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Hormonal and cardiovascular reflex assessment in a female patient with pure autonomic failure.

We report the case of a 72-year-old female with pure autonomic failure, a rare entity, whose diagnosis of autonomic dysfunction was determined with a series of complementary tests. For approximately 2 years, the patient has been experiencing dizziness and a tendency to fall, a significant weight loss, generalized weakness, dysphagia, intestinal constipation, blurred vision, dry mouth, and changes in her voice. She underwent clinical assessment and laboratory tests (biochemical tests, chest X-ray, digestive endoscopy, colonoscopy, chest computed tomography, abdomen and pelvis computed tomography, abdominal ultrasound, and ambulatory blood pressure monitoring). Measurements of catecholamine and plasmatic renin activity were performed at rest and after physical exercise. Finally the patient underwent physiological and pharmacological autonomic tests that better diagnosed dysautonomia.

Aged↗

Autonomic cardiac abnormalities in alcohol-dependent patients admitted to a psychiatric department.

Standardized heart rate analyses were performed in 60 drug-free patients with alcohol dependence, who were admitted consecutively to a psychiatric department, and in 60 healthy normal matched subjects. The procedure included time and frequency derived measurements of heart rate variability (HRV). The investigations were carried out 3 weeks after admission and treatment on a closed ward to avoid autonomic hyperexcitability during withdrawal or relapse. The patients showed a significantly increased heart rate (p < 0.05), a significant reduction in the coefficient of variation while resting (p < 0.01) and a significant decrease of the high frequency power of spectral analysis (p < 0.01) compared with the normal subjects. Cardiovascular autonomic dysfunction was found in 12 of the patients, but in only one of the normal subjects (p < 0.01). The results indicated moderate parasympathetic (vagal) alteration in alcohol-dependent patients treated in a psychiatric department. This may have implications for psychotherapeutic or psychopharmacological treatment strategies and prognosis in such patients with alcohol dependence.

Adult↗

Transient sympathovagal imbalance triggers "ischemic" sudden death in patients undergoing electrocardiographic Holter monitoring.

OBJECTIVES: The aim of this study was to investigate the relation between "ischemic" sudden death (arrhythmic death preceded by ST segment shift) and autonomic nervous system activity. Background. Mechanisms precipitating sudden death are poorly known despite the importance of detecting functional factors that may contribute to such a fatal event. METHODS: We analyzed the tapes of eight patients (seven men and one woman with a mean age of 66 +/- 8 years) who had ischemic sudden death during ambulatory electrocardiographic (Holter) monitoring. Four patients had unstable and four had stable angina; none was taking antiarrhythmic drugs. Twenty patients with angina and transient myocardial ischemia during Holter monitoring served as control subjects. Arrhythmias, ST segment changes and heart rate variability were analyzed by a computerized interactive Holter system. RESULTS: Five patients had ventricular tachyarrhythmias (ventricular fibrillation in three, ventricular tachycardia in two), and three had bradyarrhythmias (atrioventricular block in two, sinus arrest in one) as the terminal event; all eight patients showed ST segment shift (maximal change 0.46 +/- 0.16 mV; with ST elevation in two) that occurred 41 +/- 34 min (mean +/- SD) before sudden death. The standard deviation of normal RR intervals (SDNN) was 89 +/- 33 ms during the 10 +/- 6 h of Holter monitoring; 5 min before the onset of the fatal ST shift, SDNN measurements were significantly lower than during the initial 5-min period (48 +/- 10 vs. 29 +/- 9 ms; p=0.002). In control patients, the SDNN was 102 +/- 39 ms during Holter monitoring, whereas it measured 56 +/- 30 ms 5 min before the most significant episode of ST shift (p<0.01 vs. 29 +/- 9 ms [corrected] in the group with sudden death). CONCLUSIONS: Autonomic dysfunction, as detected by a marked decrease in heart rate variability, is present in the period (5 min) immediately preceding the onset of the ST shift precipitating ischemic sudden death. These data suggest that sympathovagal imbalance may trigger fatal arrhythmias during acute myocardial ischemia, thus resulting in sudden death.

Aged↗

Early and subtle signs in low-back sprain.

The authors have previously reported myalgic hyperalgesia as a useful localizing sign in "low-back sprain" patients with no physical findings. This paper describes some other subtle signs related to the phenomenon of denervation supersensitivity which is well known to physiologists and clinicians involved in peripheral nerve disease, yet its related signs have not been applied to low-back pain. Following denervation of some neurons, muscle and peripheral receptors become supersensitive to transmitter substances and to different forms of stimuli. Since the peripheral nerve is a mixed nerve, findings are multiphasic and include autonomic dysfunction, trophic changes, cutaneous and myalgic hyperalgesia, and increased muscle tone. One or more of these signs occurred in 30 patients with secondary low-back pain but less often in 30 patients with primary or mechanical low-back pain; their presence, though slight, in asymptomatic controls may identify those individuals with a vulnerable back.

Adolescent↗

Non-invasive cardiovascular monitoring in Shy-Drager syndrome.

The pattern of arterial blood pressure and heart rate were investigated in a patient with progressive autonomic dysfunction and nineteen healthy age-matched controls. A marked postprandial reduction of blood pressure was observed in the patient; this phenomenon was not noted in the control group; besides, the rhythmicity of blood pressure and heart rate were altered with peak values shifted approximately eight hours later with respect to the controls.

Adult↗

[The Lambert-Eaton myasthenic syndrome: a study of 110 Japanese cases].

This study was undertaken to analyse the clinical and immunological features in a large group of Lambert-Eaton Myasthenic Syndrome (LEMS) patients (n = 110). In the Japanese LEMS patients studied, there was a male predominance with a male to female ratio of 3:1. The age at onset of neurological symptoms ranged between 17 and 80 years with a mean of 62 years. Malignancy was detected in 69% of the patients, of whom 61% had small cell lung carcinoma (SCLC). Neurological symptoms preceded a diagnosis of malignancy in 84% of cases. The neurological findings were similar in all patients and consisted of lower limb weakness in 97%, upper limb weakness in 80%, hyporeflexia in 85%, autonomic dysfunction in 37% (dry mouth in 31%, constipation in 11%, impaired sweating, urinary disturbance, impotence, and blurred vision in less than 10%), blepharoptosis in 28% and ophthalmoplegia in 5%. Signs of cerebellar involvement are noted in 9% and all of these patients had SCLC. Of 110 patients with LEMS, 85% had detectable antibodies against P/Q-type voltage-gated calcium channel (P/Q-type VGCC). Seronegative patients (15%) had similar neurological findings, but a lower incidence of SCLC than seropositive patients. The clinical features of our patients were very similar to those observed in British LEMS patients (n = 50), but autonomic features in our study were less prevalent than reported in British patients.

Adolescent↗

Heart rate variability and cardiac autonomic function in systemic lupus erythematosus.

The cardiac autonomic function was evaluated in 23 patients with Systemic Lupus Erythematosus (SLE) without clinical expression of dysautonomia and in 14 healthy volunteer subjects as a control group, by analysis of Heart Rate Variability (HRV) from 24h ambulatory electrocardiography. All the patients were taking corticosteroids and 10 of them also Ciclosporin A (CsA). The following parameters of HRV were performed: Time domain: standard deviation of the RR intervals average (SDNN) and percentage of RR adjacent intervals differing from each other more than 50 msec (pNN50). Frequency domain: low frequencies (LF) and high frequencies (HF). Significant lower values were detected in SLE patients vs controls: SDNN = 69.40 vs 127.72; pNN50 = 16.44 vs 25.95; LF = 8.34 vs 34.97; HF = 3.21 vs 12.18. The incidence of autonomic dysfunction in our SLE population evaluated by considering intervals of normality is approximately 78% for SDNN; 17% for pNN50; 91% for LF and, finally, 56% for HF. The analysis of HRV may be a valuable technique in the study of the incidence of dysautonomia for these patients.

Adolescent↗

Gastrobiliary dysmotility in patients with chronic pancreatitis as assessed by a single noninvasive test.

We simultaneously assessed gastric emptying and gallbladder contraction after oral administration of a liquid meal by noninvasive ultrasonography in 17 patients with chronic pancreatitis (CP) and in 17 healthy controls. Gastrointestinal (GI) transit was also assessed by a noninvasive radioopaque marker method. Exocrine pancreatic function was evaluated by analyzing pure pancreatic juice and by analyzing the autonomic nervous system by cardiovascular reflex tests. Patients with CP showed impaired gallbladder contraction at 15 min and hastened gastric emptying. The cause of the former is unclear, whereas the latter was closely related with decreased pancreatic lipase output, but not with autonomic dysfunction. GI transit time did not differ between controls and patients with CP. In conclusion, we succeeded in clearly demonstrating impaired gallbladder contraction and hastened gastric emptying in patients with CP by a single noninvasive test, ultrasonography. We also revealed for the first time that hastened gastric emptying is associated with insufficient pancreatic lipase output.

Autonomic Nervous System Diseases↗

Multiple pituitary hormone abnormalities, fever, behavioral problems, seizures and apnoic spells in a 6-year old girl.

UNLABELLED: A 6-year old girl was examined having two years previously presented a transient Cushing's syndrome, followed by recurrent hyponatremia, attributed to inappropriate ADH secretion (SIADH). The brain MRI showed no abnormalities on repeated examinations, except for a suggestion of empty sella syndrome. During the past two years she also presented recurrent episodes of a prolonged febrile illness of unknown origin. All investigations related to infectious, autoimmune neoplastic diseases, histiocytosis-X or neurosarcoidosis were negative and the fever was characterized as central. The patient also presented episodes of tonic-clonic seizures, myoclonias and behavioral problems (alternating states of irritability, sleepiness and apathy, optic and hearing illusions and phobias) with or without hyponatremia. Her cerebrospinal fluid (CSF) examination was not indicative of encephalitis and the encephalogram (EEG) showed only slowing of background activity. At the age of 4.75 years she, started to have recurrent episodes of hypopnoea/apnoea with severe desaturation and hypercapnia, occasionally requiring intubation and ventilation. She also developed unilateral miosis corneal ulceration and bilateral ptosis (oculo-sympathetic paresis). Repeat brain MRI and CT scans of the mediastinum excluded organic causes of apnoeas and of oculo-sympathetic paresis, such as neuroblastoma or lymphoma. Furthermore, on a 24 hour electrocardiogram recording, using power spectral analysis, significantly reduced heart rate variability was observed, by comparison with age-specific normal ranges. Thus the apnoeas, ptosis, miosis and temperature instability were attributed to autonomic dysfunction. During the same period, the patient presented significant growth retardation and growth hormone (GH) deficiency was confirmed during two provocative tests (peak GH levels: 3.1 and 2.9 ng/ml (normal>10). Moreover, thyrotropin (TSH) deficiency and persistent hyperprolactinemia were detected. She was started on hGH and thyroxine. She was also put on fluid restriction and increased sodium intake for her SIADH. She was advised to use O2 administration by mask in case of apnoeas. The child died at age 6 6/12 years as a result of apnoea during sleep. IN CONCLUSION: Multiple pituitary hormonal abnormalities, together with symptoms of autonomic neuropathy (apnoeas, ptosis, miosis, tachycardia, temperature instability) and encephalopathy (seizures, myoclonias and behavioral problems) developed in a 4-year old girl. The suggested diagnoses were: 1. Neurometabolic disorder, 2. Mitochondrial disorder, 3. Post infectious autoimmune process.

Journal Article↗

Lower limb and back pain in Guillain-Barré syndrome and associated contrast enhancement in MRI of the cauda equina.

UNLABELLED: This study assesses the frequency of lower limb and back pain in children with Guillain-Barré syndrome and reviews the magnetic resonance imaging results of those undergoing spinal imaging. Over an 8-y period, nine children presented with various combinations of severe back pain, leg pains, impairment of gait and bladder dysfunction. Guillain-Barré syndrome was confirmed on clinical examination and peripheral electrophysiology (n = 8). Magnetic resonance imaging in four patients, following contrast injection, showed enhancement of the cauda equine and, additionally, of the cervical nerve roots in one of the patients. A further patient, who was not scanned with contrast, had abnormal thickening of the lumbar roots. Carbamazepine and steroids were effectively used for analgesia in three cases. All the patients recovered. CONCLUSION: Guillain-Barré syndrome should be considered in the differential diagnosis of children presenting with back and/or leg pain. Early diagnosis ensures prompt monitoring for autonomic dysfunction and respiratory compromise.

Back Pain↗

[Variability of cardiac rhythm and treatment modalities for the vegetative state dystonia syndrome].

A total of 30 patients diagnosed as having autonomous dysfunction symptomatology (VSD) were subjected to 24-monitoring of the heart's rhythm. The analysis performed disclosed VDS-related dynamics of the spectrum frequency powers, which fact can serve as an additional diagnostic criterion in identifying of the condition under consideration. The employment of acupuncture has been found to substantially enhance the efficiency of the medicamentous treatment.

Acupuncture Therapy↗

Assessment of cardiovascular reflexes is of limited value in predicting maximal +Gz-tolerance.

The importance of +Gz-induced loss of consciousness as a major cause of inflight incapacitation emphasizes the need for predicting +Gz-tolerance and investigating its possible determinants. The cardiovascular changes from +Gz-stress are initially counteracted reflexly by the cardiovascular autonomic system. The integrity of neural cardiovascular reflex control can be assessed by analysing the blood pressure (BP) and heart rate (HR) responses to different maneuvers, such as the Valsalva maneuver, standing and forced respiratory sinus arrhythmia. The aim of the present study was to investigate a possible relation between the cardiovascular responses to these tests and +Gz-tolerance. In 10 healthy subjects continuous Finapres BP and HR responses to the tests have been determined and correlated with their G-levels of peripheral light loss (PLL) during centrifuge-runs (0.1 G/s). Only mean BP recovery during Valsalva maneuver correlated marginally significantly with PLL (r = 0.63, p = 0.049). Cardiovascular findings were within normal range revealing no cardiovascular autonomic dysfunction. These results indicate that intact neural cardiovascular control seems to be a condition for tolerating +Gz-stress without determining maximal +Gz-tolerance. We conclude that assessment of cardiovascular reflexes may only confirm baroreflex integrity. However, they have limited value in predicting +Gz-tolerance.

Acceleration↗

[A transient decrease in heart rate variability in patients with sudden "ischemic" death during Holter monitoring].

BACKGROUND: Mechanisms precipitating sudden death are poorly known, in spite of the importance to detect functional factors which may contribute to such fatal event. Aim of the study was to investigate the relationship between "ischemic" sudden death (ISD: arrhythmic death preceded by acute myocardial ischemia) and autonomic nervous system activity. METHODS: We analysed the tapes of 6 patients (pts) (5 males; 67 +/- 12 yrs) suffering ISD during Holter monitoring (HM). One pt had recent onset angina, 2 had unstable and 3 stable angina; none was taking antiarrhythmic drugs. Arrhythmias, ST segment and heart rate variability (HRV) were analysed by a computerized interactive HM system, in order to obtain data on transient ischemia and sympatho-vagal balance. RESULTS: Five pts showed ventricular tachyarrhythmias (2 VF, 3 VT), and 1 had a bradyarrhythmia (advanced A-V block) as the terminal event; all pts showed ST shift (max: 0.37 +/- 0.28 mV; 1 with ST elevation; 4 with anginal pain) 53 +/- 35 min before ISD. SD of normal R-R intervals (SDNN) was 112 +/- 26 msec in the 11 +/- 8 hrs of HM, whereas it was 97 +/- 48 msec in the initial hour and 59 +/- 21 msec in the initial 5 min segment. Measurements of SDNN showed a marked decrease 5 min before the onset of fatal ischemic ST shift: 32 +/- 14 msec (p = 0.003). Also, pNN50 (percent of adjacent R-R differing > 50 msec: marker of vagal activity) was significantly reduced before ISD, when compared to the initial 5 min segment (from 10 +/- 5 to 7 +/- 4%; p < 0.03). Such changes were not observed before uncomplicated (that is not associated with malignant arrhythmias) ST shift episodes during HM. CONCLUSIONS: Autonomic dysfunction, as detected by a marked decrease of HRV, is present in the period (5 min) immediately preceding the onset of ST shift precipitating ISD; simultaneous measurements of vagal signals showed similar changes. These data suggest that sympatho-vagal unbalance may trigger fatal arrhythmias during acute myocardial ischemia, hence resulting in ISD.

Aged↗

Vasomotor instability in neonates with chromosome 22q11 deletion syndrome.

Approximately 70% of individuals with chromosome 22q11 deletion syndrome (22q11DS) have congenital heart defects. A host of other vascular problems in these patients, such as tortuous carotid arteries, Raynaud's phenomenon, unexplained hypotension, hypertension, and hypothermia, raise the possibility that there may be abnormal autonomic regulation of the vascular system. So far, however, there has been no formal report of autonomic dysfunction in patients with 22q11 deletion. We present two infants with 22q11DS, who had profound hypotension after uncomplicated surgeries for congenital heart disease. The hypotension was not responsive to vasopressor treatment (and extracorporeal membrane oxygenation in one infant) and resulted in death, due to multiorgan system failure. Obvious causes, such as poor cardiac contractility, prolonged circulatory arrest, neurological abnormality, sepsis and blood loss were excluded. On autopsy, no abnormalities were found that could explain the hypotension. We hypothesize that these infants died of severe hypotension due to abnormal vascular tone and that this is a variable feature in individuals with 22q11 deletion. The autonomic nervous system, which is responsible for the regulation of vasomotor tone, may be variably affected in 22q11DS. This could have implications for the surgical management of patients with 22q11DS. Further studies on this topic would establish or refute the association between 22q11DS and dysautonomia.

Adult↗

Midodrine improves chronic hypotension in hemodialysis patients.

BACKGROUND: The effects of midodrine on chronic hypotension in hemodialysis (HD) patients have not been well investigated. METHODS: We evaluated midodrine's effect on autonomic function and hemodynamics in 12 HD patients who had chronic systolic blood pressure less than 100 mm Hg. Midodrine (5.0 mg) twice a day was given for 4 weeks. Another 12 age- and sex-matched HD patients with normotension were selected as a control group. Autonomic function tests included the heart-rate responses to the Valsalva maneuver and 30:15 ratio as well as supine and standing blood pressure (BP) and sustained hand-grip test. Hemodynamic changes included 24-hour blood pressure, cardiac output, total peripheral resistance (TPR), and plasma renin and aldosterone concentrations. RESULTS: Compared with the control subjects, HD patients with chronic hypotension had more severe autonomic dysfunction and significantly lower TPR. After 4 weeks of midodrine therapy, sympathetic function (orthostatic and hand-grip tests) improved in conjunction with significant increases in mean arterial pressure (MAP) (79.5 +/- 4.9 to 85.0 +/- 5.1 mm Hg, P < 0.05) and TPR (768 +/- 37 versus 1097 +/- 72 dyne/sec/cm-5, P < 0.01) despite no significant change in Valsalva ratio, 30:15 ratio, and cardiac output. MAP changes were positively correlated with TPR changes (r = 0.82, P < 0.001). Supine plasma renin activity was significantly increased. In addition, MAP during HD was also significantly increased during midodrine therapy. CONCLUSIONS: Midodrine improves chronic hypotension in HD patients by modulating autonomic function and its direct effects on peripheral vessels.

Adrenergic alpha-Agonists↗

Is cranial computerized tomography useful in the diagnosis of multiple system atrophy?

Cranial computer tomographic (CT) images of 33 patients with multiple system atrophy (MSA) and of 40 age-matched controls were blindly analyzed by two neuroradiologists. All patients had autonomic dysfunction, all but one had parkinsonism, and 13 had cerebellar signs. The scans were judged entirely normal in 21%. Moderate or severe infratentorial atrophy was found in 42%. Cerebellar atrophy was present in 39%, and pontine atrophy was present in 18%. Of the 13 patients with cerebellar signs, only eight had cerebellar atrophy. Of the 20 patients without cerebellar signs, five had cerebellar atrophy. Supratentorial involvement was much less common and less severe. Thus, CT demonstrated system involvement that was not evident clinically in five of 33 cases (15%). However, in all five the clinical diagnosis was already evident from the presence of both autonomic and pyramidal signs in addition to parkinsonism. We conclude that CT imaging is of limited diagnostic use in individual patients with MSA.

Adult↗

Cardiovascular autonomic dysregulation in users of MDMA ("Ecstasy").

The present study examined resting heart rate variability (HRV; an index of parasympathetic tone) and heart rate response to the Valsalva maneuver (Valsalva ratio; an index of overall autonomic responsiveness) in 12 repeat users of 3.4-methylenedioxymethamphetamine (MDMA, "Ecstasy"), and a matched comparison group of presumed nonusers. HRV and Valsalva ratio were smaller in users than in controls. Three out of 12 MDMA users but no controls had Valsalva ratios below 1.50, the cut-off for autonomic dysfunction. In several users, there was a total absence of post-Valsalva release bradycardia. All MDMA users were polydrug users. Parasympathetic cardiovascular tone appears impaired in repeat MDMA users, although the ubiquitous problems in such epidemiologic designs (including lack of testing before the first use of the drug and confounding with use of other drugs) preclude definitive causal interpretations.

Adolescent↗

Ambulatory assessment of cardiac autonomic function in Chagas' heart disease patients based on indexes of R-R interval variation in the Valsalva maneuver.

1. The reflex cardiac autonomic function of Chagas' heart disease patients was evaluated by a simple, noninvasive and inexpensive ambulatory method as an alternative to the complex or invasive methods or drug tests hitherto used. Variations in the R-R interval during the Valsalva maneuver was quantified in 33 outpatients with Chagas' cardiopathy without heart failure aged 38 +/- 9 years, and compared to 30 healthy control subjects aged 31 +/- 8 years (P greater than 0.05). 2. Each subject carried out 3 to 4 Valsalva maneuvers in the supine position for 20 s at an intraoral pressure of 40 mmHg. Variations of R-R interval were calculated from the electrocardiogram which was recorded continuously from 10 s before to 90 s after the maneuver when the recovery phase had already started. 3. The chagasic group presented lower relative tachycardia (shortest R-R minus control R-R/control R-R) (-27.9 +/- 8.4%, mean +/- SD) and Valsalva ratio (longest R-R/shortest R-R) (1.67 +/- 0.3) than the control group (-34.2 +/- 6.5% and 1.93 +/- 0.3, respectively) (P less than 0.01). The time for maximum R-R interval variation (shortest R-R to longest R-R) was longer (18.0 +/- 7.2 s), and the velocity of this variation (longest R-R minus shortest R-R divided by shortest R-R/time for the maximum R-R variation) was lower (4.8 +/- 3.5%/s) in the chagasic patients (P less than 0.01) than in the controls (11.1 +/- 5.4 s and 10.8 +/- 6.0%/s, respectively). The mean relative bradycardia (longest R-R minus control R-R/control R-R) of the chagasic group (18.5 +/- 13.5%) was statistically similar (P greater than 0.05) to that of the control group (25.6 +/- 16.5%). 4. In 51% (17/33) of the chagasic patients, at least one significantly altered index was observed to exceed +/- 2 SD of the respective control mean, and for 3 of them (10% of the total) all the indexes were abnormal. In 49% (16/33) of the patients no abnormal index was observed. 5. These data show that varying degrees of cardiac autonomic dysfunction may be detected in a simple manner in ambulatory outpatients with Chagas' heart disease, with results similar to those obtained with application of complex or invasive tests. In all likelihood, the altered Valsalva R-R interval variation indexes in the present chagasic patients resulted from depressed parasympathetic activity on the heart consequent to the Chagas' cardiac denervation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗