MRI findings in patients with acute autonomic and sensory neuropathy

Acute autonomic and sensory neuropathy (AASN), characterized by acute onset of extensive autonomic dysfunction and severe sensory deficits, was first described by Colan et al. (1978). We present two female patients with AASN in whom magnetic resonance imaging (MRI) confirmed such findings in the posterior column of the spinal cord. One patient was a 44-year-old woman who developed an upper respiratory tract infection followed in 2 weeks by numbness of the limbs and gait disturbance. There was orthostatic hypotension with syncope, paretic ileus, anhidrosis and urinary retention. There was a loss of sensation over the entire body, including the face, and deep tendon reflexes were generally absent. Neurophysiologic studies showed that sensory nerve action potentials and SSEPs were not evoked in the nerves examined. Sural nerve biopsy demonstrated severe axonal degeneration of the myelinated and unmyelinated fibers. Our second patient, a 27-year-old woman, exhibited similar clinical and laboratory features. The autonomic dysfunction in both patients improved gradually without drug treatment, but the sensory deficits--predominantly a loss of deep sensation--persisted for several years. In both patients, MRI revealed the T2*-weighted high intensity area in the fasciculus gracilis of the posterior column of the spinal cord. Such high intensity areas were present in all spinal segments. The severe and persistent sensory disturbance in these patients may have been caused by a lesion of the posterior column of the spinal cord following the involvement of the dorsal root ganglion cells, or ganglioneuronopathy, as demonstrated by MRI.     

Ambulatory blood pressure measurement in type-II diabetic patients with autonomic neuropathy

The aim of our study was to access the 24-hr ambulatory blood pressure (BP) in diabetic patients with autonomic neuropathy (AN). Twenty-two NIDDM patients without hypertension, being treated with sulfonylureas, were studied. The 24-hr ambulatory blood pressure recordings were performed using portable non-invasive automatic system. Autonomic neuropathy was assessed by standard cardiovascular reflex tests. There were ten patients with and 12 without AN, matched for age, body mass index, duration of diabetes and glycemic control. Mean BP increased at night in four of the subjects with AN and decreased in the remaining 18 patients. The group of subjects with nocturnal increases in BP had more severe autonomic nerve dysfunction compared with those with decreases in nocturnal BP. No significant difference between clinical and ambulatory day-time measurements was found. In three patients with AN after 5 weeks intensified therapy. 24-hr BP did not show any significant difference.     

Total cardiac denervation in diabetic autonomic neuropathy

Total loss of the autonomic regulation of heart rate is described in a 28-year-old diabetic with extensive autonomic neuropathy. The patient had an almost fixed heart rate that barely responded to any of the tests that stimulate or inhibit the autonomic nerves. Its behavior was similar to that of the transplanted heart.     

Cholecystokinin and pancreatic polypeptide release in diabetic patients with and without autonomic neuropathy

The present study was undertaken to investigate postprandial responses of cholecystokinin (CCK) and pancreatic polypeptide (PP) and their interrelationship in patients with diabetes mellitus (DM) with and without autonomic neuropathy (AN). Twenty-two patients with DM (seven with AN and 15 without AN) and 14 age-matched healthy controls were studied. AN was diagnosed according to several tests of cardiovascular autonomic function. CCK and PP plasma levels were measured by specific radioimmunoassays before and at several time points after the oral administration of a test meal. Basal CCK plasma levels in DM patients were normal, whereas basal PP plasma levels were increased (139 +/- 18 vs 72 +/- 7 pg/ml; P < 0.01). Integrated postprandial CCK response was increased in DM patients (208 +/- 27 vs 110 +/- 14 pmol/liter/2 hr; P < 0.05), mainly due to the patients with AN. Postprandial PP response was increased in DM patients without AN (37,273 +/- 5241 vs 13,418 +/- 3299 pg/ml/2 hr; P < 0.001) but not in those with AN (8887 +/- 3461 pg/ml/2 hr). Moreover, PP response was closely (P < 0.002) correlated with the degree of AN. A direct and linear correlation between postprandial CCK and PP responses was found in healthy controls (r = 0.78; P < 0.005) but not in DM patients. We conclude that the CCK response to a meal is increased in diabetic patients with AN, whereas the PP response is increased only with an intact autonomic nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)     

Provocation of postural hypotension by insulin in diabetic autonomic neuropathy

The effect of insulin administration on blood pressure has been investigated in eight diabetes with autonomic neuropathy. Systolic and diastolic pressures fell considerably after insulin in all of them. This effect was aggravated by tilting to the vertical position. Five patients fainted when upright with systolic blood pressures less than 50 mm. Hg. This hypotensive effect of insulin occurs whether it is administered intravenously, intramuscularly, or subcutaneously. The onset of the effect is almost immediate after intravenous insulin, is progressive, and may last for several hours. It coincides with a falling blood glucose level and occurs before hypoglycemic levels are reached, and it may be present when the blood glucose level is still elevated. Diurnal variations of postural hypotension have been recorded in some patients, the standing blood pressure falling with the onset of insulin action and rising again as the latter declines. Some of our patients were unable to differentiate between symptoms of hypoglycemia and hypotension. Postural hypotension may account for some episodes of sudden loss of consciousness without warning, usually attributed to hypoglycemia.     

Prevalence of renal disease in elderly hypertensive patients with cardiovascular problems

Renal vascular damage caused by arterial hypertension participates in the alterations to systemic vascular function and structure. Nephrosclerosis seems to run in parallel with systemic atherosclerosis, which accounts for the increased cardiovascular morbidity and mortality seen in hypertensive patients. Parameters indicating the existence of an alteration in renal function (increased serum creatinine, proteinuria and microalbuminuria) are independent predictors for an increased cardiovascular morbidity and mortality. Hence, parameters of renal function have to be considered in any stratification of cardiovascular risk in hypertensive patients.     

A severe case of acute autonomic and sensory neuropathy

This study was conducted to explore whether anthropometric indices of obesity are associated with atherogenic risk factors in young adult working women in Japan. The subjects were 492 women in an occupational setting. Predictor variables were body mass index (BMI), the sum of triceps and subscapular skinfold thickness (SFT), and the waist to hip ratio (WHR). Outcome variables were serum total cholesterol, triglyceride and blood pressures. The average age of the subjects was 26.3 (SD 3.9) years. The upper quartiles of BMI and SFT were significantly associated with all atherogenic risk factors, while the upper quartiles of WHR were not. Multiple comparisons revealed the 4th quartiles of BMI (> 22.25) and SFT (> 39 mm) to have significantly higher values for all atherogenic risk factors. We found that BMI and skinfold thickness were more relevant to the prediction of atherogenic risk factors than WHR in young adult Japanese women.     

Idiopathic autonomic neuropathy. An important disease in differential diagnosis

HISTORY AND CLINICAL FINDINGS: Two weeks after a mild viral infection a previously healthy 22-year-old woman developed ileus, a severe abnormality of orthostasis, sicca (Sj?gren's) syndrome, bilateral miosis and generalized hyphidrosis. Pelvic endoscopy and laparotomy failed to clarify the cause of the mechanical ileus. INVESTIGATIONS: Neurological examination revealed an isolated abnormality of the autonomic system, involving both sympathetic and parasympathetic components. Schellong's, Schirmer's and the ninhydrin tests were markedly abnormal. There was no heart rate variation on breathing and a post-Valsalva hypotensive blood pressure overshoot. Further tests failed to find a cause of the neuropathy. DIAGNOSIS, TREATMENT AND COURSE: The diagnosis of idiopathic panautonomic neuropathy (pandysautonomia) was made. The ileus and hypotension were treated symptomatically with neostigmine, cisapride, midodrine and, initially, with enemas, nasogastric tube feeding and parenteral fluids. The patient was free of symptoms at follow-up examination a year later. CONCLUSIONS: Idiopathic autonomic neuropathy should be considered in the differential diagnosis of functional abnormalities of the sympathetic and/or parasympathetic nervous system, especially in previously healthy young people, in the presence of orthostatic, unexplained gastrointestinal and hidrotic symptoms.     

Variability of the circadian heart rate in diabetes mellitus-related autonomic neuropathy

For assessing the alterations of circadian heart rate variability 66 diabetic patients (age: 52.9 +/- 1.0 years; x +/- SEM) and 23 control subjects (age: 52.7 +/- 1.7 years) were investigated using 24 hours Holter monitoring. Autonomic neuropathy (AN) was evaluated by tests for cardiovascular reflexes and patients were classified as being without AN (n = 26), having mild (n = 25) or definitive (n = 15) signs of AN. Minimal heart rates were significantly higher while maximal heart rates were considerably lower in patients with than without AN (60 +/- 2 min-1 versus 54 +/- 1, min-1, p < 0.05 and 125 +/- 4 min-1 versus 146 +/- 4 min-1, p < 0.01). Diabetic groups were comparable regarding values of averaged heart rates. The difference between the mean waking and sleeping averaged heart rates was the smallest in diabetic patients with definitive signs of AN (9 +/- 2 min-1) differing from those of control subjects (17 +/- 1 min-1, p < 0.01) and diabetic patients without (17 +/- 1 min-1, p < 0.001) or with mild (15 +/- 1 min-1, p < 0.05) signs of AN. Characteristic alteration, i.e. a reduction in circadian heart rate variability could be found in diabetic patients with signs of AN. This phenomenon has primarily been a consequence of more frequent sleeping heart rates due to dominant impairment in cardiac parasympathetic innervation.     

PC-based noninvasive measurement of the autonomic nervous system. Detecting the onset of diabetic autonomic neuropathy

In this review, hyposensitization or immunotherapy will be discussed. The earliest immunotherapy was applicated in allergic respiratory diseases such as asthma and rhinitis. The most important indication has become the treatment of hymenoptera allergy. Some less frequently indications are associated with drug allergy. Immunotherapy is most frequently indicated in IgE mediated diseases, but new applications for cell mediated reactions will be described. With the introduction of molecular biology in allergology new theoretical possibilities emerged: use of peptide antigens, recombinant allergens, anticytokines.... Unfortunately, these newer approaches did not (yet) cause a breakthrough. The cost of these products will be a major draw back, even when ethical problems for using them on a larger scale will have been solved.     

Scintigraphic assessment of regionalized defects in myocardial sympathetic innervation and blood flow regulation in diabetic patients with autonomic neuropathy

OBJECTIVES: This study sought to evaluate whether regional sympathetic myocardial denervation in diabetes is associated with abnormal myocardial blood flow under rest and adenosine-stimulated conditions. BACKGROUND: Diabetic autonomic neuropathy (DAN) has been invoked as a cause of unexplained sudden cardiac death, potentially by altering electrical stability or impairing myocardial blood flow, or both. The effects of denervation on cardiac blood flow in diabetes are unknown. METHODS: We studied 14 diabetic subjects (7 without DAN, 7 with advanced DAN) and 13 nondiabetic control subjects without known coronary artery disease. Positron emission tomography using carbon-11 hydroxyephedrine was used to characterize left ventricular cardiac sympathetic innervation and nitrogen-13 ammonia to measure myocardial blood flow at rest and after intravenous administration of adenosine (140 microg/kg body weight per min). RESULTS: Persistent sympathetic left ventricular proximal wall innervation was observed, even in advanced neuropathy. Rest myocardial blood flow was higher in the neuropathic subjects (109 +/- 29 ml/100 g per min) than in either the nondiabetic (69 +/- 8 ml/100 g per min, p < 0.01) or the nonneuropathic diabetic subjects (79 +/- 23 ml/100 g per min, p < 0.05). During adenosine infusion, global left ventricular myocardial blood flow was significantly less in the neuropathic subjects (204 +/- 73 ml/100 g per min) than in the nonneuropathic diabetic group (324 +/- 135 ml/100 g per min, p < 0.05). Coronary flow reserve was also decreased in the neuropathic subjects, who achieved only 46% (p < 0.01) and 44% (p < 0.01) of the values measured in nondiabetic and nonneuropathic diabetic subjects, respectively. Assessment of the myocardial innervation/blood flow relation during adenosine infusion showed that myocardial blood flow in neuropathic subjects was virtually identical to that in nonneuropathic diabetic subjects in the distal denervated myocardium but was 43% (p < 0.05) lower than that in the nonneuropathic diabetic subjects in the proximal innervated segments. CONCLUSIONS: DAN is associated with altered myocardial blood flow, with regions of persistent sympathetic innervation exhibiting the greatest deficits of vasodilator reserve. Future studies are required to evaluate the etiology of these abnormalities and to evaluate the contribution of the persistent islands of innervation to sudden cardiac death complicating diabetes.     

Association of relative nocturnal hypertension and autonomic neuropathy in insulin-dependent diabetic children

Twenty-four hour BP and heart rate measurements were carried out in fourteen newly diagnosed-, and in twenty-eight diabetics with 5-13 years of duration; and in eight healthy control children. Mean arterial BP rose at night in five-, fell slightly (less than 10%) in five- and fall markedly (more than 10%) in eighteen diabetics with longer duration of the disease. The diurnal-nocturnal difference of mean arterial pressure was significantly lower in the groups with nocturnal BP rise and slight nocturnal BP fall, compared to the control group (< 0.001; p < 0.01, respectively). The diurnal-nocturnal differences of heart rates were significantly lower in diabetics with relative "nocturnal hypertension" compared to the control group (p < 0.05). The presence of subclinical signs of diabetic autonomic neuropathy was significantly higher in patients with nocturnal BP rise and slight nocturnal BP fall compared to patients with marked nocturnal BP fall and newly diagnosed diabetics (chi squared p = 0.02 and p = 0.01, respectively). In conclusion, the prevalence of autonomic symptoms in diabetic children could be related to change in diurnal/nocturnal arterial BP, however longitudinal studies of ABPM are needed to define, whether patients with abnormal BP profiles are candidates for the development of diabetic vascular disease.     

Corrected QT interval in relation to the severity of diabetic autonomic neuropathy

The aim of this study was to investigate to what extent the existence of objective signs of diabetic autonomic neuropathy affects the corrected QT interval (QTc) in diabetic subjects. A total of 105 diabetic subjects (type 1, n = 53; type 2, n = 52) as well as 40 matched (by age and sex) control subjects were studied. All subjects underwent the battery of five Ewing tests. Autonomic neuropathy was diagnosed if two of the five tests were abnormal. In addition, the result of each test was considered as normal (grade = 0), borderline (grade = 1) or abnormal (grade = 2), and on the basis of the sum of the scores we calculated a total score for autonomic neuropathy. The QTc interval was measured at rest, and a value > 440 ms was considered abnormal. The QTc interval was significantly more prolonged in diabetic persons with autonomic neuropathy than in those without neutopathy and in control subjects: 408.4 +/- 24.2 ms vs. 394.6 +/- 27.9 ms and 393.6 +/- 25.5 ms respectively (P = 0.001). Furthermore, multivariate analysis controlling for age, sex, systolic and diastolic blood pressure, body mass index (BMI), waist-hip ratio (WHR), smoking, type and duration of diabetes, type of treatment, HBA1c and total score of autonomic neuropathy eliminated the role of all these factors as potential confounders except for the total score of autonomic neuropathy, which was found to affect QTc interval independently and significantly (P = 0.012). In summary, the present study confirmed the well-known relation between autonomic neuropathy and QTc interval; in addition, it showed that QTc prolongation is associated with major degrees of autonomic neuropathy.     

Prevalence and risk factors for hepatitis C virus infection in continuous ambulatory peritoneal dialysis patients

BACKGROUND: Studies on hepatitis C virus antibodies (Anti-HCV) in CAPD patients are scarce and include a small number of patients. Nevertheless, risk factors related to Anti-HCV in these patients are still subject to controversy. Purpose of the study. To analyse the incidence and risk factors associated with the presence of Anti-HCV in CAPD patients. METHODS: We studied 255 patients from five different treatment centres of our region. The analysis was repeated after excluding 161 patients who had previously received haemodialysis treatment at least once. Anti-HCV testing was made by the 2nd-generation ELISA: As a supplementary test we used RIBA-4 in three centers and INNOLIA in the other two. Risk factors were analysed using logistic regression model for multivariate analysis. RESULTS: In the whole group, 29 patients (11.4%) were anti-HCV positive. Logistic regression analysis determined the following variables as independent risk factors: hepatitis previous to CAPD (P<0.001, odds ratio (OR):44.9), Anti HBc positivity (P=0.019, OR:9. 24), blood transfusions previous to CAPD (P=0.015, OR:1.05) and CAPD duration were excluded, the prevalence of HCV antibodies was 8.5% (8/94). In this group multivariate analysis showed that Anti-HCV positivity correlated with hepatitis previous to CAPD (P<0.0003, OR: 126) and Anti HBc positivity (P=0.002, OR:41.9). CONCLUSIONS: Our prevalence of hepatitis C virus (HCV) infection in CAPD patients was lower than other renal replacement therapy modalities, and correlated to events occurring mainly before starting CAPD treatment. This technique could be considered as low risk for HCV infection.     

Cardiorespiratory failure and diabetic autonomic neuropathy: a case report

Advanced autonomic neuropathy in diabetic patients is associated with homeostatic cardiovascular response. Sympathetic compensation diminishes and the organism becomes more susceptible to the depressant effect of certain drugs. The incidence of undesirable cardiovascular effects (bradycardia, hypotension and sudden heart failure) during anesthesia is higher in such patients. We report the case of a woman with diabetes who suffered two episodes of sudden heart failure after brachial plexus block through the axilla, followed one year later by sudden heart failure during general anesthesia for kidney transplantation. The possible contributing mechanisms are described.     

Prevalence of movement disorders in institutionalized elderly

The proportion of the population over age 65 years is steadily increasing in Canada and the elderly who are unable to live independently are frequently institutionalized in chronic care facilities. We report our observations on movement disorders (MD) in an institutionalized elderly population of Saskatchewan. A representative sample of 67 subjects aged > or = 65 years had a detailed neurological evaluation on three separate occasions. MD were detected in 13 (19%) cases. The majority, 11 (16%), were females. Seven (10%) had essential tremor, 4 (6%) Parkinson's disease and 2 (3%) had drug-induced parkinsonism.     

Neuronal nicotinic ACh receptor antibody in subacute autonomic neuropathy and cancer-related syndromes

BACKGROUND: Autoantibodies specific for the acetylcholine receptor (AChR) of skeletal muscle (containing the alpha1 subunit) impair neuromuscular transmission in myasthenia gravis (MG). AChRs mediating fast synaptic transmission through autonomic ganglia are structurally similar to muscle AChR, but contain the alpha3 subunit. We propose that ganglionic AChR autoimmunity may cause dysautonomia. OBJECTIVE: To test serum of patients with autonomic neuropathy for autoantibodies of neuronal ganglionic AChR specificity. METHODS: We developed an immunoprecipitation radioassay by complexing epibatidine (125I-labeled high affinity agonist) to a Triton X-100-solubilized AChR antigen from peripheral neuroblastoma membranes. Monoclonal rat immunoglobulins (IgG) specific for muscle or neuronal AChRs validated the assay's specificity. We tested serum from 52 healthy subjects, 12 patients with subacute autonomic neuropathy, and 248 patients with other neurologic disorders. RESULTS: Twelve patients had antibodies that bound unequivocally to ganglionic AChR. Five had subacute autonomic neuropathy, and three (of six tested) had Isaacs' syndrome; four of these eight had a carcinoma (lung, bladder, rectum, thyroid). The remaining four seropositive patients (two Lambert-Eaton syndrome, one dementia, one sensory neuronopathy) all had Ca2+ channel antibodies and three had small cell lung carcinoma. No healthy subject had ganglionic AChR antibodies, nor did 62 patients with MG and muscle AChR antibodies. CONCLUSION: Neuronal AChR antibodies are a novel serologic marker of neurologic autoimmunity. The pathogenicity of neuronal AChR autoantibodies in autonomic neuropathy, Isaacs' syndrome, or other neurologic disorders remains to be shown, as has been demonstrated for muscle AChR antibodies in MG. An autoimmune and potentially paraneoplastic etiology is implicated in seropositive patients.     

Muscle sympathetic nerve activity is reduced in IDDM before overt autonomic neuropathy

Studies of heart-rate variability have demonstrated that abnormal cardiac parasympathetic activity in individuals with IDDM precedes the development of other signs or symptoms of diabetic autonomic neuropathy. To determine whether IDDM patients have impaired sympathetic activity compared with normal control subjects before the onset of overt neuropathy, we directly recorded MSNA. We also examined the effects of changes in plasma glucose and insulin on sympathetic function in each group. MSNA was recorded by using microneurographic techniques in 10 IDDM patients without clinically evident diabetic complications and 10 control subjects. MSNA was compared during a 15-min fasting baseline period and during insulin infusion (120 mU.m-2.min-1) with 30 min of euglycemia. A cold pressor test was performed at the end of euglycemia. Power spectral analysis of 24-h RR variability was used to assess cardiac autonomic function. IDDM patients had lower MSNA than control subjects at baseline (8 +/- 1 vs. 18 +/- 3 burst/min, P < 0.02). MSNA increased in both groups with insulin infusion (P < 0.01) but remained lower in IDDM patients (20 +/- 3 vs. 28 +/- 3 burst/min, P < 0.01). In the IDDM group, we found no relationships between MSNA and plasma glucose, insulin, or HbA1c concentrations. BP levels did not differ at rest or during insulin. Heart-rate variability and the MSNA response to cold pressor testing in IDDM patients did not differ from those in healthy control subjects. IDDM patients had reduced MSNA at rest and in response to insulin. The lower MSNA is not attributable to differences in plasma glucose or insulin, but, rather, is most likely an early manifestation of diabetic autonomic neuropathy that precedes impaired cardiac parasympathetic control.