Though a sizeable amount of data connects mast cell activity to the neurologic system, less is known about the true clinical implications of this relationship. Even less is understood about treatment strategies in those with both allergic and neurologic complaints. This is particularly true in postural orthostatic tachycardia syndrome (POTS), a common type of dysautonomia, where patients are burdened by symptoms of orthostatic cerebral hypoperfusion and several other comorbidities that are likely influenced by autonomic tone. Some patients describe characteristic allergic symptoms, in the absence of typical IgE mediated triggers, and also improvement with traditional mast cell directed medications. Further work is necessary to determine whether these anecdotal observations are valid. The answer to this question will likely be addressed as the mechanisms of POTS are better characterized, which may include a phenotype with distinct mast cell involvement.

Recent research has demonstrated that cardiovascular deconditioning (i.e., cardiac atrophy and hypovolemia) contributes significantly to the Postural Orthostatic Tachycardia Syndrome (POTS) and its functional disability. Therefore, physical reconditioning with exercise training and volume expansion via increased salt and fluid intake should be initiated early in the course of treatment for patients with POTS if possible. The use of horizontal exercise (e.g., rowing, swimming, recumbent bike, etc.) at the beginning is a critical strategy, allowing patients to exercise while avoiding the upright posture that elicits their POTS symptoms. As patients become increasingly fit, the duration and intensity of exercise should be progressively increased, and upright exercise can be gradually added as tolerated. Supervised training is preferable to maximize functional capacity. Other non-pharmacological interventions, which include: 1) chronic volume expansion via sleeping in the head-up position; 2) reduction in venous pooling during orthostasis by lower body compression garments extending at least to the xiphoid or with an abdominal binder; and 3) physical countermeasure maneuvers, such as squeezing a rubber ball, leg crossing, muscle pumping, squatting, negative-pressure breathing, etc., may also be effective in preventing orthostatic intolerance and managing acute clinical symptoms in POTS patients. However, randomized clinical trials are needed to evaluate the efficacies of these non-pharmacological treatments of POTS.

Primary headache syndromes and chronic pain syndromes are common in patients with postural tachycardia syndrome (POTS). There is overlap in potential mechanisms for migraine, chronic pain, and POTS symptomatology. Management of chronic pain and headaches in POTS requires a judicious use of pharmacotherapies that takes into account patient comorbidities and co-existing symptoms. Patient-centric, non-pharmacologic modalities include physical exercise, cognitive behavioral therapies, and treatment of sleep disorders.

There is growing interest in the role of autoimmunity in postural orthostatic tachycardia syndrome (POTS). In recent years, investigators have described an increased rate of co-morbid autoimmune disease, and the presence of several neural receptor autoantibodies and non-specific autoimmune markers in POTS. Case reports on the efficacy of immunotherapy in highly selected POTS patients continue to appear in the literature, while no prospective clinical trials have occurred to date. This article summarizes the current state of knowledge on the role of autoimmunity in POTS, the clinical implications of these findings, and prospects for future research.

Diagnosing and treating postural orthostatic tachycardia syndrome (POTS) can be a frustrating experience for patients and physicians alike. Experienced patient leaders solicited input from the large online POTS community to identify patient suggestions and concerns, with the goal of improving the patient-physician relationship and outcomes in POTS. This review article offers practical tips to improve POTS patient care and links to credible resources for your patients. The authors emphasize the urgent need for improved physician education, a tailored treatment approach, and expanded research efforts.

Postural Orthostatic Tachycardia Syndrome is most commonly seen in women of child bearing age, however little is known about its effects in pregnancy. A systematic review was conducted in March 2015 and updated in February 2018. Medline, Embase, PsychInfo, CINHAL, and the Cochrane Library were searched from database inception. The ClinicalTrials.gov site and bibliographies were searched. MeSH and Emtree headings and keywords included; Postural Orthostatic Tachycardia Syndrome, Postural Tachycardia Syndrome, and were combined with pregnancy and pregnancy related subject headings and keywords. Searches were limited to English. Eligible articles contained key words within the title and or abstract. Articles were excluded if Postural Orthostatic Tachycardia Syndrome was not pre-existing. Eleven articles were identified as eligible for inclusion. Studies were appraised using the PRISMA 2009 guidelines. The overall quality of evidence was poor using the NHMRC Evidence Grading Matrix, which was attributed to small sample sizes and mostly observational studies, emphasizing the need for future high quality research. Findings in this review must be used with caution due to the poor quality of the literature available. Postural Orthostatic Tachycardia Syndrome should not be a contraindication to pregnancy. Symptom course is variable during pregnancy and the post-partum period. Continuing pre-conception medication may help symptoms, with no significant risks reported. Obstetric complications, not Postural Orthostatic Tachycardia Syndrome, should dictate mode of delivery. Postural Orthostatic Tachycardia Syndrome did not appear to affect the rate of adverse events. These results are important in determining appropriate management and care in this population.

Postural orthostatic tachycardia syndrome (POTS) affects up to 3,000,000 people in the United States, with at least one-third of them developing POTS before the age of 18. POTS as a disorder is similar in adult and pediatric populations, but there are factors specific to pediatric patients that affect how it presents and how it is experienced that make pediatric POTS different. This review discusses the both the similarities in this population to their adult counterparts and the unique challenges faced by pediatric POTS patients, including management of schooling and education as well as the complex interactions between these pediatric patients and their parents.

Fatigue is common in POTS, and patients often report unrefreshing sleep. These symptoms are directly correlated with a reduced quality of life, however the treatment of sleep disorders in this population remains a challenge. This article will review the current literature on the prevalence of sleep disorders in POTS, their association with the underlying pathophysiology of POTS, and current treatment paradigms.

Postural tachycardia syndrome (POTS) is a disorder characterized by the presence of orthostatic symptoms (including lightheadedness, palpitations, nausea, dyspnea, and tremulousness) as well as excessive upright tachycardia. POTS predominantly affects women of childbearing age. Treating POTS involves a multi-faceted approach using non-pharmacological and pharmacological interventions. There are no pharmacological treatments that are currently United States Food and Drug Administration (FDA) approved for POTS due to lack of randomized controlled trials. Yet, several medications can improve POTS symptoms and are supported by small prospective studies or retrospective case series. Drugs that are most commonly used for POTS target the following mechanisms 1) blood volume expansion, 2) reduction of heart rate, 3) peripheral vasoconstriction and 4) sympatholysis. Pharmacological approaches can also be used to target specific symptoms including "brain fog," fatigue, sleep, and depression. This review outlines pharmacological approaches for treating POTS and summarizes evidence supporting each treatment approach.

The diagnostic evaluation of a patient with suspected postural tachycardia syndrome (POTS) requires a thoughtful diagnostic approach utilizing a careful clinical history and examination, laboratory, and autonomic testing. This article outlines the importance of a thorough history in identifying mechanism of symptom onset, clinical features, associated clinical conditions or disorders, and factors that may result in symptom exacerbation. The clinical examination involves an assessment of pupillary responses, an evaluation for sudomotor and vasomotor signs, and an assessment for joint hypermobility. Laboratory testing helps to exclude mimics of autonomic dysfunction, recognize conditions that may exacerbate symptoms, and to identify conditions that may cause or be associated with autonomic nervous system disease. The purpose of autonomic testing is to confirm a POTS diagnosis, exclude other causes of orthostatic intolerance, and may provide for characterization of POTS into neuropathic and hyperadrenergic subtypes. Other diagnostic studies, such as epidermal skin punch biopsy, exercise testing, radiographic studies, sleep studies, gastrointestinal motility studies, and urodynamic studies should be considered when clinically appropriate.

Postural tachycardia syndrome (POTS) is one of the most common forms of chronic orthostatic intolerance. In addition to orthostatic symptoms, many POTS patients report incapacitating cognitive dysfunction or "brain fog" even while lying down or seated. Consistent with these subjective reports, there is accruing objective evidence of specific cognitive difficulties in POTS, with studies showing mild to moderate cognitive impairment using standardized neuropsychological assessment batteries. The precise profile of cognitive dysfunction in POTS patients has been shown to vary among these studies potentially due to the neuropsychological tests used, postural position, comorbidities and length of illness, inclusion of adolescent versus adult patients, and sites of recruitment. The extent of the impact that this cognitive challenge has in patients justifies ongoing investigation and research into lifestyle and pharmacological treatments. Psychologically, patients face challenges congruent with many chronic illnesses, perhaps especially early in adjusting to the condition. POTS patients often exhibit mild to moderate depression symptoms as well as symptoms of anxiety disorders. Since even low levels of anxiety can exacerbate symptoms, and a high number of patients experience sub-clinical low mood and sleep disturbances, there is a likely role for psychotherapy in helping control adjustment-related issues, and possibly aberrant physiology, in POTS.

Postural Tachycardia Syndrome (POTS) is a multi-system disorder that can be associated with significant functional disability. Likely due to the multi-system nature of the disorder, it can be difficult for physicians caring for these patients with POTS to know enough about the management of problems that fall within so many different specialties. This special issue was written for these clinicians and their patients. We have brought together experts on POTS with different backgrounds to share their approach to many of the medical issues that confront patients with POTS. The result is this special POTS Issue of Autonomic Neurosciences that can serve as a "User's Guide to POTS".

Postural tachycardia syndrome (POTS) is a heterogeneous clinical syndrome that has gained increasing interest over the past few decades due to its increasing prevalence and clinical impact on health-related quality of life. POTS is clinically characterized by sustained excessive tachycardia upon standing that occurs in the absence of significant orthostatic hypotension and other medical conditions and or medications, and with chronic symptoms of orthostatic intolerance. POTS represents one of the most common presentations of syncope and presyncope secondary to autonomic dysfunction in emergency rooms and in cardiology, neurology, and primary care clinics. The most sensitive method to detect POTS is a detailed medical history, physical examination with orthostatic vital signs or brief tilt table test, and a resting 12-lead electrocardiogram. Additional diagnostic testing may be warranted in selected patients based on clinical signs. While the precise etiology remains unknown, the orthostatic tachycardia in POTS is thought to reflect convergence of multiple pathophysiological processes, as a final common pathway. Based on this, POTS is often described as a clinical syndrome consisting of multiple heterogeneous disorders, with several underlying pathophysiological processes proposed in the literature including partial sympathetic neuropathy, hyperadrenergic state, hypovolemia, mast cell activation, deconditioning, and immune-mediated. These clinical features often overlap, however, making it difficult to categorize individual patients. Importantly, POTS is not associated with mortality, with many patients improving to some degree over time after diagnosis and proper treatment. This review will outline the current understanding of diagnosis, pathophysiology, and prognosis in POTS.

Fatigue is a significant symptom that is frequently reported by those with postural tachycardia syndrome (PoTS). There are a variety of reasons why those with PoTS might experience fatigue and as a consequence an individualised approach to management is most appropriate. In this chapter we will examine the prevalence of fatigue in those with PoTS, its overlap with conditions such as chronic fatigue syndrome and describe a clinical approach to the management of fatigue in those with PoTS.

To review the association between orthostatic intolerance syndromes and both joint hypermobility and Ehlers-Danlos syndrome, and to propose reasons for identifying hereditary connective tissue disorders in those with orthostatic intolerance in the context of both clinical care and research. We searched the published peer-reviewed medical literature for papers reporting an association between joint hypermobility or Ehlers-Danlos syndrome and orthostatic intolerance. We identified 10 relevant papers. Although methodological variability between studies introduces some limitations, the published literature consistently identifies a significantly higher prevalence of orthostatic intolerance symptoms in patients with joint hypermobility or Ehlers-Danlos syndrome than in healthy controls, and a significantly higher prevalence of cardiovascular and autonomic abnormalities both at rest and during orthostatic challenge. Postural tachycardia syndrome is the most commonly recognized circulatory disorder. The severity of orthostatic symptoms in those with EDS correlates with impairments in quality of life. There is a strong association between several forms of cardiovascular dysfunction, most notably postural tachycardia syndrome, and joint hypermobility or Ehlers-Danlos syndrome. We propose that recognition of joint hypermobility and Ehlers-Danlos syndrome among those with orthostatic intolerance syndromes has the potential to improve clinical care and the validity of research findings.

Intensive pain rehabilitation programs are effective in increasing functioning for youth with chronic pain (CP). However, the utility of such programs for youth with CP and co-morbid postural orthostatic tachycardia syndrome (POTS) is rarely examined. In addition, studies examining mediators of treatment for CP are sparse. This paper compares treatment outcomes for youth with CP (n = 117) and youth with CP + POTS (n = 118). Additionally, depression and pain catastrophizing were tested as potential mediators of treatment effects. Significant treatment improvements were found for functional disability, depression, pain catastrophizing, and perceived pain intensity but with no differences between groups. Improvements in depressed mood, pain catastrophizing (helplessness subscale), and pain severity partially mediated functioning improvement. Pain severity was not a significant mediator in the CP + POTS group. We concluded that depression and pain catastrophizing, especially the helplessness domain, can impact functioning improvement in adolescents with CP and POTS and are particularly important to target in treatment.

Postural tachycardia syndrome (POTS) is a chronic condition characterized by symptoms of orthostatic intolerance. Pregnancy can cause different physiological changes in cardiovascular parameters, that could have greater impact on POTS patients. In this review, we discuss the management of POTS in the pregnant and obstetric settings.

This article reviews the case series reported from several countries describing patients with suspected severe side effects to the HPV vaccines. The described symptom clusters are remarkably similar and include disabling fatigue, headache, widespread pain, fainting, gastrointestinal dysmotility, limb weakness, memory impairment episodes of altered awareness, and abnormal movements. This constellation of symptoms and signs has been labeled with different diagnoses such as complex regional pain syndrome (CRPS), postural orthostatic tachycardia syndrome (POTS), small fiber neuropathy (SFN), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), or fibromyalgia. It is known that autoimmunity and autoantibodies are present in a subset of patients with CRPS, POTS, SFN, ME/CFS, and fibromyalgia. This article proposes that vaccine-triggered, immune-mediated autonomic dysfunction could lead to the development of de novo post-HPV vaccination syndrome possibly in genetically susceptible individuals. Being cognizant that a temporal relationship between vaccination and symptom onset does not necessarily equate to causality, mounting evidence of case series calls for well-designed case-control studies to determine the prevalence and possible causation between these symptom clusters and HPV vaccines. Since personalized medicine is gaining momentum, the use of adversomics and pharmacogenetics may eventually help identify individuals who are predisposed to HPV vaccine adverse events.

Several groups of investigators have described the presence of small fiber neuropathy in fibromyalgia patients. This writing discusses how this new finding could renovate fibromyalgia concept, diagnosis, and treatment. Predominant rheumatology thinking proposes fibromyalgia as a "centralized pain syndrome." An alternative hypothesis views fibromyalgia as a stress-related dysautonomia with neuropathic pain features. Dorsal root ganglia may be the key autonomic-nociceptive short-circuit sites. The recent recognition of small fiber neuropathy in a large subgroup of fibromyalgia patients reinforces the dysautonomia-neuropathic hypothesis and validates fibromyalgia pain. These new findings support fibromyalgia as a primarily neurological entity, nevertheless, rheumatologist will likely remain the best equipped specialist to diagnose fibromyalgia and differentiate it from other multi-symptomatic rheumatic syndromes. Skin biopsy and corneal confocal microscopy will probably become useful fibromyalgia diagnostic tests. Dorsal root ganglia sodium channel blockers are potential fibromyalgia analgesic medications. Subgroups of young girls with "autoimmune neuropathic fibromyalgia" may respond to immunoglobulin therapy. Multimodal intervention directed to regain autonomic nervous system resilience will likely remain the cornerstone for fibromyalgia therapy.

Syncope belongs to the transient loss of consciousness (TLOC), characterized by a rapid onset, short duration, and spontaneous complete recovery. It is common in children and adolescents, accounting for 1% to 2% of emergency department visits.Recurrent syncope can seriously affect children's physical and mental health, learning ability and quality of life and sometimes cardiac syncope even poses a risk of sudden death. The present guideline for the diagnosis and treatment of syncope in children and adolescents was developed for guiding a better clinical management of pediatric syncope. Based on the globally recent development and the evidence-based data in China, 2018 Chinese Pediatric Cardiology Society (CPCS) guideline for diagnosis and treatment of syncope in children and adolescents was jointly prepared by the Pediatric Cardiology Society, Chinese Pediatric Society, Chinese Medical Association (CMA)/Committee on Pediatric Syncope, Pediatricians Branch, Chinese Medical Doctor Association (CMDA)/Committee on Pediatric Cardiology, Chinese College of Cardiovascular Physicians, Chinese Medical Doctor Association (CMDA)/Pediatric Cardiology Society, Beijing Pediatric Society, Beijing Medical Association (BMA). The present guideline includes the underlying diseases of syncope in children and adolescents, the diagnostic procedures, methodology and clinical significance of standing test and head-up tilt test, the clinical diagnosis vasovagal syncope, postural orthostatic tachycardia syndrome, orthostatic hypotension and orthostatic hypertension, and the treatment of syncope as well as follow-up.

Usnic acid, as active dibenzofuran derivative, isolated and characterized from some lichen species. The aim of manuscript was to evaluate antioxidant, anticholinergic and antidiabetic potentials of usnic acid as an important natural product. Antioxidant profile of usnic acid determined by eight distinguishes bioanalytical antioxidant methods including 1,1-diphenyl-2-picrylhydrazyl (DPPH·), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS ), superoxide anion radical (O ) and N,N-dimethyl-p-phenylenediamine (DMPD ) scavenging activities, cupric ion (Cu), ferric ion (Fe) and Fe-TPTZ reducing abilities and ferrous ion (Fe) chelating activity. Usnic acid was found as potent DPPH· (IC: 49.50 μg/mL), DMPD (IC: 33.00 μg/mL), O (IC: 18.68 μg/mL), and ABTS (IC: 10.41 μg/mL) scavenging effects. Also, the inhibition effects of usnic acid were tested against some metabolic enzymes including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) linked to neurodegenerative diseases. Both enzymes play important roles in cholinergic transmission by hydrolyzing the neurotransmitter acetylcholine in cholinergic synapses, central nervous system, neuromuscular junctions and autonomic ganglia. Their inhibitors were used for clinical treatment of some neurodegenerative conditions including myasthenia gravis, Alzheimer's disease, apathy, glaucoma, postural tachycardia syndrome and dementia. Furthermore, usnic acid showed the potent inhibition profiles against AChE (IC: 1.273 nM) and BChE (IC: 0.239 nM) enzymes. The results clearly showed that usnic acid is an important natural product with antioxidant and anticholinergic potentials.

Postural tachycardia syndrome (POTS) is a severe health problem in children. Short-term β-blockers are recommended for pharmaceutical treatment. However, there have been contradictory data about its efficacy among pediatric patients. Eight studies comparing β-blockers to conventional treatments for children with POTS were selected, where 497 cases of pediatric POTS were included. The efficacy of β-blockers was evaluated using the effective rate, the change of symptom score, the change of heart rate difference and adverse events. The results were stated as relative ratio (RR) and mean difference (MD) with a 95% confidence interval (95% CI). A random-effects meta-analysis for the effective rate indicated that β-blockers were more effective in treating pediatric POTS than controlled treatment (79.5 vs. 57.3%, RR = 1.50, 95%CI: 1.15-1.96, < 0.05). A fixed-effects model analysis showed that β-blockers were more effective in lowering the symptom score and the heart rate increment during standing test than controlled treatment with a mean difference of 0.81 (95% CI: 0.44-1.18, < 0.05) and 3.78 (95% CI: 2.10-5.46, < 0.05), respectively. There were no reported severe adverse events in included studies. β-blockers are effective in treating POTS in children and adolescents, alleviating orthostatic intolerance, and improving hemodynamic abnormalities.

To improve the metoprolol therapeutic effectiveness, we aimed to explore whether baseline heart rate variability (HRV) indicators before metoprolol treatment were useful for predicting its efficacy for postural tachycardia syndrome (POTS). We recruited 45 children with POTS who received metoprolol and 17 healthy controls. All children underwent a standing test or basic head-up tilt test and 24-h dynamic electrocardiography before treatment. After 3 months of metoprolol, therapeutic responsiveness was evaluated. The usefulness of baseline HRV parameters in predicting the effectiveness of metoprolol was studied and the long-term cumulative symptom rate was analyzed. The baseline HRV frequency domain indicators for power, ultra-low frequency, very-low frequency, low frequency (LF), high frequency (HF), and total power (TP) as well as time domain indicators were significantly lower for responders than non-responders to metoprolol; however, low-frequency normalized units and LF/HF ratio were markedly greater for responders than non-responders. On series-parallel analysis, combined baseline triangular (TR) index ≤ 33.7 and standard deviation of all normal-to-normal intervals (SDNN) index ≤ 79.0 ms as cut-off values yielded sensitivity, specificity and accuracy of 85.3, 81.8, and 84.4%, respectively, to predict therapeutic responsiveness to metoprolol. On long-term follow-up, the cumulative symptom rate was significantly higher with TR index > 33.7 and SDNN index ≤ 79.0 ms, TR index ≤ 33.7 and SDNN index > 79.0 ms or TR index > 33.7 and SDNN index > 79.0 ms than TR index ≤ 33.7 and SDNN index ≤ 79.0 ms ( < 0.05). Combined TR index ≤ 33.7 and SDNN index ≤ 79.0 ms were useful preliminary measures to predict therapeutic response to metoprolol in pediatric POTS.

Postural orthostatic tachycardia syndrome is a disorder of the autonomic nervous system. Approximately 30% of patients experience orthostatic headaches. Orthostatic headaches also are a hallmark symptom in spontaneous intracranial hypotension. While the cause of orthostatic headaches in spontaneous intracranial hypotension can be linked to the cerebrospinal fluid loss at the spinal level and consecutively reduced intracranial pressure in the upright position, the cause of orthostatic headaches in postural orthostatic tachycardia syndrome still remains unknown. The present study examined orthostatic changes of intracranial pressure using dynamic ultrasound of the optic nerve and optic nerve sheath diameter in postural orthostatic tachycardia syndrome, spontaneous intracranial hypotension and healthy subjects. Data was obtained from postural orthostatic tachycardia syndrome patients with (n = 7) and without orthostatic headaches (n = 7), spontaneous intracranial hypotension patients (n = 5) and healthy subjects (n = 8). All participants underwent high-resolution transorbital ultrasound in the supine and upright position to assess optic nerve and optic nerve sheath diameter. Group differences were found in percentage deviations when changing position of optic nerve sheath diameter (p < 0.01), but not regarding the optic nerve diameter. Pairwise comparisons indicated differences in optic nerve sheath diameter only between spontaneous intracranial hypotension and the other groups. No differences were found between postural orthostatic tachycardia syndrome patients with and without orthostatic headaches. This study shows that the size of the optic nerve sheath diameter dynamically decreases during orthostatic stress in spontaneous intracranial hypotension, but not in postural orthostatic tachycardia syndrome with or without orthostatic headaches, which indicates different underlying causes.

Lin J, Zhao H, Ma L, Jiao F. Body mass index is decreased in children and adolescents with postural tachycardia syndrome. Turk J Pediatr 2019; 61: 52-58. Our intent was to explore the predictive value of body mass index (BMI) in differentiating between vasovagal syncope (VVS) and postural tachycardia syndrome (POTS) in children and adolescents. A total of 111 children and adolescents with POTS and 154 children and adolescents with VVS were included in our study. The control group included 82 healthy children and adolescents. Height and weight were measured in all participants. The headup tilt test was performed in participants in all groups (POTS, VVS, and control). BMI was significantly lower in children and adolescents with POTS (18.3±3.4) than in children and adolescents with VVS (20.3±4.2) and the control group (20.5±2.9). The receiver operating characteristic curve was performed to determine the predictive value of BMI differentiation between POTS and VVS and showed that a BMI of 19.30 was the cutoff value for the probability of distinction. However, the results (BMI of 19.30) produced unsatisfactory sensitivity (57.1%) and specificity (28.8%) rates of correctly discriminating between patients with POTS and patients with VVS. Children and adolescents with POTS have a lower BMI compared with healthy peers or children and adolescents with VVS.