Patients with postural tachycardia syndrome (POTS) experience chronic symptoms of orthostatic intolerance. There are minimal data detailing the demographics, clinical features and clinical course of this condition. This online, community-based survey highlights patients' experience with POTS. It consists of the largest sample of POTS patients reported to date. To describe the demographics, past medical history, medications, treatments and diagnostic journey for patients living with POTS. Postural tachycardia syndrome patients completed an online, community-based, cross-sectional survey. Participants were excluded if they had not received a diagnosis of POTS from a physician. The questions focused on the patient experience and journey, rather than physiological responses. The final analysis included 4835 participants. POTS predominantly affects white (93%) females (94%) of childbearing age, with approximately half developing symptoms in adolescence (mode 14 years). POTS is a chronic multisystem disorder involving a broad array of symptoms, with many patients diagnosed with comorbidities in addition to POTS. POTS patients often experience lengthy delays [median (interquartile range) 24 (6-72) months] and misdiagnosis, but the diagnostic delay is improving. POTS patients can present with a myriad of symptoms most commonly including lightheadedness (99%), tachycardia (97%), presyncope (94%), headache (94%) and difficulty concentrating (94%). These data provide important insights into the background, clinical features and diagnostic journey of patients suffering from POTS. These data should serve as an essential step for moving forward with future studies aimed at early and accurate diagnoses of these patients leading to appropriate treatments for their symptoms.

Postural orthostatic tachycardia syndrome (POTS) is a disorder of unknown aetiology characterized by orthostatic intolerance and tachycardia with diverse other symptoms, including neurocognitive deficits. Cerebral oximetry non-invasively measures cerebral tissue saturation (SctO2) and has been shown to be informative in syncope evaluation. We aimed to assess SctO2 in POTS patients and those with normal response to orthostatic provocation, relative to haemodynamic parameters and symptoms. Thirty-four patients with POTS (29.1 ± 9.5 years; 26 females) and 34 age-/sex-matched controls with normal head-up tilt tests (HUTs) were included. SctO2 at rest and during HUT were compared between POTS and controls. The relation between SctO2, systolic blood pressure (SBP), and heart rate (HR) during HUT was linearly assessed. SctO2 values were related to dizziness or syncope during HUT. The minimum SctO2-value during HUT was lower (65.4 ± 5.6 vs. 68.2 ± 4.2%, P = 0.023) and changes in SctO2 from supine to minimum HUT value were more pronounced in POTS patients (-5.7 ± 2.9% vs. -4.3 ± 2.1%, P = 0.028). Decrease in SBP from supine to minimum HUT value (P = 0.004) and increase in HR from supine to HUT value at 3 min (P = 0.022) correlated with more pronounced SctO2 decrease in POTS but not controls. SctO2 did not predict syncope or dizziness during HUT. Postural orthostatic tachycardia syndrome patients have lower cerebral tissue saturation during orthostatic provocation compared with those subjects having normal haemodynamic response to tilt. Orthostatic decrease in cerebral saturation only weakly correlates with HR increase and does not predict vasovagal reflex in POTS. Other hitherto unknown factors may affect cerebral tissue saturation in POTS.

Background Previous studies have demonstrated that functional autoantibodies to adrenergic receptors may be involved in the pathogenesis of postural tachycardia syndrome. The objective of this study was to examine the impact of these autoantibodies on cardiovascular responses to postural changes and adrenergic orthosteric ligand infusions in immunized rabbits. Methods and Results Eight New Zealand white rabbits were coimmunized with peptides from the α1-adrenergic receptor and β1-adrenergic receptor (β1AR). Tilt test and separate adrenergic agonist infusion studies were performed on conscious animals before and after immunization and subsequent treatment with epitope-mimetic peptide inhibitors. At 6 weeks after immunization, there was a greater percent increase in heart rate upon tilting compared with preimmune baseline. No significant difference in blood pressure response to tilting was observed. The heart rate response to infusion of the β-adrenoceptor agonist isoproterenol was significantly enhanced in immunized animals, suggesting a positive allosteric effect of β1AR antibodies. In contrast, the blood pressure response to infusion of the α1-adrenergic receptor agonist phenylephrine was attenuated in immunized animals, indicating a negative allosteric effect of α1-adrenergic receptor antibodies. Injections of antibody-neutralizing peptides suppressed the postural tachycardia and reversed the altered heart rate and blood pressure responses to orthosteric ligand infusions in immunized animals at 6 and 30 weeks. Antibody production and suppression were confirmed with in vitro bioassays. Conclusions The differential allosteric effect of α1-adrenergic receptor and β1AR autoantibodies would lead to a hyperadrenergic state and overstimulation of cardiac β1AR. These data support evidence for an autoimmune basis for postural tachycardia syndrome.

See Article Li et al.

Dysautonomia and headache are 2 common diagnoses within pediatric neurology; in the case of dysautonomia, a lack of consideration may lead to misdiagnosis. Despite being common conditions, there is a lot to learn about each individually as well as collectively. Many of the symptoms between headache and dysautonomia patients overlap making the diagnosis difficult. Migraine patients often exhibit symptoms of dysautonomia, namely postural orthostatic tachycardia syndrome (POTS); yet these symptoms are overlooked or lumped in as a part of their migraine diagnosis. The distinction or coexistence between dysautonomia and headache is identified through a thorough history, a full exam, and an open mind. This is crucial for the treatment and outcomes of these patients. Struggles arise when critical treatment differences are overlooked because dysautonomia is not considered. In this review, we will look at the epidemiology of dysautonomia and headache with focus on POTS and migraine. We will then compare the clinical features of both conditions as well as some hypothesized pathophysiology overlaps. We will conclude by summarizing the diagnostic approach and multitiered treatment options for POTS and migraine.

The risk factors and associated conditions of median arcuate ligament syndrome (MALS) have not been well characterized in the literature. In this study, we aim to investigate the presentation and outcomes of MALS patients with an emphasis on the prevalence of other uncommon disorders. To this end, data of patients with MALS who underwent surgery between 2013 and 2018 were collected and compiled into a retrospective database and analyzed. Eleven patients were identified. Seven of these eleven patients underwent diagnostics to evaluate gastric emptying. Five of these seven patients (71.4%) had radiographic evidence of delayed gastric emptying. Four of the eleven patients (36.4%) were found to have anatomic abnormalities of their visceral vasculature. Two of the eleven patients (18.2%) were found to have connective tissue disorders, both with Ehlers-Danlos syndrome. Three of the eleven (27.3%) had a diagnosis of postural orthostatic tachycardia syndrome. This is the first case series reporting on an association between MALS and delayed gastric emptying. We also explored the relationship between MALS and visceral vascular abnormalities, Ehlers-Danlos syndrome, and postural orthostatic tachycardia syndrome. It is notable that these conditions are more prevalent in the MALS population than in the general population, suggesting a possible pathophysiologic relationship.

Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous autonomic disorder characterised by orthostatic intolerance and a rise in heart rate by at least 30 bpm or an absolute heart rate value of at least 120 bpm within 10 min of standing or during a tilt table test. Overwhelmingly, POTS affects young Caucasian women, which can lead physicians to miss the diagnosis in men or non-white patients. We describe a case of 29-year-old African-American man who developed lightheadedness, generalised weakness, tachycardia and palpitations and was subsequently diagnosed with POTS. We review its clinical features, differential diagnosis, pathophysiology and treatment options. We also emphasise that POTS should be considered as a differential diagnosis in any patient presenting with typical clinical features, who may not be in the usual demographics of the disorder.

Background The etiology of postural orthostatic tachycardia syndrome (POTS) is yet to be established. The disorder is often misdiagnosed as chronic anxiety or a panic disorder because the autonomic failure in these patients is not severe. A growing body of evidence suggests that POTS may be an autoimmune disorder. Antinuclear antibodies and elevations of ganglionic, adrenergic, and muscarinic acetylcholine receptor antibodies have all been reported. Methods and Results We collected detailed clinical symptoms of 55 patients diagnosed with POTS. We also evaluated serum levels of autoantibodies against 4 subtypes of G-protein coupled adrenergic receptors and 5 subtypes of G-protein coupled muscarinic acetylcholine receptors by ELISA. Our patients had a multitude of comorbidities, were predominantly young females, and reported viral-like symptoms preceding episodes of syncope. We detected a significant number of patients with elevated levels of autoantibodies against the adrenergic alpha 1 receptor (89%) and against the muscarinic acetylcholine M receptor (53%). Surprisingly, elevations of muscarinic receptor autoantibodies appeared to be dependent upon elevation of autoantibodies against the A adrenergic receptor! Four patients had elevations of G-protein coupled autoantibodies against all 9 receptor subtypes measured in our study. Five POTS patients had no elevation of any autoantibody; similarly, controls were also negative for autoantibody elevations. There was a weak correlation of clinical symptom severity with G-protein coupled autoantibodies. Conclusions Our observations provide further evidence that, in most cases, POTS patients have at least 1 elevated G-protein coupled adrenergic autoantibody and, in some instances, both adrenergic and muscarinic autoantibodies, supporting the hypothesis that POTS may be an autoimmune disorder.

Postural tachycardia syndrome (POTS) can cause orthostatic headache. However, it is difficult to differentiate POTS from spontaneous intracranial hypotension (SIH) caused by cerebrospinal fluid (CSF) leaks. We herein report a 53-year-old woman who presented with SIH associated with POTS. A cervicothoracic and lumbar epidural blood patch rapidly improved not only the headache but also the orthostatic tachycardia, suggesting POTS secondary to SIH. This case suggests that a CSF leak can cause secondary POTS. Therefore, POTS should be considered in patients with orthostatic headaches, even in the presence of a CSF leak.

Hypermobility spectrum disorder (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) can cause widespread or chronic pain, fatigue, and proprioceptive and coordination deficits resulting in functional restrictions. These conditions are common and often unrecognized, and patients are likely to present in physical therapy for musculoskeletal injuries, pain, or coordination deficits. Although physical therapy is considered central to managing these conditions, many patients report pain and iatrogenic injuries due to inappropriate interventions. The diagnostic classification for these conditions was revised in 2017 to supersede previous diagnostic categories of Joint Hypermobility Syndrome and Ehlers-Danlos Syndrome-hypermobility type/type III. It is now known that these conditions affect multiple body systems and not just joints and that patients require a holistic approach. This Perspective article will describe the 2017 diagnostic classification system, clinical presentation, examination, evaluation, and management of patients with HSD/hEDS. Both adult and pediatric cases are presented to illustrate the patient management concepts discussed. This knowledge can lead to more effective management of this patient population.

The average adult stands approximately 50-60 times per day. Cardiovascular responses evoked during the first 3 min of active standing provide a simple means to clinically assess short-term neural and cardiovascular function across the lifespan. Clinically, this response is used to identify the haemodynamic correlates of patient symptoms and attributable causes of (pre-)syncope, and to detect autonomic dysfunction, variants of orthostatic hypotension, postural orthostatic tachycardia syndrome and orthostatic hypertension. This paper provides a set of experience/expertise-based recommendations detailing current state-of-the-art measurement and analysis approaches for the active stand test, focusing on beat-to-beat BP technologies. This information is targeted at those interested in performing and interpreting the active stand test to current international standards. This paper presents a practical step-by-step guide on (1) how to perform active stand measurements using beat-to-beat continuous blood pressure measurement technologies, (2) how to conduct an analysis of the active stand response and (3) how to identify the spectrum of abnormal blood pressure and heart rate responses which are of clinical interest. Impairments in neurocardiovascular control are an attributable cause of falls and syncope across the lifespan. The simple active stand test provides the clinician with a powerful tool for assessing individuals at risk of such common disorders. However, its simplicity belies the complexity of its interpretation. Care must therefore be taken in administering and interpreting the test in order to maximise its clinical benefit and minimise its misinterpretation.

Anterograde and retrograde tract tracing were combined with neurotransmitter and modulator immunolabeling to identify the chemical anatomy of vestibular nuclear neurons with direct projections to the solitary nucleus in rats. Direct, sparsely branched but highly varicose axonal projections from neurons in the caudal vestibular nuclei to the solitary nucleus were observed. The vestibular neurons giving rise to these projections were predominantly located in ipsilateral medial vestibular nucleus. The cell bodies were intensely glutamate immunofluorescent, and their axonal processes contained vesicular glutamate transporter 2, supporting the interpretation that the cells utilize glutamate for neurotransmission. The glutamate-immunofluorescent, retrogradely filled vestibular cells also contained the neuromodulator imidazoleacetic acid ribotide, which is an endogenous CNS ligand that participates in blood pressure regulation. The vestibulo-solitary neurons were encapsulated by axo-somatic GABAergic terminals, suggesting that they are under tight inhibitory control. The results establish a chemoanatomical basis for transient vestibular activation of the output pathways from the caudal and intermediate regions of the solitary nucleus. In this way, changes in static head position and movement of the head in space may directly influence heart rate, blood pressure, respiration, as well as gastrointestinal motility. This would provide one anatomical explanation for the synchronous heart rate and blood pressure responses observed after peripheral vestibular activation, as well as disorders ranging from neurogenic orthostatic hypotension, postural orthostatic tachycardia syndrome, and vasovagal syncope to the nausea and vomiting associated with motion sickness. Vestibular neurons with direct projections to the solitary nucleus utilize glutamate for neurotransmission, modulated by imidazoleacetic acid ribotide. This is the first direct demonstration of the chemical neuroanatomy of the vestibulo-solitary pathway.

Patients with postural tachycardia syndrome (POTS) often have gastrointestinal (GI) symptoms. Occasionally, these symptoms can be so severe that nonoral nutrition/hydration support (NONHS), including intravenous fluids (IVFs), enteral nutrition (EN), and parenteral nutrition (PN), becomes necessary. This is a retrospective cohort study of adult patients diagnosed with POTS at the Mayo Clinic Arizona from January 2010 to January 2017 with a minimum of 6 months of follow up. Demographic information, symptomatology, medications, GI testing, autonomic and autoantibody testing, and healthcare utilization data were abstracted from the electronic medical record. Three-hundred thirty-two patients with POTS were included, of which 32 required NONHS. Patients receiving NONHS were more likely to be female; have lower body mass index; have GI symptoms including nausea, vomiting, diarrhea, and constipation; have abdominal pain; use opiates; have delayed gastric emptying; see more specialists; and be seen in an emergency room or be hospitalized for symptoms. Of these patients, 21 (66%) required IVF, 19 (59%) required EN, and 9 (28%) required PN. Six (19%) patients required all 3 NONHS modalities at some point during their follow-up period. NONHS may be required in a subset of patients with POTS. Those receiving NONHS have more severe symptoms and abnormal GI motility and autonomic testing and exhibit greater healthcare utilization. Management of these patients is complex and challenging and requires a multidisciplinary approach. Further prospective studies are needed to identify optimal management strategies.

Upright tilt table testing has been used to test for vasovagal syncope (VVS) but can result in "false positives" in which tilt-induced fainting (tilt+) occurs in the absence of real-world fainting. Tilt+ occurs in healthy volunteers and in patients with postural tachycardia syndrome (POTS) and show enhanced susceptibility to orthostatic hypotension. We hypothesized that the mechanisms for hypotensive susceptibility differs between tilt+ healthy volunteers (Control-Faint (N = 12)), tilt+ POTS patients (POTS-Faint (N = 12)) and a non-fainter control group of (Control-noFaint) (N = 10). Subjects were studied supine and during 70° upright tilt while blood pressure (BP), cardiac output (CO), and systemic vascular resistance (SVR), were measured continuously. Impedance plethysmography estimated regional blood volumes, flows, and vascular resistance. Heart rate was increased while central blood volume was decreased in both Faint groups. CO increased in Control-Faint because of reduced splanchnic vascular resistance; splanchnic pooling was similar to Control-noFaint. Splanchnic blood flow in POTS-Faint decreased and resistance increased similar to Control-noFaint but splanchnic blood volume was markedly increased. Decreased SVR and splanchnic arterial vasoconstriction is the mechanism for faint in Control-Faint. Decreased CO caused by enhanced splanchnic pooling is the mechanism for faint in POTS-Faint. We propose that intrahepatic resistance is increased in POTS-Faint resulting in pooling and that both intrahepatic resistance and splanchnic arterial vasoconstriction are reduced in Control-Faint resulting in increased splanchnic blood flow and reduced splanchnic resistance.

The ideal treatment of Inappropriate Sinus Tachycardia (IST) and Postural Orthostatic Tachycardia Syndrome (POTS) still needs to be defined. Medical treatment yields suboptimal results, endocardial ablation of the sinus node (SN) may risk phrenic nerve damage and open heart surgery may be accompanied by unjustified invasive risks. We describe our first experience of 50 consecutive patients (41 females, 22.83 ± 3.91 years) having undergone a novel hybrid thoracoscopic ablation for drug resistant IST (n = 39, 78%) or POTS (n = 11, 22%). The SN was identified with the help of 3D mapping. Surgery was performed through 3 (5 mm) ports from the right side. A minimally invasive approach with a radio frequency bipolar clamp was utilized to a new target sparing the SN region, to isolate the superior and the inferior caval veins, and a crista terminalis line was made. All lines were interconnected. Normal SR was restored in all patients at the end of the procedure. All patients discontinued medication during the follow-up. After a blanking period of 6 months all patients presented stable SR. At a mean of 28.4 ± 1.2 months, normal SN ruction and chronotropic response to exercise was present. In the 11 patients initially diagnosed with POTS, no syncope occurred. During the follow-up, pericarditis was the most common complication (39 patients; 78%) with complete resolution in all cases. In conclusions the preliminary results of our first experience with a SN sparing novel hybrid ablation of IST/POTS, using surgical thoracoscopic video-assisted epicardial ablation combined with concomitant endocardial 3D mapping may prove an efficient and safe therapeutic option in patients with symptomatic drug resistant IST and POTS. Importantly, in our study all patients had a complete resolution of the symptoms and restored normal SN activity.

Orthostatic intolerance (OI) is a significant problem for those with chronic fatigue syndrome (CFS). We aimed to characterize orthostatic intolerance in CFS and to study the effects of exercise on OI. CFS (n = 39) and control (n = 25) subjects had recumbent and standing symptoms assessed using the 20-point, anchored, ordinal Gracely Box Scale before and after submaximal exercise. The change in heart rate (ΔHR ≥ 30 bpm) identified Postural Orthostatic Tachycardia Syndrome (POTS) before and after exercise, and the transient, exercise-induced postural tachycardia Stress Test Activated Reversible Tachycardia (START) phenotype only after exercise. Dizziness and lightheadedness were found in 41% of recumbent CFS subjects and in 72% of standing CFS subjects. Orthostatic tachycardia did not account for OI symptoms in CFS. ROC analysis with a threshold ≥ 2/20 on the Gracely Box Scale stratified CFS subjects into three groups: No OI (symptoms < 2), Postural OI (only standing symptoms ≥ 2), and Persistent OI (recumbent and standing symptoms ≥ 2). Dizziness and Lightheadedness symptoms while recumbent are an underreported finding in CFS and should be measured when doing a clinical evaluation to diagnose orthostatic intolerance. POTS was found in 6 and START was found in 10 CFS subjects. Persistent OI had symptoms while recumbent and standing, highest symptom severity, and lability in symptoms after exercise. Trial registration The trial was registered at the following: https://clinicaltrials.gov/ct2/show/NCT03567811.

Cardiorespiratory fitness (CRF) and physical activity (PA) are associated with autonomic function, but their associations to orthostatic autonomic responses are unclear in epidemiological setting. We hypothesized that higher CRF and PA would associate with higher immediate vagal responses and lower incidence of adverse findings during orthostatic test. At age of 46, 787 men and 938 women without cardiorespiratory diseases and diabetes underwent an orthostatic test (3-minutes sitting, 3-minutes standing) with recording of RR intervals (RRi) and blood pressure (BP) by finger plethysmography. Acute responses of RRi (30:15 ratio) and BP were calculated. CRF was measured by a submaximal step test and daily amount of moderate-to-vigorous PA (MVPA) for 2 weeks by wrist-worn accelerometer. Lifelong PA was based on questionnaires at ages of 14, 31, and 46. High CRF was significantly associated with higher RRi 30:15 ratio (adjusted standardized β = 0.17, P < 0.001) and milder acute decrease of systolic BP while standing (β = 0.10, P = 0.001), while MVPA was not (β = 0.04 for RRi 30:15 ratio and β = 0.05 for systolic BP acute response). High lifelong PA was significantly associated with higher RRi 30:15 ratio (β = 0.08, P = 0.002) but not with acute systolic BP response. Those in the lowest tertile of CRF had 9.2-fold risk (P = 0.002) of having postural orthostatic tachycardia syndrome compared to more fit. Cardiorespiratory fitness and lifelong physical activity, but not current physical activity, were independently associated with higher cardiac vagal response to orthostasis. The present results underscore the importance fitness and lifelong physical activity in prevention of abnormal autonomic function and related cardiovascular risk.

Adolescents and young adults (AYAs) with postural orthostatic tachycardia syndrome (POTS) commonly report cognitive difficulties, though there is limited information regarding the objective measurement of neurocognitive deficits in this population. This study described the rates of subjectively experienced and objectively measured neurocognitive difficulties and explored effects of medications on neurocognitive functioning among AYAs with POTS admitted to an intensive outpatient pain rehabilitation program. Participants in a pain rehabilitation program diagnosed with POTS (N = 96; ages 12-22) were included in the study. Medical characteristics, reported cognitive complaints, and neurocognitive assessment results were collected through retrospective medical record review. We calculated descriptive statistics and Pearson's χ2 or Fisher's exact tests, where appropriate. While 96% of this sample reported subjective cognitive complaints, as a group, they performed in the Average range on standardized measures of intellectual functioning, attention, and memory. The majority did not demonstrate any normative (73%) or relative (54%) weaknesses in attention or memory. Those prescribed an antiepileptic (n = 19) were less likely to have visual-spatial memory weaknesses but more likely to have attention weaknesses. Despite a high frequency of reported cognitive difficulties, most AYAs with POTS did not demonstrate neurocognitive impairment on standardized, one-on-one assessment. Suggestions for further study of biopsychosocial contributors to neurocognitive difficulties and for clinical use of neurocognitive assessments in this population were provided.

Mast cell activation syndrome (MCAS) is a complex disorder hallmarked by chronic multisystem inflammatory, allergic and growth dystrophic phenomena caused by inappropriate mast cell activation. MCAS has been estimated to affect as many as 17% of the population with a severity ranging from mild to life-threatening. MCAS patients are more sensitive than the average person to chemicals in the environment, including the nondrug ("inactive") ingredients (excipients) in medications and supplements. Excipient reactivity may explain unusual side effects to medications health professionals often find puzzling, such as the patient who appears intolerant of prednisone, acetaminophen, levothyroxine, or a vitamin. We present a series of patients with MCAS to illustrate important points regarding excipient reactivity which may be useful in everyday practice.

The diagnosis of neuropathic postural tachycardia syndrome (POTS) requires research techniques not available clinically. We hypothesized that these patients will have impaired vagal and sympathetic cardiovascular control that can be characterized with clinical autonomic tests. We included 12 POTS patients with possible neuropathic subtype because of normal plasma norepinephrine and no increase in upright blood pressure. We compared them to 10 healthy subjects. We assessed hemodynamics, heart rate and blood pressure variability, baroreflex sensitivity, raw and integrated muscle sympathetic nerve activity, and blood volume. To understand the vagal/sympathetic control, we dissected the phase 2 of Valsalva maneuver (VM) into early (VM2e) and late (VM2l). POTS' upright heart rate increased 43±3 bpm. Patients had normal plasma volume but reduced red blood cell volume (1.29 L versus predicted normal values 1.58 L; P=0.02). Vagal indices of heart rate variability, HF (430±130 versus 1680±900; P=0.04), PNN50, and root mean squared of successive differences were lower in POTS. Patients showed a decrease in vagal baroreflex sensitivity (VM2e; P=0.04). In POTS, integrated muscle sympathetic nerve activity was lower at rest (12±1.5 versus 20±2 burst/min; P=0.004) and raw muscle sympathetic nerve activity spike analysis showed blunted responses during VM2e, despite a greater drop in systolic blood pressure (34±5 in POTS and 14±6 mm Hg in controls; P=0.01). This cohort of POTS patients enriched for possible neuropathic subtype had lower resting muscle sympathetic nerve activity, impaired vagal cardiac control, and exaggerated drop in blood pressure in response to VM and a delay in the sympathetic cardiovascular responsiveness during hypotensive challenge.

Though reduced cardiovagal modulation accompanies adult IBS, adolescents with functional gastrointestinal disorders (FGID) have not been studied. We aim to investigate whether adolescents with FGID have reduced cardiovagal modulation. After 10-minute supine rest, we recorded ECG for 5-minute supine and 5-minute standing without support in healthy and FGID-affected adolescents. After analysis with Kubios 2.2 for high-frequency (hf) and low-frequency (lf) heart rate variability (HRV), Wilcoxon signed-ranks test compared individual paired supine and standing HRV data, while Kruskal-Wallis and Mann-Whitney U tests compared HRV across groups. A total of 50 FGID subjects (90% females; median age 17 years [range 11-21]) and 22 healthy comparison group (HC) (59% females; median age 14 years [range 10-18]) participated. Both absolute and relative supine hfHRV exceeded standing in both groups. Absolute supine lfHRV was higher than standing in FGID patients and not in HCs, while relative supine lfHRV power was actually lower in both groups. Compared to HC, FGID group showed significantly lower absolute HRV, while relative HRV did not differ between groups. Cardiovagal modulation is lower in adolescents with FGID. This difference impacts these subjects significantly. Whether this finding reflects a cause or a consequence of FGID is unknown.

Postural tachycardia syndrome (POTS) is a disorder of the autonomic nervous system with many possible causes, characterized by an unexplained increase in heartbeat without change in blood pressure upon standing. Associated cardiac and noncardiac symptoms can severely affect quality of life. Therapy, using a combined approach of diet and lifestyle changes, plus judicious use of medications if needed, can usually improve symptoms and function.

BackgroundSuspected adverse events (AE) after human papillomavirus (HPV) vaccines include postural orthostatic tachycardia syndrome (POTS), chronic fatigue syndrome (CFS), complex regional pain syndrome (CRPS) and symptoms including headache and orthostatic intolerance.AimWe aimed to identify phenotypes of AEs after HPV vaccination, defined as patterns of AE terms (signs, symptoms, diagnoses), and to evaluate if identified phenotypes reflected previously suspected symptomatology or heightened public concerns over HPV vaccine safety since 1 January 2015.MethodsWe conducted a retrospective observational study using latent class cluster analysis of all serious AE reports (n = 963) reported by females residing in Denmark between September 2009 and August 2017. Resulting clusters were characterised according to AE terms associated with POTS, CFS and CRPS before (September 2009-December 2014) and during (January 2015-August 2017) a time of heightened media activity regarding HPV vaccines.ResultsFour clusters of AE reports were distinguished. The most common symptoms were fatigue, dizziness and headache but their frequency varied among clusters. The majority of reports in one cluster were submitted during a period of heightened media activity, including an anomalous spike in submissions in December 2015; a high proportion of these reports included the symptoms cognitive disorder (78%), abdominal pain (77%), dysuria (60%) and sleep disorder (60%).ConclusionsNon-specific symptoms including headache, fatigue and dizziness feature prominently in serious AE reports from females in Denmark. Our analysis identified a cluster of reports, likely media stimulated, with a focus on symptoms of CFS and POTS.

Associations between human leukocyte antigen (HLA) and postural orthostatic tachycardia syndrome (POTS) have not been investigated. We included patients diagnosed with POTS and showing orthostatic heart rate increases ≥ 50 during orthostatic vital sign measurement or experiencing syncope/near-syncope while standing (prominent POTS;  = 17). DQB1*06:09 was present in seven (41%) patients, a significantly higher percentage than in healthy Koreans (7%; odds ratio [OR] 8.7, 95% confidence interval [CI] 3.1-24.3, corrected  = 3.2 × 10) and epilepsy controls (8%; OR 7.9, 95% CI 2.7-23.5, corrected  = 3.2 × 10). Six (35.3%) carried the A*33:03-B*58:01-C*03:02-DRB1*13:02-DQB1*06:09 haplotype. The results signify an autoimmune etiology in prominent POTS.

Syncope is a sudden loss and gain of consciousness. Traditionally, it is caused by the abnormalities of neurological, cardiac or vasovagal systems. We present a case of a 19-year-old woman presenting with recurrent syncopal episodes with no apparent cause. Examination and investigations were unremarkable for any aetiology except positive tilt tests for postural orthostatic tachycardia syndrome. The purpose of this report is to make physicians aware of the unique presentation of this rare aetiology with recurrent syncopal episodes and the novel management approach.