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PubMed2004

Impaired cardiovascular autonomic control in newly and long-term-treated patients with Parkinson's disease: involvement of L-dopa therapy.

In idiopathic Parkinson's disease (PD), autonomic dysfunction is frequent, causing orthostatic hypotension. The respective roles of disease progression and dopaminergic treatment remain unclear. In this study, we investigated the autonomic control of cardiovascular functions and its relation to L-dopa therapy in both newly diagnosed (ND) and long-term-treated (LT) patients. Study subjects were: (1) nine ND patients never having undergone treatment with L-dopa; (2) 18 LT patients who had been receiving L-dopa treatment for a long period. ND patients were investigated before L-dopa treatment and after stabilization of their L-dopa dosage. LT patients were investigated once with their regular treatment and once after a 12-h interruption of L-dopa treatment; (3) nine healthy subjects served as controls. At each test session, blood pressure (BP), heart rate (HR), plasma catecholamines, heart rate variability (HRV), and spontaneous baroreflex sensitivity were assessed in the supine and upright positions. Before receiving L-dopa medication, ND patients had reduced E/I ratios (HR response/deep breathing) and lowered HRV when compared to controls; this was evidence of early effects of the disease on autonomic HR control. Introduction of L-dopa treatment reduced BP, HR, and plasma levels of adrenaline and noradrenaline. Similar changes were found in LT patients when contrasting the short-term treatment interruption and the usual L-dopa dosage. The treatment-linked increase in plasma dopamine also correlated with the decrease in noradrenaline. These results showed that mild impairment of autonomic cardiovascular control occurred early in the course of PD. They also provided evidence that the side effects of L-dopa aggravated the impairment of the autonomic control of BP and HR.

Aged↗

PubMed1997

Skin sympathetic nerve activity in Guillain-Barré syndrome: a microneurographic study.

To assess autonomic dysfunction, skin sympathetic nerve activity (SSNA) of four patients with Guillain-Barré syndrome was microneurographically studied in the acute and remission phase. Autonomic symptoms such as sinus tachycardia, palmar hyperhidrosis, hypertension, and orthostatic hypotension were present in the acute phase, but all subsided during remission. Basal resting SSNA and the responses to various physical and mental stimuli were all increased in the acute phase and returned almost to normal during remission. Rate of response in sweat rate and blood flow against SSNA were kept proportionally constant during both the acute and remission phases. These findings suggest that some autonomic nerve symptoms of Guillain-Barré syndrome, particularly during the acute phase, are due to increased SSNA.

Acute Disease↗

PubMed2003

Spectrum of autonomic cardiovascular neuropathy in diabetes.

OBJECTIVE: Diabetic patients with incapacitating orthostatic hypotension can have either a "hyperadrenergic" or "hypoadrenergic" presentation. Although the latter is related to overt autonomic neuropathy, the former is proposed to be explained by appropriate autonomic responses. We hypothesize, however, that both conditions are part of a spectrum of autonomic dysfunction. RESEARCH DESIGN AND METHODS: We studied 16 consecutive diabetic patients with preserved renal function referred for incapacitating orthostatic hypotension and characterized their autonomic and neurohumoral cardiovascular regulation. RESULTS: Six patients had a hyperadrenergic orthostatic response: systolic blood pressure fell 42 +/- 15 mmHg, heart rate increased 20 +/- 3 bpm, and plasma norepinephrine increased from 340 +/- 80 to 910 +/- 100 pg/ml. Ten patients had a hypoadrenergic response: systolic blood pressure fell 78 +/- 5 mmHg, heart rate increased only 7 +/- 3 bpm, and norepinephrine increased only from 130 +/- 28 to 230 +/- 40 pg/ml. Vagal (sinus arrhythmia, Valsalva ratio) and sympathetic (response to hyperventilation, postprandial hypotension) responses were impaired in both groups, but to a greater extent in the hypoadrenergic group. Notwithstanding severe orthostatic hypotension, the postural increase in plasma renin was blunted in both groups, more so in the hypoadrenergic group. Despite preserved renal function, patients had mild anemia due to impaired erythropoietin release, as seen in primary cases of autonomic failure. CONCLUSIONS: Our results suggest that diabetic patients presenting with hyperadrenergic orthostatic hypotension have an initial stage of autonomic neuropathy, with overtly abnormal vagal function and early signs of sympathetic impairment. Furthermore, altered renin response can contribute to the patients' orthostatic hypotension.

Arrhythmias, Cardiac↗

PubMed2002

[Early diagnosis of orthostatic hypotension in idopathic Parkinson's disease].

Autonomic dysfunction in idiopathic Parkinson's disease (IPD) is common and occurs in 70% of patients. The aim of the study was to evaluate autonomic mechanisms regulating cardiovascular system during tilt up test in IPD patients. The examination was performed in 35 patients with IPD (26 male and 9 female, mean age 60 +/- 9) and matched with gender and age 35 controls subjects (healthy volunteers, mean age 59 +/- 9). Patients were divided into two groups: group I--early stage of disease (n = 20) and group II--advanced stage of the disease (n = 15). The tilt test in IPD patients and in the control group lasted 3 minutes. In both groups tilt test was performed with a head-up tilt position of 60 degrees (tilt table Manumed, Netherlands). In both groups 30:15 ratio were lower than in the control group 1.03 +/- 0.08, 0.97 +/- 0.09 v 1.23 +/- 0.1 respectively (p = 0.001). In the second group the heart-rate variability after the tilt test was lower 6.2 +/- 4/min than in the control group 10.2 +/- +/- 1.9/min and group I 8.8 +/- 4/min (p = 0.01). The decrease of the systolic pressure in response to the tilt test was the highest in group II (16 +/- 14 mmHg), in the control group 4 +/- 7 mmHg, in group I 13 +/- 11 mmHg (p = 0.001). Ortostatic hypotension in IPD occurs in 36% of patients in an early stage and in 47% of patients in an advanced stage of the disease. The use of the tilt test enables the early diagnosis of cardiovascular disturbances in IPD.

Female↗

PubMed1991

[Diabetes mellitus in autonomic neuropathy of the heart].

In 48 patients suffering from diabetes I and diabetes II cardiovascular reflexes were tested in order to detect autonomic nervous system lesions of the heart. We measured the beat to beat variation in heart rate during deep breathing and the response of heart rate to change in posture (30:15 ratio). These tests were performed to prove the parasympathic function. To detect sympathic lesions the blood pressure changes were observed as response to change in posture (Schellong-Test). The patients under investigation showed a high prevalence of autonomic dysfunction depending on duration of diabetes and manifestations of other diabetic lesions. More often and earlier destructions of the parasympathic system were observed. Autonomic nervous lesions were correlated to the peripheral neuropathy. The diabetic polyneuropathy is a common complication of long term diabetes mellitus.

Adult↗

PubMed1982

Diabetic autonomic neuropathy in the surgical management of the diabetic foot.

The onset of autonomic neuropathy can often be insidious and may be associated with somatic neuropathy. Whether the autonomic dysfunction has a primary role or simply serves as a marker for other disease processes remains unclear. There is no doubt, however, that autonomic neuropathy, once present, greatly complicates the diabetic state and the management of the diabetic patient in the perioperative period and also statistically increases the mortality risk. Hopefully the testing of diabetic patients for the presence of autonomic neuropathy will become more prevalent. The heightened awareness will serve to alert the podiatric physician of possible autonomic disease sequelae in the surgical management of such patients.

Autonomic Nervous System Diseases↗

PubMed2006

Magnesium sulphate for treatment of severe tetanus: a randomised controlled trial.

BACKGROUND: The most common cause of death in individuals with severe tetanus in the absence of mechanical ventilation is spasm-related respiratory failure, whereas in ventilated patients it is tetanus-associated autonomic dysfunction. Our aim was to determine whether continuous magnesium sulphate infusion reduces the need for mechanical ventilation and improves control of muscle spasms and autonomic instability. METHODS: We did a randomised, double blind, placebo controlled trial in 256 Vietnamese patients over age 15 years with severe tetanus admitted to the Hospital for Tropical Medicine, Ho Chi Minh City, Vietnam. Participants were randomly assigned magnesium sulphate (n=97) or placebo solution (n=98) intravenously for 7 days. The primary outcomes were requirement of assisted ventilation and of drugs to control muscle spasms and cardiovascular instability within the 7-day study period. Analyses were done by intention to treat. This trial is registered as an International Standard Randomised Clinical Trial, number ISRCTN74651862. FINDINGS: No patients were lost to follow-up. There was no difference in requirement for mechanical ventilation between individuals treated with magnesium and those receiving placebo (odds ratio 0.71, 95% CI 0.36-1.40; p=0.324); survival was also much the same in the two groups. However, compared with the placebo group, patients receiving magnesium required significantly less midazolam (7.1 mg/kg per day [0.1-47.9] vs 1.4 mg/kg per day [0.0-17.3]; p=0.026) and pipecuronium (2.3 mg/kg per day [0.0-33.0] vs 0.0 mg/kg per day [0.0-14.8]; p=0.005) to control muscle spasms and associated tachycardia. Individuals receiving magnesium were 4.7 (1.4-15.9) times less likely to require verapamil to treat cardiovascular instability than those in the placebo group. The incidence of adverse events was not different between the groups. INTERPRETATION: Magnesium infusion does not reduce the need for mechanical ventilation in adults with severe tetanus but does reduce the requirement for other drugs to control muscle spasms and cardiovascular instability.

Adult↗

PubMed1998

Autonomic neuropathy: diagnosis and impact on health in adolescents with diabetes.

Symptomatic autonomic neuropathy and abnormal cardiovascular autonomic tests are associated with increased mortality due to vascular disease and increased risk of sudden deaths. Intensive therapy in the DCCT caused a significant risk reduction of developing autonomic nerve abnormalities at five years only in the Primary Prevention Group (4 vs. 9%). At the Royal Alexandra Hospital for Children, the prevalence of cardiovascular reflex abnormalities is 28%. Over 5 years, we have found no increase in the rate of single cardiovascular abnormalities and a low rate of persistence. Two or more abnormalities developed in 5%. Repeated measures of pupillary function showed a significant increase in abnormalities and a higher level of persistently abnormal tests. Spectral analysis and 24-hour BP monitoring may detect autonomic dysfunction at earlier stages but longitudinal studies are not yet available.

Adolescent↗

PubMed2003

Autonomic side effects of botulinum toxin type B treatment of cervical dystonia and hyperhidrosis.

Recently, botulinum toxin type B (BT-B) has become available to treat muscle hyperactivity in cervical dystonia (CD). When we started the clinical use of BT-B, we noticed a side effect profile not seen with botulinum toxin type A (BT-A) before. Altogether 30 consecutive patients were included in this open controlled study. 24 patients were treated for CD with 11,310 +/- 2,616 mouse units (MU) of BT-B (NeuroBloc) and 6 for focal hyperhidrosis (HH) with 4,000-10,000 MU. In 5 of them, BT-A (Botox) was used additionally for comparison of effectiveness. In CD, side effects consisted of dryness of mouth (total 21, duration 4.4 +/- 2.0 weeks, 10 severe, 7 moderate, 4 mild), accommodation difficulties (7), conjunctival irritation (5), reduced sweating (4), swallowing difficulties (3), heartburn (3), constipation (3), bladder voiding difficulties (2), head instability (1), dryness of nasal mucosa (1) and thrush (1). In HH, side effects consisted of accommodation difficulties (4), dryness of mouth (2) and conjunctival irritation (1). Autonomic side effects occur far more often after BT-B than after BT-A. Their localization suggests systemic BT-B spread. BT-B should be applied carefully in patients with pre-existent autonomic dysfunction, additional anticholinergic treatment and in conditions where anticholinergics are contraindicated.

Adult↗

PubMedDate not supplied

Low plasma renin activity in normotensive patients with diabetes mellitus: relationship to neuropathy.

To determine the effect of diabetes mellitus on the renin-aldosterone system, independent of age, nephropathy, or hypertension, 16 normotensive diabetics with long-term disease (mean duration, 15 years) and no (14) or minimal (2) proteinuria, were compared to nine age-matched, normotensive controls. Plasma renin activity (PRA) measured supine and after 4 hours of quiet ambulation, both on an ad libitum diet and on Day 4 of a 10 mEq low sodium diet, was always lower in the diabetics (31%-56% of control values). After the combined stimulus of sodium depletion and ambulation, PRA was 2.2 +/- 0.4 in the diabetics compared to 3.4 +/- 0.2 ng/ml/hr in controls (p less than 0.025). On the low sodium diet, PRA and the postural response of PRA correlated directly with the degree of autonomic dysfunction as quantitated by the velocity of esophageal peristalsis (r = 0.60, p less than 0.05; r = 0.75, p less than 0.005 respectively), suggesting that autonomic neuropathy was an important factor contributing to low PRA in these patients. No other parameters correlated with PRA. Plasma renin substrate (PRS) tended to be lower in diabetics (1053 +/- 95 vs 1358 +/- 132 ng AI/ml; p less than 0.07) but not sufficiently so to account for the substantial difference in PRA. Furthermore, PRS did not correlate with PRA. Fasting blood sugar, while higher in diabetics (209 vs 96 mg/dl), and creatinine clearance, which was lower (112 +/- 13 vs 78 +/- 4 ml/min; p less than 0.01), also did not correlate with PRA. Other factors, including serum creatinine, serum potassium, urinary aldosterone, blood pressure, and body weight, and the responses of these parameters to sodium depletion, were similar in diabetics and controls. These data implicate visceral neuropathy as a major factor in the hyporeninemia of these diabetics.

Autonomic Nervous System Diseases↗

PubMed2002

Assessment of diabetic autonomic neuropathy using twenty-four-hour spectral analysis of heart rate variability: a comparison with the findings of the Ewing battery.

A power spectral analysis of heart rate variability has been applied in order to assess diabetic autonomic neuropathy and high frequency spectra are thus considered to possibly reflect vagal nerve integrity in patients with diabetes mellitus. The purpose of this study was to investigate the relationship between the findings of high frequency spectra analysis and the results of the Ewing battery. We performed 24-hour power spectral analysis using an ambulatory ECG monitoring system and standard tests in order to assess diabetic autonomic neuropathy (Ewing battery) in 18 diabetic patients to compare their diagnostic values for diabetic autonomic neuropathy. We used the high frequency amplitude (high frequency spectra; 0.15-0.40 Hz) as a direct measure of vagal nerve integrity from each hourly spectral plot. All hourly high frequency spectra decreased along with the impaired assessment of the battery, especially during the night when the high frequency spectra showed a manifest increase in patients classified as normal according to the battery. High frequency spectra during the night while asleep (22:00-05:00) and during a 24-hour period significantly correlated with the results of the battery. These values markedly decreased even in patients classified as having early vagal damage when compared with those classified as normal. High frequency spectra during night closely reflected the intrinsic vagal nerve integrity in patients with diabetes mellitus. High frequency spectra during night or a 24-hour period is a simple and sensitive measure of diabetic autonomic neuropathy and is considered to be a useful modality for detecting even early changes in autonomic dysfunction.

Adult↗

PubMed1994

Skin complications other than pressure ulcers following spinal cord injury.

This study identifies skin and nail complications other than pressure ulcers after spinal cord injury and correlate these complications to the level of injury. A prospective study was performed at the time of 679 annual spinal cord injury clinic visits from 1988 to 1991 at which time the skin and nails were examined for changes or other lesions. Clinical skin thickening and nail hypertrophy were the most frequent findings. Skin thickening occurred in 57.9% of cervical injuries, 31.6% of higher thoracic injuries, 23.6% of lower thoracic injuries, and 16.0% of thoracolumbar injuries, p < .0001. Skin thickening was also seen more commonly with increasing time after injury, 20.3% at 1 year and 51.2% at 5 years, p < .0001. Nail hypertrophy occurred in the lower extremities and was not correlated with the level of injury. Denervation and autonomic dysfunction may be implicated in these changes.

Autonomic Nervous System Diseases↗

PubMed1999

[Syndromes of autonomic insufficiency associated with orthostatic intolerance: classification, diagnostic and therapeutic approach].

Stimulated by the widespread use of tilt table testing, disorders of autonomic function with orthostatic hypotension have recently gained attention by clinical cardiologists. At the same time, improved characterization of the underlying circulatory responses have led to a reclassification of these syndromes. In particular, three subgroups of chronic primary dysautonomia have been defined such as Pure Autonomic Dysfunction, Multiple System Atrophy, and the Postural Orthostatic Tachycardia Syndrome. On the other hand, acute dysautonomias represent a rare yet clinically sometimes dramatic form of autonomic disorders. Several diseases as well as enzymatic disorders, and pharmacological drugs may cause secondary dysautonomia. The clinical correlate of all these forms of dysautonomia is orthostatic hypotension and syncope. Thus, a careful history forms the basis of a successful diagnostic workup of the underlying cause of syncope. This review summarizes the current knowledge of autonomic disorders, their classification and diagnostic and therapy strategies.

Autonomic Nervous System Diseases↗

PubMed1991

Central conduction and autonomic nervous function in HMSN I.

CNS conduction and autonomic nervous function were investigated in 15 patients with HMSN I. Central motor conduction time (CMCT) was estimated with magnetic brain stimulation and electrical nerve root stimulation. Somatosensory evoked potential (SEP) and visual evoked potential (VEP) were used for assessment of central sensory and visual conduction. Autonomic effector organ functions were assessed with the R-R variation test for parasympathetic function, and the sympathetic skin response test (SSR) for skin sympathetic sudomotor activity. Five of the patients had prolonged CMCT. Central sensory conduction was normal in 3, and slightly prolonged in 1 of the patients, but could not be estimated in 11 due to lack of response from the cervical recording. VEP was abnormal in 2 patients. R-R variations during normal breathing were low in 8 of 15 patients, and low also during deep breathing in 1 of 15. The SSR test was pathological in 5 of 15 patients. Thus, impaired central conduction and/or autonomic dysfunction was not an uncommon finding in patients with HMSN I.

Adult↗

PubMed1994

Autonomic responsivity in generalized social phobia.

To determine whether patients with generalized social phobia exhibit evidence of abnormal autonomic nervous system (ANS) functioning, 15 non-depressed, medication-free subjects with DSM-IV social phobia (generalized type) and 15 healthy control subjects participated in a series of autonomic function tests. Generalized social phobics exhibited increased blood pressure responsivity to Valsalva and exaggerated vagal withdrawal in response to isometric exercise, but normal cardiovascular responsivity to all other tasks. Plasma norepinephrine and epinephrine levels were also normal. Studies with larger sample sizes and the use of specific neuropharmacologic probes seem warranted to further delineate a role for autonomic dysfunction in the pathophysiology of this disorder.

Adult↗

PubMed1995

Circadian rhythm and variability of heart rate in Duchenne-type progressive muscular dystrophy.

Using 24-hour Holter monitoring and time domain and power spectral measurements, we evaluated the variability of the heart rate and its circadian rhythm in 55 male patients with Duchenne-type progressive muscular dystrophy (DMD) to characterize their autonomic function versus findings in 20 normal controls. Comparisons were also made in patients with mild, moderate, and severe stages of DMD. The percent difference between successive RR intervals that exceeded 50 ms, a measure of parasympathetic tone, was significantly lower even in patients with early stage of DMD than in controls (p < 0.01). This trend became marked with disease progression. Power in the high-frequency (HF) range (0.15 to 0.40 Hz), a measure of parasympathetic tone, was lower (p < 0.01), and the ratio of the power in the low-frequency (LF) range (0.04 to 0.15 Hz) and that of HF range (LF/HF ratio), a measure of sympathetic tone, was higher in DMD patients versus controls (p < 0.01). This trend was also marked with disease progression. Patients with mild or moderate disease had a slight circadian alteration in HF and LF/HF ratio. Patients with severe disease had virtually no circadian rhythm in HF. Their LF/HF ratio was higher at night (p < 0.01), lower in the morning (p < 0.01), and still lower during the day (p < 0.01), the opposite of control findings. The autonomic abnormalities in DMD were thus characterized by a significant increase in sympathetic activity and a significant decrease in parasympathetic activity. Thus, heart rate variability and circadian rhythm were useful in assessing autonomic dysfunction in DMD.

Adolescent↗

PubMed1998

Death by "ecstasy": the serotonin syndrome?

"Ecstasy" or 3,4-methylenedioxymethamphetamine (MDMA) is a popular drug of abuse and is generally regarded as safe by the lay public. There are an increasing number of reports of MDMA-induced toxicity that exhibit features of the serotonin syndrome. We report a case of severe hyperthermia, altered mental status, and autonomic dysfunction after a single recreational ingestion of MDMA.

Adult↗

PubMed1993

Pupil cycle time and human immunodeficiency virus (HIV) infection.

The pupil cycle time (PCT) was measured in 22 HIV-positive patients and 22 age/sex-matched controls. Of the HIV-positive group, 13 (59%) met the Centre for Disease Control classification of acquired immunodeficiency syndrome (AIDS) defining illness. There was a highly statistically significant difference in the PCT between the HIV-infected group and the control group (p < 0.0001, Student's t-test). Within the HIV-infected group there was no statistically significant difference in the PCT between those patients with full-blown AIDS and the others. This study suggests that HIV infection may be associated with subclinical ocular autonomic dysfunction even in the earlier stages of HIV infection.

Acquired Immunodeficiency Syndrome↗