressure rise during handgrip) and by the cross-correlation test, a computerized technique for the analysis of respiratory sinus arrhythmia based on spectral analysis of electrocardiographic and respiratory signals. Abnormalities of cardiac autonomic tests were present in 26/40 patients (65%); considering the retinal angiographic classification, autonomic test abnormalities were found in 13/15 (86.6%) patients with ischemic retinopathy, in 7/13 (53.9%) patients with edematous retinopathy and in 6/12 (50%) patients without retinopathy. The prevalence of cardiac autonomic dysfunction was significantly higher (p less than 0.005) in the ischemic retinopathy group compared to the other groups. These results show a strong association between ischemic retinopathy and cardiac autonomic dysfunction.

Autonomic Nervous System↗

Neuromuscular respiratory failure in Guillain-Barre Syndrome: evaluation of clinical and electrodiagnostic predictors.

UNLABELLED: Guillain-Barre Syndrome (GBS) has an unpredictable clinical course with up to 30% of patients requiring assisted ventilation during the course of their illness. Successful management mandates anticipation, prompt recognition and optimal treatment of neuromuscular respiratory failure in GBS. AIMS: To identify clinical and electrodiagnostic predictors of neuromuscular respiratory paralysis in GBS. MATERIALS AND METHODS: Forty six patients of GBS were studied over a 6 year period, the study being 2 year retrospective and 4 year prospective. Clinical and electrodiagnostic data were compared between ventilated (28) and non-ventilated (18) patients. The clinical parameters assessed were median age, gender, antecedent infection, prior lung disease, time to peak disability, bifacial weakness, upper limb weakness, bulbar paralysis, neck weakness and autonomic dysfunction. Electrodiagnostic studies included motor nerve conduction studies in 11 ventilated and 13 non-ventilated patients, done prior to maximum disability in each group. Multiple logistic regression analysis was used to compare the two groups. RESULTS: Comparing the clinical data in the ventilated and non-ventilated groups, 'early peak disability', autonomic dysfunction and bulbar weakness predicted the onset of respiratory paralysis. Age, gender, neck or bifacial weakness, upper limb paralysis, or preceding infection did not influence the development of neuromuscular respiratory weakness. Electrodiagnostic testing revealed abnormal H reflex and F waves to be the commonest abnormality in either group. Although data was not sufficient for statistical analysis, the presence of markedly attenuated Compound Muscle Action Potentials inexcitable motor nerves and denervation changes on the electromyography, was commoner in the ventilated group. Thirty six patients received treatment with either plasmapheresis (12) or intravenous immunoglobulin (24). Overall mortality was 5, all 5 patients being on assisted ventilation. CONCLUSION: Early progression to peak disability, bulbar dysfunction and autonomic instability predicted the development of neuromuscular respiratory paralysis in GBS. Early electrodiagnostic studies in this series suggest axonopathic GBS as a predictor of respiratory paralysis, a finding that needs to be evaluated with sufficient data to permit statistical analysis.

Acute Disease↗

Localization of autonomic nervous system dysfunction in dialysis patients.

Autonomic nervous system dysfunction has been described frequently in uremic patients. The purpose of this study is to determine the localization of this abnormality and to study the possible relationship between autonomic dysfunction and the occurrence of dialysis hypotension. Sixteen consecutive patients participated in the study, 5 of whom had a history of dialysis-induced hypotension. These 5 patients were compared to the other 11 as regards the cardiovascular response to isoproterenol infusion, tilt test and arteriovenous (AV) fistula occlusion. None of the responses to the above mentioned stimuli was significantly different between the 2 groups. In the whole study population, an index of parasympathetic control of heart rate (variation of heart period, VHP) was reduced (31 +/- 5 vs. 59 +/- 9 ms in age-matched controls; p less than 0.025). Heart rate and diastolic blood pressure response to isoproterenol infusion was normal (+23 +/- 2 beats/min and -9 +/- 3 mm Hg; p less than 0.005 for both), indicating normal response of effector organs to beta-adrenergic agonist stimulation. Similarly, plasma norepinephrine increased significantly (+294 +/- 51 pg/ml; p = NS from normal laboratory values) in response to head-up tilt, and heart rate increased simultaneously in all but 5 patients. Blood pressure response was within normal after 10 min of head-up tilt at 60 degrees in all but 3 patients; only 1 of these 3 patients was in the group of dialysis hypotension. However, during AV fistula occlusion, heart rate did not change markedly, despite the significant increase in systolic blood pressure, suggesting an altered sensitivity of baroreceptor reflex arc.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Abnormal autonomic function in diabetic and nondiabetic patients after first acute myocardial infarction.

We performed autonomic function testing in 68 patients, 34 with diabetes mellitus (group A) and 34 without (group B), at 72 h after a first acute myocardial infarction (MI) to determine the prevalence of autonomic dysfunction in these patients. Heart rate (HR) variation during 6 breaths/min obtained from mean of longest RR interval during expiration(E)/mean of shortest RR interval during inspiration (I) (E:I ratio), immediate HR response to standing = RR at 30th beat/RR at 15th beat (30:15 ratio) and postural fall of blood pressure were evaluated. In group A, 25 (78 percent) of 32 patients had an abnormal expiration-inspiration ratio compared with 28 (85 percent) of 33 in group B. Twenty-six (76 percent) patients in group A and 16 (47 percent) in group B had an abnormal 30:15 ratio. Abnormal postural fall of blood pressure was seen in 16 (47 percent) patients in group A compared with ten (29 percent) in group B. During follow-up, four women in group A with an initial autonomic dysfunction died, and in group B, three patients with a normal autonomic function died. Thus, autonomic dysfunction does not seem to contribute to the high mortality among diabetics after an acute MI.

Adult↗

Autonomic nervous dysfunction in patients on long-term hemodialysis.

The level of plasma dopamine-beta-hydroxylase (DBH) activity in subjects at rest was found to be significantly lower in 12 patients on long-term hemodialysis than in a healthy 8-member control group: 28.3 +/- 7.2 and 13.6 +/- 7.6 IU/1, respectively (p less than 0.01). Following immersion of one hand of each subject into cold water (4 degrees C) for 1 min, a significant rise was observed in both groups, 6.1 +/- 4.8 IU/1 for the control and 1.6 +/- 1.4 IU/1 for the patient group (p less than 0.01). Upon tilting up the head of all subjects, activity in both groups increased significantly, but a markedly smaller rise was found in the patient group: 5.8 +/- 4.8 and 1.1 +/- 1.6 IU/1 for the two groups, respectively (p less than 0.01). The data suggest an autonomic nervous dysfunction in patients on long-term hemodialysis.

Adult↗

[A role of depression in chronic dorsalgia: approaches to therapeutic correction].

An impact of depression on general clinical picture was studied in 20 patients with chronic dorsalgia, who were treated with coaxil. Along with complaints to prolonged back pains, patients featured by high depression and anxiety, sleep disturbances, autonomic dysfunction and marked decrease of quality of life. Psychometric tests revealed a presence of depressive symptoms in 90% of the cases. All patients were treated with coaxil in dosage 12.5 mg 3 times daily during 6 weeks. The treatment allowed a reduction of depression and anxiety symptoms, along with muscle dysfunction and pain syndrome. Positive dynamics of autonomic dysfunction, sleep disturbances and quality of life was observed already at the initial treatment stage. The results of the study confirm the fact that depression develops in patients with chronic dorsalgia, influencing negatively on the course of pain syndrome. Coaxil was shown to have high efficacy and safety in the treatment of depression caused by chronic back pain and positively influence on the main syndrome.

Adult↗

An exploration of central dysregulation of erectile function as a contributing cause of diabetic impotence.

Diabetic impotence is generally presumed to be secondary to peripheral abnormalities of the vascular or autonomic nervous system, although central nervous control of the autonomic nervous system has not previously been studied. Measures of rapid eye movement (REM) sleep as potential indicators of central autonomic dysfunction were studied along with sleep-related tumescence for 10 impotent diabetics, nine psychogenically impotent men, and 10 men whose impotence was secondary to pelvic trauma. Low REM density was found in the diabetics with REM density correlating with measures of tumescence. These results suggest that central autonomic dysfunction may be a contributing factor in the impotence of diabetic men. A metabolic disturbance in the central nervous system of diabetics which might alter both sleep and autonomic nervous system activity is proposed to explain these results and may help in the understanding of other observed abnormalities in both the sleep and autonomic dysfunction of diabetics.

Brain↗

[Unstable blood pressure during anesthesia in diabetic patients with autonomic neuropathy].

Diabetic autonomic neuropathy (AN) as a risk factor of surgical procedures has so far been described in case reports, but no controlled clinical studies are known. Therefore, we intended to study systematically the perioperative relevance of the autonomic dysfunction. 32 ophthalmosurgical patients (20 diabetics, 12 non-diabetics) were investigated. Cardiovascular autonomic function was examined preoperatively by a combination of tests (heart rate variations during deep breathing, Valsalva ratio, 30:15 ratio, postural hypotension, sustained hand grip). A scoring system based on these tests provided the staging of the autonomic involvement of the patients (AN score). The anaesthesiological management (thiopentone, N2O, halothane) and the operative procedure (vitrectomy) were uniform. A significant correlation was found between the AN score and the coefficient of variation of the systolic (r = 0.70, p less than 0.001) resp. the diastolic (r = 0.52, p less than 0.01) blood pressure during anaesthesia. No correlation was found between the intraoperative variability of the arterial blood pressure (coefficient of variation) and the age of the patients resp. the preoperative value of the blood pressure. In diabetics with severe autonomic neuropathy (AN score greater than 5) hypotensive reactions were seen very often during the operation. The results demonstrate that the haemodynamic stability in the perioperative period depends on the severity of the autonomic dysfunction. Diabetics with severe autonomic neuropathy have a high risk of blood pressure instability. Non-invasive diagnostic methods allow to identify these patients preoperatively.

Adult↗

Paroxysmal episodic hypothalamic instability with hypothermia after traumatic brain injury.

This case report describes a patient in vegetative state after severe traumatic brain injury (TBI) with hypothalamic damage and clinical manifestations of autonomic dysfunction. He also presented late onset paroxysmal hypothermia associated with mild bradycardia and hypotension. Hypothermia due to traumatic lesions of the hypothalamus is an uncommon clinical problem and few cases have been reported; no cases could be found in the literature which evidenced periodic hypothermia associated with clinical features of autonomic dysfunction after TBI. In the article, the main causes and the primary pathophysiology of hypothermia after TBI are discussed. The manifestations in this patient have been interpreted as possible consequences of autonomic dysfunction and considered atypical and rare clinical expression of acute post-traumatic hypothalamic instability.

Accidents, Traffic↗

Paucifascicular congenital sensory neuropathy in identical twins.

A male infant had sensory and autonomic dysfunction, and his identical twin had a similar clinical finding. One twin was extensively studied, utilizing sural nerve, skin, and conjunctival biopsy specimens, to evaluate the status of peripheral sensory axons. The results support an antenatal neurodevelopmental disturbance in axonal growth that affects sensory neurons and limits their distal extension. Neuropathologic studies of this patient closely resemble findings in hereditary sensory neuropathy type II; clinically, however, this patient resembles patients with congenital autonomic dysfunction and universal pain loss. Investigation of proximal and distal sural nerve, skin, and/or conjunctival biopsy specimens is recommended in patients with sensory and autonomic dysfunction to help differentiate these patients to assist in genetic counselling, treatment, and prognosis. It is possible that clinical overlap in such patients may result from a common neuropathic process, but with varying degrees of involvement.

Conjunctiva↗

Use of demand pacemaker in children with Guillain-Barré syndrome and cardiac arrhythmias.

We report 2 patients with Guillain-Barré syndrome who exhibited autonomic dysfunction, including lability of blood pressure and heart rate, frequent episodes of profound bradycardia, and occasional asystole. Both patients required insertion of a temporary venous pacemaker which was activated a few times during the following days. The potential need for ventilatory support in patients with Guillain-Barré syndrome is well known; however, death in these patients due to acute cardiovascular failure during autonomic dysfunction continues to occur. The patients' courses emphasize the significance of cardiac monitoring and the potential use of cardiac pacing in Guillain-Barré syndrome patients who exhibit autonomic dysfunction.

Adolescent↗

Dissociation between pain and autonomic disturbances in cluster headache.

The relationship between pain and autonomic disturbances in cluster headache was studied in 54 patients whose attack always recurred on the same side, and in 7 others whose attack had affected either side on different occasions. In one of these seven patients, facial flushing and ocular sympathetic deficit was observed on the original side of headaches. In most patients, the orbital region was warmer on the painful side but in three cases this region was cooler during and between attacks. Lacrimation and rhinorrhoea were more common in severe attacks, and the temperature difference between the orbits increased with increasing severity of pain. These findings support the view that certain autonomic disturbances in cluster headache are provoked by pain. Residual autonomic dysfunction could influence autonomic activity during cluster headache. If so, residual dysfunction on the pain-free side could explain the dissociation between autonomic disturbances and pain observed in a few cases.

Adult↗

Erectile dysfunction as a sentinel symptom of cardiovascular autonomic neuropathy in heavy drinkers.

Because autonomic neuropathy (AN) is not routinely assessed in chronic alcoholism, its features and relationship with other disease parameters remain undefined. The very existence of true alcohol-related autonomic dysfunction, in the absence of alcoholic hepatopathy, is even controversial. We aimed this study at evaluating the frequency and pattern of AN in a population of heavy drinkers without liver dysfunction. We also investigated the putative risk factors for AN as well as its relationship to peripheral neuropathy (PN). Autonomic function was evaluated in 70 detoxified alcoholics and 70 well-matched controls by heart-rate response to deep breathing, heart-rate response to standing from lying position, and blood pressure response to standing up. PN was assessed by electroneurography (ENG). Detailed information about sensorimotor and autonomic symptoms, nutritional status, and parameters reflecting alcohol intake were recorded. No patients showed signs of caloric/protein malnutrition. PN was found in 74% and AN (abnormal test results in two of three tests performed) in 26%; abnormalities in at least one autonomic test were found in 62%. All patients with PN were symptomatic, mainly due to sensory disturbances. In line with this, ENG abnormalities were more evident at sural nerves. AN was symptomatic in 10 of 18 patients, and its sole clinical expression was impotence: indeed, the pattern of autonomic involvement was mainly parasympathetic. AN did not correlate with PN, nor with any parameter reflecting the amount of alcohol intake; only performances on heart-rate response to standing from lying position were related to the duration of abuse. The lack of correlation between PN and AN may suggest a different pathophysiology for these two complications. Unlike PN, AN is often asymptomatic. Among symptomatic patients (55%), erectile dysfunction seems to be the sole symptom, in line with the higher degree of parasympathetic damage.

Adult↗

[Utility of the study of the vegetative nervous system in the differential diagnosis between Parkinson's disease and multiple system atrophy].

INTRODUCTION: The aim of this study is to show if the exploration of the autonomic nervous system is useful to improve the specificity of clinical criteria of Parkinson's Disease (PD) and Multiple System Atrophy (MSA). PATIENTS AND METHODS: 20 patients with PD and 13 patients with MSA were studied. After 12 hours in off medication, NE and GH were measured in supine position and NE after 5 minutes standing. Later, GH levels were recorded at 15, 30, 45 and 60 minutes after a dose of 0.005 mg/kg of apomorphine. Finally, analysis of the symptoms of autonomic dysfunction and levodopa test were carried out. RESULTS: Sympathetic response to postural changes was significantly higher in patients with PD (NE increase in relation to basal: PD: 170.90 +/- 110.08 pg/ml; MSA: 91.33 +/- 73.79 pg/ml; p = 0.029). No differences were found in the response of GH to apomorphine (GH peak at 45 minutes: PD: 2.37 +/- 2.7 ng/ml; MSA: 1.69 +/- 1.90 ng/ml; ns). The symptoms of autonomic dysfunction were more frequently in patients with MSA. The stridor was specific to MSA. Improvement in motor scores in the levodopa test was higher in patients with PD (PD: 39.7 %; MSA: 17.89; p = 0.019). DISCUSSION: Sympathetic response to postural changes, description of symptoms of autonomic dysfunction, and motor response to levodopa test are useful tools in order to improve specificity of the diagnostic criteria of PD and MSA. The GH test with apomorphine was not useful for a differential diagnosis.

Aged↗

Progression of symptoms in neuroleptic malignant syndrome.

The neuroleptic malignant syndrome (NMS) is a rare but potentially fatal disorder characterized by mental-status changes, muscle rigidity, hyperthermia, and autonomic dysfunction. Systematic examination of early signs and the progression of symptoms in NMS may be worthwhile to facilitate prompt recognition and interventions to abort the syndrome in its incipient stage. The authors present the results of a preliminary review of the temporal sequence of the four predominant signs of NMS as described in 340 clinical reports of NMS in the literature. Of all order implications, 70.5% were consistent with the sequence of mental-status changes, rigidity, hyperthermia, and autonomic dysfunction. Changes in either mental status or rigidity were the initial manifestations of NMS in 82.3% of cases with a single presenting sign and were significantly more likely to be observed before hyperthermia and autonomic dysfunction. Methodological limitations of these data and clinical implications are discussed.

Adolescent↗

Autonomic influence on pregnancy outcome in IDDM.

We evaluated the autonomic influence on pregnancy outcome with prospective study of 100 consecutive pregnancies in women with insulin-dependent diabetes mellitus (IDDM). Tests of cardiovascular autonomic nervous function were performed at the beginning of each pregnancy, and two groups were formed. Group 1 was comprised of 23 pregnancies with autonomic dysfunction, and group 2 was comprised of 77 pregnancies with no abnormalities in cardiovascular tests. Elective abortion was later induced for medical reasons in two cases in group 1, and these women were excluded from the study. The groups were comparable with respect to age, duration of diabetes, and presence of nephropathy. Both groups also achieved comparable glycemic control during pregnancy. There were no significant differences between groups 1 and 2 in any specific pregnancy complication (spontaneous abortions, 5 vs. 3%; perinatal mortality, 10 vs. 1%; congenital malformations, 10 vs. 4%; respiratory distress syndrome, 5 vs. 8%; preeclampsia, 20 vs. 10%; maternal ketoacidosis, 4 vs. 0%; and maternal hypoglycemic accidents, 10 vs. 4%, respectively), but the frequency of pregnancies with at least one of the above complications was greater in group 1 (52 vs. 23%, P = 0.01). Stepwise logistic regression analysis showed the association between autonomic dysfunction and pregnancy outcome to be independent of high initial glycosylated hemoglobin levels, long duration of diabetes, and nephropathy. Maternal autonomic dysfunction seems to be associated with an increased frequency of overall pregnancy complications but does not significantly interfere with the achievement of tight metabolic control during pregnancy.

Adult↗

Ocular and cardiovascular autonomic function in diabetic patients with varying severity of retinopathy.

The study was conducted to assess the ocular and cardiovascular autonomic function in diabetic patients with varying severity of diabetic retinopathy. Ocular and cardiovascular autonomic function tests were performed in 30 patients with type 2 Diabetes Mellitus (10 in each group of proliferative retinopathy, non-proliferative retinopathy and no retinopathy) of more than 5 years duration and 10 normal controls. Ocular autonomic function tests were done by measuring pupil cycle time and denervation hypersensitivity with 0.125% pilocarpine and 0.5% phenylephrine. Cardiovascular autonomic function was measured by a battery of standard tests. Denervation hypersensitivity to 0.125% pilocarpine and to 0.5% phenylephrine and pupil cycle time showed statistically significant differences (P value < 0.001) between controls and patients with proliferative retinopathy (PDR) and also between no retinopathy and PDR (P < 0.001). Systemic autonomic function tests namely expiration--inspiration ratio, difference in heart rate, 30th beat and 15th beat ratio in head up tilt and difference in diastolic blood pressure in head up tilt test also showed significant difference (P < 0.01) between controls and all 3 groups of diabetics. There was statistically significant difference found in para-sympathetic ocular autonomic dysfunction between NPDR and controls. Ocular and systemic autonomic dysfunctions are related to the severity of diabetic retinopathy.

Adult↗

The effect of rapid lipid lowering with atorvastatin on autonomic parameters in patients with coronary artery disease.

Many cardiovascular disease states are associated with autonomic dysfunction, specifically sympathetic activation and parasympathetic withdrawal. Both these autonomic derangements are independently associated with adverse prognostic outcomes. HMG CoA reductase inhibitors (statins) reduce cardiovascular mortality and morbidity when compared to placebo in subjects with proven coronary artery disease (CAD), including sudden presumed arrhythmic death. As autonomic dysfunction is associated with arrhythmogenesis, statins may be having a beneficial effect on autonomic function in these subjects. We conducted a randomised, double-blind, placebo-controlled, cross-over study examining the effect of rapid short-term lipid lowering with a statin on autonomic function in CAD patients. Ten subjects with proven CAD (8 male, 2 female; mean age 63.4 years) were randomised to receive either 80 mg atorvastatin or placebo over a 4 week period followed by a 4 week washout, then the alternative treatment for a further 4 weeks. Autonomic parameters assessed were plasma noradrenaline levels on recumbency and 80 degrees head-up tilt, cold pressor testing, and heart rate variability (HRV) analysis. Plasma noradrenaline levels were significantly reduced (p=0.050) after 20 min rest in the recumbent position, with atorvastatin compared to placebo. A nonsignificant reduction in plasma noradrenaline with atorvastatin compared to placebo was observed in the prolonged 80 degrees head-up position (p=0.207). In addition, sympathovagal balance was shifted to greater vagal predominance with atorvastatin (low-frequency/high-frequency ratio in the HRV frequency domain) when compared to placebo, p=0.06. We found that rapid lipid lowering with atorvastatin reduces sympathetic nervous system in this pilot study of CAD patients. Larger trials are required to definitively address the effects of statins on autonomic activity in these patients.

Aged↗