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PubMed1999

Impaired arterial baroreceptor sensitivity before tilt-induced syncope.

Autonomic dysfunction seems to play a central role in the pathophysiology of neurocardiogenic syncope (NCS) but conflicting data have recently become available. We evaluated autonomic nervous system (ANS) function (heart rate variability (HRV), systolic blood pressure variability (SBPV) and baroreceptor gain (BRG)) and non-invasive haemodynamics (cardiac output and total peripheral resistance) in patients with neurocardiogenic syncope. Retrospectively, we evaluated 12 NCS patients (positive head-up tilt without pharmacological provocation) in the basal state and at initial tilt, 12 non-NCS patients with tilt-negative syncope and 12 aged-matched normal controls. Prospectively, we evaluated 16 NCS patients to analyse the haemodynamics and ANS activity throughout the tilt test (beginning of tilt and before syncope occurs). HRV and SBPV were accessed by fast Fourier transforms (FFT) and spontaneous BRG by temporal sequences, slope and a index. Modelflow was used to quantify the non-invasive haemodynamics. None of the autonomic and haemodynamic parameters at baseline or in the first 10 min of tilt was different among the respective NCS, non-NCS syncope and normal control groups, except for SBP, which was higher at baseline in controls. Throughout the tilt test in the prospective NCS group, the heart rate increased (88-95 beats x min(-1), P<0.05), systolic blood pressure decreased (123-109 mmHg, P<0.01), and arterial baroreceptor gain was reduced (7.6 to 5.5 ms mmHg(-1), P<0.01) and the absolute high frequency component of HRV (HF HRV) decreased (150-80 ms(-2), P<0.05), before syncope occurred. There was no change in the low frequency component of HRV (LF HRV), SBPV, cardiac output (CO) or total peripheral resistance (TPR). Tilt-induced syncope could not be predicted by non-invasive haemodynamic or autonomic parameters at rest or in the initial minutes of tilt. The decrease in arterial baroreceptor gain could be a precocious expression of the transient autonomic dysfunction that characterizes the occurrence of neurocardiogenic syncope.

Adult↗

PubMed2004

Sympathetic skin response in migraineurs and patients with medication overuse headache.

BACKGROUND: Autonomic dysfunction has been reported in patients with migraine, and it may play a role in promoting attacks. OBJECTIVE: To investigate changes in the autonomic function of migraineurs and patients with medication overuse headache via sympathetic skin response, and to determine whether psychiatric comorbidity is related to any changes recorded. METHODS: A consecutive series of patients with migraine (n = 45) and medication overuse headache (n = 53) were studied. Patients with other chronic diseases requiring medication were excluded. Sympathetic skin response latencies and amplitudes from the patients with headache (N = 98) and 40 healthy controls were compared statistically. RESULTS: Sympathetic skin response latencies in patients with medication overuse headache and in migraineurs were significantly longer than in controls. To analyze the effect of psychiatric comorbidity, patients with medication overuse headache and migraineurs were each divided into 2 groups: those with psychiatric comorbidity and those without comorbidity. When the sympathetic skin response results of these 4 groups were compared with controls, the only statistically significant difference was between the sympathetic skin response latencies of controls and the latencies of patients with psychiatric comorbidity. We could not find any difference between the results from patients without psychiatric comorbidity and those of controls. CONCLUSION: Psychiatric disease may affect the results of autonomic function testing in migraineurs and patients with medication overuse headache. Consideration should be given to excluding patients with psychiatric comorbidity from studies investigating autonomic dysfunction in patients with headache.

Comorbidity↗

PubMed2005

Autonomic neural regulation of immunity.

The 'cytokine theory of disease' states that an overproduction of cytokines can cause the clinical manifestations of disease. Much effort has been expended to determine how cytokines are regulated in normal health. Transcriptional, translational and other molecular control mechanisms protect the host from excessive cytokine production. A recent discovery revealed an unexpected pathway that inhibits macrophage cytokine production. The inflammatory reflex is a physiological pathway in which the autonomic nervous system detects the presence of inflammatory stimuli and modulates cytokine production. Afferent signals to the brain are transmitted via the vagus nerve, which activates a reflex response that culminates in efferent vagus nerve signalling. Termed the 'cholinergic anti-inflammatory pathway', efferent activity in the vagus nerve releases acetylcholine (ACh) in the vicinity of macrophages within the reticuloendothelial system. ACh can interact specifically with macrophage alpha7 subunits of nicotinic ACh receptors, leading to cellular deactivation and inhibition of cytokine release. This 'hard-wired' connection between the nervous and immune systems can be harnessed therapeutically in animal models of inflammatory disease, via direct electrical stimulation of the vagus nerve, or through the use of cholinergic agonists that specifically activate the macrophage alpha7 subunit of the ACh receptor. Autonomic dysfunction has been associated with human inflammatory diseases including rheumatoid arthritis, diabetes and sepsis; whether this dysfunction results from the inflammatory component of these diseases, or is actually an underlying cause, is now less clear. The description of the cholinergic anti-inflammatory now brings to the fore several new therapeutic strategies for inflammatory disease, and suggests that many of these diseases may actually be diseases of autonomic dysfunction.

Autonomic Nervous System↗

PubMed2006

Elapid snakebite as a cause of severe hypertension.

Snakebite is a common medical emergency in tropical countries, however, autonomic dysfunction is an uncommon manifestation of snakebite. The authors present an unusual manifestation of severe neurotoxic snake envenomation: severe hypertension requiring intravenous antihypertensives. A review of the literature on autonomic dysfunction in neurotoxic snake envenomation is also presented.

Adult↗

PubMed2004

Autonomic function and serum erythropoietin levels in chronic fatigue syndrome.

OBJECTIVE: Given previous findings, we wished to investigate whether there was evidence of autonomic dysfunction in patients with chronic fatigue syndrome, and whether this could be related to reduced erythropoietin levels and altered red blood cell indices. METHODS: We assessed autonomic function and analysed blood parameters (including erythropoietin) in 22 patients with chronic fatigue syndrome who were medication-free and without comorbid depression or anxiety. Results were compared to 23 iron-deficiency anaemia patients and 18 healthy individuals. RESULTS: Autonomic testing in patients with chronic fatigue syndrome yielded a significantly greater increase in heart rate together with a more pronounced systolic blood pressure fall on standing compared to healthy individuals. Heart rate beat-to-beat variation on deep breathing and responses to the Valsalva manoeuvre were normal. Two of 22 patients with chronic fatigue had mild normochromic normocytic anaemia with normal ferritin, vitamin B12 and folate levels. Serum erythropoietin levels were within reference range. CONCLUSION: Some autonomic dysfunction is present in chronic fatigue syndrome (CFS) patients; the explanation remains uncertain, but could relate to cardiovascular deconditioning. There were no major haematological, biochemical or immunological abnormalities in these patients.

Adult↗

PubMed2005

Lower urinary tract function in dementia of Lewy body type.

OBJECTIVE: Dementia of Lewy body (DLB) type is the second commonest degenerative cause of dementia and autonomic dysfunction has been recognised in DLB. Lower urinary tract (LUT) function in DLB has not been fully delineated. We investigated LUT function in DLB by evaluating clinical and urodynamic data. METHODS: We examined 11 patients (eight men, three women; age range 65-81; disease duration 2-14 years) with probable DLB. Urodynamic studies consisted of: measurement of postvoid residual in all patients, uroflowmetry in five, and electromyography (EMG) cystometry in seven. RESULTS: All patients had symptoms of LUT: urinary incontinence (urgency type/functional type due to dementia and immobility/both urgency and stress type in 7/2/1 patients, respectively); night-time frequency; urgency; and daytime frequency and voiding difficulty. Seven had postvoid residuals, and three had residual urine volume >100 ml. Decreased urinary flow was seen in all five and detrusor overactivity in 5/7 patients who underwent flowmetry and EMG cystometry, respectively. Low compliance detrusor (storage phase, n = 2; with bethanechol supersensitivity), an underactive detrusor (n = 4), an acontractile detrusor (n = 1), and detrusor-sphincter dyssynergia (voiding phase) (n = 1) were also seen; 2/3 patients who underwent motor unit potential analysis had neurogenic changes. CONCLUSION: LUT dysfunction is a common feature in DLB, not only due to dementia and immobility, but also to central and peripheral types of somato-autonomic dysfunction.

Aged↗

PubMed1998

Is heart rate variability a reliable method to assess autonomic modulation in left ventricular dysfunction and heart failure? Assessment of autonomic modulation with heart rate variability.

Autonomic dysfunction seems to be involved in the progression and prognosis of congestive heart failure. Measurement of heart rate variability (HRV) provides a noninvasive method to obtain reliable and reproducible information on autonomic modulation of heart rate, but there is a difficulty in using HRV as a quantitative estimate of autonomic dysfunction in heart failure. This study was aimed at testing the hypothesis that abnormal modulation of heart rate assessed by power spectrum analysis may be present also in asymptomatic patients with left ventricular dysfunction and progress in patients with overt symptoms of congestive heart failure. HRV was measured in three groups of subjects: Group 1: 30 patients with chronic heart failure; Group 2: 21 patients with asymptomatic left ventricular dysfunction; and Group 3: 25 healthy volunteers as control group. HRV was evaluated by autoregressive spectral analysis with 600-beat ECG samples, while subjects were quietly recumbent (BSI), in conditions of controlled breathing (15 acts/min) (RSC) and passive orthostatism after tilting (80 degrees) (TLT). Patients in group 1 showed a reduction in the standard deviation of the R-R intervals (SDRR) (p<0.0003) and in the low frequency component (LF) (p<0.0001) compared to normal subjects. Low frequency component was not detectable in 11 patients of group I (p<0.0008). On RSC and TLT, group 1 failed to show any modification in the low frequency and high frequency components (HF) under any stimulation. Group 2 showed no modification at baseline evaluation, no increase in the high frequency component on RSC and in LF during TLT compared to controls (p<0.01 and p<0.0001 respectively). At baseline, group 1 had a lower SDRR (p<0.03) and LF (p<0.0001) vs. group 2, whereas during stimulation the two groups exhibited the same behaviour. In conclusion, reduced heart rate variability is specific for both asymptomatic and symptomatic post-ischemic left ventricular dysfunction. Our results suggest that frequency domain analysis of heart rate variability during a stimulation test allows a more accurate definition of the degree of autonomic control of heart rate.

Autonomic Nervous System↗

PubMed2006

Dysautonomia rhinitis: associated otolaryngologic manifestations and characterization based on autonomic function tests.

CONCLUSIONS: Dysautonomia is a multisystem disorder. Beside the nasal symptoms, some otolaryngological disorders may be explained on the basis of autonomic dysfunction. Testing of the autonomic nervous system (ANS) complements the clinical findings and provides objective measurements to substantiate the presence of ANS dysfunction. The term dysautonomia rhinitis may be used to specify this autonomic-related rhinitis. OBJECTIVES: Nonallergic, noninfectious perennial rhinitis is a heterogeneous disorder comprising several pathophysiological entities. This study was designed to objectively investigate the relation of idiopathic perennial rhinitis to ANS dysfunction. PATIENTS AND METHODS: This was a prospective controlled clinical study; 78 patients, carefully diagnosed as having idiopathic perennial rhinitis, were enrolled. Workshop protocol included diagnostic measures for exclusion of other causes of rhinitis and autonomic function assessment at a clinical cardiology laboratory. Results were compared with those of 20 age- and sex-matched normal control subjects. RESULTS: In addition to their nasal symptoms, all patients reported more than one regional and multisystem complaint. Each patient had at least one autonomic function test that displayed a hypervagal response and the overall response score was as follows: 46 (59%) had hypervagal response, 32 (41%) had mixed response and none had a normal or hyperadrenergic response.

Adrenergic Fibers↗

PubMed2006

Genital sympathetic skin responses in fibromyalgia syndrome.

The study was designed to investigate the autonomic dysfunction in fibromyalgia syndrome (FMS) by recording sympathetic skin response (SSR) from palmar, plantar and genital regions. The second aim was to evaluate the relation between sexual problems and autonomic dysfunction in FMS. SSR potential was recorded from palmar, plantar and genital regions in 28 married, female FMS patients and 18 married, healthy females. Fibromyalgia Impact Questionnaire (FIQ) was used to show the clinical severity and functional disability in FMS patients. Glombok Rust Inventory of Sexual Satisfaction (GRISS), a 28-item questionnaire, was used to assess the existence and severity of sexual problems. Beck test was used to evaluate anxiety and depression. The amplitude of SSR recorded from palmar, plantar and genital regions was lower than in the control subjects (P < 0.05). GRISS (total and subscale), Beck test and FIQ scores of FMS patients were higher than in the control subjects (P < 0.05). No correlation was found between the SSR potential and GRISS scores. The results of our study reveal that abnormality in SSR recorded from palmar, plantar and genital regions reflects the abnormality in the autonomic nervous system (ANS) of FMS patients. These patients have more sexual problems than healthy subjects, and we think this finding is related to increased anxiety and depression in these patients.

Adult↗

PubMed2001

Neurogenic bladder in Lambert-Eaton myasthenic syndrome and its response to 3,4-diaminopyridine.

Autonomic dysfunction, as well as neuromuscular involvement, is a common manifestation of Lambert-Eaton myasthenic syndrome (LEMS). Dry mouth and impotence have been described as typical features of autonomic dysfunction, but neurogenic bladder is infrequent or subclinical in LEMS. We report a patient with neurogenic bladder secondary to LEMS whose condition responded to 3,4-diaminopyridine (3,4-DAP). In this patient's serum, results of repeated measurement with P/Q-type VGCC antibodies proved positive, but not with N-type VGCC and synaptotagmin antibodies. A review of the literature turned up a few patients with voiding dysfunction related to LEMS, but no urodynamic studies were done on these patients. Ours is the first case in which 3,4-DAP was efficacious in treating LEMS and neurogenic bladder. Responses of 3,4-DAP in urodynamic studies suggest that in this LEMS patient neurogenic bladder was caused by defective neurotransmission both in the autonomic detrusor and skeletal abdominal muscles.

4-Aminopyridine↗

PubMed1996

Cardiovascular variability in major depressive disorder and effects of imipramine or mirtazapine (Org 3770).

Spectral analysis of fluctuations in heart rate (HR) and blood pressure (BP) was applied to assess sympathetic and parasympathetic cardiovascular control mechanisms in patients with unipolar affective disorder before and after treatment with imipramine (IMI) or mirtazapine (MIR). In a double-blind randomized study, 10 patients received treatment with IMI and 10 patients received treatment with MIR. Cardiovascular parameters were studied before and after 4 weeks of treatment: HR and BP (Finapres) were recorded continuously during supine rest (SR) and orthostatic challenge (OC; 60-degrees head-up tilting). During SR and OC, power spectra were calculated for HR and systolic BP. Spectral density was assessed for three frequency bands: low (0.02-0.06 Hz), mid (0.07-0.14 Hz), and high (0.15-0.50 Hz). Before treatment, the depressed patients (N = 20) differed from age-matched controls (N = 20) only in their response to OC: the depressed patients showed more suppression of HR variability (both mid- and high-frequency band fluctuations), indicating stronger vagal inhibition, and a reduced increase of BP variability (mid-frequency band fluctuations), indicating reduced sympathetic activation. After 4 weeks of treatment, patients treated with either antidepressant drug showed significant changes of HR (increase) and HR variability (decrease) during SR and OC; the suppression of mid- and high-frequency fluctuations of HR was larger for IMI than for MIR. The increase in HR and decrease in HR variability may be attributed to the anticholinergic properties of IMI (strong) and MIR (weak), resulting in cardiac vagal inhibition. Whereas MIR had no effect on BP or BP variability, IMI specifically reduced mid-frequency band fluctuations of BP as the result of a suppression of central sympathetic activity. Our data confirm and extend previous observations on the presence of autonomic dysfunctions in unmedicated depressed patients: spectral analysis of HR and BP fluctuations suggested that both parasympathetic and sympathetic mechanisms are involved, specifically during OC. The preexisting autonomic cardiovascular dysfunctions were not normalized by antidepressant drugs. In fact, some of the components of the cardiovascular autonomic dysfunction were further aggravated, depending on the pharmacologic profile of the drug under investigation.

Adult↗

PubMed2005

Cardiovascular dysautonomia in de novo Parkinson's disease.

BACKGROUND: Clinical symptoms of Parkinson's disease (PD) include not only motor distress, but also autonomic dysfunction. OBJECTIVE: To clarify the progression of autonomic nervous dysfunction in PD. METHODS: The subjects were 44 patients with de novo PD. Autonomic nervous function, including cardiac sympathetic gain, was evaluated on the basis of cardiac radioiodinated metaiodobenzylguanidine (MIBG) uptake, the response to the Valsalva maneuver, and spectral analyses of the RR interval and blood pressure. RESULTS: Decreased cardiac MIBG uptake was found even in patients with early stage PD. MIBG uptake gradually decreased with increased disease severity. Hemodynamic studies using the Valsalva maneuver revealed that patients with early stage PD had reduced baroreceptor reflex sensitivity (BRS) in phase II, but not phase IV. Blood pressures normally rose in phases II and IV, but the increments decreased with disease progression. In early stage PD, the low frequency power of the RR interval (RR-LF) and the ratio (LF/HF) of RR-LF to the high frequency component of the RR interval (RR-HF) were significantly lower than the respective control values, despite no significant difference in RR-HF; these variables decreased with disease progression. CONCLUSION: Our results show that latent sympathetic nervous dysfunction without parasympathetic dysfunction, especially that involving the sinus node, is already present in early stage de novo PD. It is unclear whether the responsible lesion is central or peripheral.

3-Iodobenzylguanidine↗

PubMedDate not supplied

Diabetic autonomic neuropathy: the prevalence of impaired heart rate variability in a geographically defined population.

The prevalence of diabetic autonomic neuropathy and its relationship with other diabetic complications were studied in a geographically defined population. Heart rate variability was measured by a computerized technique at rest and in response to both a single deep breath and a Valsalva manoeuvre. Among 43 Type 1 (insulin-dependent) and 202 Type 2 (non-insulin-dependent) patients results below the 2.5 centile for age-related normal ranges occurred in 9 Type 1 and 32 Type 2 patients (16.7, 95% Cl 12.6 to 21.9, %). Symptomatic autonomic neuropathy was uncommon but was significantly more frequent in Type 1 than Type 2 patients (5 Type 1, 1 Type 2, p less than 0.001 Fisher's exact test). In Type 1 diabetes, cardiovascular autonomic dysfunction was significantly associated with impaired vibration perception and a higher logarithmic urinary albumin concentration and, in Type 2 diabetes, it was associated with a significantly higher body mass index, systolic blood pressure, and logarithm of the urinary albumin and fasting insulin concentrations. The aggregation of these factors with cardiovascular autonomic dysfunction suggests that mortality might be increased in Type 2 patients with asymptomatic autonomic neuropathy.

Adult↗

PubMed2004

Systemic autonomic function in subjects with primary angle-closure glaucoma: a comparative study of symptomatic and asymptomatic disease presentation.

BACKGROUND: Autonomic dysfunction is thought to be a contributory factor in primary angle-closure glaucoma (PACG) by precipitating pupil block in anatomically predisposed eyes. This study aimed to compare systemic autonomic function between subjects who had suffered a previous episode of acute angle closure (symptomatic PACG), those who had asymptomatic PACG, and age and sex-matched controls. METHODS: Tests for systemic parasympathetic function included the heart-rate response to standing (30:15 ratio), heart-rate variation during deep breathing, and the ratio of the heart rate at phases IV and II of the Valsalva manoeuvre (Valsalva ratio). For assessment of the sympathetic nervous system, blood pressure was recorded supine and then after 2 and 5 min of standing. A modified sweat test, the sympathetic skin response, was recorded on the palm and sole. RESULTS: A total of 30 subjects were examined: eight previous symptomatic PACG, eight asymptomatic PACG and 14 control subjects. The mean ages were similar, and all except one subject were Chinese. None of the subjects had evidence of systemic dysautonomia. There was no significant difference found between the groups for the 30:15 ratio, heart-rate variation during deep respiration and the Valsalva ratio. No significant orthostatic hypotension was detected in subjects with PACG. Abnormal sympathetic skin response was not more common in PACG subjects compared to control subjects. CONCLUSIONS: This study identified no systemic autonomic dysfunction in people with PACG.

Autonomic Nervous System↗

PubMed2001

Abnormal sympathovagal balance in men with fibromyalgia.

OBJECTIVE: It is possible that there are differences in clinical manifestations between men and women with fibromyalgia syndrome (FM), especially in autonomic dysfunction; we assessed the interaction between the sympathetic and parasympathetic systems in postural change in men with FM using power spectral analysis (PSA) of heart rate variability (HRV), and investigated the pathogenesis of the orthostatic intolerance. METHODS: We studied 19 men with FM and 19 controls matched for age and sex. A high resolution electrocardiogram was obtained in supine and standing postures during complete rest. Spectral analysis of R-R intervals was done by the fast Fourier transform algorithm. RESULTS: PSA of HRV revealed that men with FM at rest are characterized by sympathetic hyperactivity and concomitantly reduced parasympathetic activity. During postural changes, male patients demonstrated an abnormal sympathovagal response. These results provide the physiological basis for the orthostatic intolerance in men with FM. CONCLUSION: This report of autonomic dysfunction in men with FM revealed an abnormal autonomic response to orthostatic stress. This abnormality may have implications regarding the symptoms of FM.

Adult↗

PubMed1990

A quantitative evaluation of pontine volume by computed tomography in patients with cerebellar degeneration.

We used CT to make a quantitative evaluation of the pontine volumes of 55 patients with adult-onset cerebellar degeneration and compared the results with their clinical records. Patients with pontine atrophy showed significantly more autonomic dysfunction and extrapyramidal signs; their other clinical features did not differ from patients without pontine atrophy. After dividing the patients into 2 groups, those with and without autonomic dysfunction or extrapyramidal signs, we found that those with these manifestations also had pontine atrophy, a later onset and shorter duration of the disease, and impairment of higher brain functions. The group without these manifestations had relatively normal pontine volume, a greater familial tendency for cerebellar degeneration, and longer duration of the disease. Our results suggest that quantitative volume evaluation of the pons by CT is important for the clinical categorization of cerebellar degeneration.

Atrophy↗

PubMed1997

Complex regional pain syndromes: including "reflex sympathetic dystrophy" and "causalgia".

"Reflex sympathetic dystrophy" and "causalgia" are now classified by the International Association for the Study of Pain as Complex Regional Pain Syndromes I and II. Sympathetically maintained pain is a frequent but variable component of these syndromes, as the sympathetic and somatosensory pathways are no longer functionally distinct. Pain is the cardinal feature of CRPS, but the constellation of symptoms and signs may also include sensory changes, autonomic dysfunction, trophic changes, motor impairment and psychological changes. Diagnosis is based on the clinical picture, with additional information regarding the presence of sympathetically maintained pain or autonomic dysfunction being provided by carefully performed and interpreted supplemental tests. Clinical experience supports early intervention with sympatholytic procedures (pharmacological or nerve block techniques), but further scientific data is required to confirm the appropriate timing and relative efficacy of different procedures. Patients with recurrent or refractory symptoms are best managed in a multi-disciplinary pain clinic as more invasive and intensive treatment will be required to minimize ongoing pain and disability.

Causalgia↗

PubMedDate not supplied

Failure of improved glycaemic control to reverse diabetic autonomic neuropathy. The St Thomas's Diabetic Study Group.

A prospective trial was conducted in 20 insulin-treated diabetic patients with established autonomic dysfunction to test the effect of a 2-year improvement in glycaemic control. On entry, the patients aged 34.6 +/- 10.8 years (mean +/- SD), duration 20.2 +/- 10.4 years, had evidence of poor control (HbA1 greater than 9.5% on at least two consecutive tests, and at least one abnormality in the 11 different neuropathic function tests used. These included four of pupillary function, six of cardiovascular function and one of vibration sensitivity. The method used to improve control was conventional insulin treatment combined with home monitoring of blood glucose and regular adjustment of insulin dosage under the supervision of a diabetic specialist nursing sister. The HbA1 level on entry was 13.0 +/- 0.7% (mean +/- SEM) which fell to 10.4 +/- 0.4% at 3 months and to 9.3 +/- 0.4% at 24 months. The neuropathy tests were performed at 0, 3, 6, 12, 18, and 24 months and significant changes were recorded in five. These changes (in two pupillary and three cardiovascular tests) all indicated worsening function which exceeded that explicable by aging. One cardiovascular test showed slower rates of deterioration in patients achieving the greatest improvements in control. It was concluded that a prolonged period of improved control failed to reverse established autonomic dysfunction of diabetes.

Adolescent↗