Parasympathetic Function Tests Research Articles

Association of Diabetic Autonomic Neuropathy with Red Blood Cell Aldose Reductase Activity

Activation of polyol pathway based on increased activity of aldose reductase (AR) has been implicated in the development of diabetic complications including diabetic autonomic neuropathy (DAN). The relationship between DAN and hyperglycemia-induced activation of polyol pathway is still uncertain. In the present study, we investigate the association between aldose reductase activity and diabetic autonomic neuropathy by measuring AR level in red blood cells (RBC). In this study, 145 subjects with diabetes with or without DAN and 32 subjects without diabetes have been included. All subjects have been investigated for autonomic function tests and RBC aldose reductase activity. DAN was defined if results of any 2 of the tests of parasympathetic function were abnormal. RBC aldose reductase level was determined spectrophotometrically and expressed as unit/g of hemoglobin. The values were expressed as mean ± standard deviation, and ANOVA test has been applied for comparison between groups. RBC aldose reductase activity was found to be significantly higher in people with diabetes with autonomic neuropathy in comparison to people with diabetes without autonomic neuropathy and healthy individuals without diabetes. Aldose reductase (AR) level ranges from 0.8 units/g Hb to 14.2 units/g Hb. The mean AR level was 8.6±2.95 units in subjects of DM with autonomic neuropathy, while mean AR level was 4.1±1.78 units and 2.0±0.89 units in people with diabetes without neuropathy and normal healthy individuals, respectively (p<0.001). High aldose reductase activity is associated with the presence of autonomic neuropathy in subjects of type 2 DM.

A study of autonomic functions in the patients of episodic migraine

Background: Autonomic disturbances are common in the patients of migraine, predominantly sympathetic hypofunction was observed while parasympathetic system also showed abnormal behavioral response. There is no comprehensive study regarding these aspects in migraineurs in India. Aims & Objective: To study the state of autonomic nervous system in the patients of episodic migraine during interictal period. Materials and Methods: This case control study done employing a sample of 54 migraine cases selected from the outpatient department, GB Pant hospital Delhi. Selection of patients was based on the clinical diagnosis by neurologists and each case fulfilling the International headache society criteria 2004 irrespective of aura status. The control pool was formed by 30 normal healthy participants from Maulana Azad Medical College. All participants were aged between 20 to 40 years. Informed consent was taken from all the participants and the ethical clearance was obtained from the college. Sympathetic function tests: handgrip test, cold pressor Test, sympathetic skin response and parasympathetic function tests: resting heart rate, standing to lying Ratio, 30: 15 ratio, Valsalva Ratio and tachycardia Ratio. Assessment of the autonomic system was carried out during headache free interval. Results: Of the sympathetic tests, the sympathetic skin response showed a significant statistical difference between cases and controls while remaining parameters showed no statistical significance. Of the parasympathetic tests, none of them revealed any statistical significance between cases and controls. Conclusion: In contrast to many western studies which showed sympathetic hypofunction, we observed sympathetic hyperfunction during the interictal period, while parasympathetic system was normal. Key Words: Migrain

Assessment of parasympathetic autonomic functions in ulcerative colitis patients

Background: Ulcerative colitis has been reported to be associated with autonomic dysfunction, mainly of vagal involvement.&#x0D; Objectives: To Determine whether there is a parasympathetic dysfunction in ulcerative colitis patients in remission state or not.Results: For all of the three tests, patients group gave significantly lower results (P˂ 0.05) which was the least level of significance. Materials and methods: Three standardized tests of parasympathetic function, based on heart rate variation in response to certain stimuli (heart rate response to Valsalva maneuver, to deep breathing and to standing from supine position) were used on 54 ulcerative colitis patients in remission, and 41 healthy volunteers as a control group.&#x0D; Conclusion: Ulcerative colitis is associated with vagal dysfunction which could be a hidden cause for the underlying inflammatory status because of the recently established anti-inflammatory role of vagus nerve.

Cardiovascular autonomic function in lateral medullary infarction

Even though the medulla contains the baroreceptor regulatory centers, few studies have focused on the autonomic dysfunction of lateral medullary infarction (LMI). Therefore, cardiac parasympathetic and sympathetic functions were compared in LMI patients and age-matched controls. We prospectively recruited 25 LMI patients who had ipsilateral Horner's sign and cardiac autonomic function testing without a history of diabetes, cardiac disease, or previous stroke. Parasympathetic function tests included beat-to-beat heart rate variation during deep breathing, 30:15 heart rate ratio testing while standing, and the valsalva ratio. Sympathetic function tests included blood pressure during active standing and sustained handgrip. The composite autonomic score (CAS) was measured as a total of 10 points; parasympathetic dysfunction was designated as ≥3 points in the parasympathetic subscores and sympathetic dysfunction as ≥2 points in the sympathetic subscores. Multiple regression analysis was performed to predict parasympathetic or sympathetic dysfunction. The mean age and stroke risk factors of the study population were not significantly different between the LMI group (n = 25) and control group (n = 29). However, cardiac autonomic functions were significantly different in the groups: parasympathetic dysfunction (14 vs. 4 patients, p = 0.011) and sympathetic dysfunction (3 vs. 13 patients, p = 0.008). In univariate analysis, male-gender (p = 0.011), right-side involvement (p = 0.035) and ventral involvement (p = 0.007) were significantly associated with parasympathetic dysfunction (CAS subscore ≥3). In multivariable analysis, the ventral involvement remained to be the independent predictor for parasympathetic dysfunction (OR 16.0; 95% CI 2.2-118.3, p = 0.007). This study suggests that LMI patients are susceptible to cardiac parasympathetic dysfunction, especially in the ventral medulla.

English

ABSTARCT: Autonomic neuropathy has been reported in patients with alcoholic liver disease but information on its occurrence in patients with non-alcoholic liver disease is contradictory. To make the things more clear the present study was conducted to assess autonomic functions in patients with non-alcoholic liver disease and its relationships with the severity of liver damage. Autonomic function using five standard tests was examined in 50 cirrhotics. The extent of autonomic dysfunction was determined in the patients and a comparison between the characteristics of patients with and without autonomic neuropathy was made. Out of 50 patients 35 (70%) were found to have autonomic neuropathy The alteration of the parasympathetic function [20 out of 35(57%)] was significantly more frequent than that of sympathetic function [15(43%)]. The prevalence of autonomic neuropathy was more (80%) in patients with Child-Pugh grade C cirrhosis as compared to those having Child-Pugh grade B cirrhosis (54%). The results were clinically significant but statistically insignificant (p>0.05). It was seen that out of total 50 cases of non alcoholic cirrhosis, the majority (68%) were due to hepatitis C infection. A high prevalence of abnormalities in both sympathetic and parasympathetic function tests, and a poor relationship with liver function parameters, has been found in patients with non-alcoholic chronic liver disease.

The effect of smoking on the cardiovascular autonomic functions: a cross sectional study.

Smoking is a worldwide major cause of preventable morbidity and mortality. Smoking affects the cardiovascular system by several mechanisms. The present study was planned to study the effect of smoking on the cardiovascular autonomic functions among smokers. Hundred male subjects who were in the age group of 25 to 40 years, who included 50 smokers and 50 non - smokers who formed the control group were selected for the present study. The participant subjects were selected from among the staff members, residents and the patients from the routine OPD. Prior informed written consents were obtained from them after explaining to them, the procedure and the purpose of the study tests. The Cardiovascular Autonomic Function Tests were assessed by using a CANWIN AUTONOMIC ANALYSER which was available in the department. After applying the 'Z'-test for the difference between the two sample means, it was observed that there was a highly significant difference between the mean values of the para-sympathetic function tests among the smokers and the non - smokers (i.e. p<0.01) The Resting Heart Rate had significantly increased and the Expiration: Inspiration Ratio, the 30:15 Ratio (Response to standing) and the Valsalva Ratio had significantly decreased in the smokers as compared to those in the non - smokers. After applying the 'Z'-test for the difference between the two sample means, it was observed that there was no significant difference between the mean values of the Postural hypotension test (i.e. p>0.05) and that there was a highly significant difference between the mean values of the Sustained handgrip test in the smokers and the non - smokers (i.e. p<0.01).

Abnormal sympathetic hyper-reactivity in patients with myasthenia gravis: A prospective study

IntroductionPatients with myasthenia gravis, especially those in crises, are not infrequently observed to demonstrate wide fluctuation in heart rate and blood pressure. ObjectiveThis study was conducted to assess autonomic function in patients with myasthenia gravis. MethodsPatients with myasthenia gravis diagnosed on the basis of typical clinical details, edrophonium or neostigmine test, decremental response on repetitive nerve stimulation testing and anti acetyl choline receptor antibody testing, were compared with age and gender matched controls. Apart from detailed clinical evaluation, all subjects underwent tests of autonomic function, viz. heart rate and blood pressure response on orthostatic tests and isometric handgrip test, Valsalva maneuver, R–R interval variation (RRIV) and the sympathetic skin response (SSR). Results were compared with those in the control group using repeated measures ANOVA and the paired t-test. ResultsSixty-four patients (27 males, 37 females) with a mean age of 40.5±17years) with myasthenia gravis of an average 3±4years duration, and 241 normal controls were enrolled. On the orthostatic tests, patients showed rise in heart rate, systolic and diastolic blood pressure, as did controls, however, the rate and the duration of rise was significantly higher than in the controls (p<0.01). Similar difference between patients and controls, in rate of rise of these parameters was observed on the isometric hand grip test. No significant difference was observed between the two groups on tests of parasympathetic function (Valsalva ratio, RRIV). These effects could also partially be due to pyridostigmine, which all patients were receiving. ConclusionThis study suggests sympathetic hyper-reactivity in patients with myasthenia gravis, which could be responsible for serious hemodynamic instability in patients in crisis.

Relationship of gender and lipid profile with cardiac parasympathetic reactivity

Background: Lower heart rate variability has been proven to be associated with a greater risk for developing hypertension among normotensive men, and hypertension is one of the major risk factor of coronary heart disease. Hormonal factors in premenopausal women may cause variance in heart rate variability and impact lipid profile. Objectives: The study was designed to evaluate the relationship of gender and lipid profile with cardiac parasympathetic reactivity. Materials and Methods: Sixty premenopausal and 60 postmenopausal women along with 60 young and 60 elderly, age and body mass index (BMI) matched men without any apparent illness were selected. Cardiac parasympathetic reactivity during Valsalva maneuver, deep breath test, and 30:15 R–R interval ratios were studied and lipid profile analyzed. Results: Lipid profile showed significant increase in values of total cholesterol, low density lipoprotein (LDL), triglyceride, and significant decrease in high density lipoprotein (HDL) values in younger males when compared with premenopausal females and no difference in these parameters were noticed when comparison was done between elderly males and females. Deep breath test and 30:15 R–R interval ratios showed significant decrease in values in younger males when compared with age matched premenopausal females. Total cholesterol, triglyceride, LDL were negatively correlated with parasympathetic function tests; whereas HDL was positively correlated with parasympathetic function tests. Conclusion: Sex hormone levels may alter the autonomic nervous system response and lipid metabolismand lipids play an important role in modulation of autonomic functions.

Autonomic dysfunction in non-paraneoplastic sensory neuronopathy: beyond sensory abnormalities

Sensory neuronopathies (SN) represent a subgroup of peripheral nervous system disorders which are becoming increasingly recognized. Despite a few reports of autonomic dysfunction, this complication has not been fully appreciated. Autonomic function was quantified through tests of sympathetic and parasympathetic function (forming the Autonomic Tests Score, ATS), and through a 40-item questionnaire assessing autonomic symptoms (constituting the Autonomic Questionnaire Score, AQS). Twenty patients were enrolled. Forty-six age- and gender-matched controls were evaluated for the AQS and 15 for the ATS. All patients reported symptoms of autonomic dysfunction. Of the patients, 60% had one or more abnormal cardiovagal test, 60% orthostatic hypotension and 20% abnormal pupillary function. Their ATS was significantly different from the controls (p<0.0001). Neither the ATS nor AQS were different between groups of SN associated disorders. Autonomic dysfunction is a frequent and important complication in SN, and it does not seem to be related to a specific etiology, as previously thought.

Treatment‐induced diabetic neuropathy: A reversible painful autonomic neuropathy

To describe the natural history, clinical, neurophysiological, and histological features, and outcomes of diabetic patients presenting with acute painful neuropathy associated with glycemic control, also referred to as insulin neuritis. Sixteen subjects presenting with acute painful neuropathy had neurological and retinal examinations, laboratory studies, autonomic testing, and pain assessments over 18 months. Eight subjects had skin biopsies for evaluation of intraepidermal nerve fiber density. All subjects developed severe pain within 8 weeks of intensive glucose control. There was a high prevalence of autonomic cardiovascular, gastrointestinal, genitourinary, and sudomotor symptoms in all subjects. Orthostatic hypotension and parasympathetic dysfunction were seen in 69% of subjects. Retinopathy worsened in all subjects. Reduced intraepidermal nerve fiber density (IENFD) was seen in all tested subjects. After 18 months of glycemic control, there were substantial improvements in pain, autonomic symptoms, autonomic test results, and IENFD. Greater improvements were seen after 18 months in type 1 versus type 2 diabetic subjects in autonomic symptoms (cardiovascular p < 0.01; gastrointestinal p < 0.01; genitourinary p < 0.01) and autonomic function tests (p < 0.01, sympathetic and parasympathetic function tests). Treatment-induced neuropathy is characterized by acute, severe pain, peripheral nerve degeneration, and autonomic dysfunction after intensive glycemic control. The neuropathy occurred in parallel with worsening diabetic retinopathy, suggesting a common underlying pathophysiological mechanism. Clinical features and objective measures of small myelinated and unmyelinated nerve fibers can improve in these diabetic patients despite a prolonged history of poor glucose control, with greater improvement seen in patients with type 1 diabetes.

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.

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.

Cardiac Autonomic Dysfunction in Children and Adolescents with Type 1 Diabetes Mellitus

Introduction: Autonomic neuropathy is less well documented in children with type 1 diabetes mellitus and has received less attention than other diabetic complications. Sudden death and cardio-respiratory arrest in patients with type 1 and type 2 diabetes mellitus have been attributed to cardiac autonomic dysfunction. Aim: The aim of this study was to determine the prevalence of autonomic neuropathy in a cohort of children and adolescents with type I diabetes and to examine the relationship between this complication, and duration of diabetes and degree of glycemic control. Material and Methods: Seventy-six type 1 diabetic children and adolescents below age 18 years of age, and 76 nondiabetic school children, matched for age and sex, had their cardiac autonomic nerve function assessed using four autonomic function tests. Namely the respiratory sinus arrhythmia test ; the Valsalva ratio test; the heart rate response to standing, and the blood pressure response to standing. The first three are tests of parasympathetic function, while the last one is a sympathetic function test. Results: The diabetic patients had a median age of 12 years and their median duration of diabetes mellitus was 43 months. They showed a significantly higher resting heart rate and a significant drop in systolic and diastolic blood pressures upon standing compared to the control group. The duration of diabetes mellitus showed linear correlation to the symptoms of autonomic dysfunction. Conclusion: We conclude that cardiac autonomic neuropathy is not rare in young diabetic patients of relatively short duration of illness where glycemic control is less than optimal. Such tests may serve as long-term prognostic indicators in diabetic patients.Keywords:autonomic neuropathy, peripheral neuropathy, glycemic control, Middle East Sudan Journal of Medical Sciences Vol. 2 (2) 2007: pp. 95-100

Evidence of cardiovascular autonomic impairment in mitochondrial disorders

To investigate autonomic nervous system (ANS) function in mitochondrial disorders (MD). MD are characterized by a wide range of clinical features, including heart abnormalities and peripheral and central nervous systems involvement. Rarely autonomic symptoms have been reported. 22 patients with MD underwent a battery of cardiovascular reflex tests including five tests of parasympathetic function and four tests of sympathetic function. Power spectral analyses (PSA) of heart rate variability in the supine and upright positions were also evaluated. Plasma levels of adrenaline, noradrenaline and dopamine were determined in the standing and lying positions. Only 4/22 patients referred symptoms related to ANS dysfunction. 46% of patients had a definite autonomic damage (i. e. an autonomic score >/= 4). 36% showed moderate alterations with an autonomic score in the range 2-3 and 18 % had a normal autonomic function. MD patients had a significantly (p <0.03) lower increase of adrenaline level after standing. Our data indicate an autonomic dysfunction in more than 80% of MD patients, even in the absence of a clinically manifested autonomic involvement. Cardiovascular autonomic investigation might be systematically employed in the characterization of MD.

Does autonomic dysfunction in cirrhosis liver influence variceal bleed?

Background: Autonomic dysfunction has been documented in cirrhosis liver. Its influence on variceal bleed is not known. Aim: To determine the autonomic function amongst variceal bleeders in cirrhosis of the liver.Materials and methods: Fifty cirrhotics (variceal bleeders: 34) belonging to either sex, Childs B, age more than 15 years and non diabetic constituted the study group. Parasympathetic function tests included valsalva ratio (E:I ratio) and deep breathing test. (Max.-Min. heart rate); sympathetic function included postural fall of B.P and a rise in diastolic B.P. with sustained hand grip. A cirrhotic was considered to have ‘True’ autonomic dysfunction when both parasympathetic and one of the two sympathetic tests were abnormal.Results: The mean age for men was 39.64 + 10.6 yrs and for women 39.54 + 15.8 yrs. The male female ratio was 3.5:1. Only 10 of the 50 patients (all bleeders) had ‘true’ autonomic dysfunction i.e. 20%. Parasympathetic dysfunction alone was positive in 19 (38%) and sympathetic in 10 patients (20%). The E:I ratio (p < 0.001) and an increase in diastolic B.P. during sustained hand grip (p < 0.04) were significantly positive amongst variceal bleeders.Conclusion: ‘True’ autonomic dysfunction can predispose a cirrhotic to variceal bleed.

Autonomic dysfunction in dementia

Background: There are no studies of autonomic function comparing Alzheimer’s disease (AD), vascular dementia (VAD), dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD). Aims: To assess cardiovascular autonomic...

Autonomic dysfunction in ALS: A preliminary study on the effects of intrathecal BDNF

This pilot study aimed at exploring the effects of intrathecally administered brain derived neurotrophic factor (BDNF) on autonomic functions in patients with ALS. A battery of autonomic sympathetic and parasympathetic tests was performed at baseline and after nine months of treatment in 10 ALS patients participating in a double-blind placebo-controlled phase II/III study of intrathecally administered BDNF. Results of patients treated with BDNF (25 or 150 microg/day) were compared to those receiving placebo. Sudomotor function and blood pressure response to handgrip significantly worsened during the treatment period (55.4+/-26.1 vs. 38.9+/-23.9 g/m(2)h, p<0.05; 20+/-6 vs. 13+/-4 microHg, p<0.05) whereas other sympathetic and all parasympathetic function tests only tended to be more abnormal at follow-up. Serum norepinephrine levels increased significantly during the nine-months observation period. The results of autonomic function tests were not different between patients treated with BDNF and placebo, but norepinephrine levels were higher in the BDNF group. We conclude that autonomic nervous system function deteriorates along with poorer motor performance independently from treatment with BDNF. The elevation of norepinephrine levels might reflect a non-specific up-regulation, and its association with BDNF an autocrine effect.

A Longitudinal Cardiovascular Autonomic Function Study in Mild Guillain-Barré Syndrome

To identify subclinical autonomic dysfunction in mild Guillain-Barré syndrome (GBS), a set of autonomic function tests was serially performed for up to 6 months in 5 GBS patients with mild disability at the nadir. Parasympathetic autonomic function tests consisted of Valsalva ratio and R-R interval variation during rest and deep breathing. Sympathetic autonomic function was evaluated by blood pressure responses to sustained handgrip, hand immersion in ice water, and active standing. The results showed that abnormal parasympathetic and sympathetic function was frequently encountered in all 5 patients during the acute stage of the illness. Autonomic dysfunction occurred both in axonal and demyelinating types of GBS. There was a trend of improvement in most autonomic function tests after 3 months, comparable to the recovery of motor function. In conclusion, subclinical autonomic dysfunction was present in mild GBS. It was temporary and would resolve spontaneously.

Assessing cardiovascular autonomic neuropathy in diabetes mellitus: How many tests to use?

The aim was to evaluate the relative importance of an established battery of five function tests used in the assessment of cardiovascular autonomic neuropathy (CAN) in diabetes employing spectral analysis of heart rate variability (HRV) as the reference test. In a population-based sample of 178 diabetic persons and 194 non-diabetic controls, five function tests ( E/ I ratio, Valsalva, 30:15 ratio, Orthostatic-BP, and sustained Handgrip) and power spectral analysis of a 24-h Holter recording were carried out. The high-frequency power during nighttime (LnHF NIGHT) was taken to express the parasympathetic function and the daytime low-frequency power (LnLF DAY) to express the sympathetic function. The readings were log transformation when appropriate, age-corrected, and standardized to units of standard deviation. Combinations of the three mainly parasympathetic tests and the two mainly sympathetic tests were computed by averaging the standardized readings. A high value of the mean sum of squares in LnHF NIGHT or LnLF DAY — explained in regression analysis — was assumed to represent the better test or combination of tests. The three parasympathetic function tests each correlated significantly to LnHF NIGHT. The E/ I ratio had a correlation to LnHF NIGHT similar to the combination of the three parasympathetic tests and the combination of all five function tests, whereas Valsalva and 30:15 ratio had a significantly poorer association. Sustained Handgrip-correlated significantly poorer to LnLF DAY compared to Orthostatic BP and the combination of the two sympathetic tests explained a significantly smaller part of the variation in LnLF DAY and LnHF NIGHT than did the combination of all five tests. This study indicates that: (1) no information is gained by adding the sympathetic function tests to the parasympathetic tests, (2) the most informative test is the E/ I ratio, (3) and knowledge about the degree of CAN as defined by reduced HRV is not significantly increased when the four other function tests assessed are added to the E/ I ratio.

Cardiovascular autonomic dysfunction in multiple sclerosis: correlation with orthostatic intolerance.

Autonomic dysfunction is frequently observed in patients with multiple sclerosis (MS), but clinical studies disagree on the frequency and type of abnormalities in autonomic function tests. Orthostatic dizziness (OD) has been reported in up to 49% of patients, but the pathophysiological mechanisms are poorly understood. This study investigated cardiovascular reflex tests and their association with OD in patients with MS in order to examine the hypothesis that the sympathetic nervous system is specifically involved in these patients. Forty patients with clinically active relapsing-remitting (n = 27) and secondary progressive MS (n = 13), aged 35.0+/-8.5 years, were studied by parasympathetic (heart rate responses to the Valsalva maneuver, deep breathing, and active change in posture) and sympathetic function tests (blood pressure responses to active change in posture and sustained handgrip), and by spectral analysis of heart rate variability during rest and during standing. Results were compared to those obtained in 24 healthy volunteers, aged 29.4+/-7.2 years. A standardized questionnaire was used to evaluate symptoms of orthostatic intolerance. Abnormal responses on at least one cardiovascular reflex test were observed in 40% of MS patients, compared to 17% of the control group, with a statistically significant involvement of the sympathetic vasomotor system. Orthostatic intolerance was reported in 50% of patients (controls: 14%, P<0.006). Subgroup comparison of patients with and without OD suggests that orthostatic intolerance results from impaired sympathetic vasoconstriction. These results provide further evidence that the sympathetic nervous system is involved in patients with MS.