Clinical Autonomic Research最新文献

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.

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.

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.