Pub Date : 2026-02-05DOI: 10.1016/j.autneu.2026.103393
Alfa Zamrotin Malaniale Maidi, Reema Priyanka Suram, Yasemin Deniz, Sun-Joung Leigh An, Yonggeun Hong
Objective: This study assessed heart rate variability (HRV) alterations in amyotrophic lateral sclerosis (ALS) patients compared to healthy control groups using both frequency-domain and time-domain HRV parameters.
Methods: A systematic review and meta-analysis were conducted using studies retrieved from PubMed, Embase, Web of Science, and Cochrane Library databases up to November 13, 2024. Fourteen studies were included in the qualitative synthesis and eight in the quantitative analysis.
Results: ALS patients exhibited significantly reduced Low Frequency (LF) and High Frequency (HF) HRV parameters compared to healthy controls (p < 0.001 and p = 0.02, respectively). Time-domain parameters also showed significant reductions: RMSSD (p < 0.001), SDNN (p < 0.001), and pNN50% (p = 0.01). Despite an overall decrease in HRV, the LF/HF ratio did not show a statistically significant difference (p = 0.12).
Conclusion: Patients with ALS demonstrate autonomic dysfunction, evidenced by significant reductions in key time-domain (RMSSD, SDNN, pNN50%) and frequency-domain (LF, HF) parameters, suggesting impaired parasympathetic modulation. HRV may serve as a valuable, non-invasive biomarker for the early detection and management of cardiorespiratory complications in ALS.
目的：本研究利用频域和时域HRV参数评估肌萎缩性侧索硬化症（ALS）患者与健康对照组相比的心率变异性（HRV）改变。方法：对截至2024年11月13日从PubMed、Embase、Web of Science和Cochrane Library数据库中检索的研究进行系统评价和荟萃分析。定性综合纳入14项研究，定量分析纳入8项研究。结果：与健康对照相比，ALS患者表现出低频（LF）和高频（HF） HRV参数显著降低(p)。结论：ALS患者表现出自主神经功能障碍，主要表现为关键时域（RMSSD、SDNN、pNN50%）和频域（LF、HF）参数显著降低，提示副交感神经调节功能受损。HRV可作为一种有价值的、无创的生物标志物，用于ALS患者心肺并发症的早期检测和管理。
{"title":"Heart rate variability as a non-invasive biomarker of autonomic dysfunction in amyotrophic lateral sclerosis: A systematic review and meta-analysis.","authors":"Alfa Zamrotin Malaniale Maidi, Reema Priyanka Suram, Yasemin Deniz, Sun-Joung Leigh An, Yonggeun Hong","doi":"10.1016/j.autneu.2026.103393","DOIUrl":"https://doi.org/10.1016/j.autneu.2026.103393","url":null,"abstract":"<p><strong>Objective: </strong>This study assessed heart rate variability (HRV) alterations in amyotrophic lateral sclerosis (ALS) patients compared to healthy control groups using both frequency-domain and time-domain HRV parameters.</p><p><strong>Methods: </strong>A systematic review and meta-analysis were conducted using studies retrieved from PubMed, Embase, Web of Science, and Cochrane Library databases up to November 13, 2024. Fourteen studies were included in the qualitative synthesis and eight in the quantitative analysis.</p><p><strong>Results: </strong>ALS patients exhibited significantly reduced Low Frequency (LF) and High Frequency (HF) HRV parameters compared to healthy controls (p < 0.001 and p = 0.02, respectively). Time-domain parameters also showed significant reductions: RMSSD (p < 0.001), SDNN (p < 0.001), and pNN50% (p = 0.01). Despite an overall decrease in HRV, the LF/HF ratio did not show a statistically significant difference (p = 0.12).</p><p><strong>Conclusion: </strong>Patients with ALS demonstrate autonomic dysfunction, evidenced by significant reductions in key time-domain (RMSSD, SDNN, pNN50%) and frequency-domain (LF, HF) parameters, suggesting impaired parasympathetic modulation. HRV may serve as a valuable, non-invasive biomarker for the early detection and management of cardiorespiratory complications in ALS.</p>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"264 ","pages":"103393"},"PeriodicalIF":3.3,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146159219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-04DOI: 10.1016/j.autneu.2026.103390
Wen Zhou, Tianfang Zeng, Duan Liu, Ruijuan Pang, Liang Gong
Background: Orthostatic hypotension (OH) is a common complication in Parkinson's disease (PD) patients, significantly impacting their quality of life. Recent evidence suggests a potential link between liver fibrosis, indicated by the Fibrosis-4 (FIB-4) index, and autonomic dysfunction. However, its relationship with OH in PD remains unexplored.
Methods: A cross-sectional analysis was conducted using data from 1268 PD patients. The FIB-4 index was calculated based on age, AST, ALT, and platelet count. The association between FIB-4 and OH was assessed using multivariate logistic regression, with further curve fitting and subgroup analyses to test robustness.
Results: The FIB-4 index was significantly associated with OH. For each 0.2-unit increase in FIB-4, the odds ratio (OR) for OH was 1.11 (95% CI: 1.05-1.17, p < 0.001). Tertile analysis showed ORs of 2.05 (95% CI: 1.27-3.31, p = 0.003) for T2 and 2.61 (95% CI: 1.64-4.17, p < 0.001) for T3, compared to T1. Curve fitting indicated a linear relationship, with no evidence of non-linearity. Sensitivity and subgroup analyses confirmed robustness.
Conclusions: Higher FIB-4 index values are independently associated with an increased risk of OH in PD patients, suggesting that liver fibrosis may contribute to OH development. Further longitudinal studies are needed to explore the underlying mechanisms.
{"title":"Association of FIB-4 with orthostatic hypotension in Parkinson's disease.","authors":"Wen Zhou, Tianfang Zeng, Duan Liu, Ruijuan Pang, Liang Gong","doi":"10.1016/j.autneu.2026.103390","DOIUrl":"https://doi.org/10.1016/j.autneu.2026.103390","url":null,"abstract":"<p><strong>Background: </strong>Orthostatic hypotension (OH) is a common complication in Parkinson's disease (PD) patients, significantly impacting their quality of life. Recent evidence suggests a potential link between liver fibrosis, indicated by the Fibrosis-4 (FIB-4) index, and autonomic dysfunction. However, its relationship with OH in PD remains unexplored.</p><p><strong>Methods: </strong>A cross-sectional analysis was conducted using data from 1268 PD patients. The FIB-4 index was calculated based on age, AST, ALT, and platelet count. The association between FIB-4 and OH was assessed using multivariate logistic regression, with further curve fitting and subgroup analyses to test robustness.</p><p><strong>Results: </strong>The FIB-4 index was significantly associated with OH. For each 0.2-unit increase in FIB-4, the odds ratio (OR) for OH was 1.11 (95% CI: 1.05-1.17, p < 0.001). Tertile analysis showed ORs of 2.05 (95% CI: 1.27-3.31, p = 0.003) for T2 and 2.61 (95% CI: 1.64-4.17, p < 0.001) for T3, compared to T1. Curve fitting indicated a linear relationship, with no evidence of non-linearity. Sensitivity and subgroup analyses confirmed robustness.</p><p><strong>Conclusions: </strong>Higher FIB-4 index values are independently associated with an increased risk of OH in PD patients, suggesting that liver fibrosis may contribute to OH development. Further longitudinal studies are needed to explore the underlying mechanisms.</p>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"264 ","pages":"103390"},"PeriodicalIF":3.3,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146159199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-29DOI: 10.1016/j.autneu.2026.103391
Zikai Li, Qinghua Zhu, Yanping Zhang, Wen Zhu, Lei Lv, Yan Zhang, Chuanyu Wang, Yongkun Zeng, Shuo Xu, Jianguo Wen, Qingwei Wang
Objectives: To establish a novel spinal cord hemisection-induced neurogenic bladder (SCHNB) rat model combined with sacral neuromodulation (SNM) and evaluate the immediate effects of SNM on bladder function and morphology in SCHNB.
Materials and methods: Female Sprague-Dawley rats were randomly assigned to three groups: control, SCHNB, and SCHNB + SNM groups. Rats in control group underwent only T9-T10 laminectomy, SCHNB group received right T9-T10 spinal cord hemisection and electrode implantation without electrical stimulation, SCHNB + SNM group underwent the same procedure as SCHNB group but also received daily 3-hours SNM beginning on postoperative day 1 for 3 weeks. All rats subsequently underwent motor function assessment, bladder ultrasonography and cystography, cystometric testing, and histological analysis of spinal cord and bladder tissues.
Results: Ultrasonography revealed significantly increased post void residual in SCHNB group compared to control and SCHNB + SNM groups. Bladder weight in SCHNB group was significantly higher than in control and SCHNB + SNM groups. Cystometric analysis showed a shorter voiding contraction interval in SCHNB + SNM group than control group but longer than SCHNB group. During bladder filling, SCHNB group exhibited multiple uninhibited detrusor contractions, SCHNB + SNM group showed fewer uninhibited contractions and a lower maximum pressure. Histological examination revealed that compared to control and SCHNB + SNM groups, SCHNB group displayed disorganized bladder mucosal epithelium, disrupted and loosened lamina propria, tissue edema, and increased fibrosis.
Conclusions: This model of SCHNB combined with SNM provides a new experimental platform for SNM research. Immediate SNM effectively inhibited bladder overactivity and partially improved functional and structural abnormalities of the bladder.
{"title":"Effects of immediate sacral neuromodulation on bladder in rats with spinal cord hemisection-induced neurogenic bladder.","authors":"Zikai Li, Qinghua Zhu, Yanping Zhang, Wen Zhu, Lei Lv, Yan Zhang, Chuanyu Wang, Yongkun Zeng, Shuo Xu, Jianguo Wen, Qingwei Wang","doi":"10.1016/j.autneu.2026.103391","DOIUrl":"https://doi.org/10.1016/j.autneu.2026.103391","url":null,"abstract":"<p><strong>Objectives: </strong>To establish a novel spinal cord hemisection-induced neurogenic bladder (SCHNB) rat model combined with sacral neuromodulation (SNM) and evaluate the immediate effects of SNM on bladder function and morphology in SCHNB.</p><p><strong>Materials and methods: </strong>Female Sprague-Dawley rats were randomly assigned to three groups: control, SCHNB, and SCHNB + SNM groups. Rats in control group underwent only T9-T10 laminectomy, SCHNB group received right T9-T10 spinal cord hemisection and electrode implantation without electrical stimulation, SCHNB + SNM group underwent the same procedure as SCHNB group but also received daily 3-hours SNM beginning on postoperative day 1 for 3 weeks. All rats subsequently underwent motor function assessment, bladder ultrasonography and cystography, cystometric testing, and histological analysis of spinal cord and bladder tissues.</p><p><strong>Results: </strong>Ultrasonography revealed significantly increased post void residual in SCHNB group compared to control and SCHNB + SNM groups. Bladder weight in SCHNB group was significantly higher than in control and SCHNB + SNM groups. Cystometric analysis showed a shorter voiding contraction interval in SCHNB + SNM group than control group but longer than SCHNB group. During bladder filling, SCHNB group exhibited multiple uninhibited detrusor contractions, SCHNB + SNM group showed fewer uninhibited contractions and a lower maximum pressure. Histological examination revealed that compared to control and SCHNB + SNM groups, SCHNB group displayed disorganized bladder mucosal epithelium, disrupted and loosened lamina propria, tissue edema, and increased fibrosis.</p><p><strong>Conclusions: </strong>This model of SCHNB combined with SNM provides a new experimental platform for SNM research. Immediate SNM effectively inhibited bladder overactivity and partially improved functional and structural abnormalities of the bladder.</p>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"264 ","pages":"103391"},"PeriodicalIF":3.3,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-13DOI: 10.1016/j.autneu.2026.103386
James P. Fisher , Johanna Roche , Amanda G. Duffy , Abubaker Ibrahim , Rachel Turner , Giovanni Vinetti , Matteo Cesari , Michael Furian , Ambra Stefani , Hannes Gatterer , Birgit Högl , Christoph Siebenmann
We investigated whether three days of hypoxic exposure in a hypobaric chamber, and the associated nocturnal periodic breathing (nPB), reduce sympathetic nerve activity (MSNA) transduction to blood pressure (BP). While hypoxia did not affect MSNA transduction to BP, larger drops in BP occurred following cardiac cycles without sympathetic bursts, suggesting increased reliance on sympathetic vasoconstrictor support for beat-to-beat BP. Prevention of nPB by inspiratory carbon dioxide administration did not affect MSNA transduction to BP in hypoxia.
{"title":"Sympathetic transduction to blood pressure following three days in hypobaric hypoxia: Influence of nocturnal periodic breathing","authors":"James P. Fisher , Johanna Roche , Amanda G. Duffy , Abubaker Ibrahim , Rachel Turner , Giovanni Vinetti , Matteo Cesari , Michael Furian , Ambra Stefani , Hannes Gatterer , Birgit Högl , Christoph Siebenmann","doi":"10.1016/j.autneu.2026.103386","DOIUrl":"10.1016/j.autneu.2026.103386","url":null,"abstract":"<div><div>We investigated whether three days of hypoxic exposure in a hypobaric chamber, and the associated nocturnal periodic breathing (nPB), reduce sympathetic nerve activity (MSNA) transduction to blood pressure (BP). While hypoxia did not affect MSNA transduction to BP, larger drops in BP occurred following cardiac cycles without sympathetic bursts, suggesting increased reliance on sympathetic vasoconstrictor support for beat-to-beat BP. Prevention of nPB by inspiratory carbon dioxide administration did not affect MSNA transduction to BP in hypoxia.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"264 ","pages":"Article 103386"},"PeriodicalIF":3.3,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-05DOI: 10.1016/j.autneu.2026.103379
Rodrigo Souza , Irinaldo Capítulino de Souza , Suellen Mary Marinho do Santos Andrade , Marcelo Rodrigo Portela Ferreira
Background
Autonomic nervous system (ANS) dysfunction contributes to an increased risk of cardiovascular events. Non-invasive neuromodulation methods, such as transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS), and transcutaneous vagus nerve stimulation (tVNS), have been used to modulate the ANS. However, their comparative efficacy and optimal protocols remain uncertain due to study heterogeneity. This study aimed to verify the level of evidence for the effect of these neuromodulation methods on heart rate variability (HRV) and sympathovagal balance.
Methods
This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO. Databases including Cochrane Library, Web of Science, PubMed, and Embase were searched up to October 2024. Randomized controlled trials (RCTs) that compared tDCS, TMS, or tVNS against control or sham conditions in humans, with HRV variables as an outcome, were included.
Results
Thirteen RCTs were included: 5 used tDCS, 6 used tVNS, and 2 used TMS. Significant heterogeneity was observed in the neuromodulation protocols. The meta-analysis found no statistically significant effects of tDCS on frequency-domain variables. Similarly, tVNS showed no significant effect on frequency- or time-domain variables. The quality of evidence for the main outcomes was rated as moderate for both tDCS and tVNS.
Conclusion
The current evidence on the effects of tDCS, TMS, and tVNS on HRV is limited and heterogeneous. These findings reinforce the need for methodological standardization in stimulation protocols and for studies with larger sample sizes to provide more robust clinical findings.
背景：自主神经系统（ANS）功能障碍会增加心血管事件的风险。非侵入性神经调节方法，如经颅直流电刺激（tDCS）、经颅磁刺激（TMS）和经皮迷走神经刺激（tVNS），已被用于调节ANS，然而，由于研究的异质性，它们的比较效果和最佳方案仍不确定。本研究旨在验证这些神经调节方法对心率变异性（HRV）和交感迷走神经平衡影响的证据水平。方法本系统评价和荟萃分析遵循PRISMA指南，并在PROSPERO注册。检索截止到2024年10月的数据库包括Cochrane Library、Web of Science、PubMed和Embase。随机对照试验（rct）将tDCS、TMS或tVNS与人类对照或假条件进行比较，并将HRV变量作为结果。结果共纳入13项随机对照试验：tDCS 5例，tVNS 6例，TMS 2例。在神经调节方案中观察到显著的异质性。meta分析发现tDCS对频域变量的影响没有统计学意义。同样，tVNS对频域和时域变量均无显著影响。tDCS和tVNS的主要结局证据质量均为中等。结论目前关于tDCS、TMS和tVNS对HRV影响的证据有限且具有异质性。这些发现加强了刺激方案方法学标准化的必要性，并需要更大样本量的研究来提供更有力的临床发现。
{"title":"Neuromodulation of heart rate variability: A systematic review","authors":"Rodrigo Souza , Irinaldo Capítulino de Souza , Suellen Mary Marinho do Santos Andrade , Marcelo Rodrigo Portela Ferreira","doi":"10.1016/j.autneu.2026.103379","DOIUrl":"10.1016/j.autneu.2026.103379","url":null,"abstract":"<div><h3>Background</h3><div>Autonomic nervous system (ANS) dysfunction contributes to an increased risk of cardiovascular events. Non-invasive neuromodulation methods, such as transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS), and transcutaneous vagus nerve stimulation (tVNS), have been used to modulate the ANS. However, their comparative efficacy and optimal protocols remain uncertain due to study heterogeneity. This study aimed to verify the level of evidence for the effect of these neuromodulation methods on heart rate variability (HRV) and sympathovagal balance.</div></div><div><h3>Methods</h3><div>This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO. Databases including Cochrane Library, Web of Science, PubMed, and Embase were searched up to October 2024. Randomized controlled trials (RCTs) that compared tDCS, TMS, or tVNS against control or sham conditions in humans, with HRV variables as an outcome, were included.</div></div><div><h3>Results</h3><div>Thirteen RCTs were included: 5 used tDCS, 6 used tVNS, and 2 used TMS. Significant heterogeneity was observed in the neuromodulation protocols. The meta-analysis found no statistically significant effects of tDCS on frequency-domain variables. Similarly, tVNS showed no significant effect on frequency- or time-domain variables. The quality of evidence for the main outcomes was rated as moderate for both tDCS and tVNS.</div></div><div><h3>Conclusion</h3><div>The current evidence on the effects of tDCS, TMS, and tVNS on HRV is limited and heterogeneous. These findings reinforce the need for methodological standardization in stimulation protocols and for studies with larger sample sizes to provide more robust clinical findings.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"263 ","pages":"Article 103379"},"PeriodicalIF":3.3,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-26DOI: 10.1016/j.autneu.2025.103377
Julien Rimok , Kelly A. Larkin-Kaiser
Traditional methods for assessing autonomic nervous system (ANS) function are constrained by conventional clinical settings, limited timeframes, and exclusionary protocols. These limitations prevent the accurate capture of dynamic physiological fluctuations, particularly in underserved populations and those with complex or rare autonomic disorders. This paper outlines how wearable technologies and mobile health (mHealth) platforms are redefining the landscape of ANS research. By enabling continuous, real-world monitoring and integrating multimodal data, including comprehensive physiological and behavioral signals, patient-reported outcomes, these tools offer unprecedented opportunities for personalization, decentralized and pragmatic clinical trial designs, and enable early detection and intervention. We examine the evolution of wearable sensors, the role of artificial intelligence in translating raw data into clinically actionable insights, and the economic and equity implications of digital-first research. With regulatory momentum growing and real-world evidence gaining traction, the convergence of wearable technology and autonomic science signals not just a methodological shift, but a fundamental redefinition of how, where, and for whom clinical science is conducted.
{"title":"From lab to life: Wearables, real-world data, and the future of autonomic research","authors":"Julien Rimok , Kelly A. Larkin-Kaiser","doi":"10.1016/j.autneu.2025.103377","DOIUrl":"10.1016/j.autneu.2025.103377","url":null,"abstract":"<div><div>Traditional methods for assessing autonomic nervous system (ANS) function are constrained by conventional clinical settings, limited timeframes, and exclusionary protocols. These limitations prevent the accurate capture of dynamic physiological fluctuations, particularly in underserved populations and those with complex or rare autonomic disorders. This paper outlines how wearable technologies and mobile health (mHealth) platforms are redefining the landscape of ANS research. By enabling continuous, real-world monitoring and integrating multimodal data, including comprehensive physiological and behavioral signals, patient-reported outcomes, these tools offer unprecedented opportunities for personalization, decentralized and pragmatic clinical trial designs, and enable early detection and intervention. We examine the evolution of wearable sensors, the role of artificial intelligence in translating raw data into clinically actionable insights, and the economic and equity implications of digital-first research. With regulatory momentum growing and real-world evidence gaining traction, the convergence of wearable technology and autonomic science signals not just a methodological shift, but a fundamental redefinition of how, where, and for whom clinical science is conducted.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"264 ","pages":"Article 103377"},"PeriodicalIF":3.3,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145928915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-22DOI: 10.1016/j.autneu.2025.103378
Joost J. van Middendorp , Martina Orlovic , Femke De Ruyck , Montserrat Roset , Mayara Torres , Daniel Cuadras , Josep Maria Garcia-Alamino , Satish R. Raj , Pam R. Taub , Artur Fedorowski
Introduction
Postural orthostatic tachycardia syndrome (POTS) is a complex disorder with challenging diagnosis and management.
Methods
This cross-sectional, multi-national, web-based physician chart audit described clinical features and management of POTS, offering insights into disease burden and outcomes before and after the COVID-19 pandemic.
Results
Physicians (n = 153), primarily cardiologists (77.1 %), reported data from 599 patients from two cohorts: 1) POTS not triggered by COVID-19 (n = 361) and 2) POTS triggered by COVID-19 (n = 238). Overall, most patients experienced POTS symptoms onset between the ages of 18 and 39 years (33 %), with 13 % presenting symptom onset before 18 years of age. Over 70 % had at least one pre-existing medical condition. Most patients underwent 5–8 tests to define POTS diagnosis. Around 80 % received incorrect diagnoses before POTS confirmation, and 25 % waited over a year for diagnosis. Although some patients showed reduction in symptom severity over time, symptoms were still persistent at last consultation. Non-pharmacological interventions were common in the first treatment line. In subsequent lines, there was an increase in pharmacological treatments, with beta-blockers and ivabradine being the most frequently prescribed medications. Comparative analysis between pre- and post-COVID-19 POTS showed that while POTS patients triggered by COVID-19 were somewhat older and had fewer comorbidities, differences were not clinically meaningful, suggesting similar diagnostic, management and treatment patterns. Regional differences in diagnoses and treatment patterns were observed between US and Europe.
Conclusion
This study highlights the challenges faced by POTS patients, while providing insights into the diagnostic and treatment approaches in real-world settings.
{"title":"Characterisation of Postural Orthostatic Tachycardia Syndrome (POTS): Findings from a physician chart-audit pre- and post-COVID-19","authors":"Joost J. van Middendorp , Martina Orlovic , Femke De Ruyck , Montserrat Roset , Mayara Torres , Daniel Cuadras , Josep Maria Garcia-Alamino , Satish R. Raj , Pam R. Taub , Artur Fedorowski","doi":"10.1016/j.autneu.2025.103378","DOIUrl":"10.1016/j.autneu.2025.103378","url":null,"abstract":"<div><h3>Introduction</h3><div>Postural orthostatic tachycardia syndrome (POTS) is a complex disorder with challenging diagnosis and management.</div></div><div><h3>Methods</h3><div>This cross-sectional, multi-national, web-based physician chart audit described clinical features and management of POTS, offering insights into disease burden and outcomes before and after the COVID-19 pandemic.</div></div><div><h3>Results</h3><div>Physicians (<em>n</em> = 153), primarily cardiologists (77.1 %), reported data from 599 patients from two cohorts: 1) POTS not triggered by COVID-19 (<em>n</em> = 361) and 2) POTS triggered by COVID-19 (<em>n</em> = 238). Overall, most patients experienced POTS symptoms onset between the ages of 18 and 39 years (33 %), with 13 % presenting symptom onset before 18 years of age. Over 70 % had at least one pre-existing medical condition. Most patients underwent 5–8 tests to define POTS diagnosis. Around 80 % received incorrect diagnoses before POTS confirmation, and 25 % waited over a year for diagnosis. Although some patients showed reduction in symptom severity over time, symptoms were still persistent at last consultation. Non-pharmacological interventions were common in the first treatment line. In subsequent lines, there was an increase in pharmacological treatments, with beta-blockers and ivabradine being the most frequently prescribed medications. Comparative analysis between pre- and post-COVID-19 POTS showed that while POTS patients triggered by COVID-19 were somewhat older and had fewer comorbidities, differences were not clinically meaningful, suggesting similar diagnostic, management and treatment patterns. Regional differences in diagnoses and treatment patterns were observed between US and Europe.</div></div><div><h3>Conclusion</h3><div>This study highlights the challenges faced by POTS patients, while providing insights into the diagnostic and treatment approaches in real-world settings.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"263 ","pages":"Article 103378"},"PeriodicalIF":3.3,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-19DOI: 10.1016/j.autneu.2025.103376
Rasna Sabharwal , Francois M. Abboud , Mark W. Chapleau
Acid-Sensing Ion Channel 2 (ASIC2) has been implicated in mechanosensation. We reported previously that ASIC2 is highly expressed in aortic baroreceptor neurons and contributes to baroreceptor mechanotransduction; and that ASIC2 deficient mice exhibit decreased baroreflex sensitivity (BRS), sympathovagal imbalance and neurogenic hypertension. Oxidative stress is widely considered an important contributor to hypertension. The major goal of this study was to determine if treatment of ASIC2−/− mice with the antioxidant tempol attenuates baroreflex/autonomic dysfunction and hypertension. Blood pressure (BP), heart rate (HR) and locomotor activity were measured by telemetry in conscious, control C57BL/6 and ASIC2−/− male mice, before and after administration of tempol in drinking water (1 mM) for two weeks. Cardiac sympathetic tone, mean arterial BP and BP variability were higher, and cardiac vagal tone and BRS were lower in ASIC2−/− mice, compared with controls (P < 0.05). Oxidative stress measured by mRNA expression of NADPH oxidase subunits (Nox2, Nox4, p22phox) and dihydroethidium (DHE) fluorescence was increased significantly (P < 0.05) in ASIC2−/− mice in a tissue-specific manner (sympathetic and nodose ganglia > > brain stem > > skeletal muscle, with no change in aorta). Treatment with tempol strongly attenuated DHE fluorescence and restored autonomic regulation and BP to control levels in ASIC2−/− mice, while not affecting these phenotypes in control mice. We conclude: (1) oxidative stress in ASIC2−/− mice is prominent in the autonomic nervous system but not present in aorta; and (2) the antioxidant tempol reverses decreased BRS, sympathovagal imbalance and hypertension in ASIC2−/− mice; effects that are associated with decreased oxidative stress.
{"title":"Antioxidant tempol reverses autonomic dysregulation and neurogenic hypertension in acid-sensing ion channel 2 deficient mice","authors":"Rasna Sabharwal , Francois M. Abboud , Mark W. Chapleau","doi":"10.1016/j.autneu.2025.103376","DOIUrl":"10.1016/j.autneu.2025.103376","url":null,"abstract":"<div><div>Acid-Sensing Ion Channel 2 (ASIC2) has been implicated in mechanosensation. We reported previously that ASIC2 is highly expressed in aortic baroreceptor neurons and contributes to baroreceptor mechanotransduction; and that ASIC2 deficient mice exhibit decreased baroreflex sensitivity (BRS), sympathovagal imbalance and neurogenic hypertension. Oxidative stress is widely considered an important contributor to hypertension. The major goal of this study was to determine if treatment of ASIC2<sup>−/−</sup> mice with the antioxidant tempol attenuates baroreflex/autonomic dysfunction and hypertension. Blood pressure (BP), heart rate (HR) and locomotor activity were measured by telemetry in conscious, control C57BL/6 and ASIC2<sup>−/−</sup> male mice, before and after administration of tempol in drinking water (1 mM) for two weeks. Cardiac sympathetic tone, mean arterial BP and BP variability were higher, and cardiac vagal tone and BRS were lower in ASIC2<sup>−/−</sup> mice, compared with controls (<em>P</em> < 0.05). Oxidative stress measured by mRNA expression of NADPH oxidase subunits (Nox2, Nox4, p22phox) and dihydroethidium (DHE) fluorescence was increased significantly (<em>P</em> < 0.05) in ASIC2<sup>−/−</sup> mice in a tissue-specific manner (sympathetic and nodose ganglia > > brain stem > > skeletal muscle, with no change in aorta). Treatment with tempol strongly attenuated DHE fluorescence and restored autonomic regulation and BP to control levels in ASIC2<sup>−/−</sup> mice, while not affecting these phenotypes in control mice. We conclude: (1) oxidative stress in ASIC2<sup>−/−</sup> mice is prominent in the autonomic nervous system but not present in aorta; and (2) the antioxidant tempol reverses decreased BRS, sympathovagal imbalance and hypertension in ASIC2<sup>−/−</sup> mice; effects that are associated with decreased oxidative stress.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"263 ","pages":"Article 103376"},"PeriodicalIF":3.3,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145840682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1016/j.autneu.2025.103375
Cristiane Busnardo , Lucas Barreto-de-Souza , Luana Omena-Giatti , Taíz F.S. Brasil , Heloísa H. Vilela-Costa , Fernando M.A. Corrêa , Carlos C. Crestani
Biological systems seem to be differently affected by stress, resulting in expression of both adaptative and maladaptive responses. The present study aimed to compare the neuroendocrine (plasma corticosterone), behavioral (anxiogenic- and depressive-like effects), cardiovascular (blood pressure and heart rate) and autonomic (tail skin temperature and frequency-domain analysis of blood pressure and pulse interval variabilities) responses observed during an acute (single 2 h session) versus the 21st [2 h/day for 21 consecutive days) restraint stress session. We found that acute restraint stress reduced exploration of elevated plus maze (EPM) open arms, tail skin temperature and cardiac parasympathetic tonus; along with increased plasma corticosterone levels, blood pressure, heart rate and sympathetic modulation of both blood pressure and pulse interval. Repeated exposure to restraint completely inhibited or decreased the pressor, tachycardiac and sympathetic/parasympathetic responses; indicating habituation of autonomic and cardiovascular responses. Chronically stressed animals also had enhanced immobility in the forced swimming test and decreased grooming time in the splash test and exploration of EPM open arms, indicating anxiogenic- and depressive-like effects. Furthermore, chronic restraint stress elevated basal plasma corticosterone and tail skin temperature response. In summary, analysis of extensive set of physiological and behavioral responses to a chronic homotypic stressor indicates expression of adaptative adjustments evidenced mainly as habituation of the autonomic/cardiovascular changes. Nevertheless, maladaptive changes such as anxiogenic- and depressive-like effects and increased basal corticosterone were also observed.
{"title":"Neuroendocrine, behavioral, cardiovascular and autonomic responses to acute and repeated restraint stress in male rats","authors":"Cristiane Busnardo , Lucas Barreto-de-Souza , Luana Omena-Giatti , Taíz F.S. Brasil , Heloísa H. Vilela-Costa , Fernando M.A. Corrêa , Carlos C. Crestani","doi":"10.1016/j.autneu.2025.103375","DOIUrl":"10.1016/j.autneu.2025.103375","url":null,"abstract":"<div><div>Biological systems seem to be differently affected by stress, resulting in expression of both adaptative and maladaptive responses. The present study aimed to compare the neuroendocrine (plasma corticosterone), behavioral (anxiogenic- and depressive-like effects), cardiovascular (blood pressure and heart rate) and autonomic (tail skin temperature and frequency-domain analysis of blood pressure and pulse interval variabilities) responses observed during an acute (single 2 h session) versus the 21st [2 h/day for 21 consecutive days) restraint stress session. We found that acute restraint stress reduced exploration of elevated plus maze (EPM) open arms, tail skin temperature and cardiac parasympathetic tonus; along with increased plasma corticosterone levels, blood pressure, heart rate and sympathetic modulation of both blood pressure and pulse interval. Repeated exposure to restraint completely inhibited or decreased the pressor, tachycardiac and sympathetic/parasympathetic responses; indicating habituation of autonomic and cardiovascular responses. Chronically stressed animals also had enhanced immobility in the forced swimming test and decreased grooming time in the splash test and exploration of EPM open arms, indicating anxiogenic- and depressive-like effects. Furthermore, chronic restraint stress elevated basal plasma corticosterone and tail skin temperature response. In summary, analysis of extensive set of physiological and behavioral responses to a chronic homotypic stressor indicates expression of adaptative adjustments evidenced mainly as habituation of the autonomic/cardiovascular changes. Nevertheless, maladaptive changes such as anxiogenic- and depressive-like effects and increased basal corticosterone were also observed.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"263 ","pages":"Article 103375"},"PeriodicalIF":3.3,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145821886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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