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PubMed1996

Rapid distal small bowel transit associated with sympathetic denervation in type I diabetes mellitus.

BACKGROUND: The pattern of progression of a meal from the stomach to the caecum in diabetes mellitus is controversial and the differential roles of transit through the jejunum and the ileum have not been investigated in diabetes. AIMS: To determine gastric emptying and transit rates through proximal and distal regions of the small bowel in type I diabetic patients. SUBJECTS: The study included six diabetic patients with evidence of autonomic neuropathy (DM-AN group), 11 diabetics without autonomic dysfunction (DM group), and 15 control volunteers. METHODS: Gastric emptying and small bowel transit of a liquid meal were evaluated scintigraphically in these subjects. Transit through regions of interest corresponding to the proximal and distal small intestine up to the caecum was determined and correlated with gastric emptying rates, cardiovascular measurements of autonomic function, and the occurrence of diarrhoea. RESULTS: Gastric emptying and transit through the proximal small bowel were similar in the three groups. The meal arrived to the caecum significantly earlier in DM-AN patients (median; range: 55 min; 22-->180 min) than in the DM group (100 min; 44-->180 min, p < 0.05) or in controls (120 min; 80-->180 min, p < 0.02). Accumulation of chyme in the distal small bowel was decreased in DM-AN patients, who showed values for peak activity (30%; 10-55%) significantly lower than in the DM group (49%; 25-77%, p = 0.02) and controls (50%; 30-81%, p = 0.02). In DM patients (n = 17), the time of meal arrival to the caecum was significantly correlated with both orthostatic hypotension (coefficient of contingency, C = 0.53, p < 0.01) and diarrhoea (C = 0.47, p < 0.05), but not with gastric emptying rates. CONCLUSIONS: Patients with type I diabetes mellitus and sympathetic denervation have abnormally rapid transit of a liquid meal through the distal small bowel, which may play a part in diarrhoea production.

Adolescent↗

PubMed2001

Depression, anxiety, and the gastrointestinal system.

Functional disorders of the digestive system, such as irritable bowel syndrome, are often associated with affective disorders, such as depression, anxiety, panic, and posttraumatic stress disorder (PTSD). Some of these associations are observed not only in clinical populations, but also in population-based samples, suggesting a relationship with pathophysiologic mechanisms underlying both gastrointestinal (GI) dysfunction and certain affective disorders. Sustained and acute life-threatening stressors play an important role in the onset and modulation of GI symptoms as well as in the development of affective disorders and PTSD. A neurobiological model is proposed that attempts to explain the development of visceral hypersensitivity, the neuroendocrine and autonomic dysfunction characteristic of functional GI disorders, as well as the overlap with affective disorders.

Anxiety Disorders↗

PubMed1994

Determinants of response to a prokinetic agent in neuropathic chronic intestinal motility disorder.

BACKGROUND/AIMS: Reasons for the variable efficacy of prokinetic agents in the treatment of chronic intestinal motility disorders are unclear. The aim of this study was to assess the influence of extrinsic autonomic neuropathy and motility patterns on the symptom response to cisapride in 42 such patients. METHODS: A randomized, double-blind, placebo-controlled, two-dose (10 and 20 mg, three times daily), 12-week study included (1) measurement of autonomic (including abdominal vagal) function; (2) standardized 5-hour upper gastrointestinal manometry; and (3) assessment of symptoms based on visual analog scale at baseline and 6 and 12 weeks. Statistical analysis compared symptom response among treatment and autonomic dysfunction groups and assessed the influence of absence of migrating motor complexes and presence of postprandial antral hypomotility on symptomatic responses to cisapride. RESULTS: There was no significant overall effect of cisapride in the entire group of 42 patients. Generalized sympathetic and vagal dysfunctions influence the response of patients with neuropathic chronic intestinal motility disorder to two doses of cisapride. CONCLUSIONS: Idiopathic intestinal motility disorder, unassociated with abdominal vagal dysfunction, is more likely to respond to cisapride. Detailed characterization of patient subgroups is crucial to designing treatment trials in patients with small bowel motility disorders.

Adult↗

PubMed1995

Proliferative diabetic retinopathy is related to cardiovascular autonomic neuropathy in non-insulin-dependent diabetes mellitus.

The aim of the study was to define the relationship between the presence of proliferative diabetic retinopathy and nephropathy with objectively defined autonomic neuropathy in non-insulin-dependent diabetes mellitus (NIDDM) patients. The research design used was a cross-sectional, case control study. A cohort of NIDDM patients was classified, according to five cardiovascular autonomic tests described by Ewing, as: (1) no involvement--no abnormal tests (n = 17); (2) cardiovascular autonomic neuropathy--two out of five abnormal tests (n = 18). Age, age at diagnosis, plasma creatinine, fasting plasma glucose, glycated haemoglobin and blood pressure measurements were not statistically different among the two groups. According to indirect ophthalmoscopy and the presence of macroproteinuria and microalbuminuria, respectively, patients were also classified as having proliferative, non-proliferative or no retinopathy and with or without nephropathy. The results showed a striking relationship between cardiovascular autonomic neuropathy and proliferative diabetic retinopathy. Relative odds for nephropathy, non-proliferative diabetic retinopathy and proliferative retinopathy were, respectively, 16.0, 10.1 and 34.7. When odds ratios were adjusted for the presence of nephropathy, hypertension, non-proliferative and proliferative retinopathy, only proliferative retinopathy was significantly associated (odds ratio, 7.1). It was concluded that in NIDDM the presence of cardiovascular autonomic neuropathy is strongly associated with proliferative retinopathy. Long-term prospective studies on large cohorts of patients must be done to evaluate if having autonomic dysfunction would be a risk factor or a risk indicator of an etiologic process underlying the development of proliferative retinopathy.

Adult↗

PubMed1995

Effect of long-term digoxin therapy on autonomic function in patients with chronic heart failure.

OBJECTIVES: This study was conducted to determine the effect of long-term digoxin therapy on autonomic function in patients with mild to moderate chronic heart failure. BACKGROUND: Chronic heart failure is characterized by increased sympathetic activity and decreased parasympathetic activity. Intravenous digitalis has been found to reduce sympathetic activity immediately in these patients, but whether short-term neurohormonal effects are sustained during long-term oral therapy has not been assessed. METHODS: We determined sympathetic activity in 26 patients with heart failure by measuring plasma norepinephrine levels and parasympathetic activity from variables of heart period variability derived from 24-h ambulatory electrocardiographic Holter recordings obtained before and after 4 to 8 weeks of digoxin therapy. RESULTS: After digoxin therapy, plasma norepinephrine decreased significantly from a mean +/- SEM of 552 +/- 80 to 390 +/- 37 ng/ml. In addition, the RR interval increased significantly from 719 +/- 19 to 771 +/- 20 ms. High frequency power increased from 84 +/- 24 to 212 +/- 72 ms2, and the root mean square of successive differences in RR interval increased from 20.3 +/- 1.8 to 27.0 +/- 3.4 ms, indicating a substantial increase in parasympathetic activity. Low frequency power, an index of baroreflex activity, was also significantly increased (239 +/- 80 to 483 +/- 144 ms2) by digoxin therapy. CONCLUSIONS: These results indicate 1) that long-term therapy with digoxin acts to ameliorate the autonomic dysfunction of patients with heart failure, and 2) that the short-term neurohormonal effects of digoxin are sustained during prolonged treatment with the drug.

Autonomic Nervous System↗

PubMed1999

Autonomic nerve involvement and venous leakage in diabetic men with impotence.

OBJECTIVE: To determine the neurophysiological and vascular factors in diabetic impotence, particularly the role of autonomic neuropathy on venous leakage and erectile impotence. PATIENTS AND METHODS: Thirty-four diabetic men with impotence were investigated using various neurophysiological and radiological methods. The results were compared with those from patients with idiopathic penile venous leakage for autonomic neuropathy, especially for spontaneous cavernosal activity (SCA). RESULTS: Of the neurophysiological tests, the SCA was most frequently abnormal, with the loss of normal periodic oscillations. Penile venous leakage, either alone or with arterial insufficiency, was the most frequent vascular problem (67%) in patients with diabetic impotence, in whom the SCA was absent in most (83%). Conversely, the SCA was normal in all impotent patients with idiopathic venous leakage. CONCLUSION: Venous leakage in diabetic patients is probably produced by autonomic dysfunction of the penile vascular innervation or degeneration of penile smooth muscles, because the SCA was absent more often in these patients.

Adult↗

PubMed1999

Heart rate variability during chronic hemodialysis and after renal transplantation: studies in patients without and with systemic amyloidosis.

The present study was undertaken to compare heart rate variability (HRV) values in patients on maintenance hemodialysis with no evidence of ischemic or hypertensive heart diseases to those of age- and gender-matched healthy individuals and those of patients after renal transplantation. To assess the effects of a common confounding factor, HRV values were also determined in patients with systemic amyloidosis, in chronic hemodialysis, and after successful renal transplantation. Spectral analyses of RR intervals from continuous electrocardiogram recordings were performed to quantify ultra low frequency, very low frequency, low frequency, and high frequency powers. HRV determinations were all significantly reduced in uremic patients undergoing hemodialysis compared with the healthy control subjects, especially in those with systemic amyloidosis. Renal transplantation normalized HRV in most patients; HRV, however, remained reduced in isolated amyloidosis patients with cardiac or adrenal involvement. HRV circadian day/night differences were preserved in hemodialysis patients and after renal transplantation in those without amyloidosis but not in those with amyloidosis. These data suggest that reduced HRV in chronic hemodialysis patients may precede other manifestations of cardiovascular disease. In uremic patients with amyloidosis, a more severe form of autonomic failure may occur. Successful transplantation corrects HRV abnormalities in most patients, suggesting that the autonomic dysfunction of uremia is caused by humoral factors reversed by the normalization of the renal function.

Adolescent↗

PubMed1988

Diagnosis of dysautonomia in a cat by autonomic nervous system function testing.

Clinical signs of dysautonomia, including dilated pupils, dry mucous membranes, and megaesophagus, were observed in a cat. The diagnosis was confirmed by use of autonomic nervous system function testing including 0.1% pilocarpine and physostigmine ocular response tests, plasma catecholamine assays, and cardiovascular responses to various perturbations intended to elicit autonomic responses. The cause of the autonomic dysfunction was not ascertained, and the cat was euthanatized after 5 weeks of unsuccessful treatment with pilocarpine, metoclopramide, prochlorperazine, and parenteral nutrition.

Animals↗

PubMed1986

Correlation of esophageal motility abnormalities with neuropsychiatric status in diabetics.

Esophageal motility abnormalities, neuropathy, and psychiatric illness were independently determined in 30 patients with type 1 or type 2 diabetes mellitus to clarify the interrelationship of these findings in diabetics. Fifteen patients (50%) were found to have esophageal contraction abnormalities, a specific cluster of manometric derangements. Diagnoses of depression, dysthymia, or generalized anxiety disorder were made in 87% of those with contraction abnormalities but in only 21% of the patients with normal manometric patterns (p = 0.002). Log-linear analysis confirmed that this association was independent of neuropathy effects (p less than 0.001). Several changes in individual manometric parameters related to neuropathy alone were appreciated only when the patients with psychiatric illness were excluded from the analysis. These data indicate that some of the esophageal neuromuscular dysfunction observed in diabetics is independent of neuropathy yet is strongly associated with psychiatric disorder. Such findings help to clarify the discrepant relationship of motility disturbances to neuropathy noted in prior reports. We conclude that consideration should be given to psychiatric illness as well as to neuropathy when interpreting manometric features suggestive of autonomic dysfunction in diabetic patients.

Adult↗

PubMed1998

Spectral analysis of heart rate variability in patients with irritable bowel syndrome.

BACKGROUND: Autonomic dysfunction, both adrenergic and cholinergic, has been associated with the irritable bowel syndrome (IBS). The accuracy of the methods in use, however, has been limited by the need for active co-operation by the patients, with consequent difficulties in standardization. The aim of this study was to investigate the function of the autonomic nervous system in patients with IBS by using spectral analysis of the heart rate variability, an accurate method depending very little on patient cooperation. METHODS: Eighteen patients with IBS were compared with 36 sex- and age-matched controls. Spectral analysis of heart rate variability was performed to quantify sympathetic and parasympathetic nerve activity. RESULTS: The patients with IBS had significantly higher sympathetic activity than controls (P = 0.005). There was no significant (P = 0.308) increase in parasympathetic activity. There were no significant differences in heart rate or blood pressure between the patients and controls. CONCLUSION: Spectral analysis of heart rate variability has been used to assess the function of the autonomic nervous system in patients with IBS. IBS patients have significantly increased symphathetic activity, whereas parasympathetic activity does not differ from that of controls.

Adult↗

PubMed1984

Congenital sensory neuropathies. Diagnostic distinction from familial dysautonomia.

Among congenital sensory neuropathies there are several variants that share features of diminished pain sensitivity and/or autonomic dysfunction with familial dysautonomia but can be shown to be distinct from this entity by clinical and pathologic criteria. Recognition of the unique nature of each disease type is an essential prerequisite for genetic and causative studies. We reviewed the diagnostic tests that can be used in the clinical evaluation of sensory and autonomic function. Based on this process of evaluation, we studied 13 patients who were initially considered to have familial dysautonomia but who were later shown to have five distinct syndromes that were confirmed by neuropathologic studies.

Bone and Bones↗

PubMed2006

Applied principles of neurogastroenterology: physiology/motility sensation.

Many of the symptoms prominent in the functional gastrointestinal disorders (FGIDs) are consistent with dysfunction of the sensory and/or motor apparatus of the digestive tract. Assessment of these phenomena in man can be undertaken by using a wide variety of invasive and noninvasive techniques, some well established and others requiring further validation. By using such techniques, alterations in both sensory and motor function have been reported in the FGIDs; various combinations of such dysfunction occur in different regions of the digestive tract in the FGIDs. Our understanding of the origins of this gut sensorimotor dysfunction is gradually increasing. Thus, inflammatory, immunologic, and other processes, as well as psychosocial factors such as stress, can alter the normal patterns of sensitivity and motility through alterations in local reflex activity or via altered neural processing along the brain-gut axis. In this context, a potential role of genetic factors, early-life influences, enteric flora, dietary components, and autonomic dysfunction also should be considered in the disease model. A firm relationship between sensorimotor dysfunction and the production of symptoms, however, has been difficult to show, and so the clinical relevance of the former requires continuing exploration. Based on the conceptual framework established to date, a number of recommendations for further progress can be made.

Animals↗

PubMed2006

Mechanism of constipation in familial amyloid polyneuropathy: a case report.

Previously no functional study has been available for the mechanism of constipation in familial amyloid polyneuropathy (FAP). We performed a gut function test in a 78-year-old woman with transthyretin-type FAP who had severe constipation. The gut function test showed a prolonged colonic transit time, a low anal pressure at rest and upon squeezing, loss of the spontaneous phasic rectal contractions, and weak abdominal strain. All these abnormalities suggested a peripheral autonomic dysfunction, corresponding to the enteric neuropathy that was confirmed upon autopsy.

Aged↗

PubMed1995

Nerve entrapment and reflex sympathetic dystrophy after fractures of the distal radius.

In a series of 542 conservatively-treated fractures of the distal radius 30 patients (5,5%) developed compression neuropathy: of the median nerve (n = 23), of the ulnar nerve (n = 5), and of the radial nerve (n = 2). Three patients required decompression of the carpal tunnel, and one patient's ulnar symptoms were relieved after shortening osteotomy of the ulna. The remaining neuropathies resolved spontaneously over a period of three months. Five patients developed typical reflex sympathetic dystrophy with diffuse pain, loss of hand function, and significant autonomic dysfunction. None of them had specific signs of compression neuropathy anteceding the development of reflex dystrophy. All five had their joints mobilised under regional intravenous block combined with regional perfusion of soluble corticosteroid.

Autonomic Nervous System Diseases↗

PubMed1990

Diabetic autonomic neuropathy: abnormal cardiovascular reactions under general anesthesia.

The influence of diabetic autonomic neuropathy upon the behavior of the circulatory system was investigated in 56 patients who had undergone ophthalmological surgery. A standardized test combination (variability in heart rate during deep breathing. Valsalva ratio, 30:15 ratio, change in blood pressure from lying to standing, sustained handgrip test) was used to study the patients' cardiovascular reflectory reactions. The patients were then divided into the following groups: Group I, non-diabetics. Group II, diabetics without autonomic neuropathy. Group III, diabetics with autonomic neuropathy. The anesthetic (induction by barbiturates and conduction by inhalation agents) and the surgical procedure (pars plana vitrectomy) were standardized and always identical. During anesthesia patients in group III experienced hypotensive reactions (systolic blood pressure below 90 mm Hg) significantly more often (72.2%) than patients in group I (25%). In order to achieve stability in blood pressure the patients of group III had to be given vasoactive drugs much more often (77.8%) than the patients of group I (12.5%) and those of group II (35.7%). We found a significant correlation between the degree of autonomic dysfunction and the largest drop in blood pressure under narcosis (r = -0.60, P less than 0.001). However, marked variability in heart rate and cardiac rhythm disorders during anesthesia were seen only in patients of groups I and II. These results prove the atypical hemodynamic behavior and especially the extreme instability in blood pressure in diabetic autonomic neuropathy under general anesthesia. Therefore we consider it to be very helpful to check the cardiovascular reflectory status of diabetics preoperatively.

Adult↗

PubMed1997

Postural hypotension in a patient with cervical myelopathy due to craniovertebral anomaly.

We report a patient with craniovertebral anomaly leading to cervical cord compression who presented with disabling postural hypotension. A 60-year-old electrician presented with progressive weakness of the upper and lower limbs, which had started 7 years previously. He had difficulty in holding urine for the previous year and had blacked out on standing for the past 3 months. He had upper limb wasting and lower limb spasticity, with impaired joint position sense. Autonomic dysfunctions included postural hypotension, absence of sinus arrhythmia, impaired Valsalva ratio, and lack of increase in blood pressure on cold immersion and isometric contraction. Cervical spine radiograph and magnetic resonance imaging revealed atlantoaxial dislocation, Klippel-Feil syndrome and osteophytes, resulting in cord compression at C2-C4. Partial and selective damage to the descending autonomic fibres may be responsible for postural hypotension in this patient.

Arrhythmia, Sinus↗

PubMed2005

[Guide of clinical management of HTLV patient: neurological aspects].

The Brazilian Ministry of Health (STD and Aids Program) invited specialists to make up an informative guide to deal with HTLV patients. Among the different topics, the neurological aspects associated to HTLV were contemplated. A suspected case should include changes in force and reflexes, distal paresthesiae and autonomic dysfunction. The investigation of such case should be based on the syndrome shown by the patient. For patients with spinal cord syndrome, magnetic resonance imaging or myelography as well as spinal fluid studies should be carried out. For patients with neuropathic or myopathic syndrome, electroneuromyography and CPK dosing should be done, and for those with autonomic syndrome, a search for postural hypotension, ultrasonography of urinary tract and urodynamic studies should be requested. The treatment may be symptomatic (spasticity, neurogenic bladder, intestinal constipation and neuropathic pain) and specific to be carried out in specialized centers.

Brazil↗

PubMed1992

Ocular microangiopathy in familial amyloidotic polyneuropathy, type I.

To obtain precise information on ophthalmological manifestations in patients with familial amyloidotic polyneuropathy (FAP), we performed ophthalmological and histopathological studies on 18 FAP patients and 6 asymptomatic individuals with a mutant transthyretin (TTR) gene. The incidence of vascular abnormalities of the conjunctiva and retina was surprisingly high in FAP patients. Abnormal conjunctival vessels were found mainly in the limbal area of FAP patients, but not in asymptomatic individuals with a mutant TTR gene. Conjunctival biopsy of 5 FAP patients and autopsy of another 2 FAP patients revealed that a significant amyloid deposit could be recognized in the superficial substantia propria of the conjunctiva and wall and perivascular area of the conjunctival vessels in all cases, a finding that is of diagnostic value. As for the retinal vessels, an abnormal arteriovenous ratio (A/V ratio), tortuous retinal vessels, cotton wool exudates and retinal hemorrhages were found in FAP patients. However, histopathological analysis of the retina in two autopsied cases revealed only a trace amount of amyloid deposit around the retinal vessels. Ophthalmological examination of three patients with pandysautonomia revealed that the appearance of both the conjunctival and retinal vessels of these patients was similar to that in FAP patients. These results indicate that in FAP patients ocular microangiopathy may be related to autonomic dysfunction as well as amyloid deposit.

Adolescent↗