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PubMed1988

Pathophysiological findings in a patient with Shy-Drager and alveolar hypoventilation syndromes.

This report describes the clinical, physiologic and pathologic findings in a patient with alveolar hypoventilation, acquired autonomic dysfunction, parkinsonism, and sensorimotor polyneuropathy. While there were pathologic findings in both central and peripheral nervous systems, there were no morphologic changes in the regions of the brainstem considered responsible for respiratory rhythmogenesis. A hypothesis is developed based on the assumption that the abnormalities in respiratory control which led to the patient's death are explained by abnormalities in the feedback control of respiration.

Aged↗

PubMed1999

Imaging sympathetic innervation.

The autonomic innervation of the heart modifies most cardiac functions. Especially the heart rate and the force of contraction of myocytes are modulated by the autonomic nervous system. A number of specific neurotransmitters interact with receptors on post- and presynaptic binding sites regulating the complex electromechanical system of the heart. Disturbances at this interaction result in a variety of cardioneuropathies. The clinical manifestations can be mild and may only consist of sporadic arrhythmias without hemodynamic effects. In some cases however the autonomic dysfunction may be severe, e.g. in the acute phase of the Guillain-Barré syndrome and in advanced diabetic neuropathy. At present, the only available techniques to visualise and quantitate disbalanced innervation of the myocardium are scintigraphic modalities as single photon emission tomography (SPECT) and positron emission tomography (PET) with appropriate radiopharmaceuticals. These methods are reviewed with respect to their possible clinical application and to future developments.

Autonomic Nervous System Diseases↗

PubMed2007

Decline of neuroadrenergic bronchial innervation and respiratory function in type 1 diabetes mellitus: a longitudinal study.

BACKGROUND AND AIM: Type 1 diabetes mellitus complicated by autonomic neuropathy (AN) is characterized by depressed cholinergic bronchomotor tone and neuroadrenergic denervation of the lung. We explored the effects of AN on the rate of decline of pulmonary sympathetic innervation and respiratory function during a 5-year follow-up. METHODS: Twenty diabetic patients, 11 with AN, were enrolled in 1998 and then followed-up until 2003. During follow-up, glycosylated haemoglobin (HbA1c) was measured every 3 months. In 1998 and 2003 the patients underwent respiratory function tests and a ventilatory scintigraphic study of neuroadrenergic bronchial innervation using 123I-MIBG. RESULTS: During follow-up 4 patients, all with AN, were lost, and 1 developed AN. Forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) showed comparable rates of decrease in patients with and without AN. The yearly decline of forced expiratory volume in 1 s (FEV1) was about double the physiologic rate, in both AN and AN-free patients. The MIBG clearance significantly increased both in patients with AN (T1/2: 118.88 +/- 30.14 min at baseline and 92.10 +/- 24.52 min at the end of follow-up) and without AN (135.14 +/- 17.09 min and 92.68 +/- 13.52 min, respectively), indicating a rapidly progressive neuroadrenergic denervation. The rate of the neuroadrenergic denervation was inversely related to the severity of autonomic dysfunction at baseline (Spearman's rho - 0.62, p = 0.017). Neither respiratory function indexes nor MIBG clearance changes correlated with the overall HbA1c values. CONCLUSIONS: Neuroadrenergic denervation of the lung parallels the decline of respiratory function indexes in diabetic patients both with and without AN and seems to be independent from the quality of glycemic control.

3-Iodobenzylguanidine↗

PubMed1997

Management of blood pressure instability in severe tetanus: the use of clonidine.

OBJECTIVE: To evaluate the effectiveness of clonidine in the management of unstable blood pressure in severe tetanus. DESIGN: Patients with severe tetanus and blood pressure instability were treated with clonidine and the results were compared with those of other patients with severe tetanus who were not treated with clonidine. SETTING: Intensive care unit of the Chest Hospital of Athens. PATIENTS: We studied 27 patients with severe tetanus and autonomic dysfunction. INTERVENTIONS: Patients were managed according to a protocol. MEASUREMENTS AND RESULTS: Clonidine was administered until blood pressure stability was the fully restored and the dose was then gradually reduced. Five patients from the nonclonidine group and 2 from the clonidine group died. CONCLUSIONS: These results suggest that clonidine is effective in the treatment of blood pressure instability in severe tetanus.

Adrenergic alpha-Agonists↗

PubMed2006

Mislocalization of tactile stimulation in patients with complex regional pain syndrome.

Complex-Regional-Pain-Syndromes (CRPS) are characterized by sensory,motor and autonomic dysfunctions. Patterns of sensory symptoms suggest changes within the central nervous system (CNS). Recently, we could show substantial reorganization of somatotopic maps within the central nervous system of patients with CRPS using functional imaging techniques (Maihofner et al. Neurology, 2003). These changes were predicted by CRPS pain and mechanical hyperalgesia. In the present study we looked for potential psychophysical correlates of cortical reorganization in CRPS. Sequential pneumatic non-noxious tactile stimulation was performed at digits 1 and 5 in 24 patients with CRPS of the upper extremities. Both the unaffected and affected side were examined. Patients were interviewed for tactile induced sensations. The occurrence of mislocalizations was correlated with a detailed psychophysical examination in which sensory, motor and autonomic symptoms were assessed. Eight patients (30 %) reported tactile mislocalizations, which were felt in the affected hand. In four cases the referred sensations spread into other nerve territories (ulnar/median nerve). Presence of mechanical hyperalgesia significantly predicted the occurrence of mislocalizations. In contrast, in a healthy control group, no mislocalizations were found. Thus, our results further support the concept of pain-induced reorganization in the somatosensory system of CRPS patients.

Adult↗

PubMed1983

Beta blockade in asymptomatic diabetics with abnormal rest electrocardiograms.

Diabetic patients without evidence of vascular disease often reveal non-specific ST-T changes and prolonged QTc intervals in their ECGs. In an attempt to elucidate the role of autonomic dysfunction in the etiology of these changes, we compared the ECGs and beat to beat variations in 22 patients with changes in repolarization before and one hour after beta blockade. None had clinical evidence of ischaemic heart disease or peripheral vascular disease. In 19 patients (86%) the ST-T changes persisted after beta blockade. Heart rate was 75.6 +/- 15.3/min before and 64.3 +/- 9.6/min after beta blockade, while the QTc interval was 0.43 +/- 0.02 sec before and 0.41 +/- 0.02 sec after propranolol. Beat to beat variation during deep breathing is diminished in diabetic patients. Beta blockade reversed this phenomena. We conclude that while beat to beat variations and prolongation of QTc are likely to be consequent to autonomic neuropathy, the ST-T changes do not appear to be due to increased sympathetic tone and their etiology is yet to be determined.

Adolescent↗

PubMed1999

[Complex regional pain syndrome. Clinical and autonomic disorders during acute and chronic illness stages].

In order to describe autonomic dysfunction and clinical outcome in complex regional pain syndrome (CRPS) 20 patients were followed-up. First investigation was performed in the acute stage of CRPS and the second investigation two years later after therapy (individual, not standardized). Skin temperature and sudomotor function (thermoregulatory sweating (TST) and quantitative sudomotor axon reflex (QSART)) were assessed, and a clinical follow-up was performed carefully. Skin temperature was warmer on the affected side at first investigation (p < 0.001) and colder at follow-up (p < 0.02). Sudomotor output was enhanced on the affected side both after TST (p < 0.005) and QSART (p < 0.05) at first investigation. At follow-up, however, while thermoregulatory sweating was still increased (p < 0.04) QSART was not different. While autonomic failure improves as assessed by clinical examination, therapy failed to alleviate pain significantly. But patients' self-assesment of therapy was mostly positive (16 of 20, p < 0.001). The present study has shown that the autonomic failure may be probably the result of central disturbances of thermoregulation, but secondary peripheral mechanisms also contribute to our findings. Individual based therapy seems to be efficacious for long term treatment, but for final judge controlled studies are required.

Adult↗

PubMed2004

Influence of caffeine on heart rate variability in patients with long-standing type 1 diabetes.

OBJECTIVE: The effect of caffeine on cardiovascular health remains controversial. Patients with long-standing type 1 diabetes are at risk of autonomic failure and sudden cardiac death. We investigated the effects of caffeine on autonomic dysfunction (as assessed by heart rate variability [HRV]) in this high-risk group and in a control population. RESEARCH DESIGN AND METHODS: Using a randomized blinded, placebo-controlled, crossover design trial, we examined 2 weeks of caffeine consumption (250 mg twice daily) on HRV in 20 type 1 diabetic patients and 10 matched healthy volunteers. RESULTS: Baseline HRV was blunted in the diabetic patients (P < 0.0005 vs. control subjects) and markedly increased by caffeine in both groups (+103% in the group with diabetes [P = 0.009] and +38% in control subjects [P = 0.002]). The caffeine-associated increase in HRV was not statistically different between the control and the type 1 diabetes groups (P = 0.16). CONCLUSIONS: Modest amounts of caffeine improved autonomic function in diabetic patients and healthy volunteers. For individuals with abnormal HRV, regular caffeine use may have the potential to reduce the risk of cardiovascular events.

Adult↗

PubMed2006

Association between reduced heart rate variability and cognitive impairment in older disabled women in the community: Women's Health and Aging Study I.

OBJECTIVES: To examine the independent association between heart rate variability (HRV), a marker of cardiac autonomic function, and cognitive impairment. DESIGN: Cross-sectional analysis of baseline data from Women's Health and Aging Study I. SETTING: Urban community in Baltimore, Maryland. PARTICIPANTS: A subset of 311 physically disabled, community-dwelling women aged 65 and older whose HRV data were obtained. MEASUREMENTS: Reduced HRV was defined as the lowest quartile of each of several HRV measures exploring time and frequency domains and compared with the remaining three quartiles. Cognitive impairment was defined as a Mini-Mental State Examination score less than 24. Multiple logistic regression was used to model the independent relationship between reduced HRV and prevalent cognitive impairment. RESULTS: The age-, education-, and race-adjusted prevalence of cognitive impairment was higher in those with reduced HRV than in those with nonreduced HRV. After adjusting for relevant demographic and clinical characteristics, participants with reduced HRV were significantly more likely than those with nonreduced HRV to have cognitive impairment; these findings were consistent across different HRV indices. In particular, reduced high-frequency power, indicative of decreased parasympathetic activity, was associated with 6.7 times greater odds of cognitive impairment (95% confidence interval = 2.27-20.0). CONCLUSION: Cardiac autonomic dysfunction, particularly decreased parasympathetic activity, was independently associated with cognitive impairment in older disabled women in the community. This finding may improve understanding of the pathophysiological basis of cognitive impairment. The potential role of HRV as a cause or consequence of cognitive impairment needs to be elucidated in future studies.

Aged↗

PubMed1993

Circadian rhythms of blood pressure and heart rate in patients with human T-lymphotropic virus type-I-associated myelopathy.

Noninvasive ambulatory blood pressure and heart rate monitoring were used to investigate cardiovascular dysfunction in patients with human T-lymphotropic virus type-I (HTLV-I)-associated myelopathy (HAM). The subjects were 23 patients with HAM, and 23 sex- and age-matched normotensive healthy volunteers (controls). Circadian rhythms of blood pressure and heart rate were present in both the HAM patients and controls. Amplitudes and the 24-hr mean systolic and diastolic blood pressures were significantly lower in the patients than in the controls. The 24 hr mean heart rate was significantly higher in the patients, the difference being particularly marked during the night. Differences in the acrophases of the systolic and diastolic blood pressures and heart rate between patients and controls were small but still significant. These results suggest that subclinical cardiovascular autonomic dysfunction is present in HAM patients.

Adult↗

PubMed2000

Autonomic nervous function assessment using thermal reactivity of microcirculation.

There are only a few reliable objective methods of diagnosing peripheral neuronal damage suitable for routine use; the most important is based on measurement of nerve conduction velocity, which only shows changes when severe disturbances are already present. However, it is precisely at this stage that the possibilities of therapy are no longer satisfactory. As small fibres are affected earlier in the course of most forms of PNP than the large ones, assessment of afferent as well as efferent C-fibre function gains importance in the management of this widespread disease. In assessment of autonomic dysfunction, variability of the heartbeat with deep breathing or the Valsalva manoeuvre is a good and generally accepted test, although not strongly associated with other PNP test abnormalities. However, axonal degeneration starts in the most distal parts of the axon due to impaired axonal transport. Therefore, the longest C-fibres, i.e. in the lower extremities, are affected first, and incipient changes are most prominent there. For this reason HLDF, a reflex response of the skin blood flow stimulated by heat, has advantages in assessment of early C-fibre dysfunction. Considering the fact that the afferent and efferent sympathetic C-fibres are involved in regulation of microcirculation, the skin blood flow regulation is investigated by means of laser Doppler flowmetry. The microcirculation is stimulated by heat and the reaction of microcirculation is assessed as a value for the function of afferent and efferent (sympathetic) C-fibres. The results of this method are in close correlation with electrophysiologic tests, which is not achieved with sudomotor function.

Autonomic Nervous System↗

PubMed1986

Serum noradrenaline response to standing up in patients with Parkinson's disease.

Responses of serum noradrenaline (NA) levels to standing up were determined in patients with Parkinson's disease (PD) examining 15 patients and 13 healthy subjects of similar age in order to obtain information about autonomic failure in PD. Mild symptoms of autonomic dysfunction were found in all the patients. The mean (+/- SD) increment of serum NA levels as a response to standing up of patients was 0.11 +/- 0.29 nmol/l and that of the controls 1.09 +/- 1.15, the percentage rises being 5.4 +/- 12.1 and 38.2 +/- 35.0, respectively. These results indicate that serum NA responses to standing up in patients with PD are significantly diminished describing a sympathetic nervous system deficit in PD.

Adult↗

PubMed1988

The usefulness of head-up tilt testing and hemodynamic investigations in the workup of syncope of unknown origin.

To enhance the clinical evaluation of patients suffering from recurrent syncope of unknown origin, the integrity of mechanisms controlling blood pressure was examined in 151 patients utilizing a screening tilt test. Ninety-eight patients had an abnormal blood pressure and/or heart rate response to tilt testing, including provoked syncopal attacks in 63 patients. Whenever indicated, the screening tilt test was followed by blood volume and hemodynamic determinations, as well as autonomic nervous system testing to identify contributing pathophysiological abnormalities (hypovolemia, venous pooling, autonomic dysfunction). Detailed analysis of this battery of tests allowed us to conclude that: (1) The tilt test is commonly a provocative tool in the workup of patients with recurrent syncope due to vasovagal - vasodepressor reactions and other abnormalities of blood pressure regulation; (2) Its usefulness is augmented by associated hemodynamic and blood volume evaluations; (3) The identification of contributory pathophysiological mechanisms of blood pressure control facilitates specific therapeutic interventions.

Autonomic Nervous System Diseases↗

PubMed1988

Guillain-Barré syndrome: diagnostic criteria, epidemiology, clinical course and prognosis.

Thirty-four patients were identified with Guillain-Barré syndrome (GBS) on review of 266 neuropathy cases admitted to a Copenhagen county hospital from June 1977 to January 1984. The age-adjusted incidence rate of GBS is 2.0 x 10(-5) years-1. The natural history of the disease, antecedent events, symptoms and signs, autonomic dysfunction, sequelae, CSF findings and mortality are described. Six cancer patients with GBS differed significantly from the non-cancer patients in a more protracted disease course and failure to improve. The National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) criteria for the diagnosis of GBS are discussed, and it is concluded that the criteria, although useful in comparative studies, are too restrictive when used in clinical practice.

Aged↗

PubMed1981

Autonomic nervous system activity in acute schizophrenia: I. method and comparison with normal controls.

Many reports of autonomic dysfunction in schizophrenia may have been influenced by the chronicity or medication status of patients, or both. This study eliminates these sources of variation. Skin conductance (SC) and heart rate (HR) base levels and activity were compared in 118 controls and 46 recently admitted, drug-free, acute schizophrenic patients during rest, 20 mild-tone stimuli, and reaction time (RT) and mental arithmetic tasks. Patients showed higher than normal HR and spontaneous SC responses but lower SC base levels. Schizophrenics showed less SC and HR reactivity to tones and RT stimuli, slow habituation of the SC orienting response, an attenuated tonic response to stress, and disproportionately more spontaneous than elicited SC activity. The findings are similar to previous results for unmedicated, chronic schizophrenics and suggest that autonomic activity in schizophrenics is determined relatively more by endogenous factors than by external stimuli.

Acute Disease↗

PubMed2006

Anesthesia and patients with congenital hyposensitivity to pain.

BACKGROUND: Congenital hyposensitivity to pain or hereditary sensory and autonomic neuropathy represents a variety of disorders characterized by decreased perception of nociception, loss of other modalities of sensation, and variable expression of autonomic dysfunction. Sensory loss, especially that of pain, is associated with self-mutilations that may require frequent operations. Little is known about the safety of anesthesia for these patients. METHODS: The authors performed a computerized search of the Mayo Clinic medical records database between January 1996 and November 2005 for patients with congenital hyposensitivity to pain and related disorders who underwent general anesthesia. Medical records were reviewed for demographics, anesthetic techniques and agents, use of opioids, and perioperative complications. In addition, the authors conducted a comprehensive review of the literature to summarize the current knowledge regarding anesthesia for patients with congenital hyposensitivity to pain, and compared it with the patients with hyposensitivity to pain identified at the Mayo Clinic. RESULTS: The authors identified seven patients with hereditary sensory and autonomic neuropathy II, IV, or V and undefined variants of congenital pain hyposensitivity who generated 17 anesthesia records: 12 for orthopedic operations, 3 for sural nerve biopsies, and 2 for ophthalmologic procedures. In all patients, standard doses of volatile agents were used during anesthesia. Small amounts of opioids were used during the course of eight operations. Most patients experienced mild hypothermia (lowest temperature 34.7 degrees C), and none experienced hyperthermia. All patients were hemodynamically stable during otherwise uneventful anesthesia. During recovery from anesthesia, opioids were given to only one patient, a single dose of 1 mg morphine. Even after major orthopedic operations, the patient did not require additional analgesia. CONCLUSIONS: The patients with profound congenital hyposensitivity to pain underwent anesthesia without any adverse events. The authors found that despite reduced pain perception, the requirements for volatile anesthetics were within the expected range for population with normal pain perception, but they did not require opioids postoperatively. Intraoperative mild hypothermia was easily managed by adjustment of environmental temperature.

Adolescent↗

PubMed1997

Improved cardiac iodine-123 metaiodobenzylguanidine accumulation after drug therapy in a patient with Parkinson's disease.

A 72-year-old woman with Parkinson's disease and autonomic dysfunction underwent I-123 MIBG cardiac imaging to study sympathetic neuronal integrity. This revealed a defect in the infero-posterior wall. Tc-99m sestamibi myocardial perfusion imaging revealed no abnormalities. On follow-up I-123 MIBG SPECT, the defect was less prominent and the parkinsonian symptoms were ameliorated by drug therapy. Cardiac I-123 MIBG imaging may be a promising new method for evaluating drug therapy in patients with Parkinson's disease.

3-Iodobenzylguanidine↗

PubMed1998

Electrophysiologic assessment of autonomic function in epilepsy.

Sudden unexpected death associated with epilepsy (SUDEP) is an important clinical problem. Peri-ictal autonomic dysfunction is thought to play a role in SUDEP and few means exist for clinical identification of patients at risk. Sympathetic function was assessed by measuring sympathetic skin responses (SSR) elicited in the hand by auditory or tactile stimulation or by inspiration. Parasympathetic function was assessed by recording the R-R interval (RRI) and determining its variability in subsequent heartbeats. Fifty epilepsy patients had significantly greater SSR amplitudes and latencies than controls. The RRI was shorter in patients than in controls and the mean successive difference (MSD) was less, but significance was not reached. Twenty patients at possible risk for SUDEP (male, generalized seizures, intermittent medication noncompliance, drug and alcohol abuse, traumatic or structural aetiology) differed significantly from controls in SSR and RRI. Epilepsy patients may differ in autonomic function from the general population, and these differences may be relevant to SUDEP. The SSR and the RRI may be a simple means of assessing autonomic function in epilepsy outpatients.

Adolescent↗