Clinical Autonomic Research最新文献

Purpose: Pre-clinical studies have demonstrated direct influences of the autonomic nervous system (ANS) on the immune system. However, it remains unclear if ANS-immune connections delineated in these preclinical studies underlie the relationship between autonomic dysregulation and chronic inflammatory diseases in patients with human immunodeficiency virus (HIV). The aims of this study were: (1) to examine the relationship between interleukin-6 (IL-6) and the parasympathetic/vagal component of baroreflex sensitivity in people with HIV; (2) to determine whether the subtype and severity of HIV-autonomic neuropathy (AN) would predict distinct immunotypes; and (3) to compare the burden of non-acquired immunodeficiency syndrome (AIDS)-related co-morbidities between immunotypes.

Methods: A total of 79 adults with well-controlled HIV underwent a standard battery of autonomic function tests summarized as the Composite Autonomic Severity Score (CASS) and vagal and adrenergic baroreflex sensitivity (BRS-V and BRS-A, respectively) (Low: Mayo Clin Proc 68:748-752, 1993). Levels of immune biomarkers were measured in all participants using the Target 96 Inflammation Panel on the Olink proteomics platform, and immunotypes were identified using unbiased, non-negative matrix factorization. Mass cytometry (CyTOF) was completed on a subset of participants with and without autonomic neuropathy (N = 10).

Results: Reduced BRS-V predicted higher levels of IL-6 (p = 0.002). A pro-inflammatory immunotype defined by elevations in type 1 cytokines (IL-6, IL-17) and increased numbers of CD8+ T-cells was associated with autonomic neuropathy characterized by deficits in sympathetic nervous system activity (adjusted odds ratio 4.7, p = 0.017). This pro-inflammatory immunotype was older with a greater burden of co-morbidities.

Conclusion: Deficits in the parasympathetic/cardiovagal and the sympathetic nervous system are associated with inflammation and disease burden in people living with HIV. Future longitudinal research is needed to examine causality.

Purpose: The aim of this work is to determine the relationship between the cross-sectional area (CSA) of the vagus nerve and cardiovagal function in people with multiple sclerosis (pwMS) and healthy controls (HC).

Methods: We enrolled 50 pwMS and 50 HC. All participants underwent an ultrasound of the vagus nerve and autonomic nervous system testing. The Croatian version of the COMPASS-31 questionnaire was used as a measure of autonomic symptom burden. Cardiovagal function was evaluated with the respiratory sinus arrhythmia (RSA), Valsalva ratio (VR), and heart rate variability.

Results: The mean vagus CSA in pwMS was 2.03 ± 0.49 mm² on the right side and 1.72 ± 0.38 mm² on the left side. The mean vagus CSA in HC was 2.08 ± 0.50 mm² on the right side and 1.74 ± 0.37 mm² on the left side. There was no statistically significant difference between the two groups in right (p = 0.615) or left (p = 0.866) vagus CSA. In the HC, there was a statistically significant positive correlation between the mean right CSA and both RSA (r_p = 0.331, p = 0.019) and VR (r_p = 0.327, p = 0.020). On univariable linear regression analysis in the HC group, the mean right CSA was a predictor of both RSA (B = 5.599, 95% CI 0.974-10.224, p = 0.019) and VR (B = 0.253, 95% CI 0.041-0.466, p = 0.020). These findings were not present in pwMS.

Conclusions: The loss of correlation between vagus nerve CSA and parameters of parasympathetic nervous system function in pwMS corroborates the presence of cardiovagal dysfunction in multiple sclerosis.

Purpose: To revisit the pharmacology and real-world use of carbidopa in the management of autonomic disorders.

Methods: To identify articles suitable for this review, a search of the PubMed database was conducted in January 2025 using the keywords "Carbidopa," "MK-486," and "L-alpha-methyldopa hydrazine."

Results: The pharmacotherapeutic role of carbidopa extends beyond the management of Parkinson's disease. Our literature search revealed the use of carbidopa in three primary autonomic diseases to treat either nausea or symptoms of sympathetic hyperactivity: (1) familial dysautonomia, (2) hyperadrenergic postural orthostatic tachycardia syndrome (POTS), and (3) afferent baroreflex failure (familial or acquired). Even at a dose as high as 600 mg/day, carbidopa was not associated with bothersome side effects in some of the clinical trials on familial dysautonomia. Pre-clinical evidence also suggests in vitro and in vivo inhibition of T-cell activation by carbidopa and a potential therapeutic use in cytokine release syndrome.

Conclusion: Current evidence, although limited, suggests that carbidopa has a favorable safety profile. While large, well-designed studies are warranted, observations from case series and small studies suggest that carbidopa could have utility in treating nausea in familial dysautonomia and symptoms of sympathetic hyperactivity in hyperadrenergic postural orthostatic tachycardia syndrome (POTS) and afferent baroreflex failure.

Objective: This meta-analysis evaluates the effectiveness and safety of ramicotomy versus sympathetic chain interruption (SCI) in treating primary hyperhidrosis (PH).

Methods: A comprehensive literature search was conducted across multiple databases, including PubMed, Embase, Web of Science, Ovid, Cochrane Library, CNKI, and Wanfang, covering studies from their inception through October 2024. A total of 10 studies involving 970 patients were included, with 504 patients undergoing ramicotomy and 466 receiving SCI.

Results: The analysis revealed that patients undergoing ramicotomy experienced significantly lower rates of compensatory hyperhidrosis (CH) [odds ratio (OR) 0.41, 95% confidence interval (CI) 0.20-0.85, P = 0.02], severe CH (OR 0.17, 95% CI 0.06, 0.47, P < 0.001), and postoperative hand dryness (OR 0.10, 95% CI 0.01-0.72, P = 0.02), along with a higher recurrence rate (OR 4.03, 95% CI 2.38, 6.85, P < 0.001). No significant differences were observed in operative duration [mean difference (MD) = 0.19, 95% CI -18.23, 18.60, P = 0.98 > 0.05], length of hospital stay (MD = -0.08, 95% CI -0.19, 0.04, P = 0.20 > 0.05), total postoperative complications (OR 0.41, 95% CI 0.07, 2.34, P = 0.32 > 0.05), or surgical satisfaction (OR 0.93, 95% CI 0.45, 1.91, P = 0.83 > 0.05).

Conclusions: While ramicotomy results in lower incidences of CH and postoperative hand dryness, its higher recurrence rate suggests that its application should be cautious to manage PH effectively.

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.

Purpose: This study examined occupational histories in multiple system atrophy to identify environmental associations of potential relevance to disease causation.

Methods: A total of 270 neuropathologically confirmed cases of multiple system atrophy obtained from the Mayo Clinic Brain Bank for neurodegenerative disorders in Jacksonville, Florida, were included in this case-control study. Demographic and disease information was collected from medical records. Information regarding occupational history was collected retrospectively from medical records and published obituaries. Proportions of employment by occupational sector were compared with US census data.

Results: When comparing patients with US census data, significant differences were identified for education (15.2% versus 2.3%, P < 0.001), administration (14.8% versus 4.1%, P < 0.001), clerical (10.7% versus 5.5%, P = 0.001), petroleum industry (8.9% versus 5.6%, P = 0.024), metal industry (7.8% versus 3.0%, P < 0.001), electrical engineers and electricians (5.6% versus 0.4%, P < 0.001), civil or mechanical engineering (4.4% versus 0.2%, P < 0.001), real estate (4.4% versus 0.7%, P < 0.001), information technology (4.1% versus 1.8%, P = 0.011), woodworking (3.0% versus 0.03%, P < 0.001), writing or publishing (2.6% versus 0.3%, P < 0.001), law (2.2% versus 0.4%, P = 0.001), hairdressing (0.7% versus 0.1%, P = 0.03), and social work (0.7% versus 0.1%, P = 0.03).

Conclusions: The listed occupational categories were significantly overrepresented in our series of patients with multiple system atrophy as compared with population data. We hypothesize that these occupational associations may signify environmental exposures, increasing the disease risk in genetically susceptible individuals. We cannot exclude a potential selection bias in patients willing to donate their brains to an academic center to contribute to scientific knowledge.