Standard Cardiovascular Tests Research Articles

Autonomic dysfunction and gastroparesis in Gulf War veterans

Over 25% of veterans with Gulf War illness developed chronic gastrointestinal (GI) symptoms of unknown etiology after they returned from deployment to the Persian Gulf. To determine the prevalence of...

Impact of sleep disturbances and autonomic dysfunction on the quality of life of patients with fibromyalgia.

Fibromyalgia, a painful musculoskeletal disorder is associated with sleep disturbances as well as autonomic dysfunction. Pathophysiology of fibromyalgia is yet not clear and neuroanatomical proximity of sleep and autonomic centre prompts probable involvement of the two impacting the quality of life of fibromyalgia patients. Present study was done with the objective to explore the extent of sleep disturbances and/or autonomic dysfunction in fibromyalgia and asses their impact on quality of life of fibromyalgia patients. Thirty consecutive fibromyalgia patients (diagnosed by ACR 2010) from out-patient department and 30 age-gender matched controls were enrolled after the ethical clearance. All participants were evaluated for: (1) sleep using Pittsburgh sleep quality index and medical outcomes study sleep scale-12 Revised, (2) Quality of life by 36 item short-form health survey-36v2TM and revised fibromyalgia impact questionnaire (only patients). Autonomic functions of patients were evaluated by standard cardiovascular autonomic function tests by Ewing's battery and heart rate variability (5-min) measurement. Fibromyalgia patients had increased sleep disturbances compared to controls (39.46±11, 59.61±2.31; p=0.0001) and very poor sleep quality (13.63±4.15, 3.03±1.56; p=0.0001) as well as quality of life (p=0.0001) which further deteriorated with increasing severity of fibromyalgia. Twelve patients had autonomic dysfunction but it was neither associated with sleep disturbances nor with quality of life. Mild to moderate grade fibromyalgia patients have significant sleep disturbance, poor sleep quality which remarkably impacts their quality of life. Autonomic dysfunction is not an early feature of disease. The study suggests that full spectrum of sleep disturbances and sleep quality should be explored in fibromyalgia syndrome (FMS) patients.

Classical and Delayed Orthostatic Hypotension in Patients With Unexplained Syncope and Severe Orthostatic Intolerance.

Background: Orthostatic hypotension (OH) is a major sign of cardiovascular autonomic failure leading to orthostatic intolerance and syncope. Orthostatic hypotension is traditionally divided into classical OH (cOH) and delayed OH (dOH), but the differences between the two variants are not well-studied. We performed a systematic clinical and neuroendocrine characterization of OH patients in a tertiary syncope unit.Methods: Among 2,167 consecutive patients (1,316 women, 60.7%; age, 52.6 ± 21.0 years) evaluated for unexplained syncope and severe orthostatic intolerance with standardized cardiovascular autonomic tests including head-up tilt (HUT), we identified those with a definitive diagnosis of cOH and dOH. We analyzed patients' history, clinical characteristics, hemodynamic variables, and plasma levels of epinephrine, norepinephrine, C-terminal-pro-arginine-vasopressin (CT-proAVP), C-terminal-endothelin-1, mid-regional-fragment of pro-atrial-natriuretic-peptide and pro-adrenomedullin in the supine position and at 3-min HUT.Results: We identified 248 cOH and 336 dOH patients (27% of the entire cohort); 111 cOH and 152 dOH had blood samples collected in the supine position and at 3-min HUT. Compared with dOH, cOH patients were older (68 vs. 60 years, p < 0.001), more often male (56.9 vs. 39.6%, p < 0.001), had higher systolic blood pressure (141 vs. 137 mmHg, p = 0.05), had lower estimated glomerular filtration rate (73 vs. 80 ml/min/1.73 m2, p = 0.003), more often pathologic Valsalva maneuver (86 vs. 49 patients, p < 0.001), pacemaker-treated arrhythmia (5 vs. 2%, p = 0.04), Parkinson's disease (5 vs. 1%, p = 0.008) and reported less palpitations before syncope (16 vs. 29%, p = 0.001). Supine and standing levels of CT-proAVP were higher in cOH (p = 0.022 and p < 0.001, respectively), whereas standing norepinephrine was higher in dOH (p = 0.001). After 3-min HUT, increases in epinephrine (p < 0.001) and CT-proAVP (p = 0.001) were greater in cOH, whereas norepinephrine increased more in dOH (p = 0.045).Conclusions: One-quarter of patients with unexplained syncope and severe orthostatic intolerance present orthostatic hypotension. Classical OH patients are older, more often have supine hypertension, pathologic Valsalva maneuver, Parkinson's disease, pacemaker-treated arrhythmia, and lower glomerular filtration rate. Classical OH is associated with increased vasopressin and epinephrine during HUT, but blunted increase in norepinephrine.

Cardiovascular Autonomic Neuropathy and Distal Symmetric Sensorimotor Polyneuropathy: These Two Diabetic Microvascular Complications do not Invariably Co-Exist.

Cardiovascular autonomic neuropathy (CAN) and distal symmetrical sensorimotor polyneuropathy (DSPN) are serious microvascular complications of diabetes mellitus (DM). Their simultaneous development remains disputable. The aim of the present study was to examine the correlation between CAN and the presence/severity of DSPN in DM. Subjects with type 1 (group A: n=51; mean age 40.4 years) and type 2 DM (group B: n=153; mean age 64.6 years) were studied. Evaluation of DSPN was based on neuropathy disability score. Assessment of CAN was based on the battery of 4 standardized cardiovascular autonomic function tests. In group A, patients with moderate/severe DSPN exhibited a 12-fold higher likelihood of CAN in univariate analysis (p=0.035). However, significance was lost after adjustment for gender, age, DM duration, and haemoglobin A1c. In group A, likelihood for CAN did not correlate with the presence of mild DSPN in univariate and multivariate analysis. In group B, likelihood of CAN was similar in patients with mild and in those with moderate/severe DSPN compared with patients without DSPN in univariate and multivariate analysis. In between group comparison CAN was similarly distributed in the 2 groups (p for interaction=0.367), in patients with no, mild and moderate/severe DSPN. CAN does not always co-exist with degrees of DSPN, ranging from mild to moderate/ severe and is similarly distributed in T1DM and T2DM patients with mild and moderate/severe DSPN and in patients without DSPN.

Autonomic Dysfunction in Iraqi Patients with Chronic Inflammatory Demyelinating Polyneuropathy

Objective:The purpose of this study is to evaluate the autonomic disturbance in patients with chronic inflammatory demyelinating polyneuropathy.Methods:Thirty-eight patients who fit into the AAN criteria of diagnosis of CIDP were studied. Five standard cardiovascular autonomic Ewing tests were performed for every patient in addition to the assessment of autonomic symptoms.Results: The study includes 32 males and 6 females their age ranged from 10 to 69 years. In this study we have seen one child with CIDP whose age was ten years and he had PST impairment. Sexual disturbance was the majorautonomic symptom seen in the males [40.6%], while urinary disturbance 2was the major autonomic disturbance encountered in females [66.6%]. Autonomic function tests [AFT] showed that one quarter of males and half of the females had abnormal AFT. In patients aged between 50-59 years, [40%] having normal autonomic function test, [40%] had PST impairment, while the others have mixed impairment [20%]. None of the patients had pure sympathetic impairment. Regarding the types of CIDP the largest percent [84.2%] of patients have classic type of CIDP while 7.8%, 5.2% and 2.6% had DADS, MADSAM and MMN respectively.Conclusions: Autonomic dysfunction was common in Iraqi CIDP patients. PST impairment is a major pattern of dysautonomia in CIDP. Sexual disturbance in males while urinary disturbance in females were the most common autonomic symptoms encountered. VM, HR response to standing allow an early detection of autonomic dysfunction even in asymptomatic individuals.

Prevalence of Cardiovascular Autonomic Neuropathy in a Cohort of Patients With Newly Diagnosed Type 2 Diabetes: The Verona Newly Diagnosed Type 2 Diabetes Study (VNDS).

Cardiovascular autonomic diabetic neuropathy (CAN) is a serious complication of diabetes. No reliable data on the prevalence of CAN among patients with newly diagnosed type 2 diabetes are available. Therefore, the aim of this study was to estimate the prevalence of CAN among patients with newly diagnosed type 2 diabetes. A cohort of 557 patients with newly diagnosed type 2 diabetes with cardiovascular autonomic test results available was selected. Early and confirmed neuropathy were assessed using a standardized methodology and their prevalences determined. A multivariate logistic regression analysis was modeled to study the factors associated with CAN. In the entire cohort, the prevalence of confirmed CAN was 1.8%, whereas that of early CAN was 15.3%. Prevalence did not differ between men and women. In the multivariate analyses BMI results were independently and significantly associated with CAN after adjusting for age, sex, hemoglobin A1c, pulse pressure, triglyceride-to-HDL cholesterol ratio, kidney function parameters, and antihypertensive treatment. CAN could be detected very early in type 2 diabetes. This study may suggest the importance of performing standardized cardiovascular autonomic tests after diagnosis of type 2 diabetes.

Disorders of Peripheral Innervation and Regulation of Autonomic Functions Evoked by Professional Influence of the Vibration/Noise Factor

We examined changes in the characteristics of innervation of the upper limb and peculiarities of control of the cardiovascular system in 53 male workers (riveters and fitters in an aircraft plant) who were for a long time subjected to the influence of local vibration and noise in the course of their professional activity. As was found, the mean intragroup threshold of vibration sensitivity of a finger of the working hand in these subjects significantly (P < 0.001) exceeded both normative values and corresponding values in the control group. The respective negative shifts were intensified with increase in the professional experience duration. The mean velocity of transmission of an excitation volley along motor fibers of the n. medianus and n. ulnaris of the working limb in the main group was lower by about 9% (P < 0.05) as compared with the respective index in the control group. Transmission via sensory fibers innervating the corresponding regions of the palm was slowed down by more than 20% (P < 0.05). The residual latency at generation of M responses of the palm muscles in the main group was, on average, 6% longer than in the control (P < 0.05). The mean latency of the evoked cutaneous sympathetic potential at stimulation of the finger of the contralateral palm and recording from the palm and dorsum of the hand also significantly (P< 0.05) exceeded the analogous control value. Results of five standard clinical cardiovascular tests (change in the systolic arterial pressure in the orthostatic test, change in the diastolic pressure at realization of an isometric effort by the palm muscles, calculation of the 30/15 ratio of cardiointervals in the orthostatic test and of the coefficients of duration of these intervals in the Valsalva and deep breathing tests) showed that pathological and boundary values of these indices were found in the main group in 60.3, 32.0, 26.0, 36.0, and 34.0% of the examined persons, while analogous cases in the control group were exceptional. Thus, the long-lasting influence of the intense professional activity-related vibration/noise factor results in the formation of demyelinating polyneuropathy in the upper limb nerves with the involvement of motor fiber terminals and sympathetic postganglionic fibers in the pathological process. Changes in the indices of the cardiovascular tests in subjects of the main group demonstrate that these persons frequently suffer from disorders of the peripheral and, probably, central mechanisms of autonomic control of the cardiovascular system. This results in the development of a syndrome of progressive autonomic insufficiency (with prevalence of insufficiency of the sympathetic mechanisms).

The cardiovascular form of autonomous neuropathy in the adolescents with type 2 diabetes mellitus

Objective. To estimate the prevalence of the cardiovascular form of autonomous neuropathy (CAN) and the factors associated with this condition in the adolescents suffering from type 2 diabetes mellitus (DM2) in comparison to the adolescents present- ing with type 1 diabetes mellitus (DM1). Material and methods. The study included 24 adolescents with DM2 and 30 ones with DM1 matched for the age, duration of the disease, and the quality of its compensation. The control group was comprised of 17 adolescents with exogenous constitutional obesity (ECO). All the patients were examined by means of Holter ECG monitoring with the estimation of the daily cardiac rhythm variability based on the mean weighted variation of rhythmogram (MWVR) and the length of the QTc interval. In addition, standard cardiovascular tests were performed including deep-breath test, the Valsalva maneuver, and the 30:15 intermittent fitness test. Cardiovascular autonomous neuropathy was diagnosed in the patients exhibiting deviation from the normal values in 3 of the five parameters of interest, viz. MWVR, QTc length, and three functional tests. Results. CAN at the subclincal stage was more frequently diagnosed in the adolescents with DM2 than in those suffering DM1 (29.2 and 10% of the cases respectively; p&lt;0.05). This condition was not found in any of the patients presenting with endogenous constitutional obesity. MWVR in the adolescents with DM2 was lower than in the patients with DM1 (p=0.02) or ECO (p=0.04). The QTc duration was greater in the DM2 patients than in the adolescents of the same age presenting with ECO (p=0.02) and comparable with that in the patients suffering DM1 (p=0.3). In the adolescents with DM2, positive correlation between CAN, the duration of diabetes, the quality of its compensation, and the patient’s age was documented while the length of the QTc interval negatively correlated with these three variables. Moreover, the occurrence of CAN positively correlated with peripheral neuropathy. No relationship with the severity of insulin resistance was observed.

Association of Autoimmunity to Autonomic Nervous Structures With Nerve Function in Patients With Type 1 Diabetes: A 16-Year Prospective Study

OBJECTIVE We prospectively evaluated the association between autoimmunity to autonomic nervous structures and autonomic neuropathy in type 1 diabetes in relation to clinical variables. RESEARCH DESIGN AND METHODS A cohort of 112 patients with type 1 diabetes was prospectively followed from adolescence (T0) to approximately 4 (T4) and 16 (T16) years later. Standard cardiovascular (CV) tests and neurological examination were performed and related to the presence of circulating antibodies (Ab) to autonomic nervous structures detected at T0 and T4. Quality of life was assessed by a diabetes-specific questionnaire. RESULTS Sixty-six patients (59% of the cohort) were reexamined at T16 (age 31.4 ± 2 years; disease duration 23.4 ± 3.7 years). Nineteen had circulating Ab to autonomic structures. Prevalence of abnormal tests and autonomic symptoms were higher in Ab-positive (68 and 26%, respectively) than Ab-negative (32 and 4%) patients (P < 0.05). Among Ab-positive patients, the relative risk (RR) of having at least one altered CV test was 5.77 (95% CI 1.56-21.33), and an altered deep breathing (DB) test (<15 bpm) was 14.65 (2.48-86.46). Previous glycemic control was the only other predictor (RR 1.06 [1.002-1.13]/mmol/mol HbA1c increase). Presence of Ab carried over a 68% probability of developing an altered CV test; absence of Ab carried a 91% probability of not having an altered DB test and an 89% probability of not having an altered Valsalva ratio. Autonomic neuropathy was independently associated with worse quality of life. CONCLUSIONS Circulating Ab to autonomic structures are associated with the development of autonomic dysfunction in young diabetic patients independent of glycemic control.

A Study to assess, the Extent of Autonomic Dysfunction Based on the Standard Cardiovascular Tests in Different Grades of Alcoholics

Aim: Autonomic system is the one which extensively supplies the inner organs. Much attention is not given to it clinically and there are few tests available to assess it. The tests which are available are less used in patients to assess the autonomic function. Alcoholism is a factor which affects most of the system in the human body. Its effect on autonomic nervous system is extensive. As a result of this autonomic failure there would be damage to multiple systems. Study design: In this study the effect of alcoholism in a group of people grading them as social drinkers, chronic alcoholics and alcoholic cirrhotics have been done using the seven standard autonomic function tests. The extent of autonomic damage in all these different groups was done. The results were compared against a group of controls. Results: There was autonomic damage observed in all three groups with a distribution of 50% mild damage and 30% of moderate damage in social drinkers. A 20% of severe damage (combined damage) in chronic alcoholics and 90% of severe damage in alcoholic cirrhotics were obtained. A significant difference was observed between all groups of alcoholics and the controls (p< 0.01) Conclusion: The extent of autonomic damage seems to be underestimated in alcoholics. More care should be given to high social drinkers as they too exhibited autonomic damage. Also these simple tests should be performed as a routine on all alcoholics for an early detection of the situation.

Exhaled carbon monoxide in adolescents with diabetic cardiovascular autonomic neuropathy.

The aim of the study was to determine if cardiovascular autonomic neuropathy (CAN) is associated with changed concentration of exhaled carbon monoxide (eCO) in adolescents with type 1 diabetes (T1D). A total of 46 T1D patients and 25 healthy controls (15-19 years) were enrolled. The parameters eCO and carboxyhemoglobin (HbCO) were established using a MICRO-4 Smokerlyser. CAN was examined by standard cardiovascular tests. Adolescents with T1D did not significantly differ in eCO compared to healthy subjects. eCO and HbCO were significantly lower in CAN-positive subjects (n=19) (1.36 ± 1.65 ppm vs. 3.09 ± 2.31, p=0.01 and 0.58 ± 0.49% vs. 1.04 ± 0.44, p<0.01, respectively) compared to CAN-negative subjects (n=27), whereas no significant difference was found in other measured parameters. By multivariate logistic regression, eCO and HbCO were associated with higher risk of CAN (OR=1.824, p<0.05 and OR=10.989, p<0.01). Our results indicate that eCO is decreased in CAN-positive diabetic subjects. Further studies are necessary to investigate the possible role of eCO as a marker for CAN.

Autonomic dysfunction and circadian blood pressure variations in people with impaired glucose tolerance

To assess circadian blood pressure variability in people with impaired glucose tolerance and a healthy control population. Seventy-five people with impaired glucose tolerance and 40 healthy volunteers (frequency matched on 10-year age bands and sex) underwent a detailed neurological assessment. Autonomic neuropathy was detected by the five standard cardiovascular autonomic tests and heart rate variability was characterized by the triangle index. Diurnal indices were assessed by 24-h ambulatory blood pressure monitoring. Systolic and diastolic diurnal indices were defined as: (mean daytime blood pressure - mean night-time blood pressure) × 100/mean daytime blood pressure. Mean 24-h systolic and diastolic blood pressure was significantly higher in the group with impaired glucose tolerance compared with the control group [126 ± 12 (mean ± SD) vs. 117 ± 10, 75 ± 7 vs. 71 ± 6 mmHg, both P < 0.05). Systolic and diastolic diurnal indices and heart rate variability triangular index were significantly lower in people with impaired glucose tolerance compared with control subjects (9.1 ± 7.8 vs. 13.2 ± 5.4, 14.5 ± 9.7 vs. 18.4 ± 7.1 mmHg, 28.0 ± 8.4 vs. 39.5 ± 9.3, all P < 0.05). Differences in mean diastolic blood pressure, heart rate variability triangular index and the frequency of non-dippers between those with impaired glucose tolerance and control subjects seemed to be independent of BMI and the presence of cardiovascular autonomic neuropathy, as simultaneous adjustment for BMI and cardiovascular autonomic neuropathy had no major effect on the results. Our data suggest that people with impaired glucose tolerance have increased diastolic blood pressure and abnormal circadian blood pressure regulation, independent of obesity and the presence of cardiovascular autonomic neuropathy.

The association between glutathione S-transferase T1 and M1 gene polymorphisms and cardiovascular autonomic neuropathy in Slovak adolescents with type 1 diabetes mellitus

Glutathione S-transferase (GST), as antioxidant enzyme, protects tissue from oxidative damage typical for many pathologic conditions as type 1 diabetes (T1D) and its chronic complications. The aim of the study was to compare the prevalence of GST T1/M1 gene polymorphisms between diabetic adolescents with (CAN+) and without (CAN−) cardiovascular autonomic neuropathy. Forty-six subjects with T1D at the age 15–19years were enrolled. CAN was diagnosed in 19 patients (41.3%) based on standard cardiovascular tests. GST M1 null genotype was more prevalent in CAN+subjects but this was not statistically significant (OR=1.889, 0.61–6.55, p>0.05). GST T1 wild genotype nearly 5-fold increased the risk of CAN (OR=4.952, 1.13–21.739, p<0.05). Regarding genotype combination, GST T1/M1 wild/null genotype was significantly more frequent in CAN+compared to the CAN− subjects (OR=3.96, 1.024–15.302, p<0.05). No significant difference was found in any biochemical parameters between CAN+and CAN− subgroups. Multivariable logistic regression showed that none of the biochemical parameters estimated was considered a risk factor for CAN, however GST T1 wild and GST T1/M1 wild/null represented a risk factor for CAN development (OR=2.227, 1.079–4.587, p<0.05 and OR=1.990, 1.026–3.859, p<0.05, respectively). GST T1 wild allele and GST T1/M1 wild/null genotype can be considered as risk factors for CAN in Slovak adolescents with T1D.

Determination of sensitivity among various cardiovascular autonomic function tests in diabetic patients of Bijapur

Eleven diagnosed diabetic patients and fifteen healthy age-matched control subjects were subjected to six standardized cardiovascular autonomic reflex function tests. The aim of the study was to identify the best sympathetic and parasympathetic autonomic function tests in diabetic patients and to determine their sensitivity. Several diabetic patients showed an abnormal response to various autonomic function tests. Among the three sympathetic tests studied, the coefficient of variation of all tests was found to vary; hence, the most sensitive test could not be determined. The heart-rate response to standing was found to be the most sensitive as it showed the lowest coefficient of variation. More parasympathetic than sympathetic tests showed abnormal responses in diabetics, particularly for heart rate responses to a deep breathing test. The results indicate that all autonomic function tests have to be performed for a proper evaluation/diagnosis of diabetic autonomic neuropathy.

W2077 Rapid Gastrointestinal Transit in Patients with Alcohol-Related Chronic Pancreatitis Is Related to Impaired Distal Small Bowel Meal Accumulation and Autonomic Neuropathy

Background: Patients with alcohol-related chronic pancreatitis (ARCP) may have accelerated mouth-to-cecum transit, particularly in the presence of autonomic neuropathy. Nevertheless, the roles of gastric emptying (GE) and transit throughout proximal and distal small bowel in the origin of the abnormal gastrointestinal transit (GIT) in ARCP have not been much studied. Aim: To assess GIT and to determine the roles of GE and segmental transit throughout the proximal and the distal small bowel in ARCP patients. Method: Eighteen healthy controls and 40 male ARCP patients were studied, including 17 with diabetes mellitus and malabsorption, 10 with diabetes only, 3 with malabsorption only and 10 without diabetes or malabsorption. Autonomic neuropathy was detected in 20 patients by standardized cardiovascular tests. GIT was assessed by scintigraphy after ingestion of a liquid meal labeled with 99mTechnetium-phytate and defined as the time of meal arrival to the cecum. Abdominal scans were serially taken for 180 min with a gamma camera. Counts for regions of interest defined for the stomach, proximal and distal small bowel, and cecum yield data for calculation for GE half-time, and the times of meal arrival to the proximal and to the distal small bowel and the cecum. Accumulation of the meal in the distal small bowel was estimated as the proportion of ingested radioactivity found in this region by the time that cecum filling started. Results: GIT was significantly shorter (p 180min vs 102min; 50->180min) and 11 patients were considered as having definite abnormally accelerated GIT. There were no significant differences (p>0.20) between patients and controls concerning GE half-time (50min; 5-13min vs 55min; 16-83min). There were also no differences (p>0.50) between patients and controls regarding the times of meal arrival to the proximal (15min; 1-45min vs 13min; 3-70min) and distal small bowel (23min; 4-64min vs 30min; 12-83min). However, accumulation of the meal in the distal small bowel was lower (p 0.1). Univariate analysis showed that rapid GIT is associated with both impaired accumulation of the meal in the distal small bowel (7/11 vs 3/29; p=0.001) and autonomic neuropathy (10/11 vs 10/29; p= 0.003). Conclusion: Abnormally rapid GIT in ARCP patients does not seem to be due to accelerated GE but is related to impaired accumulation of the meal in the distal small bowel and to autonomic neuropathy.

Determination of sensitivity among various cardiovascular autonomic function tests in diabetic patients of Bijapur

Eleven diagnosed diabetic patients and fifteen healthy age-matched controls were subjected to six standardized cardiovascular autonomic reflex function tests. The aim of the study was to identify the best sympathetic and parasympathetic autonomic function tests in diabetic patients and to determine their sensitivity. Several diabetic patients showed an abnormal response to various autonomic function tests. Among the three sympathetic tests studied, the coefficient of variation of all tests was found to vary and hence most sensitive test could not be determined. The heart-rate response to standing was found to be the most sensitive as it showed the lowest coefficient of variation. More parasympathetic than sympathetic tests showed abnormal responses in diabetics, particularly for heart rate responses to a deep breathing test. The results indicate that all autonomic function tests have to be performed for a proper evaluation/diagnosis of diabetic autonomic neuropathy.

Upper abdominal symptoms in patients with Type 1 diabetes: unrelated to impairment in gastric emptying caused by autonomic neuropathy

Diabetic gastroparesis is a common condition occurring in some 30-50% of patients with long-term diabetes. Some studies have found a relationship between autonomic neuropathy and diabetic gastroparesis. In addition to autonomic neuropathy, acute changes in plasma glucose concentration can also affect gastric emptying. The objective was to examine the relationship between autonomic nerve function, glucose concentration, gastric emptying, and upper abdominal symptoms in Type 1 diabetic patients. Gastric emptying of solids and liquids was measured with scintigraphy in 27 patients with longstanding Type 1 diabetes with upper abdominal symptoms. Autonomic nerve function was examined by standardized cardiovascular tests, and plasma glucose concentrations were measured during scintigraphy. Severity of abdominal symptoms and quality of life were explored by validated questionnaires. Seven patients (26%) had delayed gastric emptying of solids and three (11%) of liquids. Mean gastric half-emptying time of solids was 128 +/- 116 min and of liquids 42 +/- 30 min. Of the 26 patients undergoing tests, 16 (62%) had autonomic nerve dysfunction. Autonomic neuropathy score (1.6 +/- 1.7) correlated positively with the gastric emptying rate of solids (P = 0.006), a rate unrelated to symptom scores or plasma glucose concentrations during scintigraphy. Quality of life in patients with abdominal symptoms was lower than in the normal Finnish population. Impaired gastric emptying of solids in patients with Type 1 diabetes is related to autonomic neuropathy, but not to actual glycaemic control. The upper abdominal symptoms observed in these patients cannot be explained, however, by impaired gastric emptying.

Non-invasive assessment of cardioregulatory autonomic functions in children with epilepsy

We aimed to evaluate the interictal cardiovascular autonomic functions in pediatric patients with idiopathic epilepsy, both partial and generalized. The study included 25 patients with idiopathic epilepsy and 50 control subjects. Patients underwent five standardized clinical cardiovascular reflex autonomic tests [resting heart rate (HR), HR response to deep breathing and to Valsalva maneuver, the 30:15 ratio of HR response to standing, and blood pressure response to standing], as well as a 12 lead surface electrocardiogram. Heart rate variability (HRV) was tested via 24-h Holter monitoring and the time domain parameters (SDNN, PNN50, rMSDD) were assessed. Excretion of vanillyl mandelic acid and metanephrine was measured in 24-h urine collection. Clinical reflex autonomic tests showed mild dysfunction in 8%, moderate dysfunction in 44% and severe dysfunction in 4% of patients. The HRV parameter, SDNN, was reduced in all age groups, while rMSDD and PNN50 were reduced only in the older age group. Metanephrine levels were significantly reduced in the patients group. Patients with uncontrolled epilepsy had a significantly higher frequency of autonomic dysfunction as assessed by clinical scoring. Cardiac autonomic dysfunction is not uncommon in pediatric patients with epilepsy. Altered cardiovascular regulation seems to be related to the epilepsy itself rather than to the characteristics of the disorder.

Effect of Bortezomib on the Autonomic Nervous System.

BackgroundPeripheral neuropathy is one of the most frequent adverse events associated to bortezomib therapy; among neuropathic syndromes, postural hypotension is described as well. However, information on disautonomic toxicity are limited and there are no studies addressed to this particular issue so far.Before starting this study we had observed a case of dramatic acute autonomic failure during bortezomib treatment in a patient with advanced multiple myeloma, who developed severe orthostatic hypotension, tachycardia and impairment to tolerate the sitting and orthostatic posture for several weeks.MethodsWe prospectively studied 12 consecutive patients, treated with bortezomib at our Institution between February 2005 and July 2006. Assessment included neurological examination, INCAT Disability scale, INCAT sensory sum score, MRC sum score, nerve conduction studies, and standard cardiovascular autonomic tests including Lying to standing, Deep breathing and Postural hypotension. These tests were conducted baseline and after each bortezomib 21-days cycle up to three consecutive cycles.ResultsTwo pts showed a clinically evident autonomic involvement with orthostatic hypotension; a change to a pathological score in 2 out of 3 tests anticipated clinical disautonomic signs in 1 and 11 weeks respectively. Clinical impairment showed to be reversible in both cases. Four pts presented only 1 pathological test (without any clinical sign or symptom of postural hypotension) and 6 patient had normal results. There was no apparent correlation between autonomic impairment and disease response to therapy or patients baseline characteristics (disease stage, Ig class, previous anti-myeloma therapies, concomitant thalidomide or anti-hypertensive treatment); furthermore, none had evidence of amyloidosis.ConclusionsOur prospective study confirms that autonomic dysfunction is a potential adverse effect of bortezomib. Autonomic, non invasive, cardiovascular testing may reveal subclinical involvement and precede clinical evidence of disautonomic neuropathy. Further studies in larger cohorts of patients are needed to clarify the interactions between proteasome inhibitor activity and autonomic nervous system, in order to assess the frequency, the ability of available test in early pre-clinical diagnosis and the potential of the reversibility of neuropathic signs after drug discontinuation.

Validation of the nerve axon reflex for the assessment of small nerve fibre dysfunction

Objective: To validate nerve–axon reflex-related vasodilatation as an objective method to evaluate C-nociceptive fibre function by comparing it with the standard diagnostic criteria. Methods: Neuropathy was evaluated in 41 patients...