Clinical Autonomic Research最新文献

Background: Disorders of gut-brain interaction (DGBI) are common in pediatrics. Though the name clearly implies a neural contribution, the role of the autonomic nervous system remains unclear. Heart rate in healthy subjects (HC) follows a circadian pattern with dipping during the night with increased high frequency (hf) heart rate variability (HRV) and root mean square of successive differences (RMSSD). Our hypothesis was that reduced vagal modulation in adolescents with DGBI is associated with blunted rise in nocturnal vagal modulation.

Methods: An institutional review board (IRB) approved this study, which included children aged 12-18 years with a DGBI and carefully screened HC. All subjects underwent 24 h HRV recording. The following questionnaires/tools were included: Pain Catastrophizing Scale for Children (PCS-C), Pain Catastrophizing Scale for Parents (PCS-P), Revised Child Anxiety and Depression Scale (RCADS), Trauma Symptom Checklist for Children (TSCC), and Functional Disability Inventory (FDI).

Results: In total, 12 HC and 15 participants with DGBI participated (female individuals with DGBI versus HC: 93% versus 58%, p = 0.08). There was no age difference (median [range] HC 16.6 years [13.4, 18.2]; DGBI 16.8 years [13.8, 18.7], p = 0.92). The 24 h, daytime and nighttime HRV demonstrated that RMSSD, low-frequency (lf) HRV, and high-frequency (hf) HRV were lower in the DGBI group (p < 0.001). A nocturnal rise in RMSSD was present in the DGBI group, but less so in the HC group (p = 0.021). Higher catastrophizing correlated with lower nocturnal RMSSD (PCS-C correlation coefficient [CC]: -0.46), depression (RCADS depression CC: -0.51), and post-traumatic stress disorder (PTSD; TSCC PTSD CC: -0.58).

Conclusions: HRV is reduced in patients with DGBI with a blunted rise in nocturnal RMSSD at night. As expected, vagal modulation is inversely correlated with catastrophizing, depression, PTDS, and FDI, with nocturnal HRV showing generally better correlations than daytime HRV.

Purpose: Many methods have been developed for the assessment of dysautonomia, but they are often unreliable and not readily applicable to daily practice. Among the available investigation methods, the Ewing battery, which includes five non-invasive cardiovascular reflex tests, have become the reference standard in assessing dysautonomia and have been utilized for more than four decades. This systematic review evaluates the diagnostic thresholds and diagnostic performance of Ewing tests across studies in identifying autonomic nervous system (ANS) disorders.

Methods: We conducted a comprehensive multi-database literature search, including PubMed, EMBASE, Web of Science, Scopus, and the Cochrane Library, using a pre-defined search strategy, for studies that applied the Ewing tests to assess autonomic dysfunction. We focused on studies that used continuous recordings and those reporting extractable numerical data, including either normative values or diagnostic cutoff thresholds for the Ewing tests. The Ewing parameters that were tested were Valsalva manoeuvre, heart rate variability during deep breathing (E/I ratio), the isometric handgrip, heart rate response to standing (30:15 ratio) and blood pressure response to standing.

Results: Our analysis demonstrates good diagnostic performance of the Ewing tests, with sensitivity for individual components reaching up to 91% for Valsalva ratio (VR) in some cohorts. The normative data and respective cutoff points are influenced by age and sex. Optimal diagnostic performance was achieved when the Ewing battery was interpreted using the conventional criterion of ≥ 2/5 abnormal tests particularly when age-adjusted cutoffs were applied.

Conclusion: The Ewing battery remains a highly effective tool for diagnosing ANS disorders, especially when age-adjusted normative thresholds are used. To further enhance its diagnostic performance, each laboratory should establish its own normative data reflective of the specific population it serves.

Purpose: Muscle sympathetic nerve activity (MSNA) is valuable for managing postural tachycardia syndrome (POTS), but microneurography is clinically impractical. We investigated whether the Valsalva phase 2 diastolic blood pressure rise (DBP_{VM2l_rise}) serves as a sympathetic marker and proposed enhanced neurovascular transduction as a pathophysiological mechanism in hyperadrenergic POTS.

Methods: We included 21 POTS women and 22 healthy women to perform Valsalva and microneurography. MSNA spike rate was obtained using stationary wavelet transformation. The DBP_{VM2l_rise} cut point for hyperadrenergic POTS was optimized by the golden section search with its correlation to phase 2 MSNA spike rate as an objective function. We defined peripheral sympathetic neurovascular transduction (psNVT) as a ratio of DBP_{VM2l_rise} to early phase 2 MSNA increase. We compared Valsalva responses between the identified hyperadrenergic and non-hyperadrenergic POTS.

Results: The DBP_{VM2l_rise} strongly correlated with the Valsalva phase 2 MSNA spike rate percentage change from baseline in healthy (r = 0.874, p < 0.001). The DBP_{VM2l_rise} cutoff criterion of 15 mmHg optimally separated POTS into 7 hyperadrenergic (≥ 15 mmHg, r = 0.902, p = 0.014) and 14 non-hyperadrenergic (< 15 mmHg, r = 0.629, p = 0.021). Although similar MSNA spike rate, the hyperadrenergic group had higher baseline systolic blood pressure (118 ± 10 vs 105 ± 12 mmHg, p = 0.026), shorter pressure recovery time (1.15 ± 0.75 vs 2.59 ± 1.17 s, p = 0.048), and higher psNVT (2.60 ± 1.02 vs 0.58 ± 0.46 mmHg/spike·s^-1, p < 0.001) than the non-hyperadrenergic POTS.

Conclusion: DBP_{VM2l_rise} ≥ 15 mmHg could be a sympathetic clinical marker and could identify hyperadrenergic POTS, characterized by enhanced neurovascular transduction despite comparable MSNA levels. This novel pathophysiological insight underscores the importance of sympathetic markers in POTS clinical management.

Purpose: This study aimed to investigate autonomic alterations associated with periodic limb movements during sleep (PLMS) by comparing linear and non-linear heart rate variability (HRV) parameters across whole-night recordings and stage N2 non-rapid eye movement (NREM) sleep (N2).

Methods: From 8082 polysomnographic (PSG) recordings, we identified 21 patients with PLMS and 28 age- and sex-matched controls. Linear and non-linear HRV indices were analyzed for whole-night recordings and the longest N2 segment. Periodic limb movement (PLM) indices and arousal-related parameters were also evaluated.

Results: Compared with controls, patients with PLMS showed significantly higher standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive differences (RMSSD), increased low-frequency (LF) power, and reduced approximate entropy (ApEn) and sample entropy (SampEn) across the whole night, together with a lower Stress Index (SI). No significant group differences were observed in high-frequency (HF) power or in the composite sympathetic/parasympathetic nervous system (SNS/PNS) indices. During stage N2, the PLM group exhibited significantly greater SDNN, Poincaré plot long-axis standard deviation (SD2), detrended fluctuation analysis alpha-1 exponent (DFA α1), and very-low-frequency (VLF) power, along with lower ApEn values. A significant increase in the SD2/SD1 ratio was also observed specifically during N2, whereas the LF/HF ratio showed only a non-significant upward trend. PLMS counts, indices, and arousal-related parameters were markedly elevated during stage N2.

Conclusions: PLMS are characterized by increased autonomic variability (SDNN, SD2, DFA α1) but reduced complexity (ApEn, SampEn), particularly during stage N2. Stage-specific HRV assessment may provide novel insights into the cardiovascular implications of PLMS.

Purpose: Paroxysmal sympathetic hyperactivity (PSH) is a severe complication of acquired brain injuries (ABIs), characterized by sudden autonomic surges that exacerbate clinical outcomes. Its pathophysiology remains debated, and early biomarkers are lacking. This study aims to investigate autonomic changes preceding PSH and assess the feasibility of predictive modeling using heart rate variability (HRV).

Methods: Continuous electrocardiogram (ECG) recordings were obtained from six male patients with disorders of consciousness (DoC), including unresponsive wakefulness syndrome and minimally conscious state. A total of 24 PSH episodes and 24 matched control (noPSH) events were analyzed. HRV metrics, including entropy measures and power spectral density (PSD), were evaluated. A support vector machine (SVM) classifier was implemented to differentiate PSH from control events and to predict PSH onset.

Results: PSH events were associated with significant heart rate increases, reduced entropy-based complexity, and decreased PSD in both low-frequency (LF) and high-frequency (HF) bands. An increased very-low-frequency (VLF)/(LF + HF) ratio suggested potential involvement of the renin-angiotensin-aldosterone system (RAAS) in PSH pathogenesis. The SVM classifier achieved perfect classification during the event. In addition, 10 min prior to onset, the model reached 67% sensitivity, 100% specificity, and 83% balanced accuracy.

Conclusions: HRV analysis reveals distinct autonomic signatures preceding PSH and suggests, as a working hypothesis, that dysregulation of the RAAS may play a role. However, VLF power is influenced by multiple mechanisms and cannot be considered a specific or exclusive marker of RAAS activity. SVM-based predictive modeling offers a promising tool for PSH detection, providing a basis for investigating autonomic/neuroendocrine regulation, including RAAS.

Objective: Our overarching objective was to determine whether autonomic reflex dysfunction and heightened sensory sensitivity contribute to orthostatic intolerance (OI) in patients with migraine.

Methods: Adults with migraine (N = 30) underwent autonomic function tests summarized as the Composite Autonomic Severity Score (CASS) and vagal/adrenergic baroreflex sensitivity (BRS-V/A). Postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension/hypertension were diagnosed during tilt table testing. A cold pressor test (CPT) evaluated sympathetic vasomotor function. Participants completed the Migraine Disability Assessment (MIDAS), the 2011 Fibromyalgia (FM) Survey Criteria, and chronic overlapping pain condition (COPC) screening.

Results: The number of headache days per month correlated with CASS (p = 0.001), BRS-V (p < 0.001), and the CPT (p = 0.003) in the expected direction, with increasing autonomic nervous system (ANS) reflex dysfunction correlating with increasing number of headache days. During tilt testing, OI was prevalent (25/30; 83%) and was reported by all patients with chronic migraine. An abnormal cardiovascular response to tilt was present in 63%; POTS was the most common etiology (56.2%). Patients reporting OI during tilt table testing despite a normal cardiovascular response (33%) had higher FM scores (15.8 ± 3.6 vs. 7.5 ± 4.6; p < 0.01) and a greater prevalence of non-headache COPCs (88.8% vs. 20.0%, p = 0.02) than asymptomatic patients.

Conclusions: Increased headache frequency correlates with increasing ANS reflex dysfunction. The high prevalence of OI in patients with migraine may be due to both autonomic reflex dysfunction and an abnormal cardiovascular response to tilt (i.e., concordant OI) and heightened sensory sensitivity (i.e., discordant OI).

Background: Patients with postural orthostatic tachycardia syndrome (POTS) experience disabling symptoms such as brain fog related to reduced cerebral perfusion.

Objective: The objective of this study is to determine the mediating role of carbon dioxide in the relationship between stroke volume and cerebral blood flow.

Methods: A total of 15 female patients with POTS underwent head-up tilt testing under two conditions: with lower-body compression (higher stroke volume) and without (lower stroke volume). We analyzed cerebral blood flow velocity, respiratory, and cardiovascular responses using linear mixed-effects and mediation models to examine stroke volume-cerebral blood flow interactions. Granger causality and wavelet coherence assessed cerebral autoregulation.

Results: Lower-body compression attenuated the reduction in stroke volume (-34 ml versus -23 ml; p < 0.01), end-tidal CO₂ (-6.4 mmHg versus -3.2 mmHg; p < 0.01), and mean middle cerebral artery blood flow velocity (-11.2 cm/s versus -4.2 cm/s; p < 0.01) during tilt. Mediation analysis revealed that carbon dioxide completely mediated the relationship between stroke volume and middle cerebral artery blood flow velocity, with a significant indirect effect (0.18 cm/s/ml, 95% confidence interval (CI) 0.058-0.33) and a nonsignificant direct effect (0.04 cm/s/ml, p = 0.5). Compression attenuated the association between stroke volume and carbon dioxide (-0.07 mmHg/ml; 95% CI -0.12 to -0.010; p = 0.02), as shown by the linear mixed-effect model, and reduced the directional influence of blood pressure on cerebral blood flow (ΔGranger causality: 0.12 (0.05-0.18) versus 0.05 (0.02-0.08); p < 0.01).

Conclusions: Reduction in stroke volume leads to reduced cerebral perfusion in POTS, an effect likely mediated by decreased carbon dioxide.

Purpose: To explore the relationship between primary focal hyperhidrosis (PFH) and generalized autonomic dysfunction, we assessed autonomic symptom burden using a comprehensive and validated measure of autonomic symptoms.

Methods: In this case-control study, we compared 132 patients with PFH with 74 matched healthy controls. Autonomic symptoms were assessed using the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire. Propensity score matching minimized confounding. Mann-Whitney U tests compared COMPASS-31 scores between groups. A sensitivity analysis using multivariate linear regression accounted for specific hyperhidrosis sites and demographic factors.

Results: PFH cases demonstrated significantly higher median COMPASS-31 scores compared to controls (18.7 [IQR 7.7-34.8] vs. 11.2 [IQR 3.5-19.3], p < 0.001). Significant differences were observed in orthostatic (2.0 [0-20] vs. 0 [0-12], p = 0.028), vasomotor (0 [0-0] vs. 0 [0-0], p = 0.005; 24.2% vs. 9.5% non-zero scores, respectively), secretomotor (3.2 [2.1-8.6] vs. 0 [0-3.8], p < 0.001), and gastrointestinal (5.4 [1.8-8] vs. 1.8 [0.9-5.4], p = 0.004) domains. Sensitivity analysis confirmed PFH status as a significant predictor of higher COMPASS-31 scores (additional 7.5 points on average, 95% CI 1.6-13.4, p = 0.012) after adjusting for demographic factors and hyperhidrosis sites. Craniofacial and truncal hyperhidrosis were associated with higher autonomic symptom burden.

Conclusion: PFH is associated with a broader spectrum of autonomic symptoms beyond localized sweating, establishing a link to more generalized autonomic dysfunction. These findings underscore the need for a comprehensive approach to evaluating and managing patients with PFH.