Severity Of Autonomic Neuropathy Research Articles

The Autonomic Nervous System (ANS)-Immune Network in People Living With HIV.

Pre-clinical studies have demonstrated direct influences of the sympathetic and vagal/parasympathetic branches of the autonomic nervous system (ANS) on the immune system. The relevance of these pathways to the development of inflammatory disorders in humans remains unknown. We hypothesized that a comprehensive examination of the ANS-immune network in patients with HIV, would reveal that the type and severity of autonomic neuropathy (AN) would predict immune phenotypes with distinct clinical and demographic characteristics. This is a cross-sectional study of 79 adult people with a history of well-controlled HIV on stable combination antiretroviral treatment (CART) recruited from a primary care clinic network within the Mount Sinai Health System in New York City. All participants underwent a standardized battery of autonomic function tests summarized as the Composite Autonomic Severity Score (CASS) and vagal and adrenergic baroreflex sensitivity (BRS-V and BRS-A). Immune profiling included: 1) measurement of interleukin-6 (IL-6) as part of the Olink assay Target 96 Inflammation Panel, 2) non-negative matrix factorization (NMF) clustering analyses on Olink immune biomarkers, and 3) mass cytometry (CyTOF) on a subset of participants with and without autonomic neuropathy (N = 10). Reduced activity of caudal vagal circuitry involved in the cholinergic anti-inflammatory pathway (CAP) predicted higher levels of IL-6 (Spearman's rho = -0.352, p=0.002). The comprehensive assessment of the ANS-immune network showed four immunotypes defined by NMF analyses. A pro-inflammatory immunotype defined by elevations in type 1 cytokines (IL-6, IL-17) and increased numbers of CD8+ T-cells was associated with autonomic neuropathy (AN). This association was driven by deficits in the cardiovascular sympathetic nervous system and remained strongly significant after controlling for the older age and greater burden of co-morbid illness among participants with this immunotype (aOR=4.7, p=0.017). Our results provide novel support for the clinical relevance of the CAP in patients with chronic inflammatory AN. These data also provide insight regarding the role of the sympathetic nervous system and aging in the progression and development of co-morbidities in patients with chronic HIV and support future research aimed at developing therapies focused on modulation of the sympathetic and parasympathetic/vagal nervous system.

Study on autonomic neuropathy of the digestive system caused by bortezomib in the treatment of multiple myeloma

ABSTRACTObjectiveTo research the effects of autonomic neuropathy of the digestive system induced by bortezomib on clinical efficacy and quality of life.MethodsA total of 150 patients with newly diagnosed multiple myeloma (MM) were hospitalized in our department from January 2018 to December 2021, and treated with bortezomib-based combination regimens. To observe the incidence of autonomic neuropathy of the digestive system and analyse the correlations between the severity of autonomic neuropathy and the efficacy, survival, age, underlying diseases and personal history.ResultsThe incidence of autonomic neuropathy of the digestive system was 60.0%. The overall response rate (ORR), 2-year progression-free survival (PFS) rate and 2-year overall survival (OS) rate in the grade 3 group of autonomic neuropathy were significantly lower than those in the grade 1–2 group, and the differences were statistically significant (P < 0.05). Age, constipation, diabetes, fracture/spinal cord compression in bed and history of alcoholism were positively correlated with the risk of autonomic neuropathy of the digestive system (P < 0.05). The autonomic neuropathy of the digestive system was significantly alleviated in most patients after the timely adjustment of the treatment regimen, and bortezomib could continue to be administered.ConclusionsThe incidence of autonomic neuropathy of the digestive system induced by bortezomib is high, and its severity is closely related to efficacy, advanced age, constipation, diabetes, fracture/spinal cord compression in bed and history of alcoholism. Early detection and early treatment are necessary to better treat the disease and reverse the autonomic neuropathy.

Amyloid neuropathy and autonomic dysfunction

AbstractThe clinical phenotype of amyloid neuropathy is not uniform. Especially in patients with hereditary amyloid neuropathy, the age at onset and severity of autonomic neuropathy are strongly influenced by the patient’s family history and the mutant gene of transthyretin. In the past 30 years, liver transplantation has been actively performed in the hereditary amyloid neuropathy patients with an early onset, resulting in much longer survival with this disease. Furthermore, new information on the pathogeneses of transthyretin‐derived amyloidosis has been accumulating via the analysis of tissue samples biopsied or autopsied from post‐transplanted hereditary amyloid neuropathy patients. The recent introduction of non‐invasive drug therapies has given rise to the possibility of treating amyloid neuropathy. The concept of amyloid neuropathy, including autonomic dysfunction, has changed. This review discusses the clinical picture, pathology, diagnosis, therapy, and post‐treatment changes of amyloid deposition in patients with amyloid neuropathy and autonomic neuropathy.

Autonomic neuropathy in Rheumatoid Arthritis: Relationship with seropositivity of Rheumatoid factor and disease activity

Background: Autonomic neuropathy (AN) has been recognized as a strong predictor of sudden cardiac death in Rheumatoid Arthritis (RA). Autonomic neuropathy may be assessed by five cardiovascular reflex tests. Objective: To find out the prevalence and severity of AN in RA and also to assess the correlation of inflammatory markers, disease severity and serological factor, Rheumatoid factor (RF) with autonomic reflex test parameters. Method: This cross sectional study was conducted on sixty (60) female RA patients, age range 18-50 years enrolled from the Out- Patient Department of Rheumatology Wing, Department of Medicine, of Bangabandhu Sheikh Mujib Medical University (BSMMU). Age matched 30 apparently healthy females were control. Cardiac autonomic reactivity was assessed by five cardiovascular reflex tests as described by Ewing include heart rate response to standing, deep breathing, valsalva maneuver and blood pressure response to standing and sustained hand grip. Inflammatory activity in RA was assessed by serum rheumatoid factor (RF)level which was estimated by the latex agglutination test ,C-reactive protein(CRP) and ESR and marker of disease activity was assessed by Disease activity score(DAS- 28 score) value. For statistical analysis, independent sample ‘t’ test chi-square test, pearson correlation coefficient test, spearman correlation test were used. Results: Among 60 RA patients, 43 (71.6%) patients were RF positive. Frequency of AN in RA patients was significantly higher (p&lt; 0.001) compared to control. AN was detected in 78% of RA patients. Among the RA patients 17.38% showed severe,13.04% showed definite, 54.35% showed early involvement and 17.38% showed evidence of atypical pattern of AN. In addition, valsalva ratio and difference between maximum and minimum heart rate during deep breathing showed significant(p&lt;0.05) negative correlation with autoantibody Rheumatoid factor(RF) whereas no significant correlation of autonomic nerve reactivity parameters with DAS- 28, CRP and ESR were found. Conclusion: Autonomic neuropathy was associated with RA. Autonomic neuropathy may be related to the presence of autoantibody RF in RA patients. J Bngladesh Soc Physiol 2021;16(1): 70-76

Cardiovascular Autonomic Neuropathy and Glucose Variability in Patients With Type 1 Diabetes: Is There an Association?

The oxidative stress associated with glucose variability might be responsible for neuronal damage while autonomic neuropathy (AN) has a detrimental effect on metabolism. The aim of the study was to find relationship between AN and GV in type 1 diabetic patients and to identify further factors that affect GV. Twenty type 1 diabetic patients were involved (age: 39.5 ± 3.4 years, duration of diabetes: 17.5 ± 2.5 years; HbA1c: 8.1 ± 0.2%, mean ± SE). AN was assessed by the cardiovascular reflex tests. The interstitial glucose levels were determined following insertion of a subcutaneous electrode during the continuous glucose monitoring (CGM) method on six consecutive days. GV was characterized by calculation of four parameters. SD of interstitial glucose values correlated positively with the overall AN score and the degree of the orthostatic reduction of systolic blood pressure (AN-score-SD ρ = 0.47, p < 0.05; orthostasis-SD: ρ = 0.51, p < 0.05). Mean absolute glucose (MAG) correlated with three parameters of AN (AN-score-MAG: ρ = 0.62, p < 0.01; 30/15 ratio-MAG: ρ = -0.50, p < 0.05; orthostasis-MAG: ρ = 0.59, p < 0.01). The HbA1c also correlated with two parameters of GV (HbA1c-continuous overlapping net glycemic action: ρ = 0.56, p < 0.05; HbA1c-MAG: ρ = 0.45, p < 0.05). The frequency of hypoglycemia did not exhibit any correlation with measures of GV. Severity of glucose variability but not overall glucose load correlates with both parasympathetic and sympathetic dysfunctions in type 1 diabetes. Higher HbA1c is associated with more severe glucose variability. The observed correlation between increased glucose variability and the severity of AN necessitates the further exploration of this relationship.

Prevalence of Autonomic Neuropathy in Patients of Rheumatoid Arthritis and Its Correlation with Disease Severity.

Autonomic Neuropathy (AN), found to be a strong predictor of sudden cardiac death, has been reported variably in patients with Rheumatoid Arthritis (RA). Manifesting as sweating disturbances, gastrointestinal irregularities, bladder or erectile dysfunction, AN can significantly affect a patient's quality of life and alter the course of the disease. This study was undertaken to find out the prevalence and severity of AN in RA patients attending the Rheumatology Clinic at a Tertiary Care Hospital in New Delhi, India and also to investigate its correlation with patient and disease factors such as age, gender, disease severity, duration and serological status. In this cross-sectional study, AN was assessed subjectively by a survey of autonomic symptoms. Cardiac autonomic involvement was assessed by five cardiovascular reflex tests as described by Ewing: Heart Rate (HR) response to deep breathing, standing, and Valsalva and Blood Pressure (BP) response to standing and sustained handgrip. A total of 31 RA patients and 31 age and sex matched healthy volunteers were recruited. Upon analysis it was found that the prevalence of cardiac AN was significantly higher in patients (80.65%) as compared to controls (51.61%) (p=0.016). Positive correlation with disease severity was observed with the patient reported questionnaire but not with the objective cardiovascular reflex tests. No significant correlation between grade of AN and patient's age, gender, disease duration or serological status was established. At the end of the study, it was concluded that the pathological mechanisms responsible for autonomic dysfunction are more active in RA as compared to others.

Cardiac Autonomic Neuropathy and QTc Interval in Type 2 Diabetes

Context: An association between cardiac autonomic neuropathy and QT interval prolongation was demonstrated in many studies and it may predispose to sudden death in diabetes mellitus. Aims: To find out the prevalence of cardiac autonomic neuropathy and its relation to QTc interval and QTc dispersion in type 2 diabetes. Settings and Design: Observational study. Materials and Methods: Fifty patients with type 2 diabetes mellitus of more than 5-years duration and 30 age- and sex-matched controls without any history of diabetes were selected. A battery of five autonomic function tests was done in all cases. Heart rate, QTc values, and QTc dispersion were measured and compared among patients with and without autonomic neuropathy and controls. Statistical analysis used: Students t test/Chi-square test. Results: Among the 50 patients in the study population, 21 (42%) had severe autonomic neuropathy and 12 (24%) had early autonomic neuropathy. Mean heart rate was significantly more in patients with autonomic neuropathy than those without neuropathy. Diabetics with autonomic neuropathy had significantly higher QTc mean and QTc max values compared to diabetics without autonomic neuropathy and controls. QTc dispersion was significantly more among patients with autonomic neuropathy compared to those without autonomic neuropathy and controls. Conclusions: Diabetic autonomic neuropathy is associated with increase in resting heart rate and prolongation of QTc intervals. QTc max was correlating with severity of autonomic neuropathy. QTc dispersion is significantly high in diabetes mellitus with autonomic neuropathy.

Clinical assessment of the autonomic nervous system in diabetes mellitus and its correlation with glycemic control

Clinical assessment of the autonomic nervous system in Diabetes mellitus (DM) and its correlation with glycemic control. Cross sectional study of 50 adult diabetes patients. Fifty patients with DM who were on regular treatment with either insulin and/or oral hypoglycemic agents were studied. Cardiovascular autonomic neuropathy (CAN) score was calculated using the clinical test variables. Of the 50 patients 30 had no CAN, 10 had early CAN and 10 had severe CAN. The mean of CAN score increased with duration of diabetes. The mean HbA(1C) was 7.73. The mean CAN score was higher in patients who had complication of diabetes as compared to patients without complications. The heart rate variability with respiration was found to be 15.84 ± 7.02/min. The mean valsalva ratio was 1.31 ± 0.23. The mean drop in BP on standing was 7.30 ± 7.24 mmHg. The mean 30:15 ratio was 1.06 ± 0.04. The mean rise in diastolic BP on sustained hand grip was 16.04 ± 4.11 mmHg. The prevalence of autonomic neuropathy in DM as assessed by CAN score was 40%. The CAN score did not correlate with the duration of DM. The HbA(1C) had a significant correlation with the severity of autonomic neuropathy. Occurrence of CAN correlated with the presence of peripheral neuropathy but not with the presence of retinopathy or nephropathy. All individual tests in the battery of CAN score were significantly associated with the presence of autonomic neuropathy, except 30:15 ratio.

Assessment of the exocrine pancreatic dysfunction and the effects of enzyme substitution in patients with non-pancreatic diabetes

The consequences of the exocrine pancreatic insufficiency are well-known in pancreatic diabetes (DM). Aim: The aim of this study was to determine the frequency of low stool elastase activity in type-1 and type-2 DM patients (pts). The metabolic parameters and the chronic complications were evaluated in pts with normal and abnormal exocrine function and the effects of enzyme substitution were analysed. Patients and Methods: Stool elastase of 146 pts with non-pancreatic DM was measured by ELISA. Autonomic neuropathy (AN), peripheral sensory function, retinopathy, HbA1c, BMI, microalbuminuria (MAU), quality of life (QoL) were measured. Results: 41 pts (28%) had an affected exocrine function (elastase: 417±37 vs. 141±11 ug/g; mean of pts with normal vs. abnormal values, p 0.05). The severity of AN decreased (AN score: from 3.09±0.61 to 2.36±0.66, p>0.05). Conclusions: A moderately impaired exocrine pancreatic function is a characteristic finding in a high number of patients with both types of diabetes. This altered function is more severe in older patients. The enzyme substitution might have an important role in the treatment of diabetic patients with higher age, severe neuropathy and unstable glycemic control.

Daily blood pressure variations in patients with type 1 diabetes mellitus and nephropathy

То study a relationship between systemic hemodynamic parameters, albuminuria, and autonomic dysfunction in patients with type 1 diabetes mellitus (DM-1) without obvious nephropathy, the authors examined 55 patients in the inpatient setting. Twenty-nine patients had a normal urinary albumin excretion (CAE), 26 patients had microalbuminuria. 24-hour blood pressure monitoring (24-h BPM) was occillometrically made. The average daily, average diurnal and nocturnal values of systolic and diastolic blood pressure (BP) were significantly higher in DM-1 patients with microalbuniuria than in those with normal UAE. Routine autonomic cardiovascular tests showed that the incidence and severity of autonomic neuropathy were also higher in patients with microalbuminuria. Arterial hypertension (AH) diagnosed in compliance with the 24-h BPM criteria was detected. in 17.2%) of the DM-1 patients with normal UAE and in 42.3%) of the patients with microalbuminuria. According to the data of 24-h BPM, the incidence of arterial hypertension was 1.7 times as high as that evidenced by single BP measurements. The specific feature of circadian hemodynamic variations in patients with DM-1 was a low nocturnal BP decrease. 37.9%) of the patients with normoalbuminuria and 61.5%) of the patients with microalbuminuria had no normal (&gt;10%)) nocturnal BP lowering. Stepwise regression analysis has ascertained that in patients with DM-1 without obvious nephropathy, systemic hemodynamic disorders are associated with albuminuria, autonomic dysfunction, and glycemic monitoring quality.

Autonomic neuropathy in end-stage cirrhotic patients and evolution after liver transplantation

Autonomic neuropathy (AN), which is frequently observed in cirrhosis patients, has been associated with a higher mortality. We have prospectively evaluated the prevalence of AN, its relationship with the degree of liver dysfunction and circulatory disturbances, and the evolution of AN after liver transplantation (LT) in 62 end-stage liver cirrhosis patients. AN was evaluated by seven cardiovascular tests assessing sympathetic or parasympathetic function before and 6 months after LT. Patients were classified as showing absent (A), early (E), or definite dysfunction (D). AN appeared in 67.7% of cases (E: 24.2%, D: 43.5%) without relation to liver disease etiology. Parasympathetic dysfunction was more prevalent than sympathetic dysfunction (59.7% vs. 20.9%). AN was significantly related to Child-Pugh score. Hyperdynamic circulation was more marked in the D than the A group as shown by a greater cardiac output (CO)(9 vs. 7.3 L/min) and a lower peripheral resistance (SVR)(666 vs. 866 dyn.s.cm −5). Moreover, AN scores significantly correlated with CO and SVR. Overall the prevalence of AN decreased 6 months after LT (67.7 % vs 48%) due to a significant reduction in definite AN (43.5 vs. 14.8%; P < .05). AN improved in 70% of cases after LT. Sympathetic dysfunction remained in only one patient. We conclude that AN is frequent in liver transplant candidates; its severity is associated with the degree of liver failure. Systemic circulatory disturbances seem to correlate with the severity of AN. AN is clearly improved by LT. The evaluation of AN may contribute to a better selection of LT recipients.

Postprandial but not fasting upper gastrointestinal dysmotility correlates with the severity of autonomic neuropathy in diabetes mellitus

Postprandial but not fasting upper gastrointestinal dysmotility correlates with the severity of autonomic neuropathy in diabetes mellitus

Cardiovascular autonomic tests in diabetic patients with gastroparesis.

The aim of this report was to study the cardiovascular autonomic tests in the evaluation of diabetic patients with gastroparesis. Forty diabetic subjects were divided into two groups: one group with gastroparesis (GP, n = 20) and another group paired by age and duration of diabetes without any complaint of autonomic neuropathy (DC, n = 20). They were evaluated clinically and submitted to a battery of five cardiovascular autonomic tests. The presence and severity of autonomic neuropathy were defined according to the number of normal cardiovascular tests. Each test had a score: zero (normal), one (borderline) and two (abnormal). The GP group showed a higher abnormal total score in the cardiovascular autonomic test than the group without any complaint (6.6 +/- 3.0 vs. 2.7 +/- 1.4, p < 0.01). These data suggest that diabetic with gastroparesis presents more abnormal cardiovascular autonomic tests than diabetic without autonomic neuropathy and these tests should be included in the evaluation of diabetic patients with gastroparesis.

Bronchial hyperreactivity in patients with familial amyloidotic polyneuropathy and autonomic neuropathy.

To investigate the role of autonomic regulation on airway reactivity, we performed bronchial inhalation tests of methacholine (MCh) and histamine (Hist) in Japanese patients with familial amyloidotic polyneuropathy (FAP) and autonomic neuropathy. First we examined the FEV1 and Raw in seven patients with FAP and in six normal subjects, then we administered aerosols of increasing concentrations of MCh (0.075 to 25 mg/ml) at about 5-min intervals via a nebulizer controlled by a dosimeter. We measured the FEV1 until either the concentration of MCh producing a 20% reduction from the basal value (PD20) or the maximal concentration was reached. Five of the seven patients with FAP showed bronchial hyperreactivity to MCh, and PD20 to MCh was significantly lower than that of the normal subjects (p < 0.01). Furthermore the PD20 tended to correlate inversely with the severity of autonomic neuropathy (p = 0.052). The bronchial hyperreactivity to MCh was completely blocked by pretreatment inhalation of ipratropium bromide, suggesting the muscarinic receptor-mediated mechanism. Of these five patients with hyperreactivity to MCh, three with low PD20 to MCh (< 50 units) did not respond to Hist, but two with high PD20 (> 50 units) to MCh did, suggesting different mechanisms of hyperreactivity to MCh and Hist in FAP. The PD20 to Hist significantly correlated inversely to the PD20 to MCh (p < 0.05). Histochemical examination revealed marked amyloid deposition in the vagus nerves and tracheal wall in an autopsied patient with FAP and severe autonomic symptoms. These data suggest that patients with FAP and advanced autonomic neuropathy have bronchial hyperreactivity to MCh and/or Hist, probably because of denervation supersensitivity resulting from amyloid deposition in the peripheral autonomic nerves of the airways.

Pancreas transplantation restores epinephrine response and symptom recognition during hypoglycemia in patients with long-standing type I diabetes and autonomic neuropathy.

Impaired epinephrine secretion and symptom unawareness are characteristic of severe hypoglycemia in individuals with long-standing type I diabetes. Recently, the avoidance of clinical hypoglycemia has been reported to improve epinephrine and symptom responses to hypoglycemia in type I patients. However, the extent to which these defects can be restored in individuals with long-standing type I diabetes and autonomic neuropathy has not been assessed, nor has it been determined whether pancreas transplantation, which not only obviates hypoglycemia but also prevents hyperglycemia, results in the complete recovery of either epinephrine response or symptom awareness during insulin-induced hypoglycemia. We performed stepped hypoglycemic clamp studies in successful pancreas transplantation recipients to assess epinephrine and other counterregulatory hormone responses during hypoglycemia and to determine the degree to which hypoglycemic symptom recognition could be restored. Thirteen pancreas transplant recipients and matched control subjects were studied utilizing stepped hypoglycemic clamp protocol to achieve target glucose levels of 3.9, 3.3, 2.8, and 2.2 mmol/l (70, 60, 50, and 40 mg/dl, respectively). Plasma epinephrine response was significantly greater in healthy control subjects and pancreas transplant patients compared with type I subjects at the glucose plateaus of 3.9, 3.3, and 2.8 mmol/l. However, epinephrine response in pancreas transplant recipients was significantly less than that seen in either healthy control subjects or nondiabetic kidney transplant recipients at each of these glucose plateaus. The magnitude of the epinephrine response in pancreas transplant type I patients did not correlate with either the duration of diabetes, the duration of transplantation, or the measures of autonomic nerve function. Hypoglycemic symptom recognition was significantly greater in pancreas transplant subjects than type I patients and did not differ between pancreas transplant and control groups. No improvement in norepinephrine response was observed after pancreas transplantation, while glucagon responses to hypoglycemia were normalized in pancreas transplant patients. In conclusion, these studies uniquely demonstrate that successful pancreas transplantation improves epinephrine response and normalizes hypoglycemia symptom recognition in patients with long-standing diabetes and established autonomic neuropathy. No correlation was observed between the severity of autonomic neuropathy or the duration of diabetes and the recovery of either the epinephrine or symptom responses to hypoglycemia.

Gastric myoelectrical activity in patients with type I diabetes mellitus and autonomic neuropathy

In patients with diabetes mellitus and gastroparesis, dysrhythmias of gastric myoelectrical activity, especially tachygastrias, are thought to be involved in the pathogenesis of dyspeptic symptoms. Using surface electrogastrography we studied the prevalence of these abnormalities, and their relationships to dyspeptic symptoms and the extent of cardiac autonomic neuropathy in 30 euglycemic patients with type I diabetes mellitus and 12 controls. Neither in the fasting nor in the postprandial state were differences in mean frequency of gastric electrical control activity and its variability found between patients and controls. In the fasting state, the power content of the 3 cpm component in the power spectrum of the electrogastrogram was even higher in patients than in controls (P = 0.049). In the fasting state, second harmonics of the 3 cpm fundamental gastric signal were seen more often in patients than in controls (P = 0.03). In patients with symptoms during the study, no second harmonics were found after the meal. The postprandial/fasting power ratio was decreased in patients with symptoms during the study as compared to patients without symptoms and controls (P < 0.05). The incidence of dysrhythmias, such as tachygastrias and bradygastrias, was not higher in patients than in controls (17% and 8%, respectively). No correlation was found between electrogastrographic parameters and the severity of autonomic neuropathy or dyspeptic symptoms scored before the study. In conclusion, this study has shown that patients with type I diabetes mellitus and autonomic neuropathy studied under euglycemic conditions do not have grossly disturbed myoelectrical activity, except when symptomatic during the study.

High Frequency of Human Immunodeficiency Virus—Associated Autonomic Neuropathy and More Severe Involvement in Advanced Stages of Human Immunodeficiency Virus Disease

We conducted a controlled trial to determine frequency and severity of autonomic neuropathy in patients infected with the human immunodeficiency virus (HIV). We studied 25 HIV-seropositive patients and 10 seronegative controls in HIV risk groups by means of five cardiovascular tests, and autonomic neuropathy was graded with a scoring system. The overall autonomic test score differed between patients and controls and was higher in patients with advanced (Centers for Disease Control class IV) disease than in those with earlier (class II or III) HIV disease. Of the patients, 60% had findings of autonomic dysfunction. Our data demonstrate a high prevalence of autonomic neuropathy in HIV-infected patients. Advanced HIV disease is associated with more severe involvement than earlier disease states.

The Reflex Control of Vasopressin in Haemodialysis Patients

We studied the reflex arginine vasopressin (AVP) response to hypotensive, isosmotic fluid subtraction (by isolated UF) in 14 uraemic patients on renal dialysis treatment: five with normal autonomic function and nine with autonomic involvement of various degrees. Fluid subtraction caused a comparable mean arterial pressure (MAP) decrease in the two groups. The reduction in right atrial pressure was inversely related with the severity of autonomic neuropathy (rs = -0.72, P = 0.004), being distinctly attenuated in the second group (P = 0.006). Plasma arginine vasopressin increased similarly in patients with normal autonomic function and in those with autonomic involvement. The response of patients with haemodialysis hypotension was similar to that of other patients. Reflex control of arginine vasopressin is preserved even in the presence of afferent/central neuropathy or more advanced, widespread autonomic damage in uraemic man. The data suggest that it is unlikely that altered release of arginine vasopressin is involved in the pathogenesis of haemodialysis hypotension.

Medial arterial calcification and diabetic neuropathy

The aim of this study was to detect linear arterial calcification (Mönckeberg's sclerosis) localized in feet, ankles, legs, knees and hands in an attempt to correlate the extent of calcification with the presence and severity of autonomic neuropathy as well as with microangiopathy (proliferative retinopathy, proteinuria greater than 200 mg/die) and peripheral neuropathy. Typical linear calcification were observed in 37 out of 41 (90.2%) patients with autonomic neuropathy and in none of those without autonomic neuropathy (p less than 0.001). These 37 patients were divided into two subgroups by cluster analysis: Subgroup A, including 18 subjects with calcification length ranging from 8 to 26 cm and moderate autonomic neuropathy, and Subgroup B, including 19 subjects with calcification length between 58 and 126 cm and severe autonomic neuropathy (p less than 0.0001 by Spearman's test). No difference in the length of arterial calcification was detected between patients with proteinuria greater than 200 mg/24h and/or proliferative retinopathy and patients without these complications. A possible relationship between arterial calcification and peripheral neuropathy is difficult to evaluate; in fact, the majority of subjects having autonomic neuropathy had peripheral neuropathy, too. Vice versa, around 10% of patients without peripheral neuropathy but with autonomic neuropathy did not have Mönckeberg's sclerosis. Autonomic neuropathy is the principal factor responsible for calcification of the arterial media, and in addition the severity of the neuropathy, rather than the patient's age or the known disease duration seems to determine the extent of calcification.

Evaluation of oral cisapride and metoclopramide in diabetic autonomic neuropathy: an eight‐week double‐blind crossover study

Nineteen diabetic patients with autonomic neuropathy were enrolled in a double-blind crossover study of cisapride, metoclopramide and placebo. Symptoms were evaluated from diary cards and from assessments undertaken at the end of each eight week treatment period. Measurements of oesophageal transit, gastric emptying and whole gut transit were made before treatment began and at the end of each treatment period. Three patients dropped out early in the study, and the results from 16 patients were analysed. The severity of autonomic neuropathy, judged from cardiovascular reflex tests, correlated with delayed oesophageal transit and prolonged gastric emptying, but abnormal oesophageal transit and gastric emptying were often unrelated to the presence of upper gastrointestinal symptoms. Neither cisapride nor metoclopramide had a statistically significant effect on oesophageal transit, gastric emptying or whole-gut transit, nor was any significant effect on symptoms identified, although a trend towards reduced nausea and vomiting with metoclopramide and reduced epigastric fullness and diarrhoea with cisapride was suggested. Upper gastrointestinal symptoms correlate poorly with objective abnormalities of gastrointestinal motor function in diabetes. In consequence, the symptomatic benefit to be expected from correction of these motor abnormalities remains uncertain.