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PubMed2000

The postural orthostatic tachycardia syndrome: a potentially treatable cause of chronic fatigue, exercise intolerance, and cognitive impairment in adolescents.

Head upright tilt table testing has become an accepted method to measure an individual's predisposition to autonomically mediated periods of hypotension and bradycardia severe enough to cause frank syncope. At the same time it has become increasingly apparent that less profound falls in blood pressure, while not sufficient to result in loss of consciousness, may cause symptoms such as near syncope, vertigo, and dizziness. We describe a subgroup of adolescents that have a mild form of autonomic dysfunction that exhibit disabling symptoms such as postural tachycardia and palpitations, extreme fatigue, lightheadedness, exercise intolerance, and cognitive impairment. During baseline tilt table testing at a 70 degrees angle, these patients demonstrated a heart rate increase of > or = 30 beats/min (or a maximum heart rate of > or = 120 beats/min) within the first 10 minutes upright (not associated with profound hypotension), which reproduced their clinical symptom complex. Similar observations have been made in the adult population and has been termed the postural orthostatic tachycardia syndrome (POTS). We report that POTS may also occur in adolescents and represents a mild, potentially treatable form of autonomic dysfunction that can be readily identified during head upright tilt table testing.

Adolescent↗

PubMed1990

Orthostatic hypotension, catecholamines, and alpha-adrenergic receptors in mitral valve prolapse.

The reported association of mitral valve prolapse with autonomic dysfunction and neuroendocrine abnormalities is derived from studies of patients selected because of symptoms or specifically referred for investigation. To determine whether such associations occur in nonreferred and unselected women with mitral valve prolapse, we measured blood pressure, heart rate, and norepinephrine response to standing in 13 volunteers with mitral valve prolapse and in 11 control subjects. Platelet alpha-adrenergic receptor quantity and affinity on standing also were determined in all persons. No significant differences were found between the groups in any of these measurements. Although small subsets of women with mitral valve prolapse may indeed have associated neuroendocrine epiphenomena and autonomic dysfunction, it is probably incorrect to generalize these findings to the vast spectrum of those with mitral valve prolapse.

Adolescent↗

PubMed1991

Diastolic time in diabetes. Impairment of diastolic time during dynamic exercise in type 2 diabetes with retinopathy.

To evaluate the effect of microangiopathic complications and autonomic dysfunction on diastolic time (DT) during dynamic exercise, 19 patients with type 2 diabetes and ten normal subjects were studied using ear densitography. All subjects had neither an ischemic electrocardiographic response nor chest pain during maximal treadmill exercise. The DT and heart rate (HR) had an inverse nonlinear relation, and electromechanical systole (QS2) and HR had an inverse linear relation during exercise. When the exercise DT-HR and QS2-HR relations were compared, a significant lengthening of QS2, with a consequent shortening of DT, was observed in diabetic patients with retinopathy, compared to patients without retinopathy and normal subjects (p less than 0.005), while no significant differences were found between diabetic patients without retinopathy and normal subjects; however, there were no significant differences in the exercise DT-HR and QS2-HR relations among diabetic patients with and without autonomic dysfunction and normal subjects. A more prominent abbreviation in the diastolic perfusion time observed in patients with retinopathy would be meaningful because microangiopathy might already have limited subendocardial blood flow. Thus, patients with type 2 diabetes who have retinopathy have a potential risk of aggravation of left ventricular function through the deterioration of myocardial blood flow.

Autonomic Nervous System Diseases↗

PubMed1994

[Three siblings homozygous for the transthyretin-Met30 gene in familial amyloidotic polyneuropathy--evaluation of their clinical pictures with reference to those of other 10 cases reported].

We reported clinical pictures of three siblings homozygous for a transthyretin-Met30 (TTR-Met30) gene in a family with familial amyloidotic polyneuropathy (FAP) type I residing in Kanazawa city, and evaluated their clinical pictures with reference to those of other 10 cases previously reported. Ages at onset of two homozygous patients with FAP were 58 and 68 years. They showed sensory-dominant polyneuropathy and mild autonomic dysfunctions. One of them showed vitreous opacities and the other showed multifocal white sheaths along the retinal blood vessels and obstruction of the vessels. A morphometric study of the sural nerve in one patient showed a marked reduction in both myelinated and unmyelinated nerve fiber densities. The third subject was an asymptomatic carrier aged 59 years. The studies of our cases and those in the literature have shown the clinical features of homozygotes for the TTR-Met30 gene as follows: (1) all the homozygous subjects belong to families with incomplete penetrance of the disorder; (2) the clinical features common to 10 symptomatic homozygotes are late onset, mild autonomic dysfunctions, and high frequency of ocular amyloidosis; (3) there are three asymptomatic cases. In addition to TTR-Met30 abnormality, some unknown mechanisms that control its deposition into the tissues are presumed to be involved for the onset of FAP.

Aged↗

PubMed2001

Post-neonatal tetanus: issues in intensive care management.

Tetanus is an acute neurological disease characterized by muscle rigidity and spasms, autonomic dysfunction and in severe forms requires respiratory and hemodynamic support. Though it is entirely preventable by immunization, it still occurs in developing countries causing significant morbidity and mortality. Intensive care management of tetanus is fraught with problems of ventilator-associated pneumonia, nosocomial sepsis and a variety of other complications. Various treatment protocols have been tried in managing diverse manifestations of severe tetanus but the consensus is yet to emerge. In this review we have discussed the pathophysiology, clinical features and management controversies and suggest on basis of our experience use of high dose diazepam (20-120 mg/kg/day) and vecuronium with mechanical ventilation if required for control of spasms, and early detection of autonomic dysfunction and use of propranolol, in our circumstances.

Child↗

PubMed1994

Fever of central origin in traumatic brain injury controlled with propranolol.

Central fevers are known to develop in traumatic brain injury (TBI) and are believed to be caused by injury involving the hypothalamus. Described are three patients admitted with very severe TBI secondary to motor vehicle accidents. Initial Glasgow Coma Score ratings were 3 or 4. Head computed tomography (CT) scans showed intraventricular hemorrhage in two cases and no focal injury or bleeding in the third. All patients had decorticate posturing and symptoms of autonomic dysfunction, manifested by tachycardia and profuse sweating. Each of these patients developed high fevers ranging from 38.9 degrees C to 40.6 degrees C during their hospitalization course. Centrally mediated fevers were indicated after fever workups failed to show an infectious or inflammatory source. Propranolol 20 to 30 mg every 6 hours reduced the temperatures at least 1.5 degree C within 48 hours. In each case, when weaning from propranolol was attempted, an increase in temperature to greater than 38.0 degrees C reoccurred within 3 days. Repeat workups for infectious or inflammatory causes of fever were negative. The fevers were reduced after a reinstitution of propranolol. The propranolol was continued until all signs of autonomic dysfunction abated. Central fevers after TBI have been reported to have been treated successfully with propranolol in two children with decerebrate posturing. Pharmacological, neurophysiological, and anatomic studies provide evidence of a significant central nervous system role in the regulation of blood pressure and temperature.

Accidents, Traffic↗

PubMed1993

[MRI findings in patients with acute autonomic and sensory neuropathy].

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

Acute Disease↗

PubMed2002

The visuo-cognitive and motor effect of amantadine in non-Caucasian patients with Parkinson's disease. A clinical and electrophysiological study.

It has been reported that non-Caucasian populations often suffer from an atypical type of Parkinson's disease (PD) characterized by poor levodopa response, early cognitive impairment and autonomic dysfunction. We tested the effect of a well known antiparkinsonian compound, amantadine, in 23 Afro-American patients with PD in a time-limited (six months), open-label, clinical and electrophysiological (simultaneously recorded primary and cognitive visual evoked potentials) trial. Patients were given amantadine either as monotherapy (first group) or added to levodopa treatment (second group). Amantadine produced a significant (p < 0.05) shortening of the latency of the event related potential (P300) obtained in a visual discrimination paradigm, while the timing of primary visual evoked potentials was little or not at all affected. Amantadine also showed significant beneficial effects (p < 0.01) on the motor score of both groups as assessed by the Rated Parkinson's Disease Neurological Exam, including items related to autonomic dysfunction. These findings suggest that amantadine alone and as adjuvant to levodopa can significantly improve both the speed of visual cognitive processing and the clinical score in non caucasian patients with PD. For these populations amantadine can be thus considered a helpful therapeutical option.

Black or African American↗

PubMed1985

24-hour blood pressure recording in patients with orthostatic hypotension.

Continuous intra-arterial blood pressure measurement and electrocardiograms were obtained in two ambulatory patients with orthostatic hypotension due to autonomic dysfunction. Systolic and diastolic arterial pressure presented marked variations which took place mainly during the day and were related to several physical activities; however, marked falls in blood pressure were also observed during sleep and at the moment of arousal. A peak incidence of hypotensive events was found in the afternoon, mainly in the hours following the afternoon meal. Recording was repeated after 3 weeks of treatment with propranolol, 40 mg t.i.d. In patient 1, beta blockade drastically reduced the number and severity of hypotensive episodes, while propranolol failed to control blood pressure in patient 2, who experienced a higher number of hypotensive events during treatment. Findings of this study may be relevant to the management of patients with orthostatic hypotension and should contribute to a more accurate characterization of blood pressure profile in autonomic dysfunction.

Blood Pressure↗

PubMed1995

[Relationship between impaired blood pressure control and multiple system involvement in chronic alcoholics].

Chronic ethyl alcohol (ethanol) abuse is associated with different types of neurological involvement. Impaired blood pressure control such as in hypertension and/or orthostatic hypotension is a known autonomic dysfunction in chronic alcoholics. Although abstinence appears to improve blood pressure, the precise mechanisms underlying the effects of alcohol remain unknown. We suspected that abnormal blood pressure might influence the outcome of alcohol-related neurological symptoms. We therefore reviewed the alcohol history of 28 male patients admitted to our hospital with multiple system involvement. No family history of spinocerebellar degeneration was found. All of the patients had a history of chronic alcohol abuse. The duration of alcohol abuse in 28 patients was 28.8 + 11.2 yrs. Daily ethanol consumption was less than 83 ml in 6 patients between 83 ml and 138 ml in 11 and more than 138 ml in 11. We assessed the relationship between impaired blood pressure control, clinical characteristics, and outcome after abstinence for a period ranging from 30 days to 6 years in 22 chronic alcoholics who had drunk more than 83 ml/day. All of the patients had various types of autonomic dysfunction, and a high incidence of impaired blood pressure control and decreased CVR-R were noted. The symptoms improved or even completely resolved after cessation of alcohol consumption, however, 8 of the 22 patients in our study reached a plateau and have permanent symptoms. Patients with no improvement as a result of abstinence had a long history of excessive drinking. Brain CT/MRI, SPECT and P300 studies were conducted. SPECT and P300 were performed in both the supine and standing position in 5 and 7 patients, respectively. Five patients who had severe orthostatic hypotension with syncope were found to have cerebrovascular lesions on MRI. Changes in P300 amplitude and/or distribution and latency were noted after a fall in blood pressure. Although the etiology of impaired blood pressure control in alcoholics remains unknown, we believe that abnormal blood pressure affects the outcome of alcohol-related neurological symptoms.

Adult↗

PubMed1992

Assessment of cardiovascular autonomic function: age-related normal ranges and reproducibility of spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses.

To establish normal ranges for assessment of autonomic dysfunction, a battery of cardiovascular reflex tests was performed in 120 healthy subjects aged 15-67 years using a computer-based technique. Tests of heart rate variation (HRV) included 8 measures at rest: coefficient of variation (CV), root mean squared successive difference (RMSSD), spectral analysis of HRV in the low frequency, mid frequency, and high frequency bands in the supine and standing postures; 5 measures during deep breathing: CVb, RMSSDb, Expiration-Inspiration (E-I) difference, E/I ratio, and mean circular resultant of vector analysis; Valsalva ratio, and max/min 30:15 ratio. In addition, the change in systolic and diastolic blood pressure in response to standing and the diastolic blood pressure response to sustained handgrip were determined. The results of all measures, the blood pressure tests excepted, declined significantly with increasing age (r = -0.16 to -0.59; p less than 0.05). Moreover, RMSSD, RMSSDb, and E-I difference decreased considerably with increasing heart rate (r = -0.37 to -0.52; p less than 0.001). The longest and shortest R-R intervals in response to standing were distributed within beats 21-39 and 6-24, respectively. All tests were independent of sex. Log transformation was used to define the age-related lower limits of normal at the 2.3 centile for all tests of HRV, except for the E/I, Valsalva, and max/min 30:15 ratios. The results of these tests had to be analysed using a log(y-1) transformation. The intra-individual reproducibility determined on two consecutive days in 20 healthy subjects and 21 diabetic patients indicated that there were no major differences between the two groups regarding the day-to-day variation of test results, which was highest for the Valsalva ratio. We conclude that: (1) all indices of spectral and vector analyses of HRV are age-dependent and have the advantage of being independent of heart rate; (2) RMSSD, E-I difference, and the 30:15 ratio as it was used previously are not suitable for evaluation of autonomic dysfunction in diabetes; (3) log(y-1) transformation is required to determine age-dependent normal ranges and reproducibility for the three ratios.

Adolescent↗

PubMedDate not supplied

Cortical, brainstem and autonomic nervous system dysfunction in infants with post-hemorrhagic hydrocephalus.

OBJECTIVE: The aim of this study was to evaluate the degree of central and autonomic dysfunction by means of electroencephalographic (EEG) and cardio-pneumographic recording (CPGR) in infants with Post-Hemorrhagic Hydrocephalus (PHH). METHODS: Nineteen infants with PHH were studied, born from October 1998 to January 2000. Clinical diagnosis was confirmed by cephalic perimeter measurement and ultrasonographic study. Eight channel bipolar EEG and CPGR were performed after sleep deprivation, EEG features studied were: Temporal organization, symmetry, synchrony, frequency of normal and abnormal patterns. CPGR features studied were: Frequency of apnea and temporal organization by means of beat to beat variability. RESULTS: Averages of birth's age and weight, Apgar scores at one and five minutes, and cephalic perimeter showed lower values in PHH infants. PHH infants showed abnormalities in EEG and CPGR such as: Higher discontinuous activity (63%), asymmetry (73%), asynchrony (89%), abnormal EEG patterns (89%), apnea (26%) and absence of heart rate variability (63%). CONCLUSIONS: EEG and CPGR recordings are a useful tools in the examination of infants with PHH. These findings suggest cortical-subcortical, and brainstem dysfunction with severe encephalopathy and autonomic nervous dysfunction related to ventricular dilatation in infants with PHH.

Apgar Score↗

PubMed2000

Lack of autonomic nervous dysfunction in progressive supranuclear palsy, a study of blood pressure variability.

Blood pressure and heart rate variability were analyzed in eight patients with progressive supranuclear palsy in comparison with two control groups (10 healthy patients and 10 patients with multiple system atrophy). Blood pressure and heart rate were recorded using digital photoplethysmography with the patient in supine position and during a head-up-tilt test (70 degrees for 10 minutes). Spectral analysis was performed using fast Fourier transformation for 512 consecutive systolic blood pressure and heart rate values. The head-up-tilt test induced a significant increase in systolic blood pressure in patients with progressive supranuclear palsy and in healthy patients and a significant systolic blood pressure decrease in patients with multiple system atrophy. During the head-up-tilt test, low-frequency energy of systolic blood pressure (70-130 mHz) that reflected baroreflex-dependent sympathetic tone also increased in patients with progressive supranuclear palsy and in healthy patients. By contrast, in patients with multiple system atrophy, the low-frequency energy of systolic blood pressure decreased significantly. The changes observed in the low-frequency band and the high-frequency band of heart rate (reflecting parasympathetic drive to the heart) were not different among the three groups. These data show the lack of impairment in autonomic nervous system activity in patients with progressive supranuclear palsy.

Aged↗

PubMed2005

Serotonin syndrome and the anaesthetist.

Serotonin syndrome results from excessive activation of serotonin (5-hydroxytryptamine; 5-HT) receptors in the nervous system, on the surface of platelets, and on the vascular endothelium. The clinical manifestations are a triad of altered conscious state, autonomic dysfunction, and neuromuscular excitability. Clinical diagnostic criteria remain poorly defined and unvalidated, and there are no available investigations to confirm the diagnosis. The syndrome is caused by the administration of one or more drugs possessing serotonergic activity. Severe forms of the syndrome usually result from overdose, but can be induced by monotherapy. The exact incidence of serotonin syndrome remains unknown, but is likely to be increasing due to increased prescription of selective serotonin reuptake inhibitor antidepressants and tramadol, as well as recreational use of amphetamine-like substances. Serotonin syndrome may complicate the administration of drugs frequently used in anaesthetic practice, including pethidine and tramadol. Although the majority of cases improve with symptomatic and supportive care, severe cases need intensive care and frequently require mechanical ventilation. Neuromuscular excitability is likely to be the cause of rhabdomyolysis seen in severe cases and should be treated with benzodiazepines and muscle relaxants. Supportive therapies are required to treat hyperthermia and autonomic dysfunction. Cyproheptadine is the most commonly administered serotonergic antagonist, but is unavailable in parenteral form.

Analgesics, Opioid↗

PubMed2004

Effect of erythropoietin on cardiovascular prognosis parameters in hemodialysis patients.

BACKGROUND: Renal anemia is an important determinant for left ventricular hypertrophy in dialysis patients and an independent prognosis parameter for the cardiovascular survival in dialysis patients. In addition, an autonomic dysfunction is associated with the uremic state and influences the cardiovascular risk in patients with end-stage renal disease (ESRD). METHODS: We investigated in this prospective longitudinal study the effect of hemoglobin normalization by a chronic treatment with recombinant human erythropoietin (rhEPO) on cardiovascular prognosis parameters in 23 patients on chronic hemodialysis with renal anemia (hemoglobin concentration < or =10.5 g/dL) and echocardiographically proven left ventricular hypertrophy. We studied muscle sympathetic nerve activity measured by microneurography; cardiopulmonary baroreflex activity by lower-body negative pressure (LBNP-) testing; left ventricular structure and mass index (LVMI) by echocardiography; blood pressure by 24-hour readings; peripheral blood flow and vascular resistance by plethysmography before (U1) and after 7 months of chronic rhEPO treatment (U2). RESULTS: In the anemic state, mean (+/- SD) muscle sympathetic nerve activity in ESRD was elevated (U1 rest, 34 +/- 13 bursts per minute) and cardiopulmonary baroreflex response during LBNP markedly lacking (U1 -15 mm Hg, 34 +/- 13 bursts per minute) reflecting a severely impaired autonomic function. Normalization of the hemoglobin concentration by chronic rhEPO treatment (U1, 10.5 +/- 0.9 g/dL versus U2, 13.4 +/- 3.1 g/dL, P <0.001) did not influence sympathetic nerve activity (U2, 34 +/- 15 bursts per minute, NS) and cardiopulmonary baroreflex sensitivity did not change (U2 -15 mm Hg, 37 +/- 16 bursts per minute, NS). LVMI decreased significantly after chronic treatment with rhEPO (U1, 134 +/- 26 g/m2 versus U2, 97 +/- 25 g/m2, P < 0.001) and left ventricular geometry developed from an asymmetric to a symmetric configuration (U1, relative wall thickness 0.58 versus U2, 0.43, P < 0.001). Under treatment with rhEPO, 24-hour systolic and diastolic blood pressure did not increase (systolic U1, 132 +/- 4 mm Hg versus U2, 128 +/- 3 mm Hg, NS, and diastolic U1, 76 +/- 2 mm Hg versus U2, 73 +/- 2 mm Hg, NS). Peripheral blood flow (U1, 6.1 +/- 3.3 mL/100 mL/min versus U2, 6.2 +/- 0.6 mL/100 mL/min, NS) as well as forearm vascular resistance (U1, 15.7 +/- 3.3 mm Hg/mL/100 mL versus U2, 14.9 +/- 3.1 mm Hg/mL/100 mL, NS) did not change by chronic rhEPO treatment. CONCLUSION: Normalization of hemoglobin by chronic rhEPO treatment in dialysis patients has beneficial cardiovascular effects with regression of left ventricular hypertrophy and improvement of left ventricular geometry. However, a reduction of sympathetic overactivity or a resetting of baroreceptor sensitivity by a rhEPO treatment in dialysis patients in the medium-term could not be demonstrated. The reason for this may be the complex and multifactorial pathomechanism of autonomic dysfunction and cardiovascular disease in ESRD.

Adult↗

PubMed2004

Heart rate variability in sarcoidosis: a frequency domain analysis.

BACKGROUND: Little is known about autonomic dysfunction in patients with sarcoidosis. Heart rate variability (HRV) studies provide information regarding sympathetic and vagal tone and are both noninvasive and relatively simple to perform. The objective of this study was to compare HRV in sarcoidosis patients and in healthy controls. METHODS: We prospectively analyzed data from 12 sarcoidosis patients and 12 healthy volunteers. Electrocardiographic (ECG) data were recorded from all study participants, and HRV analysis was performed in the frequency domain. The sarcoidosis patients underwent echocardiography as well. RESULTS: Mean values for HRV in the high-frequency (HF) domain were significantly reduced in sarcoidosis patients (182+/-102 ms(2) vs. 758+/-457 in controls, p=0.001). We also observed a trend (p=0.055) towards an increased ratio of low-frequency (LF) to high-frequency power in sarcoidosis patients. CONCLUSIONS: Our findings indicate the possibility of altered sympathovagal balance in sarcoidosis. Since 5 of these 12 sarcoidosis patients had mild echocardiographic abnormalities, possibly related to sarcoidosis, we were unable to conclude whether the HRV findings were attributable solely to an autonomic dysfunction in sarcoidosis or whether they were related to a structural myocardial involvement of the disease.

Journal Article↗

PubMed2004

Small intestinal bacterial overgrowth: a framework for understanding irritable bowel syndrome.

CONTEXT: Irritable bowel syndrome (IBS), which affects 11% to 14% of the population, is a puzzling condition with multiple models of pathophysiology including altered motility, visceral hypersensitivity, abnormal brain-gut interaction, autonomic dysfunction, and immune activation. Although no conceptual framework accounts for all the symptoms and observations in IBS, a unifying explanation may exist since 92% of these patients share the symptom of bloating regardless of their predominant complaint. EVIDENCE ACQUISITION: Ovid MEDLINE was searched through May 2004 for relevant English-language articles beginning with those related to bloating, gas, and IBS. Bibliographies of pertinent articles and books were also scanned for additional suitable citations. EVIDENCE SYNTHESIS: The possibility that small intestinal bacterial overgrowth (SIBO) may explain bloating in IBS is supported by greater total hydrogen excretion after lactulose ingestion, a correlation between the pattern of bowel movement and the type of excreted gas, a prevalence of abnormal lactulose breath test in 84% of IBS patients, and a 75% improvement of IBS symptoms after eradication of SIBO. Altered gastrointestinal motility and sensation, changed activity of the central nervous system, and increased sympathetic drive and immune activation may be understood as consequences of the host response to SIBO. CONCLUSIONS: The gastrointestinal and immune effects of SIBO provide a possible unifying framework for understanding frequent observations in IBS, including postprandial bloating and distension, altered motility, visceral hypersensitivity, abnormal brain-gut interaction, autonomic dysfunction, and immune activation.

Anti-Bacterial Agents↗

PubMed2004

Autonomic and sensory nerve dysfunction in primary biliary cirrhosis.

AIM: Cardiovascular autonomic and peripheral sensory neuropathy is a known complication of chronic alcoholic and non-alcoholic liver diseases. We aimed to assess the prevalence and risk factors for peripheral sensory nerve and autonomic dysfunction using sensitive methods in patients with primary biliary cirrhosis (PBC). METHODS: Twenty-four AMA M2 positive female patients with clinical, biochemical and histological evidence of PBC and 20 age matched healthy female subjects were studied. Five standard cardiovascular reflex tests and 24-h heart rate variability (HRV) analysis were performed to define autonomic function. Peripheral sensory nerve function on median and peroneal nerves was characterized by current perception threshold (CPT), measured by a neuroselective diagnostic stimulator (Neurotron, Baltimore, MD). RESULTS: Fourteen of 24 patients (58%) had at least one abnormal cardiovascular reflex test and thirteen (54%) had peripheral sensory neuropathy. Lower heart rate response to deep breathing (P = 0.001), standing (P = 0.03) and Valsalva manoeuvre (P = 0.01), and more profound decrease of blood pressure after standing (P = 0.03) was found in PBC patients than in controls. As a novel finding we proved that both time domain and frequency domain parameters of 24-h HRV were significantly reduced in PBC patients compared to controls. Each patient had at least one abnormal parameter of HRV. Lower CPT values indicated hyperaesthesia as a characteristic feature at peroneal nerve testing at three frequencies (2000 Hz: P = 0.005; 250 Hz: P = 0.002; 5 Hz: P = 0.004) in PBC compared to controls. Correlation of autonomic dysfunction with the severity and duration of the disease was observed. Lower total power of HRV correlated with lower CPT values at median nerve testing at 250 Hz (P = 0.0001) and at 5 Hz (P = 0.002), as well as with those at peroneal nerve testing at 2000 Hz (P = 0.01). CONCLUSION: Autonomic and sensory nerve dysfunctions are frequent in PBC. Twenty-four-hour HRV analysis is more sensitive than standard cardiovascular tests for detecting of both parasympathetic and sympathetic impairments. Our novel data suggest that hyperaesthesia is a characteristic feature of peripheral sensory neuropathy and might contribute to itching in PBC. Autonomic dysfunction is related to the duration and severity of PBC.

Aged↗