Clinical Autonomic Research最新文献

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Background: The SPRITELY study showed no differences in the recurrence of syncope in patients with bifascicular block (BFB) and syncope, regardless of whether patients received an empiric pacemaker (PM) or an implantable cardiac monitor (ICM). Whether syncope resistant to pacing can be predicted by baseline clinical variables is unknown.

Objectives: To determine whether baseline clinical characteristics predict syncope recurrence in patients with bifascicular block and a permanent pacemaker.

Methods: This was a retrospective analysis of the SPIRITELY trial, a randomized clinical trial in which patients with syncope and bifascicular block were assigned randomly to receive either a pacemaker or implantable loop recorder as an initial management strategy. In 60 patients who received a pacemaker, we tested the ability of 38 baseline clinical variables to predict a syncope recurrence. These included demographics, comorbidities, medications, and syncopal history and symptoms. Univariable and multivariate statistics were performed and a p < 0.05 was accepted as significant.

Results: In the 60 patients who received a pacemaker, 12 (20%) had recurrent syncope. Only the use of angiotensin receptor blockers (ARB) and a history of a composite of one or more of asystole, supraventricular tachycardia (SVT), or diabetes were univariable significant predictors of recurrent syncope (p = 0.042). In the multivariate analysis only a history of a composite of one or more of asystole, SVT, or diabetes significantly predicted syncope (p = 0.03). Neither SVT nor diabetes alone predicted syncope recurrence.

Conclusions: In older patients with syncope and bifascicular heart block, only a history of one or more of asystole, SVT, or diabetes significantly predicted syncope.

Purpose: Harlequin syndrome is a rare autonomic disorder characterized by unilateral facial flushing and contralateral anhidrosis. We sought to delineate underlying causes, clinical presentations, and autonomic testing profiles of patients with Harlequin syndrome.

Methods: Retrospective chart review was performed of the Mayo Clinic electronic health record for patients with a Harlequin syndrome diagnosis from 1998 to 2024. Clinical, laboratory, imaging, and autonomic function testing results, including autonomic reflex screen (ARS) and thermoregulatory sweat test (TST), were reviewed.

Results: Of 51 patients with Harlequin syndrome, 39 (76%) were women. Median age of onset was 52 years (range 8-73 years). Harlequin syndrome was often idiopathic (N = 19; 37%), followed by postsurgical (N = 9; 17%), neoplasm (N = 5; 9.8%), trauma (N = 4; 7.8%), small fiber neuropathy (N = 4; 7.8%), systemic causes (N = 3; 5.9%), autoimmune (N = 3; 5.9%), pure autonomic failure (N = 2; 3.9%), and multiple sclerosis (N = 1; 2%). Pupil abnormalities were found in 13 patients (25.5%) with abnormal muscle stretch reflexes in 17 (33.3%). Headache was a comorbidity in 20 patients (39%). Of those with postsurgical onset, various surgeries preceded Harlequin syndrome onset, including heart, lung, and neck operations. Onset was acute or subacute in the majority of postsurgical patients (57%), while insidious onset was most common in nonsurgical patients (89%; p = 0.001). Median anhidrosis on TST was 9% (range 0.6-63%; N = 27). Median composite autonomic severity score was 1 (interquartile range (IQR) 0-3; N = 31).

Conclusions: Harlequin syndrome commonly has an insidious onset and occurs without an identifiable cause, which could be considered primary Harlequin syndrome. Secondary Harlequin syndrome can occur following surgeries in the vicinity of sympathetic pathways, which most commonly leads to an acute or subacute presentation.

Purpose: Few studies have examined the association between cardiovascular autonomic failure and minor hallucinations in patients with Parkinson's disease (PD). The aim of this study was to clarify this association.

Methods: The subjects were 133 patients with PD without well-structured visual hallucinations. Visual illusory responses were evaluated using the noise pareidolia test. Cardiac ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG) uptake and neurogenic orthostatic hypotension (nOH) and supine hypertension (nSH) on head-up tilt-table testing were examined in association with the incidence of pareidolia.

Results: Fifty-one (38%) patients had pareidolia. nOH (β = 0.220, p = 0.008), cognitive impairment (β = -0.228, p = 0.028), and longer symptom duration (β = 0.273, p = 0.006) were associated with an increased incidence of pareidolia independently of age, sex, motor severity, levodopa-equivalent dose, and anticholinergic and cholinesterase inhibitor use. An increased incidence of pareidolia was also associated with nSH (β = 0.214, p = 0.009), while no such association was found with cardiac ¹²³I-MIBG uptake. Patients with severe nOH or nSH tended to have a higher incidence of pareidolia than those with mild nOH (p = 0.063) or nSH (p < 0.003), respectively.

Conclusion: nOH and nSH were associated with the severity of pareidolia in early PD patients without well-structured visual hallucinations. Further studies are required to clarify whether this association is attributable to widespread central pathological changes related to cardiovascular autonomic failure, or to degeneration of the sympathetic nervous system.

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.

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.

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.