Kulapatana S, Okamoto LE, Rigo S
… +8 more, Urechie V, Cayton TW, Han RE, Jacob G, Dupont WD, Furlan R, Biaggioni I, Diedrich A
Clin Auton Res
· 2026 Apr · PMID 41533304
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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 bloo...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) 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 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 to early phase 2 MSNA increase. We compared Valsalva responses between the identified hyperadrenergic and non-hyperadrenergic POTS. RESULTS: The DBP strongly correlated with the Valsalva phase 2 MSNA spike rate percentage change from baseline in healthy (r = 0.874, p < 0.001). The DBP 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, p < 0.001) than the non-hyperadrenergic POTS. CONCLUSION: DBP ≥ 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.
Clin Auton Res
· 2026 Apr · PMID 41528648
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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 rec...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.
Riganello F, Cortese MD, Vatrano M
… +7 more, Lucca LF, Pugliese ME, Ursino M, Leto E, Cerasa A, Schiff N, Soddu A
Clin Auton Res
· 2026 Apr · PMID 41442057
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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 deba...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.
Mueller BR, Campbell MC, Kaplan M
… +5 more, Grant J, Jean J, Vinokur M, Clauw D, Robinson-Papp J
Clin Auton Res
· 2026 Apr · PMID 41420770
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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 mig...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).
Miranda-Hurtado M, Hira R, Bourne KM
… +4 more, Ranada S, Baker JR, Sheldon RS, Raj SR
Clin Auton Res
· 2026 Apr · PMID 41398115
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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...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 CO (-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.
Clin Auton Res
· 2026 Apr · PMID 41389158
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PURPOSE: Autonomic dysfunction, including early cardiovascular parasympathetic involvement, is sustained throughout Parkinson's disease (PD). The vagus nerve, shown by ultrasonography, is atrophic in PD patients. We exam...PURPOSE: Autonomic dysfunction, including early cardiovascular parasympathetic involvement, is sustained throughout Parkinson's disease (PD). The vagus nerve, shown by ultrasonography, is atrophic in PD patients. We examined vagus nerve cross-sectional area (CSA) in controls versus PD patients, and its association with autonomic function in early PD. METHODS: We investigated 118 de novo PD patients and 29 controls. Vagus nerve CSA was measured using nerve ultrasonography at the bilateral mid-cervical area. Each patient was evaluated once by a randomly assigned sonographer; each control was measured twice by both. For accurate comparison, patients with diabetes were additionally excluded from the PD group. A 1:1 propensity score matching based on age, sex, hypertension, and dyslipidemia was performed. The CSA was compared between matched patients and controls. Clinical interviews, rating scales, and autonomic and olfactory function tests were performed. The association between these results and the CSA was analyzed. RESULTS: Median right and left vagus nerve CSA measured 1.3 and 1.2 mm, respectively, significantly lower than in controls (2.3 and 2.2 mm). Partial correlation analysis showed a negative correlation between the right vagus CSA and abnormal heart rate response to deep breathing (rho = -0.191, P = 0.045). CONCLUSION: Small right vagus nerve CSA is associated with early parasympathetic dysfunction in PD patients. These findings support the use of vagus nerve ultrasound as a potential non-invasive biomarker for identifying prodromal autonomic involvement and informing future early intervention research.
Gurau A, Nizam W, Khan H
… +13 more, Seshadri N, Kim C, Yamauchi S, de Cássia Collaço R, Ma R, Ecoff K, Vander Cruyssen J, Forrester J, Rodgers K, Barth AS, Bosmans F, Ha JS, Brock M
Clin Auton Res
· 2026 Apr · PMID 41388201
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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...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.
Go S, Kasuga A, Hayashi K
… +15 more, Murakami M, Minami S, Matsumoto W, Takahashi R, Watanabe Y, Saito N, Ohno K, Morishita N, Takeshita M, Morichi S, Ishida Y, Ishii C, Kinjo N, Kashiwagi Y, Yamanaka G
Clin Auton Res
· 2026 Apr · PMID 41335326
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PURPOSE: In pediatric postural tachycardia syndrome (POTS), presyncope is important yet undercharacterized. It undermines school participation and daily function, while objective bedside markers remain limited. We aimed...PURPOSE: In pediatric postural tachycardia syndrome (POTS), presyncope is important yet undercharacterized. It undermines school participation and daily function, while objective bedside markers remain limited. We aimed to delineate clinically usable predictors by integrating cardiovascular responses and cerebral oxygenation during active standing. We operationalized presyncope as visual darkening and examined three physiological correlates: heart rate change (ΔHR), recovery time, and cerebral oxygenation (ΔOxyHb). METHODS: We conducted a cross-sectional study of 49 pediatric patients with POTS (median age 14.2 years, 46.9% male). Continuous heart rate, blood pressure, and cerebral oxygenation were recorded during a 10-min active standing test; body mass index, inferior vena cava collapsibility index, and urinary sodium were also obtained. Robust regression identified independent predictors of visual darkening. RESULTS: ΔHR emerged as the strongest predictor of visual darkening (coefficient 0.017, 95% CI 0.005-0.030, p = 0.004), followed by recovery time (coefficient 0.005, 95% CI 0.000-0.010, p = 0.055) and ΔOxyHb (coefficient 0.029, 95% CI - 0.005 to 0.064, p = 0.098). The final model demonstrated strong discriminative ability (AUC 0.842). Patients reporting visual darkening exhibited significantly higher ΔHR (49 [42-59] vs. 41 [38-46] bpm, p = 0.009), longer recovery time (21 [19-28] vs. 19 [17-22] s, p = 0.041), and greater ΔOxyHb reduction (- 8.7 [ - 10.4 to - 2.4] vs. - 3.5 [- 7.0 to - 2.5] μmol/L, p = 0.039). CONCLUSIONS: Heart rate change upon standing is the most significant and clinically accessible predictor of visual darkening in pediatric POTS. The combined assessment of ΔHR, recovery time, and cerebral oxygenation offers a comprehensive evaluation of the risk of visual darkening, enabling personalized management strategies for pediatric patients.
Patel M, Braun J, Keatch C
… +3 more, Woods W, Kameneva T, Lambert E
Clin Auton Res
· 2026 Feb · PMID 41247414
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PURPOSE: Increased adiposity is associated with the development of cardiometabolic disturbances, with sympathetic dysregulation playing a crucial role in the early phase. Both adiposity and chronic sympathetic activation...PURPOSE: Increased adiposity is associated with the development of cardiometabolic disturbances, with sympathetic dysregulation playing a crucial role in the early phase. Both adiposity and chronic sympathetic activation may impair cerebral function, increasing the risk of neurodegenerative diseases. However, whether adiposity and sympathetic activity are associated with brain dynamics in the healthy state is not fully understood. METHODS: We performed magnetoencephalography in 29 healthy participants (12 males and 17 females; age 19-72 years; body fat percentage 7-45.3%) to record brain dynamics as neural activity index and functional connectivity. Adiposity was assessed using body fat percentage and microneurography was used to assess muscle sympathetic nerve activity. RESULTS: Individuals with higher fat percentage had higher muscle sympathetic nerve activity. Group comparison showed lower activity in the left posterior cingulate gyrus (delta and theta bands) and left precuneus (delta band) in individuals with higher fat percentage. Stronger connectivity between the right superior frontal gyrus and left temporal pole (delta band) was also seen in this group. Neural activity index in the right caudate (theta and low-gamma bands) correlated positively with muscle sympathetic nerve activity while correlating negatively with body fat percentage. CONCLUSION: We have shown that resting-state brain activity and functional connectivity are associated with adiposity and sympathetic activity even in healthy individuals with no manifest cardiometabolic diseases. Thus, the findings highlight that understanding central pathways associated with the healthy state may help to uncover the pathophysiology of obesity and associated metabolic disorders.
Schiweck N, Langer K, Maier A
… +2 more, Vilser D, Spiegler J
Clin Auton Res
· 2026 Feb · PMID 41225175
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Postural orthostatic tachycardia syndrome (POTS) is a condition defined by symptoms of orthostatic intolerance and a sustained heart rate (HR) increment of ≥ 30 beats per minute (bpm) upon postural change to the upright...Postural orthostatic tachycardia syndrome (POTS) is a condition defined by symptoms of orthostatic intolerance and a sustained heart rate (HR) increment of ≥ 30 beats per minute (bpm) upon postural change to the upright position in the absence of orthostatic hypotension, defined as a sustained decrease in systolic blood pressure (SBP) of ≥ 20 mmHg or a decrease in diastolic blood pressure (DBP) of ≥ 10 mmHg within 3 min of standing. In children, a sustained HR increment of at least 40 bpm is required for diagnosis of POTS. POTS is a common condition in adults and children suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In daily clinical practice, therapeutic recommendations are rare and evidence is missing. The objective of this review is to present the current knowledge on non-pharmacological and pharmacological approaches in POTS with a special focus on POTS therapy in children and people with ME/CFS. Of 3853 studies, 45 studies were included in the systematic review. Evidence on therapy in POTS is rare and large randomized controlled trials (RCT) on single interventions are needed. Non-pharmacological approaches such as the use of compression garments, physical training, salt supplementation and transdermal vagal nerve stimulation could be possible treatment options in POTS because they are easy to implement as first-line therapeutic measures in clinical practice. For pharmaceuticals, several studies showed significant effects following therapy with ivabradine and β-adrenergic blocking agents. There are single studies which imply that midodrine (hydrochloride) and pyridostigmine seem to have a beneficial effect on hemodynamics in POTS.
Zhang S, Tian J, Han B
… +9 more, Zhao H, Zhou M, Jobran M, Liu N, Yang L, Wang W, Liu C, Hu M, Wang Y
Clin Auton Res
· 2026 Feb · PMID 41219589
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PURPOSE: To explore changes in sympathetic nerve activity in anxiety, clarify mechanisms underlying increased sympathetic discharge, and evaluate an electrocardiogram (ECG)-derived high-frequency signal, termed skin symp...PURPOSE: To explore changes in sympathetic nerve activity in anxiety, clarify mechanisms underlying increased sympathetic discharge, and evaluate an electrocardiogram (ECG)-derived high-frequency signal, termed skin sympathetic nerve activity (SKNA), as a potential noninvasive correlate of sympathetic outflow. METHODS: Male Sprague-Dawley rats (n = 120) were divided into control and chronic unpredictable mild stress (CUMS) groups (n = 60 each). Anxiety-like behavior was assessed using the open field test and elevated plus maze. Stellate ganglion nerve activity (SGNA) and SKNA were recorded. The relationship between SGNA and SKNA was assessed in both time and frequency domains. The NMDAR1 inhibitor AP-5, Tat-fused α2δ-1 C-terminal peptide, or control peptide were microinjected into the hypothalamic paraventricular nucleus (PVN). PVN expression of GluN1 and α2δ-1 was analyzed via qPCR, western blotting, and co-immunoprecipitation. Plasma norepinephrine (NE) and corticosterone (CORT) levels were measured by ELISA. RESULTS: CUMS rats showed significant anxiety-like behaviors (reduced center time and open arm entries, p < 0.001), along with elevated SGNA and SKNA (p < 0.001). SGNA and SKNA were significantly correlated in the time domain (r = 0.538, p < 0.001) and showed strong concordance in their power spectral density (PSD) profiles, though not linear coherence. PVN GluN1 and α2δ-1 mRNA and protein levels were upregulated, with enhanced interaction. AP-5 and the Tat-fused α2δ-1 peptide normalized SGNA/SKNA in CUMS rats. No further reduction was seen when both were applied sequentially. Control peptide had no effect. CONCLUSION: Anxiety increases sympathetic activity via upregulation of the PVN α2δ-1-NMDAR1 complex. SKNA is an ECG-derived high-frequency signal that correlates with SGNA under anesthesia and shows potential as a noninvasive index for sympathetic function in anxiety research.
Beach PA, Hyland S, Chen X
… +1 more, Huddleston DE
Clin Auton Res
· 2026 Feb · PMID 41171539
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PURPOSE: We compared locus coeruleus (LC) structural integrity, as measured by neuromelanin-sensitive magnetic resonance imaging (NM-MRI), between patients with Parkinson's disease (PD) and those with multiple system atr...PURPOSE: We compared locus coeruleus (LC) structural integrity, as measured by neuromelanin-sensitive magnetic resonance imaging (NM-MRI), between patients with Parkinson's disease (PD) and those with multiple system atrophy (MSA) and tested whether orthostatic hypotension (OH) impacted differences in LC volume between PD and MSA. Substantia nigra (SNc) volumes were compared between these groups to determine whether effects observed in LC were specific to that structure. Last, we tested whether LC integrity is associated with orthostatic hemodynamic responses. METHODS: Presence or absence of (±)OH was determined with active stand testing. Automated segmentation of LC and SNc volumes took place using NM-MRI. Structural volumes were first compared between PD and MSA groups and, second, after stratification by OH status. Last, correlations between LC volumes and orthostatic vitals were calculated. RESULTS: Of 71 patients with PD, 19 were (+)OH. Of 19 patients with MSA, 12 were (+)OH. LC volumes were larger in PD than MSA (p = 0.002), and LC volumes in PD(-)OH were larger than PD(+)OH and MSA(±)OH (p < 0.05). All comparisons involving SNc were nonsignificant. Primarily in PD(-)OH, LC volumes correlated negatively with supine mean arterial pressure (MAP) and positively with supine heart rate. In PD(+OH) and MSA(+)OH, lower LC volumes were correlated with greater orthostatic falls in MAP. CONCLUSIONS: Similar levels of LC neurodegeneration were observed in PD(+)OH and MSA(±)OH. Therefore, LC measurement may be useful to differentiate PD(-)OH from MSA. Lower LC volumes additionally correlated with greater drops in MAP in both PD(+)OH and MSA(+)OH, suggesting that LC neurodegeneration may contribute to OH in both conditions.
Walsh EG, Birdee GS, Bonnet K
… +6 more, Schlundt DG, Broadbent C, Kelly EC, Rogalski K, Archer KR, Gamboa A
Clin Auton Res
· 2026 Feb · PMID 41166031
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PURPOSE: Despite the central role of exercise in treating postural orthostatic tachycardia syndrome (POTS) there have been no studies on the subjective experience of exercise interventions and/or recommendations among th...PURPOSE: Despite the central role of exercise in treating postural orthostatic tachycardia syndrome (POTS) there have been no studies on the subjective experience of exercise interventions and/or recommendations among this patient population. The purpose of this mixed-methods study was to provide greater understanding of the perceived barriers, preferences, perceptions of exercise, and experiences implementing exercise recommendations for adults with POTS in order to optimize treatment recommendations and intervention design. METHODS: This study consisted of a series of focus groups (n = 29) and an online survey of adults with POTS (n = 255) focusing on exercise engagement, beliefs, barriers, and facilitators. Qualitative data were analyzed using an iterative inductive-deductive approach, informed by social cognitive theory, which resulted in a conceptual framework and a series of themes. RESULTS: Survey results showed that participants reported a wide range of exercise frequency prior to the onset of POTS symptoms, and overall lower exercise engagement post-POTS. In both survey results and qualitative findings, participants reported believing that exercise is important in managing POTS, but identified barriers to exercise training, including most saliently, their symptom burden. Participants also identified important needs and facilitating factors that could support them in engaging in regular exercise to help manage their condition. CONCLUSION: These findings shed light on the patient experience of exercise in POTS, which can inform both the tailoring of exercise recommendations and the design of interventions to support exercise engagement specific to the POTS population.
Kaufmann H, Palma JA, Vickery R
… +4 more, Norcliffe-Kaufmann L, Zheng B, Lewin D, Guerin T
Clin Auton Res
· 2026 Feb · PMID 41134458
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PURPOSE: Establish the minimally clinically important difference (MCID) for the Orthostatic Hypotension Questionnaire (OHQ). BACKGROUND: Neurogenic orthostatic hypotension (nOH) causes disabling symptoms that impair dail...PURPOSE: Establish the minimally clinically important difference (MCID) for the Orthostatic Hypotension Questionnaire (OHQ). BACKGROUND: Neurogenic orthostatic hypotension (nOH) causes disabling symptoms that impair daily function and quality of life. The OHQ is a validated patient-reported outcome with a symptom assessment (OHSA) and daily activity scale (OHDAS), widely used in clinical trials, despite the MCID being unestablished. METHODS: We analyzed data from two phase 3, randomized placebo-controlled trials (SEQUOIA and REDWOOD), evaluating ampreloxetine for symptomatic nOH in patients with Parkinson disease, multiple system atrophy, and pure autonomic failure. Using anchor-based and distribution-based methods, we calculated the MCID for the total OHQ score, OHSA and OHDAS composite subscales, and for the single dizziness/lightheadedness question (OHSA1). RESULTS: The analysis included 184 subjects from SEQUOIA and 128 from REDWOOD. The total OHQ MCID for improvement was a reduction of 0.9-1.2 points and for worsening was an increase of 0.7-1.1 points. The MCID for the OHSA composite ranged from a reduction of 0.9-1.3 points for improvement and an increase of 0.7-1.1 points for worsening. For the single-item OHSA1, the MCID was a reduction of 2.0-3.0 points for improvement and an increase of 1.0 point for worsening. Owing to poor correlation with the symptom-based anchors, a reliable MCID for the OHDAS component was not established. CONCLUSIONS: These MCID thresholds for the OHQ, OHSA and OHSA item 1 alone, enhance the interpretability of scores and support their use in evaluating clinical benefit.