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[Dynamic scintigraphy of gastric emptying in non-insulin dependent diabetics with autonomic neuropathy].

To ascertain whether gastric emptying of solids is affected by visceral autonomic neuropathy, 30 noninsulin-dependent diabetics (10 with autonomic neuropathy, 10 with peripheral and 10 without neuropathy) and 10 control subjects were studied. Subjects were screened by clonidine test and two parasympathetic tests of cardiovascular reflexes to identify the presence of autonomic neuropathy. The peripheral neuropathy was diagnosed by classic neurological examination and EMG. Delayed gastric emptying was assessed by dynamic scintigraphy, using 99mTc labeled ham and eggs. The gastric emptying of solids was markedly delayed in diabetics, particularly in diabetics with poor metabolic control (p < 0.01) and those with autonomic and peripheral diabetic neuropathy (p < 0.05). The results of our study suggest that dynamic scintigraphy may be a more sensitive method than other tests for autonomic dysfunction of the gut in diabetics with the early manifestation of diabetic gastroparesis.

Autonomic Nervous System Diseases↗

Sensory and autonomic polyneuropathy associated with hypergammaglobulinemia.

Sensory and autonomic polyneuropathy is a rare disease characterized by a sensory nerve disorder and postganglionic autonomic dysfunction. The etiology of this disease is unknown. We described a 51-year-old woman who had a chronic sensory dominant polyneuropathy and dysautonomia associated with hypergammaglobulinemia. In the previous reports of sensory and autonomic polyneuropathy, not much attention was given to coexisting hypergammaglobulinemia. By reviewing the literatures, hypergammaglobulinemia was frequently present in these case reports. This fact leads us to consider that an immunological mechanism may be playing a role in the pathogenesis of this disorder.

Autonomic Nervous System Diseases↗

Early autonomic malfunction in normotensive individuals with a genetic predisposition to essential hypertension.

One of the primary pathologies associated with hypertension is a complex autonomic dysfunction with evidence of sympathetic hyperactivity and/or vagal withdrawal. We investigated the possibility for early detection of essential hypertension on the basis of the analysis of heart rate (HR) and blood pressure fluctuations, which reflect autonomic control. Young adult normotensive offspring of one hypertensive parent (KHT; n = 12) and normotensive offspring of two normotensive parents (YN; n = 14) participated in this study. ECG, continuous blood pressure, and respiration were recorded during steady-state conditions and under various autonomic challenges. Time-frequency decomposition of these signals was performed with the use of a continuous wavelet transform. The use of the wavelet transform enables the extension of typical HR variability analysis to non-steady-state conditions. This time-dependent spectral analysis of HR allows time-dependent quantification of different spectral components reflecting the sympathetic and parasympathetic activity during rapid transitions, such as an active change in posture (CP). During an active CP from the supine to standing position, KHT demonstrated a significantly greater increase in the low-frequency fluctuations in HR than YN, indicating enhanced sympathetic involvement in the HR response to CP, and a reduced alpha-index, indicating decreased baroreceptor sensitivity. On recovery from handgrip, vagal reactivation was more sluggish in KHT. These results indicate the early existence of malfunctions in both branches of autonomic control in individuals at increased risk of hypertension.

Adult↗

Ganglionitis in paraneoplastic subacute sensory neuronopathy: a morphologic study.

A 69-year-old woman presented with subacute sensory neuropathy and autonomic dysfunction of 9 months' duration, associated with high serum titers of anti-Hu antibodies. A small cell carcinoma of the lung was diagnosed by biopsy. She died after cardiorespiratory arrest. At autopsy, spinal and autonomic ganglia showed subacute inflammation with diffuse endoneurial T-cell, B-cell, and plasma cell infiltration. The cytoplasm and nuclei of some ganglion neurons displayed IgG immunocytochemical positivity. CD8+ T cells were tightly attached to, and indented the cell surface of, IgG-positive and IgG-negative neurons. This observation suggests that both cytotoxic T-cell-mediated attack against neurons and humoral mechanisms play a role in paraneoplastic subacute sensory neuronopathy.

Aged↗

Severe orthostatic hypotension in carcinoma of the pancreas.

Autonomic dysfunction has been described in patients with advanced forms of cancer. We report a case of severe orthostatic hypotension in a patient with carcinoma of the pancreas in whom there was no clinical evidence of autonomic failure to account for the severity of the hypotension. Despite normal circulating levels of nor-adrenalin and an appropriate rise in the erect position, the vascular system appeared unresponsive. We suggest that in this patient the orthostatic hypotension was due to a paraneoplastic complication of the pancreatic tumour.

Adenocarcinoma↗

Autonomic function tests in diabetes mellitus.

Five tests of autonomic function were evaluated in a group of twenty-five diabetics. The Valsalva ratio proved to be the most valuable single indicator of generalised autonomic dysfunction, whilst the blood pressure response to sustained handgrip, the pupillary response to a dilute solution of methacholine and the fall in blood pressure on standing, all proved to be less valuable as indices of autonomic neuropathy either when considered individually or when taken together. The cold pressor test was shown to be of no value in the assessment of patients with autonomic neuropathy. It is suggested that of those examined the Valsalva procedure is the most valuable simple outpatient test for autonomic neuropathy.

Adult↗

Adverse influence of baroreceptor dysfunction on upright exercise in congestive heart failure.

To test the hypothesis that baroreceptor autoregulation is an important determinant of exercise performance, the hemodynamic responses to the gravitational stress of head-up tilt and upright exercise were assessed in 41 patients with severe chronic congestive heart failure. Three patterns of autonomic dysfunction during head-up tilt were identified. Group A patients had near-normal circulatory reflexes whereas Group B patients experienced orthostatic hypotension and Group C patients lacked the afferent stimulus of venous pooling. Group A patients had a significantly longer exercise duration than both Groups B and C (607 +/- 104 versus 330 +/- 86 and 365 +/- 53 seconds, respectively, p less than 0.05) and a significantly higher double product at peak exercise (17,779 +/- 956 versus 12,235 +/- 869 and 13,760 +/- 998, respectively, p less than 0.05). Thus, baroreceptor abnormalities in the autoregulatory response to postural change are important determinants of the cardiovascular responses required during exercise and influence exercise performance. These abnormalities may help clarify the discrepancies between supine and upright exercise performance and may influence the long-term efficacy of vasodilator therapy in chronic congestive heart failure.

Adult↗

Autonomic nervous function in progressive supranuclear palsy.

Autonomic nervous function was assessed in 11 patients with progressive supranuclear palsy, 26 patients with Parkinson's disease, matched for age, medications, disease severity, and disease duration, and 19 age-matched controls. Results of both parasympathetic (heart rate response to deep breathing and Valsalva maneuver) and sympathetic (blood pressure decrease on standing and increase on sustained handgrip) tests were abnormal in both patient groups. Abnormalities in the group of patients with progressive supranuclear palsy were similar to those in the group with Parkinson's disease but were more pronounced. Autonomic dysfunction may have to be considered a feature of progressive supranuclear palsy.

Aged↗

Autonomic and peripheral neuropathy in primary biliary cirrhosis.

Autonomic and peripheral nerve function was examined in a group of patients with primary biliary cirrhosis using standard cardiovascular reflex tests and peripheral nerve conduction studies. Sixty-three percent had cardiovascular autonomic dysfunction with predominantly parasympathetic abnormalities. Symptoms of peripheral neuropathy were rarely volunteered spontaneously but occurred frequently when specifically sought; 40.7% had definite peripheral neuropathy, with symptoms and/or signs plus peripheral neurophysiological abnormalities. A close association between autonomic and peripheral nerve function was found with correlation between the heart rate variation on deep breathing and both peroneal nerve conduction velocity (r = 0.67, P < 0.001) and sural nerve conduction velocity (r = 0.52, P < 0.008). Correlations were also noted between other autonomic tests and peripheral nerve function. Both autonomic and peripheral nerve function correlated with serum bilirubin and albumin; no significant association was noted with vitamin E deficiency or hyperlipidaemia. A generalised neuropathy with peripheral and autonomic abnormalities is common in primary biliary cirrhosis and could be related to hepatic damage. Although rarely clinically disabling, the autonomic impairment associated with this neuropathy may be of prognostic significance.

Adult↗

The neurophysiology of dissociation and chronic disease.

Dissociation as a clinical psychiatric condition has been defined primarily in terms of the fragmentation and splitting of the mind, and perception of the self and the body. Its clinical manifestations include altered perceptions and behavior, including derealization, depersonalization, distortions of perception of time, space, and body, and conversion hysteria. Using examples of animal models, and the clinical features of the whiplash syndrome, we have developed a model of dissociation linked to the phenomenon of freeze/immobility. Also employing current concepts of the psychobiology of posttraumatic stress disorder (PTSD), we propose a model of PTSD linked to cyclical autonomic dysfunction, triggered and maintained by the laboratory model of kindling, and perpetuated by increasingly profound dorsal vagal tone and endorphinergic reward systems. These physiologic events in turn contribute to the clinical state of dissociation. The resulting autonomic dysregulation is presented as the substrate for a diverse group of chronic diseases of unknown origin.

Animals↗

Interaction of human chagasic IgG with the second extracellular loop of the human heart muscarinic acetylcholine receptor: functional and pathological implications.

Circulating antibodies from human and murine chagasic sera are able to interact with myocardium-activating neurotransmitter receptors. Here we reported the presence of autoantibodies against the second extracellular loop of the human heart muscarinic acetylcholine receptors (mAChR) in patients with Chagas' disease by using a synthetic 24-mer peptide in immunoblotting and enzyme immunoassay. Affinity-purified antipeptide IgG from chagasic patients, similar to monoclonal antihuman M2 mAChR, recognized bands with a molecular weight corresponding to the cardiac mAChR. The binding was inhibited by the peptide, assessing the specificity of the interaction. The antipeptide autoantibody also displayed an "agonist-like" activity modifying the intracellular events associated with mAChR activation, i.e., decreased contractility, increased cGMP, and decreased cAMP production. All of these effects on rat atria by chagasic antipeptide autoantibodies resemble the effects of the authentic agonist and those of the total polyclonal chagasic IgG, being selectively blunted by atropine and neutralized by the synthetic peptide corresponding in aminoacid sequence to the second extracellular loop of the human M2 mAChR. A clinical relevance of these findings is demonstrated by a strong association between the existence of circulating antipeptide autoantibodies in chagasic patients and the presence of dysautonomic symptoms, making these autoantibodies a proper early marker of heart autonomic dysfunction.

Acetylcholine↗

Unawareness of hypoglycaemia in insulin-treated diabetic patients: prevalence and relationship to autonomic neuropathy.

Three-hundred and two insulin-treated diabetic patients were questioned about hypoglycaemia using a structured questionnaire interview. Two-hundred and twenty-six patients (75%) had normal symptomatic awareness, 48 (16%) had partial awareness, 21 (7%) had absent awareness of hypoglycaemia, and 7 (2%) denied ever experiencing hypoglycaemia. Patients with complete loss of awareness of hypoglycaemia had diabetes of longer duration; none had a HbA1 concentration within the non-diabetic range. Loss of awareness of hypoglycaemia was associated with an increased incidence of severe hypoglycaemia, 19 (91%) of the patients with absent awareness, and 33 (69%) with partial awareness of hypoglycaemia experiencing severe hypoglycaemia over 1 year compared with only 41 (18%) of patients with normal awareness of hypoglycaemia (p less than 0.001). Cardiovascular autonomic function tests were performed in 226 (75% of the whole group). Of the patients who had diabetes for more than 15 years, 54% (n = 39) with normal awareness of hypoglycaemia, compared with 59% (n = 10) with absent awareness of hypoglycaemia, had evidence of cardiovascular autonomic impairment (NS). Seven (41%) of the 17 patients with absent awareness of hypoglycaemia and diabetes of greater than 15 years duration had no evidence of autonomic dysfunction. Loss of hypoglycaemia awareness is a common problem in patients with insulin-treated diabetes of long duration, is associated with an increased incidence of severe hypoglycaemia, but is not invariably associated with abnormal cardiovascular autonomic function tests.

Adolescent↗

Heart involvement and systemic sclerosis.

Scleroderma heart involvement (SHI) is often manifest, and virtually always present when accurately searched and holds a significant prognostic value. Myocardial involvement by patchy fibrosis (secondary to both repeated ischaemia and immunoinflammatory damage) leads to ventricular diastolic dysfunction, whereas right ventricle overload and failure may complicate pulmonary hypertension. Left ventricular systolic dysfunction is present in a minority of patients, namely those presenting atherosclerotic coronary artery disease and/or arterial hypertension, sometimes triggered by sclerodermic renal involvement. Dysrhythmias and conduction disturbances are considered an hallmark of SHI, facilitated by autonomic dysfunction. SHI is frequently linked to parenchimal and/or vascular lung disease; they determine symptom occurrence, particularly dyspnoea, fatigue, palpitations and chest pain when pericardium is affected. Accurate cardiologic baseline screening and subsequent follow-up are mandatory in all patients, initially consisting in some noninvasive diagnostic procedures: visit, electrocardiogram (EKG), chest X-ray, Doppler-echocardiography. When needed, these examinations should be integrated by EKG Holter-monitoring, cardiopulmonary stress tests, cardiac magnetic resonance imaging, nuclear studies of myocardial function and perfusion, cardiac catheterization to better estimate pulmonary hypertension, and cardiac natriuretic hormone evaluation. Several vasodilator approaches (prostacycline or NO/endothelin) may counteract the microvascular dysfunction at peripheral and cardiopulmonary level, and fight the sequelae of pulmonary hypertension.

Fibrosis↗

Dependency of blood pressure upon cardiac filling in patients with severe postural hypotension.

Autonomic denervation of the vascular bed results theoretically in a stronger dependency of blood pressure upon intravascular volume, and the study described aimed at an investigation of the relation between cardiac filling and arterial blood pressure in patients with severe postural hypotension. Seven patients were studied during head-up tilt at three different tilt angles using intra-arterial blood pressure recordings and estimates of left ventricular volumes by radioisotope ventriculography. Blood pressure fell dramatically during head-up tilt due to reductions in cardiac output unopposed by vasoconstriction. The reduction in cardiac output resulted from reductions in left ventricular end-diastolic volumes with unchanged left ventricular ejection fractions and only moderate increments in heart rate. The study was demonstrated that blood pressure is strongly dependent upon cardiac filling in severe autonomic dysfunction, and that volume expansion is an important measure against postural hypotension.

Aged↗

[Autonomic tone and energy metabolism in students during productive learning activities].

Energy expenditures, autonomic functions, the severity of autonomic dysfunctions and personality traits were examined in 41 male students aged 18 to 23 years during their routine daily learning activities and after taking an exam in normal physiology. According to the characteristics of the baseline autonomic tone, all the examinees were divided into 3 groups: 1) those with elevated sympathetic tone EST; 2) those with elevated parasympathetic tone (EPT) and 3) an intermediate group with normal tone (NT). The EPT students showed the lowest energy exchange during routine daily learning activities. Examination-induced stress causes an elevation of mainly aerobic process in EST and EPT students. Anaerobic process increase in NT students at examinations. The parameters of autonomic functions due to examination stress also vary in students with different autonomic control. The students with EPT and worst marks showed significant changes in the measured parameters while these changes were significantly lower in EST students, but the changes in autonomic functions were much more profound in EST students who got good marks.

Adolescent↗

Autonomic nervous system derangement in fibromyalgia syndrome and related disorders.

Fibromyalgia syndrome is a chronic, painful musculoskeletal disorder of unknown etiology and/or pathophysiology. During the last decade many studies have suggested autonomic nervous system involvement in this syndrome, although contradictory results have been reported. This review focuses on studies of the autonomic nervous system in fibromyalgia syndrome and related disorders, such as chronic fatigue syndrome and irritable bowel syndrome on the one hand and anxiety disorder on the other, and highlights techniques of dynamic assessment of heart rate variability. It raises the potentially important prognostic implications of protracted autonomic dysfunction in patient populations with fibromyalgia and related disorders, especially for cardiovascular morbidity and mortality.

Adult↗

[Hypotension after turning to the prone position].

Hypotension after positioning is sometimes seen especially in patients with cervical spinal lesion operated on under prone position. Patients with spinal lesion and those with brain lesion are compared in the frequency of hypotension after positioning to prone. Sixty-one cases operated on with prone position were studied. Ages ranged from 40 to 82 (mean 61) years and ASA grade was 1 or 2 in each case. Cervical laminoplasty (group C) or craniotomy (group B) are performed in 40 and 21 patients, respectively. Ephedrine was administrated when the systolic blood pressure decreased under 80 mmHg and the frequency of ephedrine use was compared. There were no differences in age and sex distribution between group C and B. The induction doses of propofol and fentanyl in group B were larger than those of group C, but ephedrine use in group C was more frequent than in group B. In T2-weighted image of the cervical cord, high signal intensity areas were depicted in cases with hypotension. The sympathetic flow descends in the medial part in the lateral funiculus. Damage of this pathway would cause autonomic dysfunction in patients with cervical spinal lesion and strict monitoring is necessary during positioning to prone.

Adult↗

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

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

Autonomic Nervous System Diseases↗