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PubMed1989

Autonomic neuropathy in familial amyloidotic polyneuropathy. A clinical study based on heart rate variability.

Familial amyloidotic polyneuropathy (FAP) is characterized by both sensimotor and autonomic dysfunction. Autonomic disturbance involving the gastrointestinal tract, the urinary bladder, the cardiac conduction system, and the peripheral circulation has been described. In this study simple, non-invasive tests of autonomic function based on heart rate variability were applied to 12 patients with FAP and 12 healthy volunteers. The heart rate variation during normal breathing, deep breathing and during tilt from recumbent to standing position was measured. All tests showed significantly less heart rate variation in patients than in controls and the heart rate variation decreased with increasing severity of neurological disability, but the small number of patients in our study does not allow any further comparison between subgroups. Our study thus indicates impaired cardiovascular autonomic function in patients with FAP and we believe that these findings might also be of importance in other forms of systemic amyloidosis.

Adult↗

PubMed1982

Clinical aspects of autonomic nerve dysfunction of the gut.

Autonomic dysfunction leads to a variety of clinical disorders involving all parts of the gut. These neural disorders are distinct from the four other recognised categories of disorders involving myogenic function, myoelectric activity, hormonal regulation and abnormal humoral factors. Criteria for establishing that a disorder has a neurogenic aetiology vary in different diseases. Absence of a neural mediated response with intact muscle function has been the major criterion used in most studies. Neural mediated responses of peristalsis, sphincteric relaxation and intestinal contraction following distension or feeding are the major parameters of assessment. Abnormalities in neural function have been demonstrated in achalasia, symptomatic diffuse oesophageal spasm, diabetes mellitus, amyloidosis, scleroderma and chronic idiopathic intestinal pseudoobstruction. The anatomical site and type of gut neurological disorder varies in each condition. Morphological studies have been helpful in demonstrating specific intranuclear inclusion bodies in some pseudoobstruction patients, and vagal and ganglionic lesions in achalasia. Intact muscle ad myoelectric function as well as normal responsiveness to drugs acting directly upon muscle may be established by morphological study. Advancement in basic technology should provide a rewarding area for future study of the pathogenesis and treatment of the gut neurological disorders.

Amyloidosis↗

PubMed1994

Correlation of altered Q-T interval and sympathetic nervous system dysfunction in diabetic autonomic neuropathy.

We examined the relationship between the Q-T interval and autonomic dysfunction in 74 diabetic patients and age-matched controls. The expected Q-T interval was standardized as a function of the R-R interval in 646 healthy controls, and the delta Q-T defined as the difference from the expected value. Propranolol increased delta Q-T, confirming this as a parameter of autonomic function. No relationship between delta Q-T and duration of disease, glucose control, retinopathy or proteinuria was observed. However, significant correlations were found between the delta Q-T and delay of nerve conduction velocity, orthostatic hypotension, altered Valsalva ratio, abnormal Valsalva overshoot, cold pressor response, decreased norepinephrine concentration and sympathetic function score in diabetic patients.

Adult↗

PubMed2002

Cardiovascular autonomic function in systemic lupus erythematosus.

AIM: To determine whether cardiovascular autonomic function is impaired in systemic lupus erythematosus (SLE). METHODS: A case-control study of 23 patients with SLE was performed. Autonomic symptoms were assessed using a standard questionnaire. Cardiovascular autonomic function was measured using 10 non-invasive investigations. There were significant differences between patients and controls in three out of 24 parameters measured during the different tests (P < 0.002). These were reduction in systolic blood pressure at 5 min on head-up tilt, and heart rate responses to isometric exercise and cutaneous cold. Eleven out of 23 patients had an abnormal heart rate, blood pressure or Valsalva response (value below the age corrected 5th centile) while testing compared with six of the controls. Plasma adrenaline and noradrenaline levels were significantly lower in patients vs controls in both the supine (P < 0.05) and tilt position (P < 0.01). Twenty-one of the 23 patients had one or more symptoms that may be attributable to abnormalities in autonomic function. There was no significant association between the number of symptoms and presence of autonomic dysfunction. Cardiovascular autonomic impairment may be demonstrated in some patients with SLE. Symptoms attributable to autonomic dysfunction are common in SLE and autonomic assessment may be required.

Adult↗

PubMed1989

Increased intraoperative cardiovascular morbidity in diabetics with autonomic neuropathy.

Thirty-eight consenting subjects scheduled for elective ophthalmologic surgery were classified as nondiabetics (n = 21) or diabetics (n = 17) and were tested preoperatively for autonomic dysfunction. The autonomic tests consisted of respiratory sinus arrhythmia and heart rate responses to the Valsalva maneuver to test cardiac vagal function and diastolic blood pressure responses to head-up tilt and cold pressor test to assess sympathetic efferent integrity. At a separate time, anesthesia was established with fentanyl (2 micrograms/kg), sodium thiopental (3-5 mg/kg), and vecuronium (0.1 mg/kg), and maintained with isoflurane, oxygen, and nitrous oxide. An anesthesiologist, blinded to the autonomic test results, recorded perioperative blood pressure and heart rate. The autonomic test results revealed significant autonomic dysfunction among the diabetics. Heart rate and blood pressure declined to a greater degree (P less than 0.05) during induction of anesthesia in diabetics compared with controls and there was less of an increase in these same parameters following tracheal intubation in diabetic patients. Thirty-five percent of diabetics required intraoperative vasopressors compared with only 5% of control patients (P less than 0.05). A major finding was that the diabetics who required intraoperative blood pressure support had significantly greater impairment of autonomic test results compared with those diabetics who did not need vasopressors. Diabetics are at increased risk for cardiovascular lability during anesthesia and preoperative screening of diabetics with simple noninvasive autonomic tests may be useful in identifying those at high risk for perioperative cardiovascular instability.

Anesthesia, Inhalation↗

PubMed1998

Association of autonomic nervous dysfunction and esophageal dysmotility in systemic sclerosis.

OBJECTIVE: The primary event in the pathogenesis of gastrointestinal involvement in systemic sclerosis (SSc) has been hypothesized to be an early neural lesion. We investigated the association of autonomic nervous dysfunction and esophageal involvement in SSc. METHODS: Thirty-six consecutive patients with SSc were investigated by esophageal manometry and autonomic nervous function tests for cardiovascular and pupillary autonomic dysfunction. RESULTS: In 27 of 36 patients, esophageal manometry showed esophageal dysfunction. Twelve patients had either pupillary (n = 6) or cardiovascular (n = 5) dysfunction or both (n = 1). All patients with autonomic dysfunction had esophageal dysfunction. Patients with autonomic dysfunction had significantly reduced mean distal esophageal contraction amplitudes compared to patients without autonomic nervous dysfunction (p < 0.05). The association of autonomic dysfunction and esophageal dysfunction was significant (p = 0.02). CONCLUSION: Our results support the concept of a role for neurogenic defects in the development of esophageal dysfunction in SSc.

Adolescent↗

PubMed1986

Autonomic system dysfunction and polyneuropathy in nondiabetic uremia. A one-year follow-up study after renal transplantation.

Polyneuropathy and autonomic dysfunction were studied in 15 patients with nondiabetic terminal uremia before renal transplantation and again at 6 and 12 months after the transplantation. Beat-to-beat variation of the electrocardiogram (ECG) relative to mean beat interval was used as an observation of the function of the parasympathetic vagal reflex arc. Marked autonomic dysfunction--i.e., reduced beat-to-beat variation and a mild diffuse polyneuropathy--was found. The neuropathy was mainly of axonal type, but a slowing of conduction velocities was also found. The latter was markedly improved after transplantation and is suggested to be caused by a toxic metabolic factor, possibly causing nodal dysfunction. Action potential amplitudes and autonomic function did not improve during the study. This implies a structural damage that is not repaired in 12 months. Neurological examination should be included in the care of patients with uremia, and the results should be one of the factors considered when transplantation is discussed.

Autonomic Nervous System↗

PubMed2002

Cardiovascular and respiratory consequences of bilateral involvement of the medullary intermediate reticular formation in syringobulbia.

We studied five patients with clinical and radiological evidence of syringobulbia (SB) to determine whether the distribution of lesions in relationship to the cardiorespiratory control networks in the medullary intermediate reticular zone (IRt) correlates with the presence of abnormalities in autonomic cardiovascular and respiratory control in these patients. All patients underwent high resolution MRI to characterize the size, volume and distribution of the SB lesions, cardiovascular autonomic function testing and polysomnography. One patient with bilateral IRt involvement at both the rostral and caudal medulla had orthostatic hypotension (OH), absent HR(DB), abnormal Valsalva ratio, exaggerated fall of BP during phase II and absent phase IV during VM, and a dramatic fall of BP during head up tilt; this patient also had severe obstructive sleep apnea (OSA) and exhibited BP drops during each respiratory effort. A second patient, with bilateral IRt involvement restricted to the caudal medulla, had less severe cardiovascular autonomic dysfunction but also exhibited severe OSA. The other three patients had small SB cavities sparing the IRt and had sleep apnea but no autonomic dysfunction. Autonomic dysfunction could not be related to the size of the syrinx or the degree of atrophy in the cervical spinal cord in any of the five patients. Bilateral involvement of the IRt by SB produces cardiovascular autonomic failure and sleep apnea. In patients with more restricted lesions, autonomic and respiratory dysfunction may be dissociated. Clinico-radiological correlations using high resolution MRI assessment of medullary lesions can provide insight into the central organization of cardiovascular and respiratory control in humans.

Adult↗

PubMed1994

Autonomic reflex dysfunction in patients presenting for elective surgery is associated with hypotension after anesthesia induction.

BACKGROUND: Autonomic reflex dysfunction in patients with diabetes is associated with an increased incidence of hypotension after induction of anesthesia. Whether this finding can be extrapolated to patients with autonomic dysfunction from other causes (e.g., advanced age, hypertension, altered ventricular function) has not been established. METHODS: The authors investigated whether autonomic reflex dysfunction in a more generalized patient group (26 consecutively consenting day-surgery patients older than 39 yr) was similarly associated with the occurrence of hypotension after induction. Preoperative tests of autonomic function included: Valsalva maneuver, change in heart rate with forced breathing, change in heart rate and blood pressure with standing, and spectral analysis of heart rate variability. Anesthesia was induced with 3-5 mg/kg thiopental, 2 micrograms/kg fentanyl, and 60% N2O; 0.1 mg/kg vecuronium was used for paralysis; 0-1.5% isoflurane was added for maintenance of anesthesia after intubation. Noninvasive measurements of mean blood pressure were obtained every minute for 10 min after induction and then every 3 min until skin incision. RESULTS: Twelve patients developed hypotension (mean blood pressure < 70 mmHg), and 14 patients did not. Measurements of autonomic reflex function were significantly more abnormal in the patients who developed hypotension (P < 0.006 for Valsalva measurements, heart rate variability parameters, and change in heart rate with forced breathing). Using critical test values for autonomic tests, the incidence of hypotension was 67-83% in patients with autonomic nervous system dysfunction versus 9-17% in other patients. CONCLUSIONS: The results document that: (1) some degree of autonomic reflex dysfunction is not uncommon in patients older than 39 yr presenting for elective surgery, and (2) such dysfunction is associated with an increased incidence of hypotension when using the described induction technique.

Adult↗

PubMed1997

Autonomic nervous dysfunction in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA): possible pathogenic role of autoantibodies to autonomic nervous structures.

Autonomic nervous dysfunction has been previously reported in SLE, RA and systemic sclerosis, but the pathogenesis of such a complication is poorly understood. In the present study, four standard cardiovascular autonomic function tests were performed in 34 female patients with connective tissue diseases and in 25 healthy control subjects, and results expressed as cardiovascular (CV) test scores. Moreover, in each subject the presence of circulating complement-fixing autoantibodies directed against sympathetic and parasympathetic nervous structures, represented by superior cervical ganglia and vagus nerve, respectively, was simultaneously assessed by an indirect immunofluorescent complement-fixation technique, using rabbit tissue as substrate. None of the patients reported autonomic symptoms. However, an abnormal CV test score (> or = 5) was detected in 15% of the patients and in none of the healthy control subjects, approaching statistical significance (P = 0.07). No correlation was found between CV test results and disease duration, type of therapy or presence of conventional autoantibodies. One or two autoantibodies to autonomic nervous structures were detected in six patients (18%) and not in the control subjects (P < 0.05). Values of deep breathing test were significantly lower in autoantibody-positive patients compared with those amongst the control subjects (P < 0.05), and an abnormal CV test score was significantly associated with the presence of autoantibodies to autonomic nervous structures (P < 0.05). In conclusion, we confirm that autonomic nervous function can be impaired in patients with connective tissue diseases, and suggest that autoantibodies directed against autonomic nervous system structures may play a role in the pathogenesis of the autonomic dysfunction.

Adolescent↗

PubMedDate not supplied

Cardiovascular and pupillary autonomic nervous dysfunction in patients with rheumatoid arthritis - a cross-sectional and longitudinal study.

OBJECTIVES: Patients with inflammatory diseases often demonstrate autonomic nervous dysfunction. This study was initiated to investigate cardiovascular (CAD) or pupillary autonomic dysfunction (PAD) in patients with rheumatoid arthritis (RA). METHODS: Between 1997 and 1998, 33 RA patients were examined for characteristics, and parameters of CAD and PAD. In a longitudinal part of this study, thirty patients have been re-evaluated 8.3 +/- 0.1 yr later (response rate = 91%). RESULTS: A total of 18 patients (60%) demonstrated either CAD or PAD. The prevalence of CAD was 6/30 (20%) and the prevalence of PAD was 15/30 (50%). Of all cardiovascular tests, the Ewing test demonstrated the worst results (13/30 patients were below the 5th percentile). Similar as in other diseases, several RA patients demonstrated autonomic nervous hyperreflexia with values above the 95 th percentile (relative variation coefficient: 7/30; respiratory sinus arrhythmia measure: 12/30; Valsalva measure: 1/30; Ewing measure: 0/30; latency time of pupillary light reflex: 5/30; maximal pupillary area: 0/30). During the 8-year observation period, 4/30 RA patients died. Non-survivors as compared to survivors had increased heart rate variation in the respiratory arrhythmia test (p= 0.038, hyperreflexia) but largely decreased heart rate variation in the Ewing test (p= 0.009, hyporeflexia). Non-survivors as compared to survivors demonstrated more frequent pupillary autonomic dysfunction (100% vs. 42%, p= 0.035). CONCLUSION: This study demonstrates that CAD and PAD were frequent in patients with RA. Patients with a poor test result in the Ewing test and PAD might have an increased risk of death. This study in RA patients demonstrates similar results as in patients with diabetes mellitus.

Adult↗

PubMed1998

Differing haemodynamic and catecholamine responses to exercise in three groups with peripheralautonomic dysfunction: insulin-dependent diabetes mellitus, familial amyloid polyneuropathy and pure autonomic failure.

The haemodynamic and catecholamine responses to supine exercise, and the effect on standing blood pressure (BP), were studied in three groups with peripheral autonomic dysfunction; insulin-dependent diabetes mellitus (IDDM), familial amyloid polyneuropathy (FAP) and pure autonomic failure (PAF). Healthy normal subjects were studied as controls. With exercise, BP increased in controls, was unchanged in IDDM and FAP, and fell in PAF. Heart rate (HR) increased more in controls than IDDM, FAP or PAF. Cardiac index (CI) increased less in IDDM than controls, FAP or PAF. Systemic vascular resistance (SVR) fell similarly in controls and IDDM, with a greater fall in FAP and PAF. Plasma noradrenaline increased in controls and IDDM only; plasma adrenaline did not change and plasma dopamine was undetectable in all groups. On standing, BP was unchanged in controls; BP fell pre- and post-exercise in IDDM, FAP and PAF, with a significantly greater fall post-exercise in FAP and PAF. In conclusion, the haemodynamic responses to supine exercise and to standing after exercise differed in the three groups with peripheral autonomic dysfunction. These differences, and also the similarities, between different forms of peripheral autonomic dysfunction, may be of relevance to the clinical assessment and therapy of these patients.

Adult↗

PubMed1978

Evaluating dysfunction of the autonomic nervous system.

Simple bedside measurements of blood pressure and systolic pressure response to the Valsalva maneuver will confirm a clinical impression of orthostatic hypotension. Careful questioning of the patient usually elicits other symptoms of autonomic nervous system dysfunction, such as impotence, urinary and fecal incontinence, constipation or diarrhea, blurred vision, or sweating changes. Drugs are the most common cause of autonomic dysfunction, and their benefits should be weighed against the severity of the dysfunction. In addition, diabetes mellitus, uremia, amyloidosis, acute intermittent porphyria, myeloma, tabes dorsalis, and alcohol-nutritional problems may produce symptoms of autonomic dysfunction. Thus, patients who present with autonomic features but no history of dysfunction-producing drugs should undergo complete laboratory evaluation. A regimen of tyramine or L-dopa or a diet rich in cheese, processed meats, and wine (a monoamine), coupled with a monoamine oxidase inhibitor have beneficial effects in patients with orthostatic hypotension due to preganglionic autonomic dysfunction. Patients who do not respond to catecholamine precursors have stable, isolated orthostatic hypotension or a polyneuropathy such as that caused by diabetes.

Aged↗

PubMedDate not supplied

Autonomic system dysfunction in moderate diabetic polyneuropathy assessed by sympathetic skin response and Valsalva index.

30 patients with moderate diabetic polyneuropathy (Stage 2 according to Dyck) were evaluated for autonomic symptoms, sympathetic skin response (SSR) and Valsalva index. Their SSR were compared to a control group of 30 healthy normal subjects. Neuropathy was confirmed by history, clinical examination and nerve conduction measurements. Although our patients had only moderate polyneuropathy autonomic dysfunction was frequent. Two thirds reported autonomic symptoms. Impotence was present in 60% of males. SSR amplitudes were significantly lower in diabetics (changed in 53%, absent in 20%) than in the controls. SSR abnormality correlated to some clinical and electroneurographic signs of neuropathy, suggesting similar affection of sympathetic and somatic fibres. Valsalva index was abnormal in 37% of patients showing no correlation to clinical, electroneurographic or SSR changes.

Adult↗

PubMedDate not supplied

[Achalasia, alacrima without adrenal insufficiency with peripheral and autonomic neurological dysfunction (Allgrove's syndrome)].

OBJECTIVE: To present a patient with Allgrove's syndrome and peripheral and autonomic neurological dysfunction. This pathological entity has not been previously reported in national medical literature. BACKGROUND: Allgrove's syndrome is comprised of achalasia, alacrima and adrenal insufficiency. It is a rare disease. Some isolated cases have been informed in the literature. The most extensive series was published by Grant et al in 1993. In this study, 20 patients from various european countries were analyzed. METHOD: We describe a patient with diagnosis suggestive of Allgrove's syndrome and expose the results of a review of the medical literature concerning this syndrome. We emphasize in neurological dysfunction of these patients. Such abnormalities are not actually well defined in this syndrome. RESULTS: A twelve-year-old male patient was admitted to the hospital for dysphagia. A diagnosis of achalasia was performed with endoscopy and esophagogram and confirmed with esophageal manometry. Physical examination showed alacrima and neurological dysfunction. Stimulation of adrenal function with ACTH (Cortosin) was normal. Neurologic examination revealed: peripheral neuropathy, autonomic dysfunction; corticospinal, psychomotor and intellectual impairment. CONCLUSION: Allgrove's syndrome must be in mind in physicians who see children with achalasia. Nevertheless adrenal insufficiency is not always present in cases when diagnosis is performed. It may appear several years afterwards. Neurological dysfunction seems to be the most prominent feature.

Adrenal Insufficiency↗

PubMed1984

Evidence for cardiovascular autonomic nerve dysfunction in multiple sclerosis.

In 21 patients with multiple sclerosis and 20 healthy controls, the following tests of autonomic function were examined: (1) variation in heart rate during deep breathing, (2) the variations in heart rate and systolic blood pressure during a standardised Valsalva manoeuvre, (3) the changes in heart rate and systolic blood pressure during arm ergometry starting at 30 W with increments of 20 W every 3 min. In the control subjects the maximum variation in heart rate from inspiration to expiration was greater than 16 beat/min (range 17-43). In patients with multiple sclerosis, five had a maximum variation in heart rate of less than 13 beat/min which was considered as the lower limit of normal. The Valsalva ratio in the control subjects ranged from 1.33-3.24. Four patients had Valsalva ratios of less than 1.30. In patients with multiple sclerosis the heart rate and systolic blood pressure responses to exercise were attenuated significantly in four and seven subjects respectively. It is concluded that a significant number of patients with multiple sclerosis show evidence of autonomic dysfunction involving the cardiovascular system.

Adult↗

PubMed1997

Clinical dysautonomia in diabetes mellitus--a study with seven autonomic reflex function tests.

Thirty-eight patients of NIDDM, 12 of IDDM and 10 healthy age matched controls were subjected to seven standardised autonomic reflex function tests. A scoring criteria was utilised for diagnosing and grading the severity of dysautonomia. Eight patients of IDDM and 24 of NIDDM had dysautonomia. One-third of the patients in each group had grade IV autonomic dysfunction. Severity of autonomic dysfunction was directly related to the duration of disease in NIDDM whereas in IDDM this relation was not seen. Peripheral neuropathy was almost always associated with dysautonomia in NIDDM. On the contrary, in IDDM dysautonomia was independent of peripheral neuropathy. Charcot's arthopathy, dysphagia, constipation and nocturnal diarrhea were always associated with evidence of dysautonomia. Other symptoms viz. gustatory sweating, postural dizziness and impotence did not necessarily indicate dysautonomia.

Adult↗

PubMed1996

Mitochondrial encephalomyopathies presenting with features of autonomic and visceral dysfunction.

Three children are reported with mitochondrial encephalomyopathy who presented with autonomic dysfunction. Autonomic dysfunction included gastrointestinal dysmotility, apnea, cardiac arrhythmias, decreased lacrimation, supersensitivity to metacholine, altered sweating, and postural hypotension. These patients illustrate that in some mitochondrial encephalomyopathies autonomic features may be prominent and can mimic the clinical features associated with hereditary sensory and autonomic neuropathies.

Autonomic Nervous System Diseases↗