Limited data exist on long-term outcomes associated with postural orthostatic tachycardia syndrome (POTS). We designed an online questionnaire to assess outcomes for patients formerly managed in a single-center pediatric POTS program. Here, we report the educational, economic, and social long-term impacts of pediatric POTS. In part, the Long-Term POTS Outcomes Survey (LT-POTS) sought to evaluate education, employment, and social impact of POTS. Patients aged ≤18 years at the time of POTS diagnosis were included. The survey was emailed to patients diagnosed or managed in the Children's Hospital of Philadelphia POTS Program. Of 862 patients surveyed, 227 returned questionnaires with enough data for interpretation. Respondents were predominantly women (85%) and White individuals (97%). Half of patients missed >100 days of school, and 20% temporarily dropped out of school. More than 90% of patients graduated high school, and <50% graduated college. Only 26% of patients were able to work >40 hours/week, with 35% having reduced hours due to POTS symptoms. Significant loss of income and financial expenditures were associated with POTS. Loss of social relationships and inability to live independently were additional associated social impacts. POTS is a long-term disorder associated with significant physical disability as well as adverse educational, economic, and social impacts. Although certain accommodations may mitigate the impact of the disease on education and employment, POTS poses significant educational, economic, and socioemotional risks, requiring further understanding of its pathophysiology and optimization of its management to reduce individual and societal impact.

While syncope is characterized by a sudden and temporary loss of consciousness caused by decreased blood flow to the brain and is easily recognized by its clinical features, presyncope involves a sensation of impending fainting, often accompanied by autonomic symptoms. Presyncope is less characterized and studied than syncope, presenting a particular diagnostic challenge in neurology clinics. Neurologists commonly encounter patients with presyncope in outpatient settings or during consultation at the emergency department after cardiopulmonary causes have been excluded. Differential diagnosis of recurrent presyncope is broad but from a neurologic standpoint falls into multiple neurologic categories, including complex partial seizures, basilar or vestibular migraine, dysautonomia, cataplexy, alteration in cerebrospinal fluid flow, Meniere's disease, posterior circulation transient ischemic attacks and others. Here, we review presyncope as a feature of dysautonomia and common autonomic disorders, such as neurocardiogenic syncope, postural orthostatic tachycardia syndrome, orthostatic hypotension and orthostatic intolerance. We discuss clinical and neurologic exam findings, diagnostic tests, differential diagnosis and treatment of presyncope as a manifestation of common autonomic disorders.

  Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous disorder of autonomic regulation characterised by unexplained orthostatic tachycardia in the absence of postural hypotension. POTS is a complex and challenging diagnosis owing to the non-specific nature of the presentations, which frequently overlap with other medical conditions. There is limited availability of data and research describing the spectrum of clinical presentations, diagnostic pathways, comorbidities, and management outcomes. This study aims to describe the above in a single-centre district general hospital setting.   We conducted a retrospective case series study of 37 patients diagnosed with POTS at Queen's Hospital Burton (QHB) between August 2023 and August 2024. We used electronic health records to acquire relevant data. This included demographics, presenting complaints, associated conditions, time to diagnosis, specialist involvement, management strategies, and treatment outcomes. 'Time to diagnosis' was defined as the period between the first symptom onset and obtaining a confirmed diagnosis with a positive tilt-table test. Microsoft Excel (Redmond, USA) was utilised for descriptive statistical analysis.   The cohort was predominantly female (n = 36, 97%) with a mean age of 28.2 years (SD, 8.3; range, 18-48). The most common presenting complaints were presyncope (49%) and presyncope with syncope (41%). These were often associated with palpitations and chest discomfort. Systemic conditions coexisting with POTS included anxiety/depression, hypermobility spectrum disorders (notably Ehlers-Danlos Syndrome), fibromyalgia, autoimmune diseases, and migraine. The median time to diagnosis was one year (IQR 1-4). However, delays of up to 20 years were observed. Speciality referrals involved cardiology (65%), neurology (13%), and internal medicine (10%). Management strategies included non-pharmacological therapy alone (19%), additionally pharmacological monotherapy (62%), and combination therapy with multiple drugs (19%). Symptomatic improvement was reported in 65% overall, with the highest rates observed in the multi-drug therapy group.    This study highlights the demographic profile, burden of comorbidities, and diagnostic challenges in patients with POTS. Our single-centre study has demonstrated meaningful progress towards reducing the average time to diagnose POTS with varying treatment outcomes across therapeutic strategies. Multi-drug therapy in conjunction with non-pharmacological therapy proved to be the most efficacious in this cohort. These findings emphasise the importance of early recognition, streamlined referral pathways, and the need for further large-scale multi-centre research into patient-tailored, evidence-based management of POTS.

SARS-CoV-2 vaccination (SC2V) can be complicated by post-acute COVID-19 vaccination syndrome (PACVS). One manifestation of PACVS is small fibre neuropathy (SFN). A positive effect of intravenous immunoglobulins (IVIGs) even 3 years after the onset of PACVS is not known. The patient is a 52-year-old woman who developed PACVS after the second BNT162b2 vaccination in June 2021, which manifested clinically with SFN, myopericarditis, coagulopathy, and ocular, dermatologic, immunologic, and central nervous system (CNS) abnormalities. The SFN itself manifested as sensory disturbances, arterial hypotension and postural tachycardia syndrome (POTS). After the patient received three cycles of IVIGs, starting in June 2024, three years after the onset of PACVS, there was a significant positive effect on her SFN and other symptoms, as evidenced by various specific investigations. This case demonstrates that symptoms and signs of SFN as a manifestation of PACVS may benefit from the administration of IVIGs even years after onset.

Postural Orthostatic Tachycardia Syndrome (POTS) is an autonomic dysfunction characterized by symptoms of orthostatic intolerance, associated with an increase in heart rate within 10 minutes of assuming an upright position or head-up tilt, in the absence of hypotension. There are three phenotypes of POTS - neuropathic, hypovolemic, and hyperadrenergic - and all result in tachycardia and altered cerebral perfusion. Pharmacological therapy is indicated in certain cases; however, no specific medication has yet been approved for this condition. Some studies have shown that ivabradine may be beneficial, as it reduces heart rate without affecting blood pressure. To evaluate the efficacy and safety of ivabradine in the treatment of POTS. Systematic review using the descriptors "Ivabradine" and "Postural Orthostatic Tachycardia Syndrome" in the PubMed, Scielo, LILACS, and Google Scholar databases. Articles were grouped and assessed using the PICO strategy. A total of 52 articles were identified, of which seven were included in the review - three prospective and four retrospective studies. In total, 203 patients were evaluated, the majority of whom were female. All studies reported a significant reduction in heart rate and improvement in symptoms of orthostatic intolerance, with most patients not reporting adverse effects, regardless of their POTS phenotype. Ivabradine proved to be effective and safe in the treatment of patients with POTS.

The phenotypic similarities and genetic heterogeneity occurring in diverse forms of Ehlers Danlos Syndrome (EDS) subtypes and many heritable connective tissue disorders can pose a diagnostic challenge. In the wake of the growing applications of next-generation sequencing technologies including exome and genome sequencing, opportunities for achieving definitive genetic diagnosis are increasingly arising. We present a 46-year-old man with joint laxity, recurrent joint subluxations, pelvic floor dysfunction, and postural orthostatic tachycardia syndrome (POTS), who was referred for EDS assessment. His medical history included morbid obesity requiring gastric bypass surgery, hearing loss, asthma, retinopathy, myopia, atrial septal defect, narcolepsy with cataplexy, polyneuropathy, folliculitis, lichen simplex chronicus, atopic dermatitis, and hypogonadism. His family history was significant for multiple first- and second-degree relatives who died from cardiac diseases including cases of childhood deaths. Physical examination showed joint laxity with Beighton score of 3/9, bilateral pes planus, hearing loss and macrocephaly. Exome sequencing revealed heterozygous variants LMNA c.1262 T > C p.L421P [classified as likely pathogenic], FLG c.2282_2285del p. S761Cfs*36 [classified as pathogenic], and FLG c.1501 C > T p. R501* [classified as pathogenic]. Mitochondria sequencing revealed a variant of uncertain significance (VUS), MT-ND2 m.5047 T > C p.V193A that is present at 9% heteroplasmy in blood. These findings show co-occurrence of pathogenic sequence variants in neighboring genes located in chromosome 1q2 region [LMNA and FLG] in a patient with features of hereditary connective tissue disorders. Our study highlights the capability of exome sequencing in achieving some actionable diagnosis in cases of co-morbid genetic disorders with overlapping and non-specific symptoms.

Postural Orthostatic Tachycardia Syndrome (POTS) is a variant of autonomic dysfunction (AD) defined by an increase in heart rate (HR) ≥ 30 bpm within 10 minutes (min) of a change from the supine to an upright position, in the absence of orthostatic hypotension. Many studies suggest that AD is common in active cancer patients and is associated with variable symptoms and decreased survival. Based on this evidence, we hypothesized that POTS can be associated with active cancer and might contribute to some of these patients' symptoms and survival. Consecutive 220 active cancer patients aged 19-59 were enrolled. They were asked to lay flat for 5-10 min then to stand for 10 min without support. Total of 5 blood pressure (BP) and HR readings were taken (immediately before standing up then immediately after, and at 3, 6, and 10 min while standing). All patient's symptoms were recorded. 213 patients were included. Age was 48 ± 8, 76% were females,18% had metastasis and 43% were on chemotherapy. 55% reported symptoms of AD, with symptoms associated with standing were reported in 28%. Baseline HR was 76 ± 13 bpm, and systolic BP was 129 ± 20. Upon standing, HR increased by 10 ± 3 bpm and systolic BP dropped by 1.3 ± 0.4. Immediately after standing, 47 (22%) Patients developed symptoms.18 patients (8.5%) met the criteria for POTS, where HR increased by 37 ± 5 with an increase in systolic BP by -1.6 ± 6. Patients with POTS had higher HR upon standing (p = 0.000), HR at 3 min (p = 0.005), HR at 6 min (p = 0.002), and HR at 10 min (p = 0.000). In contrast, baseline HR and BP showed no significant difference between patients with and without POTS (p = 0.74 and 0.11). After 16.9 ± 5.5 months, there was no statistical deterrence in all-cause mortality between POTS and non-POTS patients. POTS and orthostatic intolerance are prevalent in active cancer, where onset of symptoms started after cancer diagnosis in many patients. These patients have a significant association with higher HR upon standing and overall prognosis comparable to that of patients without POTS.

This study aimed to explore physical activity and sedentary time in adults with post-COVID-19 condition, and to identify associated factors. Cross-sectional, observational study. Adults with post-COVID-19 condition. Physical activity and sedentary time were measured using activity monitors alongside assessment of potential associated factors. Among 159 participants (mean age: 50 years, women: 64%), 36% took < 5,000 steps, 60% spent < 22 min in brisk walking, and 57% spent ≥ 8 h sedentarily daily. Additionally, 29% exhibited low activity combined with prolonged sedentary time. Postural orthostatic tachycardia syndrome and palpitations were associated with taking fewer steps, while paraesthesia, greater distance in the 6-min walk test, previous activity levels, and self-rated health were associated with taking more steps. Palpitations were associated with less brisk walking, whereas greater distance in the 6-min walk test and lung function were associated with more brisk walking. Postural orthostatic tachycardia syndrome was associated with increased sedentary time and with exhibiting low activity combined with prolonged sedentary time. A substantial proportion of individuals with post-COVID-19 condition exhibit low physical activity and prolonged sedentary behaviour, posing potential health risks. The associated factors underscore the importance of comprehensive assessments to inform safe, individualized interventions.

Symptoms of dizziness, syncope, and palpitations are common presentations in outpatient and emergency care, frequently attributed to stress and anxiety when conventional neurological and cardiac evaluations are normal. Joint hypermobility (JH) syndromes including hypermobile Ehlers-Danlos syndrome (hEDS), and hypermobility spectrum disorders (HSD) are under-recognised as potential causes. Our retrospective cohort study examined the clinical features, diagnostic findings, and responses to treatment in patients with JH syndromes, who are referred to a specialised syncope clinic within a UK teaching hospital. It involved 218 patients with joint hypermobility, predominantly young females (median Beighton score: 6), reporting chronic orthostatic intolerance, dizziness, and palpitations. Common comorbidities included joint pain, chronic fatigue, gastrointestinal dysmotility, and psychiatric conditions. Prevalence of symptoms, cardiovascular abnormalities on investigation (ECG, echocardiography, and tilt-table testing), and treatment responses were analysed. History and examination were often diagnostic. Standard cardiac tests rarely provided diagnostic value except to exclude alternate conditions. Tilt-table testing was abnormal in 82.0% of cases, revealing orthostatic hypotension, reflex syncope, or postural tachycardia syndrome (POTS). Conservative measures (hydration, salt intake, and exercise) were effective in over half of the cases; pharmacological treatments (ivabradine, fludrocortisone) were considered for refractory cases. This study emphasises that JH syndromes are a common cause of palpitations, dizziness, and syncope in young females. They are multi-system conditions affecting both physical and mental health, which remain under-recognised and are often dismissed as 'functional', particularly in women-highlighting gender bias in diagnosis. A structured diagnostic approach with routine joint assessments for JH and increased awareness can facilitate early recognition and management in general medical settings, reducing reliance on emergency services and improving patient outcomes.

Prescription of obesity medications is increasing, but our understanding of their effects in patients with cardiovascular disorders, such as postural orthostatic tachycardia syndrome (POTS), is limited. POTS was exacerbated in a 28-year-old woman with obesity after using tirzepatide for weight reduction. Her condition was effectively treated with progressive exercise training and counseling, which reduced supine and standing heart rates to normal values, before starting tirzepatide. However, while using tirzepatide, the patient's supine and standing heart rates were markedly elevated, and she experienced recurrence of orthostatic intolerance symptoms. Although small increases in resting heart rate with glucagon-like peptide-1 receptor agonist use have been reported in adults (approximately 3 beats/min), such a large increase in both supine and standing heart rate (20-30 beats/min) with tirzepatide has not been reported to our knowledge. Prescription of tirzepatide may exacerbate symptoms of orthostatic intolerance and cause marked tachycardia in patients with POTS.

This systematic review aimed to identify components of supportive self-management for postural orthostatic tachycardia syndrome and critically appraise the evidence base. Systematic review. EMBASE, MEDLINE, CINHAL and charity databases, trial registries and grey literature were searched until December 14th, 2023. The PRISMA guidelines were followed for the search strategy. Data were mapped to the Practical Reviews in Self-management Support taxonomy components and the Middle Range Theory of Self-Care in Chronic Illness. Synthesis and analysis followed guidance on reporting without meta-analysis with summary tables, a logic model, harvest plot, and narrative synthesis. 36 studies were included. Components of supportive self-management were found in 1) lifestyle advice, 2) provision of equipment, and 3) support with adherence. No studies were found on 1) education, 2) psychological well-being, 3) communication needs with health professionals and social support networks, 4) reliable sources of information, 5) training for practical self-management, or clinical action plans, and 5) social support. Studies efficacy' was hampered by poor research designs, short studies of one day duration, and appropriateness of outcome measures. Significant gaps were identified requiring further research 1) self-care monitoring activities 2) self-care management activities, 3) provision of education, information and resources 4) addressing psychological well-being and 5) addressing social support. A specific gap exists in the POTS evidence base in nurse led interventions. This review evaluates supportive self-management components and identifies key issues with the current evidence base that require addressing to improve and inform the support needs and services of this often disabling, and predominantly female condition. This review is a novel integration of the taxonomy and theory. Findings were discussed with a postural tachycardia syndrome advisory group, providing important insights into key issues with the studies validity, reliability and generalisability from their perspectives.

Postural orthostatic tachycardia syndrome (POTS) is characterized by an abnormal increase in heart rate upon standing, leading to symptoms such as dizziness, fatigue, and rapid heart rate. Time-restricted eating (TRE), which limits caloric intake to an 8-10 h daily window, has been shown to decrease inflammation and improve immune, autonomic, and mitochondrial function, as well as cardiometabolic parameters. This single arm pilot study evaluated the effects of TRE on quality of life (QOL), heart rate, and mitochondrial function in 20 participants with POTS (≥ 30 bpm increase in upright heart rate) and a baseline dietary window of ≥ 12 h. Following a 2-week baseline monitoring period, participants underwent a 12-week TRE intervention. Pre- and post-intervention assessments included QOL questionnaires, a 10-minute stand test, and plasma mitochondrial analysis. TRE significantly reduced heart rate increase upon standing (mean decrease: 11 bpm, p < 0.001) and improved QOL metrics, as assessed by the Malmö POTS Symptom Score Survey (MAPS) and the General Health Questionnaire Short Form-36 (SF-36). Notable improvements include POTS symptom severity (p < 0.0001), physical functioning (p = 0.02), and energy/fatigue (p < 0.01). Additionally TRE increased mitochondrial-derived ATP production. These findings suggest TRE as a promising lifestyle intervention to improve QOL, heart rate, and mitochondrial function in POTS patients.

The purpose of this study was to identify factors with uniquely high prevalence in vulvodynia-Ehlers-Danlos syndrome comorbid patients in order to identify patients who may need referral and to better understand management of this population. This cross-sectional study was conducted in January 2025 using the TriNetX Platform Global Collaborative Network Database with statistical comparison of vulvodynia-Ehlers-Danlos comorbid cohort and vulvodynia non-Ehlers-Danlos cohort. Bonferroni correction was performed due to analysis of 100 demographic, associated condition, and treatment factors with statistical significance at p = .0005. Five hundred seventy vulvodynia-Ehlers-Danlos patients and 49,457 vulvodynia non-Ehlers-Danlos patients were identified with a mean age of 39 and 48 ( p < .0001), respectively. Vulvodynia-Ehlers-Danlos comorbid patients had more frequent chronic pain, musculoskeletal, neurologic, gynecologic, immune, and psychiatric conditions. Vulvodynia-Ehlers-Danlos patients had higher rates of most nonsurgical interventions but similar vaginal estrogen ( p = .0412) and vulvar surgery rates ( p = .4249). Vulvodynia-Ehlers-Danlos patients had signs of more frequent medical contact with more post-op visits, vaccines, and inpatient admissions ( p < .0001). Study limitations are those inherent to the TriNetX database, with ability to see associations but not causation. Clinicians treating genital pain have a role in the treatment of vulvodynia-Ehlers-Danlos patients given the array of prevalent pelvic conditions. Clinicians should keep the high rate of muscular, neurologic, and immune conditions in mind when evaluating the vulvodynia etiology in this population, as well as the higher rate of gynecologic comorbidities, which could result in hormone-mediated etiology from chronic estrogen use. With a higher rate of mood disorders, mental health inquiry is also important.

Long COVID and cardiovascular autonomic dysfunction, including postural orthostatic tachycardia syndrome (POTS), present significant healthcare challenges. Long-term monitoring is challenging due to the evolving nature of symptoms and the limited availability of objective diagnostic tools. With over 200 million electrocardiogram (ECG)-enabled smartwatches sold worldwide, these devices offer a promising solution for at-home diagnostics and disease tracking. This study examines a 35-year-old male with long COVID, POTS, and chronic fatigue syndrome (CFS), who recorded 328 ECGs over using a Samsung smartwatch. The protocol required ECG recordings to be taken first in a sitting posture, followed by a standing position, with slow, controlled breathing. For testing, the patient used a Samsung smartwatch to perform a 30-s hand-to-hand single-lead ECG while engaging in 0.1 Hz diaphragmatic controlled breathing, consisting of 5 s of inhalation followed by 5 s of exhalation (). S-/R-peak amplitude ratios, heart rhythm changes, and other biomarkers were analysed to assess autonomic function. Fatigue levels were self-reported via the BREATHE FLOW app using a three-grade scale, and health status was tracked monthly with the EQ-5D-5L model. Initially, the patient experienced severe fatigue and heart rhythm changes consistent with POTS. Electrocardiogram analysis revealed an increased S-wave amplitude and higher S/R ratio in standing posture, along with worsening respiratory sinus arrhythmia (RSA), indicating cardiorespiratory desynchrony. Over time, as symptoms improved, heart rate responses between sitting and standing normalized, and S/R ratio and RSA index followed self-reported fatigue levels, including fluctuations due to post-exercise fatigue. Smartwatch-derived S-/R-wave amplitude ratio may serve as an accessible biomarker for tracking disease progression in long COVID. Given the widespread availability of smartwatches, standardized at-home protocols could improve diagnostics and monitoring for autonomic dysfunction.

Postural orthostatic tachycardia syndrome (POTS) is a relatively common, burdensome condition of the autonomic nervous system characterized by orthostatic intolerance. This paper presents a subset of findings from a qualitative study investigating the lived experience and perspectives of adults with POTS. Twenty-nine individuals participated in a series of focus groups. We present a conceptual model which summarizes themes related to illness-related experiences, emotional reactions, and coping strategies, and distinguishes how these vary from pre- to post-diagnosis. Our findings emphasize the myriad challenges of living with a condition with diffuse and wide-ranging symptoms, significant quality of life impacts, and limited treatment options, as well as the role of active coping strategies in facing these challenges and their emotional impacts. Additionally, we summarize themes of patient-derived suggestions for improvement in care, which highlight the importance of compassionate, patient-centered care and mental health care to support adaptive coping.

Demographic data for patients with hypermobile Ehlers-Danlos syndrome have not been well established. Hypermobile Ehlers-Danlos syndrome patients often present with a constellation of symptoms; it is important to update clinical criteria for diagnosis and provide a framework for common comorbidities. The primary objective of this study was to identify the prevalence of comorbidities in hypermobile Ehlers-Danlos syndrome patients to allow clinicians to better identify patients and their most common symptoms. The goal is to use this information to augment diagnostic and clinical demographic data to more accurately represent hypermobile Ehlers-Danlos syndrome patients. This retrospective chart review utilized patient intake forms from 154 patients diagnosed with hypermobile Ehlers-Danlos syndrome in a clinic. Patient intake forms included responses to questions about the presence of various current and previous conditions. Our study revealed numerous comorbidities with increased prevalence that differed from the current diagnostic criteria including postural orthostatic tachycardia syndrome, mast cell activation syndrome, anxiety, depression, temporomandibular joint syndrome, headaches, and gastroesophageal reflux disease. These findings will help inform clinicians of prevalent comorbidities among hypermobile Ehlers-Danlos syndrome patients and encourage further evaluation for screening and diagnosis. Hypermobile Ehlers-Danlos syndrome patients presented with a wide range of comorbidities not listed on current clinical criteria. Future studies are warranted across diverse and larger patient populations and beyond self-reported data.

The incidence of postural orthostatic tachycardia syndrome (POTS) in long COVID has been a growing concern since the first cases were reported in 2021. The aim of this study was to assess the prevalence and clinical impact of POTS in a series of well-characterized patients with long COVID. We prospectively analyzed 467 nonhospitalized, highly symptomatic (sick leave ≥50%) patients with long COVID, and studied differences in demographics and clinical assessment outcomes between those diagnosed with POTS and the remaining long COVID patients. Examinations were performed at a median of 12 months after acute COVID-19, followed by a cardiologist evaluation with 48-hour ECG, head-up tilt test, and Active Stand Test for those with clinically suspected POTS. Of all long COVID patients, 143 (31%) were diagnosed with POTS, 128 (27%) did not fulfill POTS criteria, while 196 (42%) had no clinical signs of POTS. Patients with POTS were younger (mean age, 40.0 versus 44.0 versus 47.0 years, respectively; ≤0.001) and predominantly female (91%). They had significantly lower physical activity compared with the other 2 groups, as measured with the Frändin-Grimby scale (=0.001). Heart rates during the 6-minute walk test were significantly higher in the POTS group, both during walking and at rest afterward, with a significantly shorter walking distance (448 m versus 472 m versus 509 m, respectively; ≤0.001). However, the distribution of symptoms showed no significant differences between the groups. In this cohort of predominantly younger women with highly symptomatic long COVID, POTS is common and presents with overlapping symptoms between POTS and non-POTS patients. Long COVID POTS confers lower physical activity and capacity compared with non-POTS long COVID and should be systematically assessed in this condition.

Postural orthostatic tachycardia syndrome (POTS) is a debilitating chronic condition characterized by an excessive increase in heart rate when transitioning from a lying or sitting position to standing. It impacts millions of people globally and is linked to a wide range of subsequent symptoms. This case report describes the novel use of stellate ganglion block (SGB) in a 41-year-old woman with a 15-year history of debilitating POTS symptoms. Given the failure of conservative management, the clinical team pursued a left SGB. Nine weeks postprocedure, the patient reported a pulse in the normal range under 100 beats per minute and 100% resolution of all symptoms that affected her quality of life. The application of an SGB led to a remarkable reduction in the symptoms from POTS in this patient, showcasing its promise as a novel therapeutic strategy. This innovative approach not only alleviated the patient's distress but also opened new avenues for treatment.

Postural Orthostatic Tachycardia Syndrome (POTS), an autonomic nervous system dysfunction, is frequently associated with ocular symptoms including pain and dryness. This study aimed to characterize ocular surface findings in POTS patients to clarify whether these symptoms reflect classic dry eye disease or altered sensory processing related to autonomic dysfunction. A retrospective observational study was conducted on patients with confirmed POTS who underwent standardized ocular surface evaluations at a tertiary academic center between 2019 and 2024. Demographics and medical history were extracted from records. Assessments included pain ratings (0-10 Likert scale), proparacaine response, Schirmer testing, ocular staining score (OSS), and in vivo confocal microscopy (IVCM) when available. Forty-three patients (39 females; mean age 45.1 ± 14.0 years) were included. Thirty-eight reported ocular pain and dryness. Among 21 patients with recorded pain scores, the median (IQR) was 5 (4), reduced to 4 (4.5) after proparacaine. Median Schirmer score was 5 mm (IQR 27), with 13 patients ≤5 mm. Median OSS was 0 (IQR 2), with only 4 patients showing OSS>1 with improved symptoms after proparacaine, suggesting neuropathic etiology in 34 patients. IVCM, available in six cases, revealed reduced nerve density and microneuromas. Migraine was the most common comorbidity (76.7 %) and was strongly associated with pain without staining (OR = 15.0; 95 % CI 2.65-85.0; p = 0.002). POTS patients frequently report ocular pain and dryness, yet objective signs of dry eye are uncommon. These findings underscore the need for ocular surface staining to distinguish dry eye disease from neuropathic ocular pain, suggesting that altered corneal nerve function in autonomic dysfunction may drive symptoms.

Hyperadrenergic POTS (Hyper-POTS) is characterized by excessive central sympathetic activity and impaired cardiovagal modulation. A single transcutaneous vagus nerve stimulation (tVNS) rebalanced cardiovascular autonomic control in previous studies. Repetitive tVNS may similarly restore autonomic balance and improve symptoms in Hyper-POTS. Twenty-two Hyper-POTS were studied at baseline (Pre-tVNS), after 14 days of tVNS (tVNS), and within 24 months post-discontinuation (Post-tVNS). The modified Vanderbilt Orthostatic Symptoms Score (mVOSS) quantified symptoms. ECG, arterial pressure, respiratory activity, and muscle sympathetic nerve activity (MSNA) were continuously recorded while supine and during 75° head-up tilt (HUT). Cardiac vagal modulation (high frequency power,HF), sinoatrial node sympatho-vagal interaction (low-to high-frequency ratio,LF/HF), sympathetic vasomotor control (LF) and arterial baroreflex sensitivity (α) were assessed by spectral analysis. Baroreflex sensitivity was also evaluated by spontaneous sequences (BRS) technique. At tVNS, MSNA decreased in both positions. tVNS increased HF and decreased LF/HF in supine. During HUT, αLF increased, HF increased and HR decreased compared to Pre-tVNS. Total symptom score declined in both positions, with improvements in multiple mVOSS domains during tilt. At Post-tVNS, HF and BRS increased in both positions. During HUT, αLF increased, HR and LF decreased. MSNA returned to Pre-tVNS in both positions. Total symptom score showed sustained improvement. Fourteen-day tVNS enhanced cardiovagal modulation, reduced sympathetic activity, and improved orthostatic symptoms in Hyper-POTS patients. Additionally, some benefits persisted beyond the stimulation period. Thus, tVNS could potentially be used as an additional therapeutic tool in Hyper-POTS.

: Symptoms of autonomic dysfunction are common in infection-associated chronic conditions and illnesses (IACCIs), including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This study aimed to evaluate autonomic symptoms and their impact on ME/CFS illness severity. : Data came from a multi-site study conducted in seven ME/CFS specialty clinics during 2012-2020. Autonomic dysfunction was assessed using the Composite Autonomic Symptom Scale 31 (COMPASS-31), medical history, and a lean test originally described by the National Aeronautics and Space Administration (NASA). Illness severity was assessed using Patient-Reported Outcomes Measurement Information System measures, the 36-item short-form, as well as the CDC Symptom Inventory. This analysis included 442 participants who completed the baseline COMPASS-31 assessment, comprising 301 individuals with ME/CFS and 141 healthy controls (HC). : ME/CFS participants reported higher autonomic symptom burden than HC across three assessment tools (all < 0.0001), including the COMPASS-31 total score (34.1 vs. 6.8) and medical history indicators [dizziness or vertigo (42.6% vs. 2.8%), cold extremities (38.6% vs. 5.7%), and orthostatic intolerance (OI, 33.9% vs. 0.7%)]. Among ME/CFS participants, 97% had at least one autonomic symptom. Those with symptoms in the OI, gastrointestinal, and pupillomotor domains had significantly higher illness severity than those without these symptoms. : ME/CFS patients exhibit a substantial autonomic symptom burden that correlates with greater illness severity. Individualized care strategies targeting dysautonomia assessment and intervention may offer meaningful improvements in symptom management and quality of life for those with ME/CFS and similar chronic conditions.

Muscle sympathetic nerve activity (MSNA) is valuable for POTS management, but microneurography is clinically impractical. We investigated whether the Valsalva phase 2 diastolic blood pressure rise (DBP) could be a surrogate for MSNA during the Valsalva and be used to identify hyperadrenergic POTS. We included 21 POTS females and 22 healthy females 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. 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 equal 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 ± 10vs105 ± 12 mmHg, p = 0.026), shorter pressure recovery time (1.15 ± 0.75vs2.59 ± 1.17 s, p = 0.005), and higher psNVT (2.60 ± 1.02vs0.58 ± 0.46 mmHg/spike•s, p < 0.001) than the non-hyperadrenergic POTS. DBP ≥ 15 mmHg could be a marker of hyperadrenergic response to subtype POTS. We defined this subset of POTS as functional hyperadrenergic POTS since they displayed hyperadrenergic phenotypes despite similar level of MSNA to other POTS. The higher psNVT of the hyperadrenergic group suggested a novel pathophysiology of enhanced neurovascular coupling.

The autonomic nervous system and the gastrointestinal (GI) system share a bidirectional relationship. Clinically, disruptions to either of these systems mutually influence the onset and persistence of symptoms modulated by the other system. The impact of autonomic dysfunction on GI health is especially relevant in the care of pediatric disorders of gut-brain interaction (DGBI) as these patients commonly report a diverse range of symptoms both within and outside the GI tract. Therefore, it is essential to include the role of autonomic function in the assessment and treatment of pediatric patients with DGBI.

Syncope is a temporary loss of consciousness due to cerebral hypoperfusion associated with autonomic dysfunction. Vasovagal syncope (VVS) and postural orthostatic tachycardia syndrome (POTS) are the most common causes of syncope in adolescents. Here we conducted a comparative analysis of VVS and POTS in adolescents using transcranial doppler (TCD) and autonomic function tests to identify the mechanisms underlying the occurrence of each. From August 2014 to July 2024, a tilt-table test was conducted on patients who presented with syncope or presyncope as the main symptom. Based on the head-up tilt test results, the patients were classified into the VVS or POTS groups and their medical records retrospectively analyzed. The study included 137 patients: 100 (73%) in the VVS group and 37 (27%) in the POTS group. There were no significant intergroup differences in patient characteristics. In the TCD, the diastolic blood flow velocity during symptom onset was significantly lower in the VVS versus POTS group (18.40±7.14 cm/sec vs. 22.32±8.48 cm/sec, P=0.008). Additionally, the pulsatility index was higher in the VVS group (1.51±0.41 vs 1.22±0.37, P<0.005). There were no intergroup differences in autonomic function tests results or composite autonomic severity scores. The cerebral blood flow velocity during diastole differs between VVS and POTS, suggesting that it may be a determining factor in the pathogenesis of each.

Our previous studies demonstrated that the regular practice of recumbent isometric yoga reduced the fatigue of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Some patients with ME/CFS have postural orthostatic tachycardia syndrome (POTS); however, the effects of recumbent isometric yoga on orthostatic cardiovascular responses and whether recumbent isometric yoga improves POTS remain unknown. This pilot study was done to investigate the effect of recumbent isometric yoga on the orthostatic cardiovascular response of patients with ME/CFS. Ten adult female patients with ME/CFS performed recumbent isometric yoga for 12 weeks. Changes in their systolic blood pressure (SBP), diastolic blood pressure (DBP), and the pulse rate (PR) during an active standing test were compared before and after the 12-week regimen. Among the 10 patients, 8 manifested a normal orthostatic response and 2 manifested POTS before the yoga intervention. Patients who manifested a normal orthostatic response before yoga also manifested the normal orthostatic pattern after the yoga intervention. In contrast, the two patients who manifested POTS before the regimen showed a normal orthostatic response after completing the yoga intervention. This study found that the patients who manifested POTS and performed recumbent isometric yoga for 12 weeks had a reduced increase in PR after standing up. This pilot study suggests that recumbent isometric yoga would be useful as an adjunctive nonpharmacological intervention for improving POTS in patients with ME/CFS. This finding should be confirmed in a larger number of cases.