Clinical Autonomic Research最新文献

{"title":"Blunted baroreflex-mediated sympathoinhibition and vasodilation to countdown before exercise in young women compared to men.","authors":"Kazumasa Manabe, Andrew W D'Souza, Ryosuke Takeda, Sarah L Hissen, Takuro Washio, John D Akins, Belinda Sanchez, Qi Fu","doi":"10.1007/s10286-025-01132-w","DOIUrl":"10.1007/s10286-025-01132-w","url":null,"abstract":"<p><strong>Purpose: </strong>In our previous study (Manabe et al., J Appl Physiol 128:1196-1206, 1985), we demonstrated that the cerebral and cardiovascular responses induced by a pre-exercise countdown elicited peripheral vasodilation via baroreflex-mediated sympathetic withdrawal, which is likely advantageous for rapid oxygen delivery to contracting skeletal muscles in young men. Whether this is also true in young women, who generally show different neuro-cardiovascular responses to stress compared to men, remains unknown. Thus, we examined whether biological sex would affect the neuro-cardiovascular responses to anticipation before exercise.</p><p><strong>Methods: </strong>Young healthy women (n = 11) and men (n = 10) performed 1 min of static handgrip at 30% of maximal voluntary contraction force twice; once with a 30 sec countdown and once after being immediately signaled to begin exercise (without countdown), with the order randomized. Middle cerebral artery blood velocity (V_MCA; transcranial Doppler), heart rate (HR), cardiac index [CI; HR × stroke volume (Modelflow)/body surface area], mean arterial pressure (MAP; finger photoplethysmography), muscle sympathetic nerve activity (MSNA; microneurography), and leg vascular conductance [LVC = superficial femoral artery blood flow (ultrasound)/MAP] were measured continuously.</p><p><strong>Results: </strong>During countdown, women exhibited smaller increases in CI, MAP, and LVC and a smaller decrease in MSNA than men (p < 0.05). Increases in V_MCA and HR, and the sympathetic baroreflex sensitivity did not differ between sexes (p > 0.05).</p><p><strong>Conclusion: </strong>Young women seem to have less baroreflex-mediated sympathetic withdrawal and peripheral vasodilatory responses to the countdown compared to young men, despite similar cerebral vascular responses. These findings may suggest women have reduced neuro-vascular responses to exercise anticipation, which could impact the ability of oxygen delivery at exercise onset.</p>","PeriodicalId":10168,"journal":{"name":"Clinical Autonomic Research","volume":" ","pages":"747-757"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Response: \"Re: Comprehensive linear and nonlinear heart rate variability normative data in children. Clinical Autonomic Research (September 2024)\".","authors":"Bahram Kakavand","doi":"10.1007/s10286-025-01141-9","DOIUrl":"10.1007/s10286-025-01141-9","url":null,"abstract":"","PeriodicalId":10168,"journal":{"name":"Clinical Autonomic Research","volume":" ","pages":"859"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic yield of nitroglycerin-potentiated head-up tilt test in a pediatric population with suspected reflex syncope.","authors":"Vincenzo Russo, Angelo Comune, Giangiacomo Di Nardo, Erika Parente, Giovanni Maria Di Marco, Angelica De Nigris, Maria Giovanna Russo, Berardo Sarubbi, Gerardo Nigro, Michele Brignole","doi":"10.1007/s10286-025-01145-5","DOIUrl":"10.1007/s10286-025-01145-5","url":null,"abstract":"<p><strong>Background: </strong>Syncope is a prevalent issue in pediatric patients. The nitroglycerin (NTG)-potentiated head-up tilt test (HUTT) is widely used in adults for diagnosing reflex syncope; however, few and contrasting data are available in pediatric populations. The aim of our study was to evaluate the positivity rate and types of responses to NTG-potentiated HUTT in pediatric patients with suspected reflex syncope.</p><p><strong>Methods: </strong>We conducted a retrospective multicenter analysis of 307 pediatric patients (mean age: 14.4 ± 2.8 years; 57.6% female) who underwent HUTT at two syncope units in Naples, Italy. A group of 16 healthy pediatric subjects (13 ± 3.2 years; 37.5% female) with no history of syncope was used as a control. We described the HUTT overall positivity rate and responses; moreover, the positivity rate, sensitivity, and specificity were evaluated. A multivariate analysis was performed to test the association of positive response to HUTT with a set of clinical covariates.</p><p><strong>Results: </strong>The overall HUTT positivity rate was 74.9%, ranging from 51.5% to 81.6% among pediatric patients with non-classical and classical presentation, respectively. The HUTT positivity rate among healthy control group was 18.7%; consequently the HUTT specificity was 81.3%. Younger age (OR: 0.84; p = 0.005) and female sex (OR: 2.3; p = 0.005) were independent predictors of HUTT positivity; in contrast, the non-classical presentation of syncope (OR: 0.23; p < 0.001) and situational syncope (OR: 0.2; p = 0.006) correlated negatively with HUTT positivity.</p><p><strong>Conclusions: </strong>NTG-potentiated HUTT showed a high positivity rate, good sensitivity, and specificity in pediatric patients with suspected reflex syncope. Some patients and syncope-related features independently correlated with HUTT positivity. Cardioinhibitory response was more prevalent in pediatric patients with a non-classical presentation of reflex syncope.</p>","PeriodicalId":10168,"journal":{"name":"Clinical Autonomic Research","volume":" ","pages":"799-805"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12664829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction evaluation of the Tp-Te interval in patients with vasovagal syncope.","authors":"Xiaomin Zhang, Shuting Dai, Haitao Wang, Ruirui Jiang, Qian Xie, Jing Wen, Min Han, Yi Xu, Gang Wang","doi":"10.1007/s10286-025-01148-2","DOIUrl":"10.1007/s10286-025-01148-2","url":null,"abstract":"<p><strong>Purpose: </strong>Vasovagal syncope (VVS) involves autonomic dysregulation affecting cardiac electrical activity. The Tp-Te interval, reflecting transmural repolarization dispersion, may help predict positive head-up tilt test (HUTT) responses in patients with suspected VVS.</p><p><strong>Methods: </strong>A total of 179 patients with suspected VVS were included in the study. A HUTT was performed in enrolled patients, which were divided into HUTT-negative and HUTT-positive groups, and the HUTT-positive group was further classified into three subgroups of \"vasodepressor,\" \"cardioinhibitory,\" and \"mixed-type\" responses to HUTT. QT interval, corrected QT (QTc) interval, and Tp-Te interval were measured by the baseline 12-lead surface electrocardiograph recorded before HUTT.</p><p><strong>Results: </strong>The QT interval, QTc interval, and Tp-Te interval in the HUTT-positive group were higher than those in the HUTT-negative group (P < 0.001). Tp-Te was higher in the cardioinhibitory and mixed-type subgroups than in the vasodepressor subgroup (P < 0.05). Receiver operating characteristic curve analysis showed that Tp-Te higher than 88 ms was a significant predictor of positive HUTT results (71.70% sensitivity and 75.90% specificity), with a predictive value significantly higher than QT and QTc (P < 0.05), and Tp-Te higher than 95 ms predicted cardioinhibitory and mixed-type response to HUTT (75% sensitivity, and 57.10% specificity).</p><p><strong>Conclusion: </strong>Baseline myocardial TDR is associated with VVS and susceptibility to VVS. The baseline Tp-Te interval might be used as a novel noninvasive index for differentiating cardioinhibitory, mixed-type, and vasodepressor responses to HUTT and for predicting the occurrence of cardioinhibitory responses in VVS patients.</p>","PeriodicalId":10168,"journal":{"name":"Clinical Autonomic Research","volume":" ","pages":"791-798"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetate concentration correlates with MSNA in patients with resistant hypertension.","authors":"Revathy Carnagarin, Gianni Sesa-Ashton, Natalie C Ward, Janis Nolde, Anu Joyson, Justine Chan, Ancy Jose, Markus P Schlaich","doi":"10.1007/s10286-025-01144-6","DOIUrl":"10.1007/s10286-025-01144-6","url":null,"abstract":"<p><strong>Purpose: </strong>Short-chain fatty acids (SCFAs), metabolites of colonic microflora fermentation of dietary fibre, have been implicated in experimental models and clinical trials to impact blood pressure (BP) regulation. Dietary interventions increasing serum SCFA levels have been associated with reduced 24-h systolic BP in hypertensive patients. However, the underlying mechanisms remain elusive. Given the role of the gut-brain axis and clear evidence for sympathetic nervous system activation as important modulators of blood pressure, we examined the relationship between sympathetic drive and SCFA concentration in patients with resistant hypertension (RH) and healthy control subjects (HC).</p><p><strong>Methods: </strong>A total of 21 patients with RH (68.6 ± 9.7 years, 47% male) and 28 healthy control subjects (HC) (34.6 ± 16.7 years, 75% male) were recruited to undergo microneurography for determination of muscle sympathetic nerve activity (MSNA), automated office BP (AOBP) and blood collection for serum SCFA.</p><p><strong>Results: </strong>Mean systolic AOBP was 156 ± 21 mmHg and 115 ± 10 mmHg for RH and HC, respectively (p < 0.0001). Serum acetate levels were 1340 ± 115.4 umol/L for HC and 724.5 ± 116.9 umol/L for RH (p < 0.0001). Butyrate and propionate concentrations did not significantly differ between groups. MSNA burst frequency was markedly elevated in RH compared with HCs (p < 0.001), with 25.3 ± 7.4 burst/minute in HC compared with 40.24 ± 8.3 burst/minute in RH. An inverse relationship was evident between serum acetate levels and MSNA burst frequency (p = 0.0267, R² = 0.4) along with increased sympathetic vascular transduction (p = 0.0008, R² = 0.82) in RH.</p><p><strong>Conclusions: </strong>Our findings suggest that the beneficial effects of SCFA levels, in particular acetate, on cardiovascular regulation may at least in part be mediated by sympatho-inhibition and altered sympathetic vascular transduction.</p>","PeriodicalId":10168,"journal":{"name":"Clinical Autonomic Research","volume":" ","pages":"727-734"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12664844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improvement in nocturnal blood pressure with bedtime antihypertensive administration in older adults aged 65 and above: a systematic review and meta-analysis.","authors":"Jordy Saren, Siddhartha Lieten, Mirko Petrovic, Esma Islamaj, Ivan Bautmans, Aziz Debain","doi":"10.1007/s10286-025-01159-z","DOIUrl":"10.1007/s10286-025-01159-z","url":null,"abstract":"<p><strong>Purpose: </strong>This study evaluated the effectiveness of morning versus bedtime antihypertensive medication administration in reducing ambulatory blood pressure (BP) in older adults aged ≥ 65, and to assess whether administration timing influences conversion from a non-dipper to a dipper BP profile.</p><p><strong>Methods: </strong>Eight randomized controlled trials were identified through systematically screening of the PubMed and Web of Science databases. Risk of bias was assessed using the Cochrane Risk of Bias tool. Meta-analyses were conducted with Review Manager version 5.4 to compare the efficacy of morning versus bedtime administration on ambulatory BP indices.</p><p><strong>Results: </strong>Bedtime administration resulted in significantly greater reductions in nocturnal systolic BP (mean difference [MD] - 4.52 mmHg, [lower and upper 95% confidence intervals [CI] - 7.15; - 1.90]; p = 0.0007) and diastolic BP (MD - 2.00 mmHg, [95% CI - 2.90; - 1.10]; p < 0.0001). No significant differences were observed in diurnal systolic BP (MD 1.28 mmHg, [95% CI - 0.17; 2.72]; p = 0.08), diastolic BP (MD 0.34 mmHg, [95% CI - 0.49; 1.16]; p = 0.42), 24/48-h systolic BP (MD - 0.02 mmHg, [95% CI - 1.37; 1.33]; p = 0.98), or 24/48-h diastolic BP (MD - 0.50 mmHg, [95% CI - 1.45; 0.45]; p = 0.30). Sensitivity analysis excluding the controversial data from Hermida confirmed significantly greater reductions in nocturnal systolic and diastolic BP with bedtime administration. Two of three studies reported that bedtime administration was associated with a lower proportion of non-dippers than morning treatment.</p><p><strong>Conclusion: </strong>Bedtime antihypertensive administration improves control of nocturnal BP in older adults aged ≥ 65 and may facilitate restoration to a dipper BP profile. No significant differences were observed in diurnal or 24/48-h mean BP reductions compared with morning administration.</p>","PeriodicalId":10168,"journal":{"name":"Clinical Autonomic Research","volume":" ","pages":"711-725"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of beta-blocker therapy on the sympathetic effects in stroke heart syndrome.","authors":"Gabriele Prandin, Marcello Naccarato, Giovanni Furlanis, Laura Mancinelli, Federica Palacino, Emanuele Vincis, Magda Quagliotto, Edoardo Ricci, Luigi Cattaruzza, Paola Caruso, Paolo Manganotti","doi":"10.1007/s10286-025-01139-3","DOIUrl":"10.1007/s10286-025-01139-3","url":null,"abstract":"<p><strong>Background: </strong>Sympathetic activation, inflammation, and neuro-endocrine response after an ischemic stroke contribute to the development of the stroke heart syndrome (SHS). One marker of SHS is a troponin \"rise and fall pattern\" > 30%. Among the beta-blocker drugs, the β1 antagonist class has a selective effect on the heart against sympathetic neurotransmitters. The aim of this study is to evaluate the possible role of pre-stroke chronic cardioselective β1 blocker treatment (B1B) in preventing SHS.</p><p><strong>Methods: </strong>We retrospectively analyzed data of 891 acute stroke patients admitted to the stroke unit at the University Hospital of Trieste (Italy) between 2018 and 2020. In total, 490 patients met the inclusion criteria. Clinical data, imaging characteristics and markers of cardiac injury (troponin I [TnI], N-terminal fragment of B type natriuretic peptide (NT-proBNP), and \"rise and fall pattern\" > 30%) and the chronic pre-stroke use of B1B were collected. We compared SHS against lack of SHS (no-SHS), subsequently examining the data through a multivariable analysis to determine possible SHS predictive factors.</p><p><strong>Results: </strong>No association between chronic B1B pre-stroke use and SHS (odds ratio [OR] 1.031; 95% confidence interval [CI] 0.636-1.672; p = 0.900) has been observed. The same result has been found in a sub-analysis on patients with chronic heart failure characterized by high NT-proBNP levels (> 900 pg/mL; n = 212), in which no association between chronic pre-stroke use of B1B and SHS (OR 0.807; 95% CI 0.449-1.451; p = 0.474) was identified.</p><p><strong>Conclusions: </strong>In our single-center retrospective cohort, a pre-stroke chronic B1B treatment seems not to prevent the development of SHS, including in patients with NT-proBNP > 900 pg/mL with chronic heart failure. These results should be confirmed by future randomized controlled trials to better understand the lack of effect of beta blockers on SHS.</p>","PeriodicalId":10168,"journal":{"name":"Clinical Autonomic Research","volume":" ","pages":"759-765"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and impact of orthostatic hypotension in Parkinson's disease: a systematic review and meta-analysis.","authors":"Hui Wang, Chi Zhang, Dongxun Xu","doi":"10.1007/s10286-025-01146-4","DOIUrl":"10.1007/s10286-025-01146-4","url":null,"abstract":"<p><strong>Objective: </strong>Parkinson's disease (PD) is frequently associated with orthostatic hypotension (OH). Research on the prevalence of OH in PD and its effects on patients has produced inconsistent findings.</p><p><strong>Methods: </strong>A systematic review and meta-analysis were conducted by searching for studies related to PD and OH in the PubMed, Web of Science, Embase, and Cochrane databases. Data were pooled as necessary to calculate the prevalence of OH in patients with PD, along with odds ratios (OR), weighted mean differences (WMD), or standardized mean differences (SMD) with 95% confidence intervals (CI). Heterogeneity was assessed using the I² statistic.</p><p><strong>Results: </strong>The prevalence of OH in patients with PD was found to be 33.1% (95% CI 29.3-37%) in a pooled sample of 7748 subjects. Patients with PD and OH were significantly older at the time of examination (WMD 2.92 years) and had a longer disease duration (WMD 0.71 years) compared with those without OH. There was no significant difference in the distribution of sex, or in the scores of the Unified Parkinson's Disease Rating Scale (UPDRS)/the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts I and II, as well as the total scores among patients with Parkinson's disease with or without OH. In addition, patients with PD and OH exhibited significantly higher UPDRS/MDS-UPDRS scores across part III section scores (SMD 0.41, 95% CI 0.23-0.59).</p><p><strong>Conclusions: </strong>The prevalence of OH in PD is 33.1%. Patients with PD and OH are generally older at examination, have a longer disease duration, and display more severe motor symptoms compared with those without OH.</p>","PeriodicalId":10168,"journal":{"name":"Clinical Autonomic Research","volume":" ","pages":"697-710"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progressive baroreflex dysfunction and hypotension preceding VVS: a vicious cycle?","authors":"D L Jardine, V Stott, C Frampton","doi":"10.1007/s10286-025-01147-3","DOIUrl":"10.1007/s10286-025-01147-3","url":null,"abstract":"<p><strong>Purpose: </strong>We aimed to clarify the mechanism for presyncope, defined as the gradual onset of hypotension, starting some minutes before vasovagal syncope. Although there is a fall in cardiac output and usually vasodilatation, the control of sympathetic activity during presyncope is uncertain.</p><p><strong>Methods: </strong>We retrospectively compared haemodynamics and muscle sympathetic nerve activity levels from positive tilt tests (without provocation) in patients with known vasovagal syncope (age 41 ± 3 years, 13 female, n = 27) to controls (age 39 ± 3 years, 8 female, n = 13). We used sequence methods to measure vascular sympathetic and cardiovagal baroreflex gain at baseline (lying supine) during tilt, presyncope and recovery.</p><p><strong>Results: </strong>Patients were tilted for 18.1 ± 1 min, and mean arterial pressure fell to 62 ± 3 mmHg before tilt-back. At baseline and early tilt, all haemodynamic variables were similar to controls, however sympathetic baroreflex gain was increased: -2.7 ± 0.2 bursts/100 beats/mmHg versus -2.0 ± 0.3 (p = 0.03). Cardiovagal baroreflex gain was increased at baseline 11.8 ± 0.6 ms/mmHg versus 9.3 ± 0.8 (p = 0.02). During early presyncope (from 8 to 4 min before tilt-back), sympathetic baroreflex gain fell to -2.4 bursts/100 b/mmHg and thereafter to -0.5 ± 0.3 (p = 0.01) during late presyncope, before losing correlation with mean arterial pressure. In some patients, the regression coefficient reversed before correlation was lost (n = 8) but this did not result in lower levels of nerve activity. At tilt-back, nerve activity fell below baseline levels in at least 63% of patients.</p><p><strong>Conclusion: </strong>Presyncope appeared to be initiated by a fall in sympathetic baroreflex gain despite increased levels at baseline and early tilt.</p>","PeriodicalId":10168,"journal":{"name":"Clinical Autonomic Research","volume":" ","pages":"779-790"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3,4-Dihydroxyphenylglycol levels separate multiple system atrophy from Parkinson disease with orthostatic hypotension.","authors":"David S Goldstein, Patti Sullivan, Courtney Holmes","doi":"10.1007/s10286-025-01150-8","DOIUrl":"10.1007/s10286-025-01150-8","url":null,"abstract":"<p><strong>Background: </strong>The autonomic synucleinopathy multiple system atrophy (MSA) can be difficult to distinguish clinically from Parkinson disease with orthostatic hypotension (PD+OH). ¹⁸F-Dopamine positron emission tomography separates these conditions based on cardiac noradrenergic deficiency in PD+OH and not in MSA but is available only at the NIH Clinical Center. 3,4-Dihydroxyphenylglycol (DHPG) is the main neuronal metabolite of norepinephrine. This retrospective observational study examined whether DHPG levels in cerebrospinal fluid (CSF) or plasma differentiate MSA from PD+OH.</p><p><strong>Methods: </strong>We reviewed CSF and plasma neurochemical data from all patients referred for evaluation at the NIH Clinical Center between 1995 and 2024 for chronic autonomic failure or parkinsonism. A concurrently studied comparison group included healthy volunteers or patients with orthostatic intolerance.</p><p><strong>Results: </strong>CSF DHPG was decreased in MSA (N = 67, p < 0.0001) compared to the controls but also tended to be decreased in PD+OH (N = 31, p = 0.0776). Antecubital venous plasma DHPG was decreased in PD+OH (N = 47, p = 0.0064) but not in MSA. CSF/plasma concentration ratios of DHPG were lower in MSA than in PD+OH (p = 0.0005). Cardiac arteriovenous increments in plasma DHPG and cardiac norepinephrine spillovers were strikingly decreased in PD+OH (N = 6) and were lower than in MSA (N = 20, p < 0.0001 each). Combining cardiac arteriovenous increments in plasma DHPG with norepinephrine spillovers completely separated PD+OH from MSA.</p><p><strong>Conclusions: </strong>CSF/plasma ratios of DHPG, cardiac arteriovenous increments in plasma DHPG, and cardiac norepinephrine spillovers separate MSA from PD+OH. On the basis of our results we propose that biomarker combinations involving DHPG in biofluids may enable a clinical laboratory distinction of MSA from PD+OH.</p>","PeriodicalId":10168,"journal":{"name":"Clinical Autonomic Research","volume":" ","pages":"807-815"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12664830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}