Postacute sequelae of COVID-19 syndrome (PASC) is widely attributed to dysautonomia, although sympathetic outflow has rarely been measured directly. We tested whether exercise and orthostatic intolerance in PASC reflect impaired cardiac reserve or abnormal muscle sympathetic nerve activity (MSNA) and its reflex control. Adults with PASC ( = 35; symptoms >3 mo, no significant comorbidity) and age- and sex-matched recovered controls ( = 12) underwent cardiopulmonary exercise testing (CPET), echocardiogram, resting and exercise cardiac MRI, and peroneal microneurography recordings of MSNA in supine position and during graded head-up tilt to 60°. Participants with PASC had lower peak oxygen uptake ([Formula: see text]) indexed to lean mass (43.0 ± 7.8 vs. 52.2 ± 8.2 mL/lean body mass kg/min, = 0.009) and whole body mass (26.1 ± 7.5 vs. 34.9 ± 10.2 mL/kg/min, = 0.006), lower heart rate reserve (84 ± 25 vs. 98 ± 13 beats/min, = 0.019), and impaired ventilatory efficiency. Cardiac structure and biventricular contractile reserve were normal. Supine MSNA burst frequency, burst incidence, sympathetic baroreflex gain, and neurovascular transduction did not differ between groups, and MSNA and mean arterial pressure increased similarly during tilt (time < 0.0001; group × time = 0.78). Despite these findings, 12 of 29 participants with PASC (41%) terminated the tilt protocol due to orthostatic symptoms or presyncope (Kaplan-Meier = 0.0178). Eight participants (27%) met postural orthostatic tachycardia syndrome (POTS) criteria and had lower MSNA than non-POTS participants ( = 0.045). Orthostatic intolerance occurred despite normal recruitment of MSNA and maintained arterial pressure and exercise intolerance despite preserved contractile reserve. Symptoms are therefore unlikely to originate in the efferent sympathetic limb or myocardium and more likely reflect afferent reflex dysregulation or impaired cerebral perfusion. Muscle sympathetic nerve activity (MSNA), sympathetic baroreflex gain, and neurovascular transduction were intact in people with postacute sequelae of COVID-19 syndrome (PASC), and MSNA was recruited normally during head-up tilt. However, 41% of participants could not complete the tilt. Biventricular contractile reserve was likewise preserved. Symptoms that track neither sympathetic outflow nor systemic pressure localize the disturbance upstream, to afferent reflex control, or downstream to the cerebral circulation.

Postural orthostatic tachycardia syndrome (POTS) as conventionally defined is a chronic condition (typically > 3 months duration) incorporating reproducible symptoms of orthostatic intolerance (including dizziness/lightheadedness, and near-syncope) in the absence of orthostatic hypotension (ie, absence of a sustained systolic blood pressure drop > 20mmHg with upright posture). More recently, however, the :POTS: landscape as applied by many clinicians has broadened; the term :POTS: has become increasingly used to categorize a multisystem disorder the underlying etiologies of which remain unclear but may include autonomic dysfunction and/or autoimmune disorders; as such the clinical picture has evolved to encompass a wide range of non-cardiovascular symptoms such as persistent exertional intolerance, fatigue, "brain fog", thermo-regulatory disorders, and various gastrointestinal symptoms including gastroparesis and certain food intolerance reactions. Thus, while cardiovascular disorders may be the principal manifestation of presumed "POTS" in many patients, disturbances in a variety of body systems may dominate the clinical presentation in others. This communication, derived from a diverse group of practitioners who care for the wide range of patients often referred for :suspected POTS:, offer the view that optimizing diagnostic evaluation and subsequent care of these individuals necessitates a broad range of clinical skills; in essence involvement of a "village" of dedicated multi-talented care providers.

Fibromyalgia (FM) is a persistent, heterogeneous disorder characterized by widespread pain and multiple non-pain symptoms, including fatigue, cognitive dysfunction, gastrointestinal disturbance, dizziness and balance impairment. Increasing evidence suggests that autonomic dysfunction may contribute to this multisystem presentation, with abnormalities in heart rate variability (HRV), orthostatic cardiovascular regulation and postural orthostatic tachycardia syndrome (POTS) reported in patients with FM. This narrative review examines the evidence for dysautonomia in FM, its relationship with peripheral and central mechanisms, approaches to clinical assessment, and current and emerging strategies for mechanism informed management. A literature search was undertaken using PubMed/MEDLINE, Scopus and PEDro, supplemented by citation searching and relevant grey literature. The search incorporated literature addressing FM, dysautonomia and vestibular rehabilitation, with additional recent literature included to reflect emerging evidence. Evidence supports autonomic dysfunction in a substantial proportion of patients with FM, including reduced HRV, altered sympathovagal regulation, orthostatic intolerance and POTS. Peripheral small fiber pathology and alterations within central autonomic, sensory-processing and stress-response networks may contribute to dysautonomia, supporting interactions between peripheral, central and autonomic mechanisms. Autonomic symptom screening, orthostatic vital signs, HRV and, where indicated, formal autonomic and small fiber investigations may assist in identifying clinically relevant phenotypes. Current management includes lifestyle modification, exercise and rehabilitation, with pharmacological treatment where appropriate. Emerging approaches include HRV biofeedback, non-invasive vagal modulation, vestibular rehabilitation and rehabilitation tailored to the predominant physiological phenotype. Dysautonomia appears to represent a clinically meaningful component of FM in a subgroup of patients rather than a universal feature of the disorder. Recognition of autonomic, peripheral and central contributions may facilitate more targeted clinical assessment and mechanism informed management. Improved phenotyping and further investigation of therapies targeting specific autonomic abnormalities may support more personalized approaches to FM care.

Hypermobility spectrum disorder/hypermobile Ehlers-Danlos syndrome (HSD/hEDS), mast cell activation syndrome (MCAS) and dysautonomia, including postural orthostatic tachycardia syndrome (POTS), are comorbid conditions encountered in clinical practice with possible overlapping immunologic, autonomic and connective tissue abnormalities. Clinicians frequently observe that affected individuals affected with these syndromes commonly experience disproportionate adverse events and complications from a variety of stressors. We review clinical observations and emerging evidence via PubMed on adverse events and complications experienced by patients with HSD/hEDS, MCAS and dysautonomia in response to surgery, post-operative period, anesthesia, medication side effects, substance sensitivities and infection. Patients with HSD/hEDS, MCAS and dysautonomia may be at a higher risk of adverse events and complications associated with surgery, medication, substances and infection. Recognition and awareness of these syndromes and the risks, which each disorder can carry alone or as a triad, may lead to risk mitigation, appropriate counseling and prognostication. Future studies should focus on longitudinal multicenter studies assessing risks and outcomes in this vulnerable patient population. Translational studies are also needed to elucidate the mechanisms underlying adverse events and complications in patients with HSD/hEDS, MCAS and dysautonomia.

Postural orthostatic tachycardia syndrome (POTS) is defined by a sustained increase in heart rate of ≥30 beats/min within 10 minutes of standing, accompanied by symptoms of orthostatic intolerance persisting for at least 3 months. Prior research has focused on determinants of tachycardia, raising the question of whether the tachycardia represents a compensatory mechanism or the primary driver of symptoms. In this review, we summarize the available literature on heart rate-lowering interventions in POTS and examine whether reducing heart rate is associated with symptom improvement. We systematically searched for studies of patients with POTS evaluating interventions primarily intended to lower heart rate and reporting heart rate and symptom outcomes. Because of heterogeneity, findings were narratively summarized by direction of effect. Twenty studies comprising 707 participants met inclusion criteria. Interventions included β-blockers, ivabradine, pyridostigmine, clonidine, transcutaneous vagus nerve stimulation, and sinus node-sparing hybrid ablation. All studies reported a reduction in orthostatic tachycardia or tachycardia burden, and 17/20 studies (85%) reported parallel symptomatic improvement. Across interventions, therapies that achieved a clinically meaningful and hemodynamically tolerated reduction in heart rate were most consistently associated with symptom benefit. Available evidence, including recent randomized trials directly evaluating heart rate-lowering therapy, demonstrates that reductions in orthostatic tachycardia are frequently accompanied by symptomatic improvement. These findings support the hypothesis that excessive tachycardia in POTS may not merely be an epiphenomenon nor compensatory, but a clinically relevant and treatable contributor to symptom burden. Heart rate-lowering therapy may therefore represent a useful management strategy in appropriately selected symptomatic patients.

Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous disorder of the autonomic nervous system characterized by orthostatic intolerance and involvement of multiple organ systems. It commonly coexists with conditions such as hypermobile Ehlers-Danlos syndrome (hEDS), mast cell activation syndrome (MCAS), and a spectrum of gastrointestinal (GI) disorders. These overlapping conditions frequently manifest with shared GI symptoms such as nausea, bloating, abdominal pain, early satiety, and altered bowel habits that can substantially compromise nutritional status and quality of life. This review synthesizes current evidence to outline practical, nutrition-based strategies for managing POTS and its commonly associated comorbidities. Key nutritional domains relevant to POTS management, including fluid and sodium intake, meal timing and volume, and dietary composition, along with commonly associated comorbid conditions contributing to GI symptom burden, were identified a priori by the authors. These comorbidities include gastroparesis, hEDS, MCAS, disordered eating patterns, median arcuate ligament syndrome (MALS), functional GI disorders, and food intolerances. A comprehensive PubMed search was then performed to identify and synthesize relevant literature within each of these predefined domains. Given the clinical heterogeneity of POTS and variability in associated conditions, a standardized dietary approach is unlikely to be effective. Instead, individualized nutrition strategies tailored to symptom patterns, GI tolerance, metabolic demands, and co-existing disorders are essential. Careful evaluation of overlapping comorbidities is critical to inform targeted, sustainable, and patient-centered dietary management.

Long/post COVID and related conditions such as myalgic encephalomyelitis/chronic fatigue syndrome, postural orthostatic tachycardia syndrome and post-vaccination syndrome are associated with persistent functional impairments and are met with care structures in Germany that are difficult to navigate. The rapid scoping review offers an insight into care structures, capacities, access, care pathways and gaps in care for these patient groups in the German healthcare system. It also takes into account patient and care provider perspectives. The study follows the recommendations of the Joanna Briggs Institute and the PRISMA ScR checklist for conducting (rapid) scoping reviews. A MEDLINE search was conducted from 2020 onwards with predefined inclusion and exclusion criteria for evidence sources related to care in Germany. 44 evidence sources were included. General practitioners and paediatricians act as the first point of contact. Specialised outpatient clinics and rehabilitation facilities take on complex diagnostics and patient treatment. Care networks are rare. Navigating the healthcare system is characterised by information gaps, unclear responsibilities and long waiting times, so that those affected often organise their own care. Some report stigmatisation, misdiagnoses and stressful activation recommendations despite the risk of post exertional malaise. Care is unevenly accessible, poorly coordinated and only limitedly evidence based. Shared knowledge and case databases, training, better diagnostic tools and robust efficacy studies are needed to improve access, management and safety of long/post COVID care.

Exogenous testosterone has been previously reported to have given clinical improvement in symptoms of postural orthostatic tachycardia syndrome (POTS) in reported cases of transgender patients during their transition from female to male. Herein is presented two case reports of cisgender heterosexual female patients with POTS who have used testosterone for the management of concurrent gynecologic problems, but who also found that symptoms of both POTS and joint hypermobility improved after its administration.

Alpha-synucleinopathies are a group of disorders characterized by the accumulation of the pathological form of alpha-synuclein. This group comprises Parkinson's disease, Parkinson's disease dementia, multiple system atrophy, dementia with Lewy bodies, pure autonomic failure, and idiopathic REM sleep behavior disorder. Despite sharing a similar molecular basis, these disorders differ in their clinical presentation. Characteristic manifestations include signs of autonomic failure such as orthostatic hypotension, postural orthostatic tachycardia syndrome, constipation, gastroparesis, urinary incontinence, and erectile dysfunction, among others. These symptoms significantly impair patients' daily functioning and are also negative prognostic factors. Currently, research is investigating the link between inflammation and dysautonomic symptoms. Elevated levels of pro-inflammatory cytokines, such as IFN-γ, TNF-α, IL-6, IL-1β, and IFN-α, have been found to accompany these symptoms. Notably, in other diseases characterized by chronic inflammation, autonomic dysfunction is also common. In two human studies of dysautonomic symptoms in other conditions, intravenous immunoglobulin therapy was shown to improve these symptoms. Animal studies have shown that other immunomodulatory agents reduce symptom severity. Modulation of inflammation, dietary modification, the use of probiotics and prebiotics, and fecal microbiota transplantation are potential therapeutic approaches for these diseases. These approaches offer hope for improving the quality of life of patients with alpha-synucleinopathies. Further research in this area is needed.

Postural orthostatic tachycardia syndrome (POTS) is a chronic autonomic disorder characterized by excessive orthostatic tachycardia and multisystem symptoms that affects an estimated 0.1% to 1% of the US population. POTS can substantially impair daily functioning and quality of life. Consensus criteria define POTS by chronic symptoms of orthostatic intolerance accompanied by a sustained heart rate increase of at least 30 beats/min (≥40 beats/min in adolescents aged 12-19 years) within 10 minutes of standing or head-up tilt from a supine position in the absence of orthostatic hypotension, defined as a decrease in either systolic blood pressure of at least 20 mm Hg or diastolic blood pressure of at least 10 mm Hg with positional change. POTS symptoms may include palpitations, lightheadedness, nausea, vomiting, gastroparesis, anorexia, generalized weakness, and muscle pain, despite absence of structural pathology within cardiovascular, gastrointestinal, and neurological organs. POTS predominantly affects females (approximately 90% of cases), with peak incidence from ages 13 to 29 years. However, the true prevalence remains uncertain partly due to underrecognition and lack of a specific diagnostic code for POTS until 2022. Common symptoms include lightheadedness, palpitations, fatigue, cognitive dysfunction ("brain fog"), exercise intolerance, nausea, bloating, constipation, diarrhea, and sleep disturbance. In a survey of 4835 patients, approximately 70% reported substantial functional impairment and loss of school or work participation, and median diagnostic delay was 24 months. In 30% to 40% of cases, symptoms began within 3 months after infections, such as SARS-CoV-2, Epstein-Barr virus, and influenza. Initial evaluation should exclude other conditions that cause sinus tachycardia, including thyroid disease, adrenal insufficiency, pheochromocytoma, cardiomyopathy, valvular heart disease, congenital heart disease, chronic lung disease, medication effects (eg, stimulants, norepinephrine reuptake inhibitors, and diuretics), anemia, and dehydration. First-line treatment includes nonpharmacological strategies to improve cardiac preload, including increased fluid and sodium intake, lower-body compression garments; avoidance of heat exposure, dehydration, and prolonged standing; and structured supervised aerobic training. Pharmacological therapies should be individualized and may include β-blockers, ivabradine, midodrine, fludrocortisone, and pyridostigmine, although evidence supporting many therapeutic interventions is limited by small studies and lack of large, randomized trials. POTS is a chronic autonomic disorder associated with functional impairment and reduced quality of life that is diagnosed based on characteristic orthostatic symptoms in the absence of orthostatic hypotension after excluding alternative causes of sinus tachycardia. Treatment involves nonpharmacological measures (such as increased fluid and sodium intake), lower-body compression garments, structured exercise training, and individualized pharmacological therapy.

The goal of this case series was to characterize the clinical presentation, comorbidities, and postoperative outcomes of pediatric patients who underwent surgical repair for Median Arcuate Ligament Syndrome (MALS) and/or Nutcracker Syndrome (NCS). We conducted a retrospective chart review of 17 pediatric patients who underwent open surgical repair for MALS and/or NCS at a single academic center from 2021-2025. The most common comorbidities included postural orthostatic tachycardia syndrome (POTS), hypermobile Ehlers-Danlos syndrome (hEDS), gallbladder pathology, and additional vascular compressions. All 17 patients presented with abdominal pain, and more than half reported postprandial pain and/or nausea. Open surgical repair provided patient-reported symptomatic improvement in all patients. A subset experienced recurrent pain at longer-term follow-up. Pediatric patients with MALS and/or NCS demonstrate consistent clinical features, including abdominal pain and overlapping comorbidities. In this highly selected surgical cohort, open repair was associated with early and intermediate-term patient-reported improvement in compression-related pain, though symptom recurrence was observed in a subset.

Orthostatic dysregulation (OD) is common during adolescence and may present with dizziness, palpitations, fatigue, and difficulty getting up in the morning. These symptoms overlap with those of Graves' disease, making differentiation challenging in some patients. A 14-year-old girl presented with headache, dizziness, palpitations, and difficulty getting up in the morning, with worsening symptoms during standing and walking. An active standing test reproduced her symptoms, including tachycardia, lower-extremity tremor, marked sweating, and nausea, and she was initially considered to have OD. Her resting heart rate was already elevated, and marked orthostatic tachycardia resembling postural orthostatic tachycardia syndrome (POTS) was observed during the test. However, thyroid function tests revealed severe hyperthyroidism, and positive thyroid-stimulating hormone receptor antibodies led to a diagnosis of Graves' disease. Following treatment with methimazole, potassium iodide, and propranolol, her symptoms resolved. Propranolol was discontinued after one month. Repeat orthostatic testing after improvement of thyroid function no longer reproduced her symptoms or marked tachycardia. Graves' disease may therefore mimic not only the clinical symptoms of OD but also POTS-like orthostatic tachycardia during orthostatic testing. Thyroid dysfunction may warrant consideration in patients with OD-like symptoms, particularly when accompanied by resting tachycardia, tremor, increased sweating, or weight loss.

To report the prevalence of endometriosis among female patients with postural orthostatic tachycardia syndrome (POTS) and determine which condition is more commonly diagnosed first. In a retrospective case-control analysis, we reviewed medical records for patients with POTS who presented to our autonomic center from 2018 to 2024. POTS was defined by symptoms of orthostatic intolerance accompanied by a heart rate increase of ≥30 beats per minute within the first 10 min of head-up tilt table testing. Endometriosis diagnoses were determined using surgical pathology when available or clinical documentation by a gynecologic specialist. Among 1322 female patients with POTS, 229 (17.3%) had a diagnosis of endometriosis, a prevalence significantly higher than the prevalence of 10% observed in the general female population (p < 0.001) and higher than the prevalence of 10.2% observed in our tilt-negative cohort (p < 0.001). For patients with both diagnoses, endometriosis was diagnosed before POTS in 156 patients (68%), and POTS was diagnosed first in 73 patients (32%). Endometriosis is significantly more prevalent in female patients with POTS than in the general population, with endometriosis more likely to be diagnosed first. Clinicians should be aware of the high co-occurrence and consider further workup for endometriosis in patients with POTS presenting with pelvic pain or dysmenorrhea, and vice versa.

Postural orthostatic tachycardia syndrome (POTS) is a debilitating form of orthostatic intolerance that predominantly (∼90%) affects young women, leading to diminished quality of life. Challenges associated with POTS are compounded by lengthy diagnostic delays on the order of years, repeated visits to multiple physicians, and misdiagnoses. Fundamental criteria for diagnosing POTS are (1) experiencing orthostatic symptoms (eg, lightheaded, dizzy, nausea, and heart palpitations) that improve with recumbency for at least 3–6 months and (2) a sustained increase in heart rate (HR) of ≥30 beats/min within 5–10 minutes of standing in the absence of hypotension (≥40 beats/min for people younger than 19 years). Given the nonspecific nature of patients’ symptomology, orthostatic tachycardia in the absence of hypotension is heavily relied on for diagnosis. However, inconsistency of HR responses to orthostatic stress tests conducted in clinical settings may contribute to diagnostic delays and misdiagnoses experienced by many individuals. To characterize this variability, we conducted 2 supine-to-stand tests to assess the test-retest reliability (ie, consistency) of HR responses to clinical orthostatic stress tests in people with POTS.

There is a growing body of literature evaluating both postural orthostatic tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (EDS). We conducted a systematic review to evaluate what is currently known about the co-existence of both conditions. A search of MEDLINE and EMBASE was performed in December 2025 and data were collected in tables and pooled to determine the prevalence of POTS in EDS and EDS in POTS. A total of 30 studies were included with 8421 patients with EDS and 12,983 patients with POTS. The average age across 16 studies that reported mean age was 33.3 years. POTS in patients with EDS ranges from 17.5% to 92.7% depending on the population. EDS in patients with POTS ranges from 17.9% to 50.0% depending on the population. One study suggested that patients with EDS and POTS had greater medication use, pain medications and greater number of clinic visits compared to POTS alone while another suggests that these patients have greater gastrointestinal symptoms and the odds were greatest for postprandial distress syndrome, chronic nausea and vomiting syndrome, vomiting and post-prandial fullness. We conclude that EDS and POTS frequently co-occur, and proportions of patients with POTS and EDS depends on the population evaluated. Overall, more research is needed to better understand how to effectively manage patients living with both EDS and POTS.

To characterise the symptom, comorbidity and diagnostic journey of adult and older adolescent patients with postural orthostatic tachycardia syndrome (POTS). Cross-sectional observational cohort study. Participants ≥16 years old with physician-confirmed POTS who enrolled in the Australian POTS registry between 1 May 2021 and 30 April 2024 were included. 500 participants enrolled in the Australian POTS registry. Health-related quality of life and symptom severity were assessed using validated patient-reported outcome measures, including the Composite Autonomic Symptom Score, EuroQol 5-Dimension-5 Level (EQ-5D), Gastroparesis Cardinal Symptom Index (GCSI), Fatigue Severity Scale (FSS) and the 5-point hypermobility index scores. Sociodemographics, diagnostic journey details and comorbidities were obtained via self-reported questionnaires and reconciled with medical records by the clinical team. Among 500 participants (86.8% females, 92.7% White; mean age 31.3±11.7 years), the median diagnostic delay was 3.0 years (IQR 9.0; mean 6.7 years), with 25.5% experiencing a delay of ≥10 years. Despite being young and highly educated, 22.0% were unemployed or unable to attend education. Infection was the most frequently identified proximal trigger and accounted for 39.4% of cases. Higher autonomic symptom burden, as reported on the Composite Autonomic Symptoms Score (COMPASS-31) questionnaire, was associated with greater fatigue (FSS: 56.0±8.8 vs 48.0±14.5; p<0.001), gastrointestinal symptoms (GCSI: 1.60±0.77 vs 0.89±0.63; p<0.001), increased healthcare utilisation and worse quality of life (EQ-5D utility: 0.547±0.237 vs 0.717±0.200; p<0.001), assessed using Mann-Whitney U and χ tests as appropriate. POTS is associated with significant diagnostic delays, high healthcare utilisation, substantial symptom burden, educational, social and occupational impacts. Patient-reported outcome measures such as the COMPASS-31 questionnaire can assist in identifying high-risk individuals. Systemic healthcare reform is urgently needed to improve access to timely diagnosis and effective treatment for individuals living with POTS. ACTRN12621001034820.

BACKGROUND Functional neurological disorder (FND) is characterized by neurological symptoms identified through positive clinical signs that are incongruent with recognized structural neurological disease. Postural orthostatic tachycardia syndrome (POTS), in contrast, is defined by excessive orthostatic tachycardia and is associated with a range of multisystem autonomic symptoms. Shared clinical features can blur diagnostic boundaries. As a result, new or evolving symptoms in patients with a prior functional diagnosis may be overlooked, increasing the risk of diagnostic overshadowing. CASE REPORT An 18-year-old woman with a prior diagnosis of FND presented with fluctuating lower-extremity weakness, gait disturbance, and recurrent drop attacks. She also reported persistent orthostatic intolerance and symptom improvement with recumbency. These symptoms had previously been attributed to the functional diagnosis. Neurological examination demonstrated positive signs of functional weakness, consistent with the prior FND diagnosis. The Composite Autonomic Symptom Score (COMPASS-31) was markedly elevated. Head-up tilt table testing demonstrated sustained sinus tachycardia, with reproduction of typical orthostatic symptoms; other autonomic responses were largely preserved. Generalized joint hypermobility (Beighton score 4/9 with positive historical hypermobility) met the 2017 criteria for hypermobile Ehlers-Danlos syndrome based on family history and chronic musculoskeletal pain. Over several months, functional status improved from wheelchair dependence to independent standing, with reduced symptoms during multidisciplinary care; these findings are reported as a temporal association rather than causal inference. CONCLUSIONS This case demonstrates the coexistence of POTS in a patient with established FND and highlights the importance of systematic autonomic evaluation in individuals with persistent orthostatic symptoms. A prior functional diagnosis should not preclude investigation for coexisting physiological disorders.

Lyme disease, caused by Borrelia burgdorferi sensu lato, may lead to persistent complications, including autonomic nervous system dysfunction. Although postural orthostatic tachycardia syndrome is frequently associated with orthostatic intolerance in Lyme disease, broader autonomic impairment remains insufficiently characterized. This cross-sectional study included 324 participants: 233 patients with late-stage Lyme disease and 91 healthy controls. All participants underwent cardiovascular autonomic reflex testing, beat-to-beat heart rate variability analysis, baroreflex assessment, 24-hour Holter electrocardiography, and ambulatory blood pressure monitoring. Compared with controls, patients with Lyme disease demonstrated significantly higher rates of sympathetic and parasympathetic dysfunction (p<0.05). Heart rate variability spectral parameters, including very low frequency, low frequency, and high frequency components, were significantly reduced, while baroreflex sensitivity and baroreflex effectiveness index were also impaired (p<0.05). Holter monitoring additionally revealed reduced time-domain heart rate variability parameters and an elevated low-frequency/high-frequency ratio, suggesting relative sympathetic predominance in patients with Lyme disease (p<0.05). These findings support the presence of cardiovascular autonomic dysfunction in patients with late-stage Lyme disease and highlight the importance of comprehensive autonomic evaluation in this population. Keywords: Autonomic Dysfunction; Lyme disease; Heart rate variability; Neurocardiology.

Patients with severe manifestations of disorders of gut-brain interaction (DGBI) have higher rates of concomitant Orthostatic Intolerance (OI) and Postural Orthostatic Tachycardia Syndrome (POTS). These conditions diminish quality of life and increase health care use. We conducted a systematic review to assess OI and POTS prevalence in patients with DGBI. Databases were searched through January 2026 for articles reporting the prevalence of OI and POTS among patients with DGBI. Pooled prevalence rates, odds ratios (ORs), and confidence intervals (CIs) were calculated using a random-effects model. Thirteen studies included 869 patients with DGBI and 1951 controls. OI prevalence in DGBI patients was DGBI (PP=50.0%, 95% CI: 35.0-64.9). The odds of OI in patients with DGBI were significantly higher compared with controls (OR=5.17, 95% CI: 1.73-15.50, P=0.003). Pediatric patients with DGBI had a higher prevalence of OI (59.7%, 95% CI: 36.4-79.3) than adults (32.5%, 95% CI: 19.3-49.4). The prevalence of OI in patients with DGBI was significantly higher when diagnosed using the Rome IV criteria (66.1%, 95% CI: 43.3-83.3) compared with the Rome III criteria (30.6%, 95% CI: 21.4-41.6). The prevalence of OI in DGBI was higher with questionnaire-based diagnosis (54.5%, 95% CI: 9.7-93.0) compared with physician-based diagnosis (48.8%, 95% CI: 35.2-62.7). Finally, POTS was prevalent in 31.5% (95% CI: 17.3-50.2) of patients with DGBI. OI is more prevalent in patients with DGBI as compared with controls without DGBI. POTS occurs in over one-third of patients with DGBI. While OI and DGBI are associated, clinical heterogeneity suggests low-quality evidence, warranting cautious interpretation.

Postural orthostatic tachycardia syndrome (POTS) is common in post-COVID-19 condition and is associated with high symptom burden and reduced quality of life. Although physical exercise is recommended for POTS, evidence of its effectiveness remains limited. The objectives of the study was to evaluate the effectiveness of tailored exercise on health-related quality of life (HRQoL), upright time, physical function, and symptom burden in individuals with COVID-19-induced POTS. Adults with COVID-19-induced POTS were randomized to standard care or standard care plus tailored exercise with weekly supervision. Assessments were conducted at baseline and 16 weeks. Primary outcomes were HRQoL and upright time. Secondary outcomes included daily steps, sedentary time, orthostatic autonomic response, muscle strength, physical capacity, patient-reported activity limitations, mental health, and symptom burden. Analyses used mixed models. Data were analyzed from sixty participants (85% females, mean age 37 years). No time-by-group interaction effects were observed for HRQoL. Upright time was reduced in the intervention group compared with controls, with an estimated between-group difference of -31 min/day, (95% CI -57 to -6). For secondary outcomes, daily steps were reduced in the intervention group, whereas both groups improved in POTS symptoms, activity limitations, and physical capacity, with a trend toward reduced postexertional malaise. No other secondary outcomes showed significant effects. Tailored exercise did not outperform standard care in HRQoL and was associated with reduced upright time, whereas improvements in several secondary outcomes were observed in both groups. Heterogeneity supports an individualized approach to exercise, integrated with pharmacological and multimodal management strategies.

Hyperadrenergic and neuropathic features have been described in postural tachycardia syndrome (POTS). This study describes the prevalence, autonomic testing characteristics, and symptom severity of individuals with hyperadrenergic and neuropathic features in a laboratory-diagnosed POTS cohort. We performed a cross-sectional study of individuals with a laboratory diagnosis of POTS. Hyperadrenergic POTS (HyperPOTS) features were defined as an upright norepinephrine level of > 600 pg/mL and/or > 3 times their respective supine norepinephrine. Neuropathic POTS (NeuroPOTS) features were defined by a CASS ≥ 2 and/or ≥ 1 sudomotor abnormalities. Autonomic symptom severity was determined by the Composite Autonomic Symptom Score (COMPASS-31). Other standard autonomic reflex testing components, including heart rate response to deep breathing (HRDB), Valsalva, and 10-min head-up tilt testing, were also performed. Of the 223 participants (mean age 31.6 years; female 89%), 161 (41%) had HyperPOTS features, 113 (29%) exhibited NeuroPOTS features, and 40 (18%)/48 (22%) demonstrated neither or both, respectively. NeuroPOTS features were associated with higher supine HR and rates of abnormal HRDB than those without NeuroPOTS. No significant differences in COMPASS-31 scores were found between all groups studied. HyperPOTS and NeuroPOTS are common, co-occurring features in adults with POTS. Autonomic symptom burden did not differ significantly between phenotypes, likely reflecting insensitivity of the COMPASS-31 to phenotype-specific domains. NeuroPOTS was associated with impaired cardiovagal function, consistent with involvement in cardiac postganglionic parasympathetic pathways, though this is partly confounded by HRDB's inclusion in our NeuroPOTS definition. These findings support the concept that POTS phenotyping may aid in therapy selection, and the need for phenotype-sensitive symptom instruments.

Hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorder (HSD) are increasingly recognized among orthopedic physicians to cause joint instability, frequent dislocation, and chronic musculoskeletal pain. Yet, patients with these disorders frequently have coexisting conditions, such as postural tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), autoimmune and allergic disease, and neuropsychiatric conditions including anxiety, depression, ADHD, and autism. These comorbidities complicate diagnosis and treatment, therefore potentially decreasing the overall quality of care these patients receive. Despite the clinical relevance of comorbidities, the extent of research linking hypermobility disorders to these conditions has not been comprehensively examined. A bibliometric analysis was conducted using the Web of Science Core Collection to identify articles and journals related to the topic. Articles with hEDS and hypermobility spectrum disorder (HSD) as the main topic and addressing at least one of the four comorbidity domains (orthopedic, autonomic, immunologic, or neuropsychiatric) were included without restriction on the type of document. The trend in the year of publication was graphed using the Web of Science Analyze results tool, while the collected bibliographic data was analyzed using VOSviewer to assess the coauthorship network and keyword co-occurrence patterns. Microsoft Excel was also utilized to visualize the articles with the most citations. Between 1967 and June 18, 2026, 1,281 publications were published, with 97.1% in English. About 65.8% of the articles were published within the last ten years, showing the rapid growth of research in this field. The country with the highest number of publications was the United States (482, 37.6%), followed by England (223, 17.4%) and Italy (114, 8.9%). The organization contributing the greatest number of articles in the dataset was the University of London, with 97 articles. Isolated author collaboration networks were observed, featuring small clusters with rare interactions, typically separated by country. Research connecting hEDS and HSD to their orthopedic, autonomic, immunologic, and neuropsychiatric comorbidities has expanded rapidly over the past decade, driven largely by a few geographically isolated research clusters. Despite this growth, the immunologic and mast cell activation literature remains substantially underdeveloped, and collaboration across these research groups remains limited. Future efforts should prioritize cross-disciplinary and cross-national collaboration, with particular attention to expanding research on the immunologic and mast cell activation dimensions of hypermobility disorders.

Postural orthostatic tachycardia syndrome is a chronic autonomic disorder with limited effective treatment therapy. Non-invasive transcutaneous vagus nerve stimulation has emerged as a promising intervention that improves autonomic balance and has anti-inflammatory properties. This systematic search and narrative synthesis brings together all available clinical evidence including landmark studies from 2025 to 2026 unavailable to all prior reviews and advances novel arguments to guide future trial design. We searched in 5 databases (PubMed, Embase, Cochrane, Scopus and Web of science) from inception to March 2026 to extract studies evaluating the role of tVNS in treatment of POTS following the PRISMA 2020 guidelines. Because of the small number of clinically and methodologically heterogeneous studies, findings were combined by narrative synthesis rather than meta-analysis, and reported in line with the Synthesis Without Meta-analysis (SWiM) guideline. A total of 105 patients with POTS from 3 primary studies (Stavrakis et al. (2024), Wang et al. (2025), Shiffer et al. (2026) were included in this review. Across the studies, tVNS consistently reduced orthostatic tachycardia and improved multiple autonomic parameters, with reductions in GPCR autoantibodies, inflammatory markers, and the emerging biomarker NPY. Patient-reported symptoms improved in two studies that reported them. These outcomes sustained up to 1-2 years. In this systematic review, we found that tVNS is safe, non-invasive and consistently effective in reducing the orthostatic tachycardia and improving autonomic indices in POTS patients and may contribute to disease modification.

Vasovagal syncope (VVS) is the most common form of cardiovascular dysautonomia that has multiple etiologies. Post-vaccination dysautonomia, in the form of VVS and postural orthostatic tachycardia syndrome, has been reported in the literature after various vaccines, including COVID-19 mRNA vaccination. Treatment of post-vaccination syndromes has not been explored leaving patients with post-vaccination dysautonomia with limited therapeutic options. We report a 42-year-old woman who developed post-vaccination VVS after COVID-19 mRNA vaccination and improved significantly with semaglutide treatment. The patient's COMPASS-31 score decreased by 44% post-treatment, Orthostatic Hypotension Questionnaire score decreased by 59%, and an average 24-hour heart rate decreased from 97 beats per minute (bpm) to 80 bpm, indicating significant reduction in the autonomic symptom burden. In addition, her post-vaccination neuropathic pain in the legs completely resolved after treatment with semaglutide. This case report suggests that GLP-1 receptor agonists might be beneficial for treatment of recurrent VVS, other forms of dysautonomia and post-vaccination syndromes with neuropathic pain, and may be considered as candidates for randomized placebo-controlled trials in this patient population.