Clinical Autonomic Research最新文献

Purpose: Identifying features of patients who remain pure autonomic failure has implications on disease definition and offers insights into synucleinopathy progression. We sought to determine symptom timeline and autonomic features in patients who retain the pure autonomic failure phenotype with prolonged follow-up.

Methods: We reviewed all patients diagnosed with pure autonomic failure from 2001 to 2011 evaluated at Mayo Clinic, Rochester, with autonomic reflex screen and over 1 year of in-person follow-up. Clinical evaluations and patient telephone calls were used to assess timeline of symptoms.

Results: Of 202 patients, 133 remained pure autonomic failure with median follow-up time of 9.05 years (interquartile range (IQR) 4.2-13.1). Additional autonomic symptoms included constipation (N = 60; 45%), bladder symptoms (N = 78; 59%), which were severe in 50 patients (37.6%) with incontinence or requiring catheterization, sexual dysfunction (N = 53; 40%) and thermoregulatory dysfunction (N = 51; 38%). Assessment of dream enactment behavior was completed in 86 patients and endorsed in 45 patients (52%). Median time to dream enactment behavior onset from orthostatic hypotension was 7.00 years (1.55-13.50). Other autonomic symptoms tended to occur near orthostatic hypotension. Autonomic testing showed moderate to severe autonomic failure with median composite autonomic score of 6 (IQR 4-8; N = 133) and median percentage anhidrosis of 51% (IQR 3-93%; N = 105).

Conclusions: Patients with pure autonomic failure typically have symptom onset near development of orthostatic hypotension while dream enactment behavior may occur later. Our findings underscore that not all patients with pure autonomic failure will develop motor or cognitive symptoms, even with prolonged follow-up.

Aim: Individuals with spinal cord injury (SCI) have an increased prevalence of orthostatic hypotension (OH). Diagnosis of OH is made with active standing or tilt table testing, with limited the use in individuals with SCI.

Methods: An alternative approach to assess OH is the sit-up test, which involves passive repositioning from the supine to the seated position. The purpose of this study was to document the reliability and validity of the sit-up test, and determine whether the level or severity of injury related to orthostatic blood pressure (BP) responses in a large, diverse group of individuals with SCI.

Results: A total of 166 participants-119 individuals with SCI and 47 uninjured control-completed two sit-up tests, and 36 individuals who completed the sit-up tests also underwent a head-up tilt test. Change in BP from sit-up test 1 to sit-up test 2 was not significantly different for either systolic BP or diastolic BP. Neither level nor severity of injury contributed to the reliability assessments, which showed disappointing results with generally low interclass correlation coefficients (ICC), with values ranging from 0 to 0.63, and large standard error of measurements (SEM), ranging from 5.2 to 13.7 mmHg. Comparison between BP responses to the sit-up test and the head-up tilt showed good sensitivity and specificity, with positive predictive values > 75%.

Conclusion: Prevalent BP instability likely contributed to the poor reliability of the sit-up test, but the test is easy to perform with a high likelihood ratio for the valid assessment of OH in individuals with SCI.

Clinical trial registration: NCT01758692.

Purpose: Recent studies have reported blunted increases in blood pressure (BP) during static handgrip (SHG) in patients with heart failure with preserved ejection fraction (HFpEF), which may be attributed to abnormal sympathetic reactivity during exercise and/or impaired muscle metaboreflex function. However, it is unknown whether the sympathetic neural response to SHG and isolated muscle metaboreflex activation via post-exercise circulatory occlusion (PECO) are attenuated in HFpEF.

Methods: Thirty-nine patients with HFpEF and 24 age-matched non-HFpEF controls were studied in the supine position. BP, heart rate (HR), and muscle sympathetic nerve activity (MSNA) were measured during SHG at 40% of maximal voluntary contraction until fatigue followed by 2-min PECO.

Results: Resting mean arterial pressure (MAP) was lower and peak increase (Δ) in MAP was smaller in patients with HFpEF than in controls during SHG (Δ23 ± 15 [standard deviation] vs. Δ34 ± 15 mmHg; P = 0.007) and PECO (Δ15 ± 11 vs. Δ19 ± 9 mmHg; P = 0.047). HR was greater in patients at rest but did not differ between the two groups at peak SHG. Patients had higher resting MSNA burst frequency than controls (37 ± 14 vs. 27 ± 13 bursts/min; P = 0.031); however, burst incidence was not different between the groups (P = 0.226). There were no differences in MSNA responses to SHG (Δ19 ± 15 vs. Δ18 ± 10 bursts/min at peak; P = 0.841) or PECO (Δ3 ± 12 vs. Δ5 ± 7 bursts/min; P = 0.495) between groups.

Conclusion: The patients with HFpEF maintained sympathetic reactivity but had an attenuated pressor response during fatiguing SHG. Additionally, muscle metaboreflex activation of vasomotor sympathetic outflow appeared to be minimal in both groups, with no significant difference between patients and controls.

Purpose: This review aims to summarize the complex nature of the trigeminocardiac reflex into a brief overview, focusing on its mechanism, anatomy, classification, manifestations, and treatment approaches.

Method: By examining the latest clinical studies and anatomical insights, we outline the neural pathways of trigeminocardiac reflex, identify subtypes on the basis of stimulation points, and describe the physiological responses it elicits.

Results: Trigeminocardiac reflex is a brainstem reflex characterized by symptoms, such as bradycardia, hypotension, hypertension, apnea, and gastric hypermotility. It has been reported in surgical procedures involving stimulation of sensory branches of the trigeminal nerve. Trigeminocardiac reflex management typically involves prophylactic measures to prevent intraoperative cardiovascular complications.

Conclusion: A comprehensive understanding of trigeminocardiac reflex mechanisms and subtypes is essential to anticipate and mitigate its effects during procedures that may trigger this reflex. This knowledge ensures patient well-being and optimizes surgical outcomes, highlighting the importance of continued research in this area.

Purpose: Increased beat-to-beat heart rate variability (HRV) is a feature of patients with Parkinson's disease (PD) who carry the G2019S mutation in the LRRK2 gene (LRRK2-PD). Since LRRK2 mutations have incomplete penetrance, HRV changes preceding PD conversion would likely be observed only in a subset of LRRK2 non-manifesting carriers (NMC). We aimed to assess HRV in a subgroup of NMC with distinctive characteristics of LRRK2-PD, identified through clustering analysis.

Methods: HRV measures derived from 300 normal heartbeat intervals extracted from the electrocardiograms of 25 NMC, 32 related non-carriers (RNC), 27 unrelated healthy controls, and 14 patients with LRRK2-PD were analyzed. Clinical symptoms were evaluated using questionnaires and scales, and three NMC subgroups were identified using a k-means cluster analysis on the basis of the deceleration capacity of heart rate (DC) and Rényi entropy. Standard and advanced HRV measures were compared using multiple regression analysis, controlling for age, sex, and mean heart rate.

Results: Beat-to-beat HRV markers were significantly increased in a subgroup of seven NMC (NMC2, 28%) compared with RNC and controls. Increased irregularity and DC were also verified in the NMC2 compared with controls, and were typical traits in both the NMC2 and RNC. Overall, the HRV profile of NMC2 was comparable to that of patients with LRRK2-PD. NMC2 further exhibited greater motor and non-motor traits than the other NMC, RNC, and controls.

Conclusions: Our results confirmed that HRV characteristics of LRRK2-PD are also found in a subset of NMC displaying clinical traits of LRRK2-PD. Further research is needed to clarify whether higher HRV represents a LRRK2-PD prodromal manifestation.

Background: Postural orthostatic tachycardia syndrome (POTS) is a complex disorder with serious health consequences, while its etiology remains largely elusive.

Objective: The purpose of this study was to investigate the genetic landscape of POTS using genomic approaches in a unique pediatric cohort.

Methods: We conducted a combined genome wide genotyping and whole exome sequencing (WES) study to systemically examine the molecular mechanisms of POTS pathogenesis. The patients were genotyped as two independent cohorts: a family cohort of 100 complete families and a case-control cohort of 207 unrelated European cases and 4063 ethnicity-matched control subjects. The WES component consisted of a subset of the genotyped subjects, including 87 unrelated European cases and 2719 unrelated European control subjects.

Results: The heterogeneous phenotype of POTS made achieving genome-wide significance improbable. Instead, 5670 SNPs with nominal significance (P < 0.05) were identified in both the family and case-control cohorts, with effects in the same direction. We conducted an over-representation analysis (ORA) by considering all genes that showed nominal significance. The ORA identified gene sets linked to cell-cell junction, early estrogen response, and substance-related disorders with statistical significance. Moreover, WES revealed 55 genes with genome-wide significance through rare variant burden analysis, harboring 92 variants classified as pathogenic or likely pathogenic by ClinVar.

Conclusions: This study showcases the complex interplay between common and rare genetic variants in POTS development, marking a pioneering step forward in deciphering its complex etiologies. The insights from this research enrich our understanding of POTS, offering new avenues for precise treatment strategies and highlighting areas for further research.