Laryngological manifestations of connective tissue diease with hypermobility such as ehlers-danlos syndrome (EDS) are not well defined in the literature. EDS is an inherited, hetrogeneous, connective tissue disorder characterized by joint hypermobility, skin extensibility, and joint dislocations. A case series of 9 patients is presented with varying laryngological complaints. Common comorbities include postural orthostatic tachycardia syndrome (POTS), fibromyalgia, irritable bowel syndrome (IBS), and gastroesophageal reflux disease (GERD)/laryngopharyngeal reflux disease (LPRD). Six patients were singers. Videostroboscopic parameters and treatment courses are described. It may be beneficial to view patients with EDS and laryngological complaints through a holistic lens as many may need interdisciplinary assessment and management. Laryngoscope, 134:894-896, 2024.

Low-level transcutaneous stimulation of the auricular branch of the vagus nerve at the tragus is antiarrhythmic and anti-inflammatory in animals and humans. Preliminary studies show that transcutaneous vagus nerve stimulation (tVNS) is beneficial in animal models of postural tachycardia syndrome (POTS). In this study the authors conducted a sham-controlled, double-blind, randomized clinical trial to examine the effect of tVNS on POTS over a 2-month period relative to sham stimulation. tVNS (20 Hz, 1 mA below discomfort threshold) was delivered using an ear clip attached to either the tragus (active; n = 12) or the ear lobe (sham; n = 14) for 1 hour daily over a 2-month period. Postural tachycardia was assessed during the baseline and 2-month visit. Heart rate variability based on 5-minute electrocardiogram, serum cytokines, and antiautonomic autoantibodies were measured at the respective time points. Mean age was 34 ± 11 years (100% female; 81% Caucasian). Adherence to daily stimulation was 83% in the active arm and 86% in the sham arm (P > 0.05). Postural tachycardia was significantly less in the active arm compared with the sham arm at 2 months (mean postural increase in heart rate 17.6 ± 9.9 beats/min vs 31.7 ± 14.4 beats/min; P = 0.01). Antiadrenergic autoantibodies and inflammatory cytokines were lower in the active arm compared with the sham arm at 2 months (P < 0.05). Heart rate variability was better in the active arm. No device-related side effects were observed. Our results support the emerging paradigm of noninvasive neuromodulation to treat POTS. Mechanistically, this effect appears to be related to reduction of antiautonomic autoantibodies and inflammatory cytokines, and improvement in autonomic tone. Further studies are warranted. (Autoimmune Basis for Postural Tachycardia Syndrome; NCT05043051).

The therapeutic effectiveness of the empirical and unselected use of oral rehydration salts (ORS) on postural tachycardia syndrome (POTS) is not satisfactory in children. Therefore, looking for suitable predictors of the therapeutic effects of ORS before treatment is extremely necessary to implement individualised treatment for paediatric patients with POTS. A retrospective case-control analysis of 130 patients (aged 5-18 years) who suffered from POTS with a 3-month treatment of ORS was conducted. A nomogram model was developed in the training set (n = 87) to predict the therapeutic response to ORS. Univariate analysis and logistic regression were applied to select the most useful predictors. ROC curves were applied to evaluate the discriminative performance of the nomogram model. The nomogram was then evaluated by calibration curves and the Hosmer-Lemeshow (H-L) test. The results were further validated using 1000 bootstrap resamples. External validation was performed in an independent validation set (n = 43). Among the ten variables with significant differences between the responders and non-responders in univariate analysis, five variables were found to be independently associated factors for ORS therapeutic efficacy among POTS children in the further logistic regression, including mean corpuscular haemoglobin concentration (MCHC), mean corpuscular volume (MCV), mean arterial pressure (MAP) at the first minute of the upright position, urine specific gravity (SG), and P-wave voltage peaking ratio (PWP). The nomogram model was established in the training set (AUC 0.926 [95% CI: 0.865-0.988], yielding a sensitivity of 87.8% and a specificity of 86.8%). The calibration curves showed good agreement between the prediction of the nomogram and actual observation in both the training and validation sets. The nomogram also effectively predicted the external validation set (sensitivity 82.1%, specificity 73.3%, and accuracy 79.1%). We established a feasible and high-precision nomogram model to predict the efficacy of ORS, which would help implement individualised treatment for children with POTS. This study was supported by National High-Level Hospital Clinical Research Funding (Multi-centre Clinical Research Project of Peking University First Hospital) (2022CR59).

This study assesses response to intravenous immunoglobulin (IVIG) in presumed autoimmune postural orthostatic tachycardia syndrome (POTS). POTS may be associated with autoimmune disorders, serum autoantibodies, or recent infection. Uncontrolled case studies suggest that IVIG is beneficial for treating autoimmune POTS. No previous randomized controlled trials have been conducted. This single-site randomized controlled trial compared IVIG with intravenous albumin infusions. Albumin comparator ensured blinding and control for effects of volume expansion. Eligible patients with POTS had COMPASS-31 total weighted score ≥ 40 and met predetermined criteria suggesting autoimmunity. Over 12 weeks, participants received eight infusions (0.4 gm/kg each). Four infusions were given weekly followed by four infusions every other week. Primary outcome measure was improvement in COMPASS-31 2 weeks after final infusion. A total of 50 participants consented; 30 met inclusion criteria and received study drug (16 IVIG and 14 albumin; 29 female). Group baseline characteristics were well matched; 27 participants completed treatment protocol. Change in COMPASS-31 did not differ between groups (median change [IQR]; IVIG: -5.5 [-23.3, 2.5] versus albumin: -10.6 [-14.1, -4.7]; p-value = 0.629). The IVIG group had a higher response rate (46.7% versus 38.5%), but this was not statistically significant. Adverse events were common but usually mild and did not differ between treatment groups. This small randomized controlled trial of IVIG in POTS found no statistical difference in response compared with albumin infusion. Both groups showed improvement possibly related to volume expansion or other effects obscuring group differences. These findings inform development of future immunomodulatory clinical trials in POTS.

Postural tachycardia syndrome (POTS) is a disorder characterized by a constellation of symptoms including lightheadedness, fatigue, and palpitations when upright, associated with an increase in the heart rate (HR) of > 30 beats per minute when changing from a lying down to standing position or head-up tilt position and not associated with orthostatic hypotension. The causes as well as the management of POTS are not quite fully understood. We performed a literature review on the diagnosis and management of POTS, and this article includes an overview of novel pharmacotherapeutic options for the treatment of (POTS), although an effective treatment has not been established. POTS is a clinical syndrome characterized by a constellation of symptoms that are nonspecific. No single etiology or unified hypothesis could be identified. In fact, multiple pathophysiological mechanisms have been proposed, and none of the suggested medications have been approved by the FDA for this indication. Further understanding of the autonomic nervous system and its adjustment to standing position is needed to provide better management strategies.

SARS-CoV-2 vaccinations can lead to complications, including post-acute COVID-19 vaccination syndrome (PACVS). There has been no report of a patient with PACVS presenting with Guillain-Barre syndrome (GBS), myocarditis/pericarditis, immunodeficiency, or coagulopathy after the second BNT162b2 dose. The patient is a 51-year-old woman with chronic myopericarditis, coagulopathy due to factor-VIII increase and protein-S deficiency, GBS, and a number of other ocular, dermatological, immunological, and central nervous system abnormalities related to the second dose of the BNT172b2 vaccine. GBS manifested with mild, multiple cranial nerve lesions, small fibre neuropathy (SFN) affecting the autonomic system with postural tachycardia syndrome (POTS) and orthostatic hypotension, and sensory disturbances in the upper and lower limbs. PACVS was diagnosed months after onset, but despite the delayed diagnosis, the patient benefited from glucocorticoids, repeated HELP apheresis, and multiple symptomatic treatments. The case shows that SARS-CoV-2 vaccination can be complicated by PACVS manifesting as chronic myopericarditis, coagulopathy, GBS with predominant dysautonomia, and impaired immune competence, and that diagnosis of PACVS can be delayed for months. Delayed diagnosis of PACVS may result in a delay in appropriate treatment and the prolongation of disabling symptoms. Patients and physicians should be made aware of PACVS to improve diagnostic and therapeutic management in terms of patient and healthcare system costs.

Postural orthostatic tachycardia syndrome (POTS) is a common accompaniment of a variety of chronic, inflammatory diseases, including long COVID, as are small, insoluble, 'fibrinaloid' microclots. We here develop the argument, with accompanying evidence, that fibrinaloid microclots, through their ability to block the flow of blood through microcapillaries and thus cause tissue hypoxia, are not simply correlated with but in fact, by preceding it, may be a chief intermediary cause of POTS, in which tachycardia is simply the body's exaggerated 'physiological' response to hypoxia. Similar reasoning accounts for the symptoms bundled under the term 'fatigue'. Amyloids are known to be membrane disruptors, and when their targets are nerve membranes, this can explain neurotoxicity and hence the autonomic nervous system dysfunction that contributes to POTS. Taken together as a system view, we indicate that fibrinaloid microclots can serve to link POTS and fatigue in long COVID in a manner that is at once both mechanistic and explanatory. This has clear implications for the treatment of such diseases.

Autonomic symptom questionnaires are frequently used to assess dysautonomia. It is unknown whether subjective dysautonomia obtained from autonomic questionnaires correlates with objective dysautonomia measured by quantitative autonomic testing. The objective of our study was to determine correlations between subjective and objective measures of dysautonomia. This was a retrospective cross-sectional study conducted at Brigham and Women's Faulkner Hospital Autonomic Laboratory between 2017 and 2023 evaluating the patients who completed autonomic testing. Analyses included validated autonomic questionnaires [Survey of Autonomic Symptoms (SAS), Composite Autonomic Symptom Score 31 (Compass-31)] and standardized autonomic tests (Valsalva maneuver, deep breathing, sudomotor, and tilt test). The autonomic testing results were graded by a Quantitative scale for grading of cardiovascular reflexes, sudomotor tests and skin biopsies (QASAT), and Composite Autonomic Severity Score (CASS). Autonomic testing, QASAT, CASS, and SAS were obtained in 2627 patients, and Compass-31 in 564 patients. The correlation was strong between subjective instruments (SAS vs. Compass-31, r = 0.74, p < 0.001) and between objective instruments (QASAT vs. CASS, r = 0.81, p < 0.001). There were no correlations between SAS and QASAT nor between Compass-31 and CASS. There continued to be no correlations between subjective and objective instruments for selected diagnoses (post-acute sequelae of COVID-19, n = 61; postural tachycardia syndrome, 211; peripheral autonomic neuropathy, 463; myalgic encephalomyelitis/chronic fatigue syndrome, 95; preload failure, 120; post-treatment Lyme disease syndrome, 163; hypermobile Ehlers-Danlos syndrome, 213; neurogenic orthostatic hypotension, 86; diabetes type II, 71, mast cell activation syndrome, 172; hereditary alpha tryptasemia, 45). The lack of correlation between subjective and objective instruments highlights the limitations of the commonly used questionnaires with some patients overestimating and some underestimating true autonomic deficit. The diagnosis-independent subjective-objective mismatch further signifies the unmet need for reliable screening surveys. Patients who overestimate the symptom burden may represent a population with idiosyncratic autonomic-like symptomatology, which needs further study. At this time, the use of autonomic questionnaires as a replacement of autonomic testing cannot be recommended.

Postural tachycardia syndrome (POTS), a subset of orthostatic dysregulation, has been reported to be associated with anxiety. POTS can be classified into two forms based on the degree of tachycardia during orthostasis. Reportedly, POTS with decreased orthostatic heart rate increase is associated with suppressed cardiac parasympathetic activity and increased sympathetic activity in the supine position. In this study, the relationship between the two types of POTS and anxiety was evaluated in terms of autonomic function. Fifty-two patients (23 male, age 10-15 years) who were diagnosed with POTS at the Department of Pediatrics, Osaka Medical and Pharmaceutical University from 2019 to 2021, completed a standing test and were accordingly classified into a Su group, with tachycardia from the supine position and a low heart rate increase on standing, a SI group, with a high heart rate increase during standing. They then completed the State-Trait Anxiety Scale for Children (STAIC) questionnaire. Autonomic function was assessed by frequency analysis (MemCalc method) based on heart rate, blood pressure changes, heart rate and blood pressure variability during the orthostatic test. Patients in the Su group had higher trait anxiety and state anxiety, lower cardiac parasympathetic activity (RR-HF) in the supine position, and greater variability in cardiac parasympathetic activity during orthostasis than were found for patients in the SI group. The Su group had a greater decrease in cardiac index on standing than that of the SI group. The Su group results may be partly attributed to chronically low venous return. We also found that patients in the Su group had low parasympathetic activity in the supine position, which may interact with the anxiety-prone characteristics of these patients. Therefore, it seems necessary to consider both physical and psychosomatic treatment approaches for patients with POTS.

Coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory coronavirus-2 (SARS-CoV-2). Several explanations for the development of cardiovascular complications during and after acute COVID-19 infection have been hypothesized. The COVID-19 pandemic, caused by SARS-CoV-2, has emerged as one of the deadliest pandemics in modern history. The myocardial injury in COVID-19 patients has been associated with coronary spasm, microthrombi formation, plaque rupture, hypoxic injury, or cytokine storm, which have the same pathophysiology as the three clinical variants of Kounis syndrome. The angiotensin-converting enzyme 2 (ACE2), reninaldosterone system (RAAS), and kinin-kallikrein system are the main proposed mechanisms contributing to cardiovascular complications with the COVID-19 infection. ACE receptors can be found in the heart, blood vessels, endothelium, lungs, intestines, testes, neurons, and other human body parts. SARS-CoV-2 directly invades the endothelial cells with ACE2 receptors and constitutes the main pathway through which the virus enters the endothelial cells. This causes angiotensin II accumulation downregulation of the ACE2 receptors, resulting in prothrombotic effects, such as hemostatic imbalance via activation of the coagulation cascade, impaired fibrinolysis, thrombin generation, vasoconstriction, endothelial and platelet activation, and pro-inflammatory cytokine release. The KKS system typically causes vasodilation and regulates tissue repair, inflammation, cell proliferation, and platelet aggregation, but SARS-CoV-2 infection impairs such counterbalancing effects. This cascade results in cardiac arrhythmias, cardiac arrest, cardiomyopathy, cytokine storm, heart failure, ischemic myocardial injuries, microvascular disease, Kounis syndrome, prolonged COVID, myocardial fibrosis, myocarditis, new-onset hypertension, pericarditis, postural orthostatic tachycardia syndrome, pulmonary hypertension, stroke, Takotsubo syndrome, venous thromboembolism, and thrombocytopenia. In this narrative review, we describe and elucidate when, where, and how COVID-19 affects the human cardiovascular system in various parts of the human body that are vulnerable in every patient category, including children and athletes.

Postural orthostatic tachycardia syndrome (POTS) presents heterogeneously and is diagnosed when appropriate symptoms are present in conjunction with a heart rate increase of at least 30 beats-per-minute upon standing without orthostatic hypotension. Much of the current understanding of POTS is based on clinical expertise, particularly regarding POTS phenotypes and their potential role in targeting pharmacologic treatment. This study describes the symptom presentation of POTS by phenotypes at a subspecialty POTS clinic. Data was collected prospectively during clinical visits between April 17, 2014 and February 8, 2021. This data was abstracted retrospectively by chart review. Most of the 378 study participants were female (89.9%) with a mean age 23.0 ± 4.9 years. Lightheadedness was the most common (97.6%) symptom and the most disruptive of quality of life (29.9%). Patients reported substantial functional impairment across multiple life domains, with 3.0 ± 2.8 days lost and 4.7 ± 2.3 unproductive days per week. There were no differences in symptom presentation among POTS phenotypes. POTS phenotypes are not distinguishable based on symptoms alone; if phenotyping is sought, testing is necessary. Further research is needed in better classifying POTS phenotypes with the potential goal of tailoring treatment.

Bier anemic spots, cyanosis with urticaria-like eruption (BASCULE) syndrome is a recently described entity with episodic urticarial lesions and white anemic halos on a background of erythrocyanosis, commonly affecting the lower extremities. Possible association with autonomic dysfunction remains poorly understood. Existing publications are limited, but the condition is suggested as highly underrecognized. To further characterize clinical and epidemiologic data for BASCULE syndrome. We performed an IRB-approved retrospective chart review on patients with BASCULE syndrome evaluated at Mayo Clinic from April 2021 to November 2022. A total of 17 patients were identified (13 female, 4 male). Median age of onset was 12 years (range 9-17). Lower extremities were involved in all patients (17). Most patients were symptomatic with pruritus (8) or burning pain (8); three were asymptomatic. Triggers were standing (11), hot showers or hot environments (7), or no clear trigger (4). Autonomic dysfunction was present in 10 patients. Treatment responses were observed from propranolol (3) and high-dose cetirizine (1). Novel epidemiologic data from 17 pediatric and young adult patients with BASCULE syndrome further supports an association with autonomic dysfunction and suggests a higher prevalence than previously acknowledged.

Coronavirus disease 2019 (COVID-19) sequelae, also known as long COVID, can present with various symptoms. Among these symptoms, autonomic dysregulation, particularly postural orthostatic tachycardia syndrome (POTS), should be evaluated. However, previous studies on the treatment of POTS complicated by COVID-19 are lacking. Therefore, this study aimed to investigate the treatment course of long COVID complicated by POTS. The medical records of patients who complained of fatigue and met the criteria for POTS diagnosis were reviewed. We evaluated the treatment days, methods and changes in fatigue score, changes in heart rate on the Schellong test, and social situation at the first and last visits. Thirty-two patients with long COVID complicated by POTS were followed up (16 males; median age: 28 years). The follow-up period was 159 days, and the interval between COVID-19 onset and initial hospital attendance was 97 days. Some patients responded to β-blocker therapy. Many patients had psychiatric symptoms that required psychiatric intervention and selective serotonin reuptake inhibitor prescription. Changes in heart rate, performance status, and employment/education status improved from the first to the last visit. These outcomes were believed to be because of the effects of various treatment interventions and spontaneous improvements. Our study suggests that the condition of 94% of patients with POTS complicated by long COVID will improve within 159 days. Therefore, POTS evaluation should be considered when patients with long COVID complain of fatigue, and attention should be paid to psychological symptoms and the social context.

Hypermobile Ehlers-Danlos Syndrome (hEDS) is a connective tissue disorder characterized by joint hypermobility and other systemic manifestations, such as cardiovascular symptoms, musculoskeletal pain, and joint instability. Cardiovascular symptoms, such as lightheadedness and palpitations, and types of dysautonomia, including postural orthostatic tachycardia syndrome (POTS), are frequently reported in adults with hEDS and have been shown to negatively impact quality of life (QoL). This brief review will be an overview of co-occurring symptoms in POTS and hEDS to inform potential cardiovascular screening procedures. While many patients with hEDS report cardiovascular symptoms, few have structural abnormalities, suggesting that dysautonomia is likely responsible for these symptoms. One validated screening measure for dysautonomia symptom burden is the Composite Autonomic Symptom Scale (COMPASS-31). Studies have found that adults with POTS, hEDS, and both POTS and hEDS have higher COMPASS-31 scores than the general population, suggesting a high symptom burden due to dysautonomia, which leads to impaired QoL. While studies have examined cardiovascular symptoms and the impact of dysautonomia in adults with and without hEDS, there is scant literature on dysautonomia in pediatric patients with hEDS. Therefore, more studies on cardiovascular symptoms and dysautonomia, as they relate to the quality of life in pediatric patients with hEDS, are needed. This brief review summarizes the current literature on dysautonomia and cardiovascular symptoms in pediatric and adult populations with hEDS.

Gastrointestinal (GI) symptoms are common in postural orthostatic tachycardia syndrome (POTS). We aimed to explore the prevalence and severity of GI symptoms in POTS, and to investigate immunological factors, hemodynamic findings, and their possible association with GI symptoms in POTS. Forty-three patients (93% female, median age 30.6 (26.0-41.0) years), previously diagnosed with POTS and 74 healthy controls (78% female, median age 35.6 (28.8-41.7) years) were included. The participants completed a questionnaire including prevalence of GI symptoms, the irritable bowel syndrome severity scoring system (IBS-SSS), and visual analog scale for IBS (VAS-IBS). All POTS patients were previously examined by tilt test (2010-2021) and the vast majority with more recent active standing test (2017-2021), which included monitoring of heart rate (HR). ΔHR was calculated as difference between supine and upright position. Continuous variables from IBS-SSS and VAS-IBS were correlated to ΔHR. A microarray containing several autoantigens commonly targeted in systemic autoimmune disorders was used to assess prevalent autoantibodies in POTS and controls. Total IgE and S-tryptase were analyzed. GI symptoms were more prevalent and severe in POTS than in controls; nausea being the most prevalent (79.1% vs 4.9%, < 0.001) and bloating and flatulence being the most severe (median 65 (25-88) vs 0 (0-14), < 0.001). The median total IBS-SSS was 213 (135-319) in POTS vs 13 (0-54) in controls ( < 0.001). Total IBS-SSS was associated with low psychological wellbeing (r = 0.539, < 0.001) in POTS. ΔHR correlated inversely with abdominal pain (r = -0.406, = 0.007). After adjustments for psychological wellbeing, total IBS-SSS still associated inversely with ΔHR (β: 4.748; 95% CI: -9.172 to -0.324; = 0.036). Similar results were seen with active standing test. The prevalence of autoantibodies did not differ between POTS and controls (29.4% vs 33.3%, = 0.803). There was no association between GI symptoms and autoantibody status. Total IgE and tryptase were elevated in a few cases. This study confirms the high prevalence of GI symptoms in POTS. More pronounced tachycardia upon tilt table testing seems to be inversely correlated with severity of chronic GI symptoms in POTS. This study did not support the hypothesis that POTS is associated with immunological factors.

Dysautonomia, or dysfunction of the autonomic nervous system (ANS), may occur following an infectious insult and can result in a variety of debilitating, widespread, and often poorly recognized symptoms. Dysautonomia is now widely accepted as a complication of COVID-19 and is an important component of Post-Acute Sequelae of COVID-19 (PASC or long COVID). PASC shares many overlapping clinical features with other infection-associated chronic illnesses including Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post-Treatment Lyme Disease Syndrome (PTLDS), suggesting that they may share common underlying mechanisms including autonomic dysfunction. Despite the recognition of this complication of Lyme disease in the care of patients with PTLD, there has been a scarcity of research in this field and dysautonomia has not yet been established as a complication of Lyme disease in the medical literature. In this review, we discuss the evidence implicating as a cause of dysautonomia and the related symptoms, propose potential pathogenic mechanisms given our knowledge of Lyme disease and mechanisms of PASC and ME/CFS, and discuss the diagnostic evaluation and treatments of dysautonomia. We also outline gaps in the literature and priorities for future research.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, multifaceted disease that affects millions globally. Despite its significant impact, the disease's etiology remains poorly understood, and symptom heterogeneity poses challenges for diagnosis and treatment. Joint hypermobility, commonly seen in hypermobile Ehlers-Danlos Syndrome (hEDS), has been observed in ME/CFS patients but its prevalence and clinical significance within this population are not well-characterized. To compare the characteristics of ME/CFS patients with and without joint hypermobility (JH+ and JH-) as assessed using the Beighton scoring system, and to explore whether JH+ ME/CFS patients exhibit distinct disease characteristics, comorbidities, and health-related quality of life (HRQOL). The study used cross-sectional, self-reported data from 815 participants of the You + ME Registry. Participants were categorized as JH+ or JH- based on self-assessed Beighton scores and compared across demographics, comorbidities, family history, and symptoms. HRQOL was assessed using the Short Form-36 RAND survey and Karnofsky Performance Status. 15.5% ( = 126) of participants were classified as JH+. JH+ participants were more likely to be female, report Ehlers-Danlos Syndrome (EDS), Postural Orthostatic Tachycardia Syndrome (POTS), and a family history of EDS. They experienced worse HRQOL, particularly in physical functioning and pain, and a higher number of autonomic, neurocognitive, headache, gut, and musculoskeletal symptoms. Sensitivity analysis suggested that ME/CFS with concurrent JH+ and EDS was associated with more severe symptoms and greater functional impairment. ME/CFS patients with joint hypermobility, particularly those with EDS, demonstrate distinct clinical characteristics, including more severe symptomatology and reduced HRQOL. These findings highlight the need for comprehensive clinical assessments of ME/CFS patients with joint hypermobility. Understanding these relationships could aid in subgroup identification, improving diagnosis, and informing targeted therapeutic approaches. Further research is warranted to explore these associations and their implications for clinical practice.

The impact of COVID-19 has been far-reaching, and the field of neurology is no exception. Due to the long-hauler effect, a variety of chronic health consequences have occurred for some post-COVID patients. A subset of these long-hauler patients experienced symptoms of autonomic dysfunction and tested positive for postural orthostatic tachycardia syndrome (POTS) via autonomic testing. We conducted a chart review of a convenience sample from patients seen by neurologists at our tertiary care center for suspicion of post-COVID POTS. Patients included in our study had clearly defined POTS based on clinical criteria and positive tilt table test, were 81.25% female, and had an average age of approximately 36. Out of 16 patients, 12 had a confirmed positive COVID test result, with the remaining 4 having strong clinical suspicion for COVID infection. Our analysis examined the most bothersome 3 symptoms affecting each patient per the neurologist's note at their initial visit for post-COVID POTS, clinical presentation, comorbidities, neurological exam findings, autonomic testing results, and COMPASS-31 autonomic questionnaire and PROMIS fatigue survey results. Palpitations (68.75%) and fatigue (62.5%) were the most common of the impactful symptoms reported by patients in their initial Cleveland Clinic neurology visit. The most frequent comorbidities in our sample were chronic migraines (37.5%), irritable bowel syndrome (IBS) (18.75%), and Raynaud's (18.75%). Neurological exam findings and autonomic testing results other than tilt table yielded variable findings without clear trends. Survey results showed substantial autonomic symptom burden (COMPASS-31 autonomic questionnaire average score 44.45) and high levels of fatigue (PROMIS fatigue survey average score 64.64) in post-COVID POTS patients. Our sample of post-COVID POTS patients are similar to the diagnosed POTS general population including in comorbidities and autonomic testing. Fatigue was identified by patients as a common and debilitating symptom. We hope that our study will be an early step toward further investigation of post-COVID POTS with focus on the trends identified in this chart review.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) presents substantial challenges in patient care due to its intricate multisystem nature, comorbidities, and global prevalence. The heterogeneity among patient populations, coupled with the absence of FDA-approved diagnostics and therapeutics, further complicates research into disease etiology and patient managment. Integrating longitudinal multi-omics data with clinical, health,textual, pharmaceutical, and nutraceutical data offers a promising avenue to address these complexities, aiding in the identification of underlying causes and providing insights into effective therapeutics and diagnostic strategies. This study focused on an exceptionally severe ME/CFS patient with hypermobility spectrum disorder (HSD) during a period of marginal symptom improvements. Longitudinal cytokine profiling was conducted alongside the collection of extensive multi-modal health data to explore the dynamic nature of symptoms, severity, triggers, and modifying factors. Additionally, an updated severity assessment platform and two applications, ME-CFSTrackerApp and LexiTime, were introduced to facilitate real-time symptom tracking and enhance patient-physician/researcher communication, and evaluate response to medical intervention. Longitudinal cytokine profiling revealed the significance of Th2-type cytokines and highlighted synergistic activities between mast cells and eosinophils, skewing Th1 toward Th2 immune responses in ME/CFS pathogenesis, particularly in cognitive impairment and sensorial intolerance. This suggests a potentially shared underlying mechanism with major ME/CFS comorbidities such as HSD, Mast cell activation syndrome, postural orthostatic tachycardia syndrome (POTS), and small fiber neuropathy. Additionally, the data identified potential roles of BCL6 and TP53 pathways in ME/CFS etiology and emphasized the importance of investigating adverse reactions to medication and supplements and drug interactions in ME/CFS severity and progression. Our study advocates for the integration of longitudinal multi-omics with multi-modal health data and artificial intelligence (AI) techniques to better understand ME/CFS and its major comorbidities. These findings highlight the significance of dysregulated Th2-type cytokines in patient stratification and precision medicine strategies. Additionally, our results suggest exploring the use of low-dose drugs with partial agonist activity as a potential avenue for ME/CFS treatment. This comprehensive approach emphasizes the importance of adopting a patient-centered care approach to improve ME/CFS healthcare management, disease severity assessment, and personalized medicine. Overall, these findings contribute to our understanding of ME/CFS and offer avenues for future research and clinical practice.

To co-create expert guidelines for the management of pregnancy, birth, and postpartum recovery in the context of hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD). Scoping Review and Expert Co-creation. United Kingdom, United States of America, Canada, France, Sweden, Luxembourg, Germany, Italy, and the Netherlands. Co-creators (n = 15) included expertise from patients and clinicians from the International Consortium on the Ehlers-Danlos syndromes and Hypermobility Spectrum Disorders, facilitated by the Ehlers-Danlos Society. A scoping review using Embase, Medline, the Cochrane Central Register of Controlled Trials and CINHAL was conducted from May 2022 to September 2023. Articles were included if they reported primary research findings in relation to childbearing with hEDS/HSD, including case reports. No language limitations were placed on our search, and our team had the ability to translate and screen articles retrieved in English, French, Spanish, Italian, Russian, Swedish, Norwegian, Dutch, Danish, German, and Portuguese. The Mixed Methods Appraisal Tool was used to assess bias and quality appraise articles selected. The co-creation of guidelines was based on descriptive evidence synthesis along with practical and clinical experience supported by patient and public involvement activities. Primary research studies (n = 14) and case studies (n = 21) including a total of 1,260,317 participants informed the co-creation of guidelines in four overarching categories: 1) Preconceptual: conception and screening, 2) Antenatal: risk assessment, management of miscarriage and termination of pregnancy, gastrointestinal issues and mobility, 3) Intrapartum: risk assessment, birth choices (mode of birth and intended place of birth), mobility in labor and anesthesia, and 4) Postpartum: wound healing, pelvic health, care of the newborn and infant feeding. Guidelines were also included in relation to pain management, mental health, nutrition and the common co-morbidities of postural orthostatic tachycardia syndrome, other forms of dysautonomia, and mast cell diseases. There is limited high quality evidence available. Individualized strategies are proposed for the management of childbearing people with hEDS/HSD throughout pregnancy, birth, and the postpartum period. A multidisciplinary approach is advised to address frequently seen issues in this population such as tissue fragility, joint hypermobility, and pain, as well as common comorbidities, including dysautonomia and mast cell diseases.

Postural orthostatic Tachycardia Syndrome (PoTS), sometimes also written as 'POTS', is a form of dysautonomia (dysfunction of the autonomic nervous system) and orthostatic intolerance (which causes symptoms to be worsened when standing). This paper explores the extant literature on the lived experiences of those living with PoTS in relation to interactions between patients and healthcare providers as well as interactions at the level of the individual between PoTSies and those around them. My title contains the word 'salty' because it can be used to describe the feeling of being frustrated, while also reflecting a specific dietary change recommended to many (but not all) PoTS patients when they are told to consume additional sodium to minimise symptoms. COVID-19 is thought to have led to an increased prevalence of PoTS so this topic is particularly relevant to contemporary discussions and debates. In this sociological article, I refer not only to existing research on the lived experiences of having PoTS but also that of other chronic illnesses when relevant. The following themes are explored through auto/biographical and theoretical analysis: Undiagnosed and Invalidated; (In)Visible; Impacts of Diagnosis; Recovery and Expectations; Community. Reflecting auto/biographically, I have included analysis of interactions related to my lived experiences of presyncope, COVID-19 and dysautonomia, as I have been diagnosed with PoTS myself, which is thought to have been significantly exacerbated by the COVID-19 virus. This research is sociological, rather than medical or psychological, and conclusions are drawn about what is known so far about the lived experiences of living with PoTS, as well as discussion about what remains unknown, as there is currently a paucity of research on the lived experiences of individuals with PoTS and its comorbidities.

Functional neurological disorder (FND) is a common neurologic disorder associated with many comorbid symptoms including fatigue, pain, headache, and orthostasis. These concurrent symptoms lead patients to accumulate multiple diagnoses comorbid with FND, including fibromyalgia, chronic fatigue syndrome, postural orthostatic tachycardia syndrome, persistent post-concussive symptoms, and chronic pain. The role of physical activity and exercise has not been evaluated in FND populations, though has been studied in certain comorbid conditions. In this traditional narrative literature review, we highlight some existing literature on physical activity in FND, then look to comorbid disorders to highlight the therapeutic potential of physical activity. We then consider abnormalities in the autonomic nervous system (ANS) as a potential pathophysiological explanation for symptoms in FND and comorbid disorders and postulate how physical activity and exercise may provide benefit via autonomic regulation.

Postural Orthostatic Tachycardia Syndrome (POTS) is a heterogenous disorder of the autonomic nervous system that is often disabling. There are no FDA-approved therapies for the treatment of this condition. While some patients recover with baseline non-pharmacological intervention, others require repeated trials of off-label pharmacological therapies. The reasoning for this variable treatment response is unknown. The purpose of this work is to identify potential factors that are associated with higher odds of starting pharmacotherapy and/or a higher rate of POTS treatment changes. Chart review of demographic, disease and treatment descriptions, medical history, and tilt table examinations of 322 POTS patients who were diagnosed between 2018 and 2020 at our tertiary care center was completed. We first identified the most significant factors associated with an increased odds of starting pharmacotherapy using variable selection techniques and logistic regression. We then identified the most significant factors associated with changes in POTS treatment strategies using variable selection techniques and negative binomial regression modeling. A significance level of 0.05 was utilized. A total of 752 POTS-specific treatment courses were cataloged, and 429 treatment changes were observed. The most cited reason for a change in management was uncontrolled symptoms. History of migraine headaches, reported fatigue, reported palpitations and a previous POTS diagnosis at an outside institution were found to be associated with a higher odds of starting pharmacotherapy for POTS symptoms (Odds Ratio of 2.40, 1.94, 2.62, 2.08, respectively). History of migraine headaches, reported fatigue, and higher heart rate differences on tilt table examination were found to be associated with an increase in the rate of POTS treatment changes (44, 66, 13% increase in incidence rate, respectively), while reported neck pain was associated with a decrease (27% decrease in incidence rate). Our work identifies important areas of focus in the development of high-quality trials involving both the non-pharmacological and pharmacological treatment of POTS and highlights several characteristics of patients that may be more refractory to both baseline non-pharmacological treatments and current pharmacological treatment strategies.

Postural orthostatic tachycardia syndrome (POTS) is one of the orthostatic intolerance syndromes that are common in young adolescents and impair quality of life. POTS is a multi-systemic disease. Many mechanisms have been defined in POTS etiology, such as autonomic denervation, hypovolemia, hyperadrenergic stimulation, low condition, and hypervigilance. Recently, mast cell activation (MCA) has also been on the agenda in etiology. There are few studies in the literature on the relationship between MCA and POTS in adulthood. However, data on children and adolescents is limited. In light of this information, we aimed to evaluate the relationship between POTS and MCA by measuring serum tryptase levels, a specific marker for MCA. This prospective study included patients who were admitted to Kocaeli University Faculty of Medicine Hospital Pediatric Cardiology outpatient clinic for syncope-presyncope between November 2018 and August 2019. Patients who underwent the TILT-table test were enrolled in the study. Patients with structural heart disease or chronic heart disease were not included in this study. Serum tryptase levels were obtained from all patients before the TILT-table test, and serum tryptase levels were re-studied after the test was terminated in patients with positive TILT-table tests for POTS. Patients diagnosed with POTS were classified as Group 1, and other patients were classified as Group 2. Twenty-eight of the 58 patients included in the study (mean: 14.4±2.0 years; 38 girls, 20 boys) were diagnosed with POTS. The remaining 30 patients were diagnosed with vasovagal syncope and included in Group 2. The increase in mean heart rate during the test was 38±6 beats/min and 47.05%±15.65% in patients with POTS. Basal serum tryptase levels were not different between groups (3.2±1.3 ng/ml and 3.84±1.78 ng/ml, respectively; p=0.129), while serum tryptase levels (both baseline and after 45-60 min of the TILT-table test) were higher in patients presenting with symptoms related to MCA compared to others. In the literature, MCA was considered to be one of the mechanisms leading to POTS. Although other mechanisms, such as neuropathic and hypovolemic POTS, may be active in the patients, the symptoms of MCA in these patients should be routinely questioned.

There has been an increasingly reported association between Ehlers-Danlos syndrome (EDS), postural orthostatic tachycardia syndrome (POTS) and gastrointestinal disorders. EDS is a hereditary connective tissue disorder which may manifest as a spectrum of symptoms stemming from collagen defects. The prevalence of EDS is estimated to affect 1 in 5000 individuals which underscores its clinical significance. Notably the hypermobile form (hEDS) accounts for the majority of cases. POTS is characterized by orthostatic intolerance with an increase in heart rate on standing in the absence of hypotension. This condition predominantly affects women between 15 and 45 years of age. Gastrointestinal symptoms in the form of reflux, bloating and abdominal pain significant impact this population. Gastroparesis is a chronic disorder involving symptoms of delayed gastric emptying and may be closely associated with hEDS and POTS, and may be underreported. Autonomic dysfunction associated with hEDS has been proposed as the likely mechanism underlying POTS and gastrointestinal dysfunction though a clear pathophysiological process has not been established.