Clinical Autonomic Research最新文献

Purpose

We previously reported that single doses of the norepinephrine transporter inhibitor, atomoxetine, increased standing blood pressure (BP) and ameliorated symptoms in patients with neurogenic orthostatic hypotension (nOH). We aimed to evaluate the effect of atomoxetine over four weeks in patients with nOH.

Methods

A randomized, double-blind, placebo-controlled crossover clinical trial between July 2016 and May 2021 was carried out with an initial open-label, single-dose phase (10 or 18 mg atomoxetine), followed by a 1-week wash-out, and a subsequent double-blind 4-week treatment sequence (period 1: atomoxetine followed by placebo) or vice versa (period 2). The trial included a 2-week wash-out period. The primary endpoint was symptoms of nOH as measured by the orthostatic hypotension questionnaire (OHQ) assessed at 2 weeks.

Results

A total of 68 patients were screened, 40 were randomized, and 37 completed the study. We found no differences in the OHQ composite score between atomoxetine and placebo at 2 weeks (−0.3 ± 1.7 versus −0.4 ± 1.5; P = 0.806) and 4 weeks (−0.6 ± 2.4 versus −0.5 ± 1.6; P = 0.251). There were no differences either in the OHSA scores at 2 weeks (3 ± 1.9 versus 4 ± 2.1; P = 0.062) and at 4 weeks (3 ± 2.2 versus 3 ± 2.0; P = 1.000) or in the OH daily activity scores (OHDAS) at 2 weeks (4 ± 3.0 versus 5 ± 3.1, P = 0.102) and 4 weeks (4 ± 3.0 versus 4 ± 2.7, P = 0.095). Atomoxetine was well-tolerated.

Conclusions

While previous evidence suggested that acute doses of atomoxetine might be efficacious in treating nOH; results of this clinical trial indicated that it was not superior to placebo to ameliorate symptoms of nOH.

Trial registration

ClinicalTrials.gov; NCT02316821.

Background: The autonomic nervous system (ANS) is critical in regulating involuntary bodily functions, including heart rate. Heart rate variability (HRV) reflects the complex interplay between the ANS and humoral factors, making it a valuable noninvasive tool for assessing autonomic function. While HRV has been extensively studied in adults, normative data for HRV in children, primarily based on long-term rhythm recordings, are limited.

Objective: This study aimed to establish comprehensive normative data for HRV in children.

Methods: In this retrospective study, we examined 24-h Holter monitors of children aged 1 day to 18 years, divided into six age groups, at Nemours Children's Health in Orlando, Florida, spanning the years 2013-2023. HRV analysis encompassed time-domain, frequency-domain, and nonlinear indices.

Results: Holter data for a total of 247 patients in six age groups were included. An age-related uptrend was observed in all time- and frequency-domain variables except the normalized unit of low-frequency power. Entropy analysis revealed contradictory results among different entropy techniques. Sample and approximate entropy analyses were consistent and showed less complexity and more predictability of HRV with decreasing heart rate, while Shannon entropy analysis showed the opposite. Fractal detrended fluctuation analysis exhibited significant decreases across the age groups, suggestive of diminishing self-similarity of HRV patterns.

Conclusion: Control of heart rate and HRV is a highly complex process and requires further study for a better understanding. It seems that no single parameter can fully elucidate the entire process. A combination of time-domain, frequency-domain, and nonlinear indices may be necessary to explain HRV behavior in the growing body.

Purpose: This work's purpose was to quantify rapid sympathetic activation in individuals with spinal cord injury (SCI), and to identify associated correlations with symptoms of orthostatic hypotension and common autonomically mediated secondary medical complications.

Methods: This work was a cross-sectional study of individuals with SCI and uninjured individuals. Symptoms of orthostatic hypotension were recorded using the Composite Autonomic Symptom Score (COMPASS)-31 and Autonomic Dysfunction following SCI (ADFSCI) survey. Histories of secondary complications of SCI were gathered. Rapid sympathetic activation was assessed using pressure recovery time of Valsalva maneuver. Stepwise multiple linear regression models identified contributions to secondary medical complication burden.

Results: In total, 48 individuals (24 with SCI, 24 uninjured) underwent testing, with symptoms of orthostatic hypotension higher in those with SCI (COMPASS-31, 3.3 versus 0.6, p < 0.01; ADFSCI, 21.2 versus. 3.2, p < 0.01). Pressure recovery time was prolonged after SCI (7.0 s versus. 1.7 s, p < 0.01), though poorly correlated with orthostatic symptom severity. Neurological level of injury after SCI influenced pressure recovery time, with higher injury levels associated with more prolonged time. Stepwise multiple linear regression models identified pressure recovery time as the primary explanation for variance in number of urinary tract infections (34%), histories of hospitalizations (12%), and cumulative secondary medical complication burden (24%). In all conditions except time for bowel program, pressure recovery time outperformed current clinical tools for assessing such risk.

Conclusions: SCI is associated with impaired rapid sympathetic activation, demonstrated here by prolonged pressure recovery time. Prolonged pressure recovery time after SCI predicts higher risk for autonomically mediated secondary complications, serving as a viable index for more "autonomically complete" injury.

Purpose: Prior studies reported evidence of autonomic involvement in motor neuron disease and suggested more severe dysfunction in upper motor neuron predominant syndromes. Hence, we sought to characterize autonomic impairment in primary lateral sclerosis.

Methods: Neurological evaluations, thermoregulatory sweat tests, and autonomic reflex screens were analyzed retrospectively in 34 primary lateral sclerosis patients (28 definite and 6 probable). Patients with other potential causes of autonomic failure and patients with autonomic testing results compromised by artifact were excluded.

Results: A total of 17 patients reported autonomic symptoms. Orthostatic lightheadedness was most frequent (8 patients), followed by bladder (7), bowel (5), and erectile dysfunction (3). The autonomic reflex screens of 33 patients were reviewed; 20 patients had abnormal studies. The thermoregulatory sweat tests of 19 patients were reviewed; 11 patients had abnormal studies. Composite Autonomic Severity Score was calculated for 33 patients and found abnormal in 20/33 patients (60.6%): 15/20 patients (75%) had mild impairment, and 5/20 patients (25%) had moderate impairment. The frequencies of testing abnormalities were: sudomotor 18/20 (90%), cardiovagal 9/20 (45%), and adrenergic 6/20 (30%). Sweat loss pattern analysis showed global, regional, and mixed patterns to be more common than length-dependent and distal patterns.

Conclusion: We found evidence of frequent autonomic dysfunction in primary lateral sclerosis, which is generally of modest severity akin to prior reports for amyotrophic lateral sclerosis, but more commonly in a pattern consistent with preganglionic/ganglionic localization. This suggests that primary lateral sclerosis, as with amyotrophic lateral sclerosis, is a multisystem disease that affects the autonomic nervous system.

Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous autonomic disorder. All patients have exaggerated tachycardia upon standing, but the pathophysiology may be diverse. We present a young adult Thai male with a chief complaint of palpitations while in an upright posture since childhood. The patient underwent a modified Ewing test battery which included standing test, deep breathing, and Valsalva maneuver. His heart rate increased more than 30 beats per minute (bpm) during repeated active stand tests (65 to 110 bpm and 77 to 108 bpm), while upright diastolic blood pressure increased more than 10 mmHg. Normal Valsalva ratio (2.01 and 1.86) and baseline heart rate variability (HF_RRI = 4030.24 ms² and 643.92 ms²) indicated intact vagal function. High low-frequency systolic blood pressure variability (LF_SBP = 20.93 mmHg²), increased systolic blood pressure overshoot in phase IV of Valsalva (42 mmHg), and increased upright diastolic blood pressure indicated a hyperadrenergic state. In conclusion, the overall autonomic profile was compatible with hyperadrenergic POTS. Thus, we confirmed the first male POTS case reported in Thailand. We demonstrated the importance of autonomic function testing with continuous measurements to confirm POTS. There is a need for further research in POTS in Thailand.

This is a self report. It is age related because I am 96 years old; about 5 years ago I was asymptomatic in this respect. I describe the difficulties to think to have to take a breath without getting evidence of hypoxia such as flashes of light and other evidence of hypoxia such as loss of muscle tone. The problem I have is loss of autonomic function which normally controls breathing without the need to think to take a breath.

Purpose: The goal of this manuscript was to review the biological and clinical evidence that serotonin neurotransmission might play an important role in the  physiology and treatment of vasovagal syncope.

Methods: The authors reviewed PubMed and handsearches of secondary sources for papers related to the Bezold-Jarisch reflex and serotonin, the plausible involvement of the Bezold-Jarisch reflex in vasovagal syncope, and three lines of clinical evidence involving serotonin and the syncope.

Results: The Bezold-Jarisch reflex was first described following the infusion of veratrum alkaloids into animals in the 19th century. The reflex is triggered by serotonin stimulation chemoreceptors and mechanoreceptors in the the left ventricle. The afferent component of the reflex is carried by unmyelinated type C vagal nerve fibers, which results in parasympathetic efferent stimulation that causes bradycardia. The similarity of the combination of hypotension and bradycardia in the Bezold-Jarisch reflex and in vasovagal syncope led to the suggestion that the reflex was the cause of the syndrome.  Three lines of evidence implicate the serotonin 5HT3 receptors in the heart in the reflex. There is genetic and physiologic evidence for the serotonin 5HT1A and 5HT3 receptors and the serotonin reuptake transporter (SERT). Acute blockade of SERT induces vasovagal syncope in humans undergoing head-up tilt table testing, and SERT inhibition reduces hypotension and bradycardia during spinal anaesthesia. Finally, three randomized clinical trials of SERT inhibitors uniformly reported that they significantly reduce the likelihood of vasovagal syncope recurrences.

Conclusion: Multiple lines of evidence implicate serotonin neurotransmission in the cause of vasovagal syncope.