Autonomic Nervous Function Tests Research Articles

Parasympathetic Neuropathy Associated with Left Ventricular Diastolic Dysfunction in Patients with Insulin-Dependent Diabetes Mellitus

Patients with insulin-dependent diabetes mellitus (IDDM) may develop autonomic neuropathy (AN) and cardiac complications. The association between AN and cardiac dysfunction was assessed in 34 IDDM patients (age 40 years, diabetes duration 21 years, 15 women) by echocardiography/Doppler and autonomic nerve function tests. The expiration/inspiration ratio (E/I) was used to assess parasympathetic damage, and the acceleration and brake indices for assessment of sympathetic impairment. AN was present in 21 patients. Patients with abnormal E/I (n = 11) had lower E/A ratios than patients without AN; early to atrial peak filling ratio (E/A) was median 1.1 (inter-quartile range 0.2) vs 1.4 (0.7), p = 0.022; early to atrial integral filling ratio (E/A) was 1.7 (0.3) vs 2.3 (1.2), p = 0.006. Patients with AN and normal E/I (sympathetic neuropathy, n = 10) and patients without AN had similar E/A ratios. E/A was also lower in patients with abnormal E/I compared with patients with AN and normal E/I; 1.7 (0.3) vs 2.2 (0.7), p = 0.008. Systolic function and cardiac dimensions were generally unaffected and similar in the three groups. In conclusion, diastolic dysfunction and parasympathetic neuropathy are related in IDDM patients.

２０歳代健常男子の喫煙習慣の有無による自律神経機能検査のＣＶ変動について

２０歳代健常男子の喫煙習慣の有無による自律神経機能検査のＣＶ変動について

Association of autonomic nervous hyperreflexia and systemic inflammation in patients with Crohn's disease and ulcerative colitis

The autonomic nervous system modulates gastrointestinal motility, secretion and mucosal immunity. Its dysfunction may be of pathogenetic importance in inflammatory bowel disease (IBD). This study aimed at investigating the autonomic nervous function in patients with IBD. Forty-seven patients with IBD, 28 with Crohn's disease (CD) and 19 with ulcerative colitis (UC), were investigated by means of 5 cardiovascular and 2 pupillary standardized autonomic nervous function tests. In CD and UC, cardiovascular autonomic neuropathy was very rare (0%, 5%), whereas pupillary autonomic neuropathy was more prevalent (21%, 21%). In contrast to autonomic neuropathy, overall cardiovascular (CD:29%, UC:26%) and pupillary autonomic hyperreflexia (46%, 37%) were found more often. Patients with CD and UC demonstrated elevated percentiles in the respiratory sinus arrhythmia test as compared to controls (RSA: 82.3±3.9%, 80.0±5.9%, controls: 50.0%±1.5%, p<0.0001). CD patients with, as compared to patients without, RSA hyperreflexia had significantly higher CDAIs ( p<0.001), increased erythrocyte sedimentation rates ( p<0.005) and more often extraintestinal disease manifestations ( p<0.001). UC patients with, as compared to patients without, pupillary latency time hyperreflexia had lower hemoglobin ( p<0.05), lower albumin ( p<0.01) and increased erythrocyte sedimentation rates ( p<0.05). Autonomic hyperreflexia was significantly associated with more severe inflammation and systemic disease in IBD. Hyperreflexia may be a response to inflammation or a pathogenetic element that drives mucosal inflammation.

Autonomic nervous system functions in children with nocturnal enuresis

Nocturnal enuresis is involuntary urination during night sleep. The pathogenesis of nocturnal enuresis is controversial. Developmental delay, genetic factors, stress and psychological factors, and sleep abnormalities are considered to be the etiologic factors. Various urodynamic studies showed bladder hyperactivity in enuretic children. Since the cause of vesical hyperactivity is not clear, we investigated the possible role of autonomic nervous system dysfunction in these children. The study groups consisted of 41 enuretic (25 boys and 16 girls) and 30 healthy children (18 boys and 12 girls). Four non-invasive autonomic nervous system function tests (orthostatic test, Valsalva ratio, 30:15 ratio, heart rate responses to deep breathing) were carried out in both groups. The differences between the enuretic and control groups were statistically significant in the Valsalva and 30:15 ratios ( P<0.0005 and P<0.005, respectively). The results of these two tests demonstrated parasympathetic nervous system hyperactivity. No abnormality of the sympathetic nervous system was found. We suggest that the parasympathetic nervous system hyperactivity shown in our study may be a cause of vesical hyperactivity in enuretic children.

Estimation of the cut-off value in cardiovascular autonomic nervous function tests: Not-age-related criteria or the age-related 5th percentile

The aim of the study was to estimate the cut-off value of cardiovascular tests using not-age-related criteria or the age-related 5th percentile in 165 diabetic patients. The cANP, pANP, and smNP were assessed using previously recommended standardized test procedures. Prevalence of overall definite (borderline) cANP was 35.2% (23.0%) when using the 5th percentile or 16.4% (27.9%) when using not age-related criteria ( p for the difference <0.0001) ( p = 0.3205). Prevalence of pANP was 54.0% and of smNP 37.0%. Concerning cANP, the number of test results below the 5th percentile (N 5) correlated significantly with the number of abnormal test results using not age-related criteria (N nar) ( p < 0.000001) but the slope of the regression line differed substantially from 1. Using the 5th percentile as the cut-off value for cANP testing, sensitivity and specificity were calculated for not age-related criteria for respiratory sinus arrhythmia (90.5%, 80.2%), Valsalva test (30.4%, 98.0%), lying-to-standing test (46.3%, 98.7%), orthostatic systolic blood pressure fall (69.0%, 78.3%), and overall definite cANP (44.8%, 92.8%). The statistical analysis revealed that the age-related 5th percentile is superior to the not-age-related cut-off values in diabetic patients. We therefore suggest that age-related normal values (percentiles) have to be applied when cANP is estimated.

カロリック刺激時のモルモット血圧変動と視床下部の関係

We investigated the effects of caloric stimulation on arterial blood pressure (AP) and neural activity in the hypothalamic paraventricular nucleus (PVN) in anesthetized guinea pigs. Hot water stimulation of the labyrinth produced a decrease in AP in 56 of 73 cases tested, and AP decrease followed by increase in 12 cases. In the cases where AP initially decreased and then increased, 92% of PVN neurons responded as excitatory or inhibitory to caloric stimulation. When the AP change was a decrease alone, the responsive rate of the PVN neurons was 63%, and no change in PVN neural activity was seen in the group which showed no AP change after caloric stimulation. The ratio of the PVN neurons showing inhibition in the group that showed AP decrease-increase sequence was significantly higher than that in the group showing AP decrease alone. AP changes following caloric stimulation were greatly reduced after electric destruction of the anterior and middle parts of the hypothalamus. This indicates that the activation of the hypothalamic neurons by the vestibular input is important to produce the vestibulovasomotor response and its pattern. When the same amount of stimulus was applied periodically to the labyrinth, the AP increment component was increased with time. It is suggested that the pattern of AP changes is greatly influenced by level of consciousness. It is suggested that the basal activity level of the autonomic nervous system, and the variety and magnitude of the vestibular stimuli should be synthetically evaluated when the autonomic nerve function test is applied to patients suffering dizziness.

Changes in autonomic nervous function during the 4-year follow-up in middle-aged diabetic and nondiabetic subjects initially free of coronary heart disease.

To study the changes in autonomic nervous function during the 4-year follow-up period in diabetic patients and to investigate factors predicting autonomic nervous dysfunction. A 4-year follow-up study. At baseline the study subjects without known cardiovascular disease were recruited from a large group of diabetic and nondiabetic subjects selected randomly from a baseline population. Middle-aged control subjects (n = 44), patients with insulin-dependent diabetes mellitus (n = 32) and patients with non-insulin-dependent diabetes mellitus (n = 32) were studied at baseline and after the 4-year follow-up. Autonomic nervous function tests and exercise test at baseline and after the 4-year follow-up. At the baseline, heart rate variation during deep breathing was significantly lower in patients with insulin-dependent diabetes (13.0 +/- 1.2 beats min-1; P < 0.05) and in patients with non-insulin-dependent diabetes (12.9 +/- 1.5 beats min-1; P < 0.05) than in control subjects (16.6 +/- 1.1 beats min-1). At baseline, autonomic nervous function score was significantly higher indicating disturbed autonomic nervous function in patients with insulin-dependent diabetes (1.74 +/- 0.19; P < 0.01) than in control subjects (1.24 +/- 0.14), but the difference was not significant between control subjects and patients with non-insulin-dependent diabetes (1.47 +/- 0.12). During the follow-up, autonomic nervous function score increased in patients with non-insulin-dependent diabetes to 2.00 +/- 0.21 (P < 0.001, as compared to baseline), but did not change in patients with insulin-dependent diabetes (1.77 +/- 0.18) or control subjects (1.22 +/- 0.12). In both diabetic groups, the deterioration of autonomic nervous function score during the 4-year follow-up was associated with poor glycaemic control at baseline. Clinical manifestation of coronary heart disease was found in three (7%) control subjects, 12 (37%; P < 0.001) patients with insulin-dependent diabetes and 11 (34%; P < 0.01) patients with non-insulin-dependent diabetes mellitus at follow-up examination. Autonomic nervous function was more abnormal in those insulin-dependent diabetic patients with coronary heart disease than those without. During the 4-year follow-up the impairment in autonomic nervous function occurred mainly in patients with noninsulin-dependent diabetes. Poor glycaemic control appears to be an important determinant of the progression of autonomic nervous dysfunction in diabetes.

Autonomic nervous system functions in childhood essential hypertension.

The etiopathology of essential hypertension (EH) is still controversial, different pathologic mechanisms have been estimated as a cause of EH. One of these mechanisms is autonomic nervous system dysfunction (ANSD). Although there are different studies showing ANSD in adult EH, limited studies on ANSD in childhood EH are present. The present study was planned to investigate the role of ANSD in childhood EH. The study group (SG) consisted of 24 children with EH and the control group (CG) was 24 healthy children. Non-invasive autonomic nervous system function tests: the orthostatic test, Valsalva ratio, 30/15 ratio and heart rate responses to deep breathing were performed on members of both groups. The mean differences in systolic blood pressure between supine resting and standing positions in the study and control groups were significant (z = -2.577, P = 0.0051). The mean differences in diastolic blood pressure between supine resting and standing positions in SG and CG were found to be statistically meaningful (z = -2.722, P = 0.0033). The mean differences in heart rate variation during hyperventilation in SG and CG were significant (z = -2.54, P = 0.0055). The mean differences in the Valsalva ratio between SG and CG were not statistically meaningful (z = 1.52, P = 0.0643). The mean differences in the 30/15 ratio in SG and CG were not found to be significant (z = -1.455, P = 0.0735). In the light of these results, both sympathetic and parasympathetic autonomic nervous system dysfunction in childhood essential hypertension were found.

Atrial natriuretic factor and digoxin-like immunoreactive factor in diabetic patients: their interrelation and the influence of the autonomic nervous system.

In diabetic patients, several factors contribute to volume expansion and have to be counteracted by humoral and neuronal feedback control systems. We investigated N-terminal proatrial natriuretic factor (ANF1-98) and digoxin-like immunoreactive factor (DLIF), which are two counteracting hormones, and their interrelationship, with additional consideration given to autonomic nervous function in diabetic patients. ANF1-98 and DLIF were measured in 64 diabetic patients. Autonomic nervous function was assessed using nine autonomic nervous function tests. The patients were subdivided into two groups, one with four or more (group 1) and one with less than four abnormal results in autonomic function tests (group 2). Compared with group 2, group 1 demonstrated detectable DLIF levels less often (17.2 vs. 45.7, P = 0.0195) and increased levels of ANF1-98 (mean +/- SEM: 850.0 +/- 108.8 vs. 554.8 +/- 45.9 pmol/L, P = 0.0099). However, the groups did not differ in blood pressure, daily sodium, and daily potassium excretion. The number of abnormal autonomic function tests correlated significantly with ANF1-98 (P = 0.0002). In patients with detectable DLIF, DLIF correlated with ANF1-98 (P = 0.0080). These results demonstrate close interactions between the autonomic nervous system and the two natriuretic hormones. In patients with autonomic nervous dysfunction, higher levels of ANF may possibly compensate for the lack of the natriuretic DLIF to counteract hypertension and chronic volume expansion.

Evaluation of cardiac sympathetic neuronal integrity in diabetic patients using iodine-123 metaiodobenzylguanidine.

Autonomic dysfunction is associated with increased mortality in diabetic patients. To evaluate the cardiac autonomic dysfunction in these patients, a prospective study was undertaken using iodine-123 metaiodobenzylguanidine (MIBG) single-photon emission tomography (SPET). The study groups consisted of ten diabetic patients with cardiac autonomic neuropathy (group I) and six without autonomic neuropathy (group II). Autonomic nervous function tests, thallium scan, radionuclide ventriculographic data including ejection fraction and wall motion study, and 24-h urine catecholamine levels were evaluated. 123I-MIBG SPET was performed at 30 min and 4h following injection of 3 mCi of 123I-MIBG in groups I and II and in normal subjects (n=4). On planar images, the heart to mediastinum (H/M) ratio was measured. Defect pattern and severity of MIBG uptake were qualitatively analysed on SPET. Compared with control subjects, diabetic patients had a reduced H/M ratio regardless of the presence of clinical autonomic neuropathy. There was no difference in H/M ratio between groups I and II. On SPET images, focal or diffuse defects were demonstrated in all patients in group I, and in five of the six patients in group II. The extent of defects tended to be more pronounced in group I than in group II. In conclusion, 123I-MIBG scan was found to be a more sensitive method than clinical autonomic nervous function tests for the detection of autonomic neuropathy in diabetes.

MANAGEMENT OF DIABETIC PREGNANCY COMPLICATED BY CORONARY ARTERY DISEASE AND NEUROPATHY

Various manifestations of diabetic neuropathy may complicate pregnancies of young diabetic patients. Of all forms of diabetic neuropathy, autonomic neuropathy, and, in particular, gastropathy, may cause the most devastating complications. Because neuropathy is a common abnormality in young asymptomatic diabetic women, screening for this disorder may be advisable and can be accomplished by relatively simple and noninvasive tests. Screening is best performed before conception or early in pregnancy, because pregnancy itself and its possible complications later modify the autonomic nervous function tests and make testing unreliable. Practitioners and obstetricians who provide care and counseling to young diabetic patients should be familiar with the risks and consequences to maternal and fetal health that may be imposed by the different forms of neuropathy. Moderate-to-severe autonomic dysfunction may be considered a relative contraindication to pregnancy, especially if gastropathy is part of the clinical presentation. The management dilemmas and high mortality and morbidity associated with symptomatic diabetic neuropathy may justify the addition of a new independent class, class N (neuropathy), to the current classification systems for diabetes in pregnancy.

Responses of workers exposed to vibration in autonomic nervous function tests.

Heart rate variation in quiet breathing and deep breathing tests and the response of blood pressure in a cold pressor test were measured in 34 railway workers and 13 lumberjacks. The age-adjusted results showed a significant relationship between exposure to hand-arm vibration and the coefficient of beat-to-beat variation in the quiet breathing test (CVS) in the railway workers. The vibration-induced white finger (VWF) and non-VWF subjects showed non-significant differences in respect of all the indices used. This investigation, in common with previous results, suggests that vibration might cause changes in cardiovascular reflexes, but the indices used here seem to be of low sensitivity, at least partially due to wide physiological variation; other more suitable indicators and studies of the pathophysiological background of the suspected effect are needed to confirm the results.

Clinical Usefulness of MemCalc 1000 to Assess the Autonomic Nerve Function Test in Patients with Diabeses Mellitus

Clinical Usefulness of MemCalc 1000 to Assess the Autonomic Nerve Function Test in Patients with Diabeses Mellitus

Autonomic nerve dysfunction in patients with bolus-specific esophageal dysmotility

The pathogenetic mechanisms causing esophageal dysmotility is not well understood. We examined 13 patients with solid bolus dysphagia in a radiologic barium study including the swallowing of a 14-mm tablet. In all 13 patients the tablet was caught in the proximal or midesophagus. In 8 patients, the entrapment was associated with symptoms (Group 1) whereas in 5 patients (Group 2), no symptoms were reported. All 13 patients together with a control group of 56 healthy, nondysphagic subjects were tested for autonomic nerve function. Autonomic nerve function tests included registration of electrocardiographic R-R interval variation during deep breathing test (E/I ratio), a test of parasympathetic, vagal, nerve function. The results showed that the E/I ratio was significantly lower in patients with symptoms of bolus-specific esophageal dysmotility (-2,19 [1.76]) (median [interquartile range]) compared with patients without symptoms (0.05 [2, 87], p = 0.0192) and controls (-0.25 [1.26], p = 0.0009). In conclusion, symptomatic bolus-specific esophageal dysmotility is associated with vagal nerve dysfunction.

Neurophysiological assessment of peripheral neuropathy in primary Sjögren's syndrome.

Peripheral nervous system complications are rare in patients with primary Sjögren's syndrome. We investigated a group of six women aged 43-64 years who complained of pain and sensory symptoms. Conventional neurophysiological tests reflecting large nerve fiber function revealed normal motor conduction in all patients, whereas sensory nerve action potentials were absent in two. On the other hand, quantitative thermometry and autonomic nerve function tests indicating small nerve fiber function were more sensitive in the assessment of nerve dysfunction; these showed abnormalities in all cases. Vibrametry showed dysfunctions in four patients. The latter methods possess great sensitivity in discovering sensory disturbances. Neurophysiological assessment of the sensory and autonomic nervous system demonstrating sensory neuropathy contributes to early diagnosis of primary Sjögren's syndrome.

The effect of 8 years of strict glycaemic control on peripheral nerve function in IDDM patients: the Oslo Study

We have investigated the effect of long-term strict glycaemic control on peripheral and autonomic nerve function in 45 IDDM patients (age 18–42 years, diabetes duration 7–23 years) without clinical signs of neuropathy or other neurological disease. They were randomly assigned to treatment either with continuous insulin infusion, multiple injections (4–6 times daily), or conventional treatment (twice daily) for 4 years and followed prospectively for 8 years. Motor and sensory nerve conduction velocities were measured at the start and after 8 years. Autonomic nerve function tests were performed only once, after 8 years. A significant reduction of nerve conduction velocity was observed during 8 years in patients with mean HbA1 more than 10% (n=12, group mean 10.9%, range 10.1–13.2%) compared to patients with HbA1 less than 10% (n=33, group mean 9.0%, range 7.5–9.9%). Change of motor nerve conduction velocity in the peroneal nerve was: −4.8±4.9 (SD) vs −2.2±5.3 m/s (p<0.01). Change of motor nerve conduction velocity in the posterior tibial nerve was: −6.8±5.7 vs −3.9±5.1 m/s (p<0.05). No significant changes were observed in the ulnar nerve. Change of sensoric nerve conduction velocity in the sural nerve was: −8.9±8.0 vs −4.6±5.3 m/s (p<0.05). Multiple regression analysis showed that a change in HbA1 of 1% resulted in a 1.3 m/s change in nerve conduction velocity during 8 years. A significantly lowered heart-rate variation during deep breathing (p<0.05) and heart-rate response to standing (p<0.01) was found in patients with HbA1 more than 10% compared to patients with HbA1 less than 10%. This study confirms that the long-term lowering of blood glucose retards the deterioration in nerve conduction velocity observed in the diabetic nerve.

Sudden cardiorespiratory arrest after renal transplantation in a patient with diabetic autonomic neuropathy and prolonged QT interval

A 31-yr male with insulin dependent diabetes mellitus for 20 years underwent general anaesthesia for renal transplantation. During transfer from operating theatre to ICU he developed bradycardia advancing to ventricular fibrillation and had to be resuscitated. Bradycardia did not respond to atropine. Postoperative autonomic nervous function tests showed advanced autonomic neuropathy. He was found to have constantly prolonged QTc interval in his pre- and postoperative ECGs (462-503 ms). Prolongation of QTc interval could be used as a valuable predictor of postoperative cardiac complications in diabetic patients with autonomic neuropathy.

Auditory brainstem latencies in type I (insulin-dependent) diabetic patients

Introduction: This study was undertaken to compare auditory brainstem response latencies in insulin-dependent diabetics, and to compare these findings with metabolic control, microangiopathy, neuropathy, and the duration of diabetes. Methods: Auditory brainstem latencies were studied in 53 type I diabetic patients and 42 randomly selected nondiabetic control subjects, aged between 20 and 40 years. Three different stimulus repetition rates (10, 30, and 50 Hz) were used. All subjects had normal hearing ability. Results: Wave V latencies were longer in diabetic patients when compared with those of control subjects at all repetition rates. At repetition rates of 10 and 50 Hz, diabetic patients had a prolonged I–V interwave latency, and at a repetition rate of 50 Hz, diabetics had a longer III–V interwave latency than control subjects. These findings indicate a central disturbance in the auditory pathway. Microvascular complications (retinopathy, nephropathy) and the duration of diabetes were associated with the prolongation of auditory brainstem latencies. In contrast, poor metabolic control (high fasting blood glucose and glycated hemoglobin A 1c) at the time of the present study was only marginally associated with prolonged auditory brainstem latencies. The changes in auditory brainstem latencies associated with diabetic neuropathy (measured with five cardiac autonomic nervous function tests) appeared simultaneously with microvascular complications and in patients with diabetes of long duration, and thus a causative role of diabetic neuropathy in the pathogenesis of prolonged auditory brainstem latencies remains unsolved. Conclusion: Delayed auditory brainstem latencies in type I diabetic patients are probably caused by the long duration of diabetes and the microvascular complications associated with it.

Autonomic Neuropathy Predicts Deterioration in Glomerular Filtration Rate in Patients With IDDM

To evaluate whether autonomic neuropathy predicts deterioration in glomerular filtration rate in IDDM patients. A prospective study in which 35 IDDM patients have been followed for 10-11 yr. Autonomic nerve function tests included heart-rate reactions to deep breathing (expiration-to-inspiration ratio) and to tilt (acceleration and brake indexes). GFR was evaluated by the 51Cr-EDTA plasma clearance method. At entry to the study, no significant differences were noted in age (39 +/- 2 [mean +/- SE] vs. 42 +/- 4 yr), duration of diabetes (20 +/- 3 vs. 23 +/- 4 yr), supine blood pressures (120/79 +/- 3/2 mmHg vs. 121/78 +/- 6/3 mmHg), and GFR (113 +/- 6 vs. 107 +/- 3 ml.min-1.1.73 m-2) between 20 patients with and 15 without autonomic neuropathy (age-corrected criteria). After 10-11 yr, GFR had decreased significantly (22 +/- 4 ml.min-1.1.73 m-2, P < 0.001) in patients with autonomic neuropathy but not (8 +/- 5 ml.min-1.1.73 m-2, NS) in patients without. In keeping with this, GFR decreased more than expected (difference in GFR/expected decrease in GFR) in patients with autonomic neuropathy, compared with those without (4.46 +/- 0.98 vs. 0.48 +/- 0.73, P < 0.005). Autonomic neuropathy predicts future deterioration in GFR in IDDM patients.

Peripheral and autonomic nerve function in 259 diabetic patients with peripheral neuropathy treated with ponalrestat (an aldose reductase inhibitor) or placebo for 18 months

The potential of the aldose reductase inhibitor ponalrestat (600 mg daily) to ameliorate diabetic neuropathy was evaluated in 259 diabetes mellitus patients with peripheral neuropathy (defined by abnormal vibration perception threshold and abnormal peroneal motor conduction velocity) in a double-blind placebo-controlled clinical trial running for 18 months. Overall, no beneficial effect of ponalrestat on vibration perception thresholds, nerve conduction velocities, and nerve action potential amplitudes was detected. Because vibration perception thresholds and conduction velocities in median, peroneal, and sural nerves did not deteriorate in the placebo group, the potential of ponalrestat to prevent the expected deterioration in peripheral nerve function that occurs with an increased duration of diabetes was not tested. Patients with an abnormal heart rate reaction to standing (abnormal 30:15 ratio; n = 84) on ponalrestat did not deteriorate in this autonomic nerve function test as shown in those on placebo. In conclusion, ponalrestat did not improve peripheral nerve function in diabetes mellitus patients with signs of peripheral neuropathy, although it did ameliorate a deterioration in autonomic nerve function in diabetic patients with signs of autonomic neuropathy.