Postural tachycardia syndrome (POTS) is one of the most frequent forms of chronic orthostatic intolerance in children and adolescents. The aim of the present study was to examine the influence of a genetic background on POTS. A total of 96 children and adolescents with orthostatic dysregulation were studied. The polymorphism of the G protein β3 subunit (GNB3) C825T and G protein α subunit (GNAS1) T131C of genes encoding components of the autonomic nervous system were determined and compared with circulatory responses to active standing. In the GNB3 gene C825T polymorphism, the CT and TT genotype had a significant lower supine heart rate and a larger increase of heart rate by standing than the CC, associated with evaluated power of the high-frequency component of heart rate variability. According to the criteria of the Japanese clinical guidelines, 48 children were diagnosed as POTS and 30 were as normal responder with somatoform disorder (SD). In GNB3 C825T polymorphism, the TT genotype was more frequently found in the POTS group (45.8%) than in the SD group (20.0%; P = 0.036) [corrected]. In the GNAS1 T393C, the genotype frequencies for the T393C polymorphisms of GNA1 did not differ significantly between the groups. The gene polymorphisms GNB3 C825T might be a risk factor for POTS through the enhanced vagal withdrawal of the heart in children and adolescents.

The symptom of fatigue is frequently described by patients attending the syncope unit with a wide range of conditions including vasovagal syncope and postural orthostatic tachycardia syndrome. It is possible that the presence of autonomic dysfunction provides the common pathogenetic mechanism linking neurally mediated hypotension and fatigue. Managing this debilitating symptom can often be challenging but, with a structured approach, immensely rewarding, and as a result improve how patients cope with their disease.

To define the neuropathology, clinical phenotype, autonomic physiology and differentiating features in individuals with neuropathic and non-neuropathic postural tachycardia syndrome (POTS). Twenty-four subjects with POTS and 10 healthy control subjects had skin biopsy analysis of intra-epidermal nerve fiber density (IENFD), quantitative sensory testing (QST) and autonomic testing. Subjects completed quality of life, fatigue and disability questionnaires. Subjects were divided into neuropathic and non-neuropathic POTS, defined by abnormal IENFD and abnormal small fiber and sudomotor function. Nine of 24 subjects had neuropathic POTS and had significantly lower resting and tilted heart rates; reduced parasympathetic function; and lower phase 4 valsalva maneuver overshoot compared with those with non-neuropathic POTS (P<0.05). Neuropathic POTS subjects also had less anxiety and depression and greater overall self-perceived health-related quality of life scores than non-neuropathic POTS subjects. A sub-group of POTS patients (cholinergic POTS) had abnormal proximal sudomotor function and symptoms that suggest gastrointestinal and genitourinary parasympathetic nervous system dysfunction. POTS subtypes may be distinguished using small fiber and autonomic structural and functional criteria. Patients with non-neuropathic POTS have greater anxiety, greater depression and lower health-related quality of life scores compared to those with neuropathic POTS. These findings suggest different pathophysiological processes underlie the postural tachycardia in neuropathic and non-neuropathic POTS patients. The findings have implications for the therapeutic interventions to treat this disorder.

Autonomic testing is used to define the role of the autonomic nervous system in diverse clinical and research settings. Because most of the autonomic nervous system is inaccessible to direct physiological testing, in the clinical setting the most widely used techniques entail the assessment of an end-organ response to a physiological provocation. The noninvasive measures of cardiovascular parasympathetic function involve the assessment of heart rate variability while the measures of cardiovascular sympathetic function assess the blood pressure response to physiological stimuli. Tilt-table testing, with or without pharmacological provocation, has become an important tool in the assessment of a predisposition to neurally mediated (vasovagal) syncope, the postural tachycardia syndrome, and orthostatic hypotension. Distal, postganglionic, sympathetic cholinergic (sudomotor) function may be evaluated by provoking axon reflex mediated sweating, e.g., the quantitative sudomotor axon reflex (QSART) or the quantitative direct and indirect axon reflex (QDIRT). The thermoregulatory sweat test provides a nonlocalizing measure of global pre- and postganglionic sudomotor function. Frequency domain analyses of heart rate and blood pressure variability, microneurography, and baroreflex assessment are currently research tools but may find a place in the clinical assessment of autonomic function in the future.

Postural orthostatic tachycardia syndrome (POTS), a heart rate (HR) rise with upright positioning, is dependent on autonomic influences. HR recovery (HR decrease after exercise cessation) is a measure of autonomic function. Characteristics of HR reduction during supine Recovery after head-up Tilt in POTS patients have not been elucidated. 113 subjects (mean age 41.7 years, 86 female), diagnosed with POTS on head-up Tilt were analyzed. HR's were recorded during baseline supine position, 70-degree Tilt, and 20 sec, 1 min and 2 min of supine Recovery. Percent HR reduction during Recovery was calculated. Baseline HR was 68.7±13.4 bpm. Maximum HR during Tilt was 109±16.9 bpm. Mean HR was 84.2±20 bpm at 20 sec, 78.5±18.9 bpm at 1-min, and 77.1±18.3 bpm at 2 min of Recovery. Younger age and slower baseline HR were associated with greater HR reductions at 20 sec (p=0.006, p=0.000, respectively). Younger age, slower baseline HR and less time to achieve POTS were associated with greater HR reductions at 1 min (p=0.025, p=0.000, p=0.000, respectively) and at 2 min (p=0.004, p=0.000, p=0.000, respectively). Gender and baseline blood pressures were not significant. In POTS patients, HR quickly decreases upon resuming supine position. Younger age, slower baseline HR and less time to achieve POTS were associated with greater HR reductions during supine Recovery. Further study is needed to determine mechanisms, as well as analyze differences in symptoms or prognosis.

Protocols for the assessment of postural tachycardia differ in both type of orthostatic challenge and test duration. We therefore compared heart rate (HR) and blood pressure responses during an active standing test (AST) and a head-up tilt test (HUT) in 34 patients with orthostatic intolerance and 31 asymptomatic subjects. A subset also performed 24-h ambulatory blood pressure monitoring (ABPM). HR responses were similar between AST and HUT both in asymptomatic and in orthostatic intolerant subjects. Specificity of HR increase ≥30 bpm for orthostatic intolerance was high (above 0.85) with both AST and HUT and was similar at 3 minutes and at 9 minutes. HR changes recorded during self-performed AST (in the context of 24-h ABPM) and circadian HR difference corresponded well to changes recorded during AST in the autonomic laboratory. We conclude that AST and HUT are comparable methods for the assessment of postural tachycardia, that 3-min and 9-min tests are appropriate, and that ABPM is a useful ancillary test in the assessment of orthostatic responses.

Chronic fatigue syndrome (CFS) is characterized by fatigue, sleep dysfunction, and cognitive deficits (Fukuda et al., 1994). Research surrounding cognitive functioning among patients with CFS has found difficulty with memory, attention, and information processing. A similar disorder, postural tachycardia syndrome (POTS), is characterized by increased heart rate, fatigue, and mental cloudiness (Raj et al., 2009). Potential implications of cognitive deficits for patients with CFS and/or POTS are discussed, including difficulties with school and/or employment. A few biological theories (i.e., kindling, impairments in the central nervous system, and difficulty with blood flow) have emerged as potential explanations for the cognitive deficits reported in both CFS and POTS Future research should continue to examine possible explanations for cognitive impairments in CFS and POTS, and ultimately use this information to try and reduce cognitive impairments for these patients.

Chronic Fatigue Syndrome (CFS) is defined as greater than 6 months of persistent fatigue that is experienced physically and cognitively. The cognitive symptoms are generally thought to be a mild cognitive impairment, but individuals with CFS subjectively describe them as "brain fog." The impairment is not fully understood and often is described as slow thinking, difficulty focusing, confusion, lack of concentration, forgetfulness, or a haziness in thought processes. Causes of "brain fog" and mild cognitive impairment have been investigated. Possible physiological correlates may be due to the effects of chronic orthostatic intolerance (OI) in the form of the Postural Tachycardia Syndrome (POTS) and decreases in cerebral blood flow (CBF). In addition, fMRI studies suggest that individuals with CFS may require increased cortical and subcortical brain activation to complete difficult mental tasks. Furthermore, neurocognitive testing in CFS has demonstrated deficits in speed and efficiency of information processing, attention, concentration, and working memory. The cognitive impairments are then perceived as an exaggerated mental fatigue. As a whole, this is experienced by those with CFS as "brain fog" and may be viewed as the interaction of physiological, cognitive, and perceptual factors. Thus, the cognitive symptoms of CFS may be due to altered CBF activation and regulation that are exacerbated by a stressor, such as orthostasis or a difficult mental task, resulting in the decreased ability to readily process information, which is then perceived as fatiguing and experienced as "brain fog." Future research looks to further explore these interactions, how they produce cognitive impairments, and explain the perception of "brain fog" from a mechanistic standpoint.

Neurocardiogenic syncope is known to be associated with autonomic nervous system dysfunction, although the mechanism has not been entirely elucidated. In this study, we sought to highlight the pathogenic role of the autonomic nervous system in neurocardiogenic syncope and to review the associated co-morbidities known to have a dysautonomic basis. Herein we discuss migraine, orthostatic hypotension, postural orthostatic tachycardia syndrome, endothelial dysfunction, chronic fatigue syndrome, and carotid sinus hypersensitivity with a focus on the pathogenic role of the autonomic nervous system and any consecutive clinical implications. Other conditions, such as pre-syncopal heart rate acceleration and/or instability and pre-syncopal breathing instability, which occur during a tilt test, are discussed in the same perspective.

The aim of this study was to determine if there is a difference in the frequency of postural orthostatic tachycardia syndrome (POTS) in patients with multiple sclerosis (MS) compared to patients with symptoms of orthostatic intolerance and with no evidence of MS or other neurological illness. We analyzed data gathered from 293 patients who underwent the head-up tilt table test protocol. Group 1 included prospectively analyzed 112 with MS and group 2 included retrospectively analyzed 181 patients who were evaluated because of symptoms of orthostatic intolerance, and with no evidence of MS or other neurological illness. If POTS was identified the head-up tilt table test was repeated and supine as well as standing serum epinephrine and norepinephrine were determined. POTS was identified in 39 patients: 21 (19%) in the MS group comparing to 18 (10%) in the non MS group (p=0.035). There was no difference between groups in the occurrence of POTS associated syncope (p=0.52). There was no difference between groups in the epinephrine or norepinephrine in supine and standing positions. While both standing epinephrine and norepinephrine levels were significantly higher compared to levels in the supine position in the non MS group, only standing norepinephrine levels were significantly higher in the MS group. The results of this study suggest that POTS is associated with MS.

POTS (postural tachycardia syndrome) is characterized by an increased heart rate (ΔHR) of ≥30 bpm (beats/min) with symptoms related to upright posture. Active stand (STAND) and passive head-up tilt (TILT) produce different physiological responses. We hypothesized these different responses would affect the ability of individuals to achieve the POTS HR increase criterion. Patients with POTS (n=15) and healthy controls (n=15) underwent 30 min of tilt and stand testing. ΔHR values were analysed at 5 min intervals. ROC (receiver operating characteristic) analysis was performed to determine optimal cut point values of ΔHR for both tilt and stand. Tilt produced larger ΔHR than stand for all 5 min intervals from 5 min (38±3 bpm compared with 33±3 bpm; P=0.03) to 30 min (51±3 bpm compared with 38±3 bpm; P<0.001). Sn (sensitivity) of the 30 bpm criterion was similar for all tests (TILT10=93%, STAND10=87%, TILT30=100%, and STAND30=93%). Sp (specificity) of the 30 bpm criterion was less at both 10 and 30 min for tilt (TILT10=40%, TILT30=20%) than stand (STAND10=67%, STAND30=53%). The optimal ΔHR to discriminate POTS at 10 min were 38 bpm (TILT) and 29 bpm (STAND), and at 30 min were 47 bpm (TILT) and 34 bpm (STAND). Orthostatic tachycardia was greater for tilt (with lower Sp for POTS diagnosis) than stand at 10 and 30 min. The 30 bpm ΔHR criterion is not suitable for 30 min tilt. Diagnosis of POTS should consider orthostatic intolerance criteria and not be based solely on orthostatic tachycardia regardless of test used.

Postural orthostatic tachycardia syndrome (POTS), estimated to affect 500,000 people in the United States alone, is a growing source of impairment and disability. Symptoms often consist of physical, cognitive, and psychological impairment. The symptoms are driven by fluctuations in cerebral blood flow. Cerebral perfusion is tightly controlled and linked to brain function as changes in posture can result in quick hemovascular regulation by the autonomic nervous system. Any delay in hemoregulation and cerebral blood flow can result in neurological symptoms. POTS is associated with chronic autonomic dysregulation, and people with POTS suffer differing degrees of cerebral hypoperfusion causing variability in symptoms. This article reviews the cases of two siblings (22 years old and 19 years old) who both suffer from POTS. They suffered physical symptoms along with difficulty organizing thoughts, sustaining attention, thinking quickly, multitasking, and recalling recent information, as well as depression and anxiety. These sisters have Full-Scale IQs (FSIQ) above average, yet they received academic accommodations and have ongoing cognitive dysfunction that prevents them from furthering their true potential. These cases illustrate the need for neuropsychologists and other treating providers to understand POTS, the related pathophysiology, and how cognitively debilitating POTS can be, even in the context of intact and high FSIQ scores.

The magnitude of increase in systolic blood pressure in response to the shift from supine to upright posture is considered to reflect the adequacy of orthostatic regulation. Orthostatic integrity is largely maintained by the interaction between the skeletal muscle pump, neurovascular compensation, neurohumoral effects, and cerebral blood flow regulation. Various physiological states and disease conditions may disrupt these mechanisms as seen in vasovagal syncope, dysautonomic orthostatic intolerance, and postural orthostatic tachycardia syndrome. Orthostatic hypotension (OH) and decreased cerebral blood flow are strongly related. Even subclinical OH has been associated to different degrees with impaired cognitive function, decreased effort, reduced motivation, increased hopelessness, and signs of attention-deficit hyperactivity disorder and dementia, diabetes mellitus, and Parkinson disease. Furthermore, subclinical levels of inadequate blood pressure regulation in response to orthostasis have been linked to increased depression and anxiety and intergenerational behavioral sequelae between mother and child. Identifying causes of subclinical and clinical OH is critical in improving quality of life for both children and older adults. A better understanding of the underlying causes responsible for the etiology of OH could lead to a rational design of novel effective therapeutic regimens for the treatment of this condition and associated comorbidities.

Chronic day-to-day symptoms of orthostatic intolerance are the most notable features of postural orthostatic tachycardia syndrome (POTS). However, we have encountered patients with such symptoms and excessive tachycardia but with no symptoms during the tilt-table test (TTT). We aimed to investigate whether POTS patients with chronic orthostatic intolerance always present orthostatic symptoms during the TTT and analyze the factors underlying symptom manifestation during this test. We retrospectively examined patients who presented with POTS at the Gyeongsang National University Hospital between 2008 and 2011. Diagnosis of POTS was based on chronic day-to-day orthostatic intolerance symptoms as well as excessive tachycardia during the TTT. The patients were divided two groups depending on the presentation of orthostatic symptoms during the TTT. Clinical data and the results of the TTT were compared between these groups. In 22 patients, 7 patients (31.8%) did not present orthostatic symptoms during the test. Diastolic blood pressure (BP) was significantly lower in the symptom-positive group. The head-up tilt resulted in a significant increase in diastolic BP in the symptom-negative group (P=0.04), while systolic BP had a tendency to decrease in the symptom-positive group (P=0.06). Significant patients with POTS did not present orthostatic symptoms during the TTT despite having chronic daily symptoms. This finding may be important for establishing definitive diagnostic criteria for pediatric POTS. Development of symptoms during TTT might be related to low diastolic BP and abnormal compensatory responses to orthostasis.

The aim of this study was to determine the prevalence of pathologic response to orthostatic challenge in patients with relapsing remitting multiple sclerosis (RRMS) and the difference of the response in patients in relapse and remission. We included 112 RRMS patients; group 1 included 53 patients in a relapse and group 2, 59 patients in remission. The head up tilt table test was used to provoke an orthostatic reaction. 71 (63%) patients (60.4% and 66% of relapse and remission subjects respectively) had a pathological response to orthostatic provocation. Syncope was found in 9 (17%) patients in group 1 compared to 22 (37.3%) in group 2 (p=0.014). Postural orthostatic tachycardia syndrome (POTS) was found in 17 (32%) patients in group 1 compared to 4 (6.8%) in group 2 (p=0.001). There was a significantly negative correlation between the Expanded Disability Status Scale (EDSS) and POTS (-0.201; p=0.034) and a positive correlation between the EDSS and syncope (0.190; p=0.044). The prevalence of distinct types of orthostatic autonomic dysfunction in different phases of RRMS seems to be in direct correlation with the EDSS. Furthermore, certain autonomic dysfunctions of orthostasis, more specifically syncope and POTS, tend to be increased in remission and relapse respectively.

Management of postural tachycardia syndrome is challenging. Although there is no cure for the condition, a combination of pharmacological management and lifestyle changes can improve patients' quality of life. Postural tachycardia syndrome is characterised by symptoms of orthostatic intolerance, including dizziness, fatigue, tiredness, syncope and presyncope. Associated tachycardia on standing is thought to be caused by dysfunction of the autonomic nervous system. This article provides an overview of postural tachycardia syndrome, including symptoms, diagnosis and management.

The objective is to study the role of nitric oxide (NO) on cardiovascular regulation in healthy subjects and postural tachycardia syndrome (POTS) patients. Reduced neuronal NO function, which could contribute to a hyperadrenergic state, and increased NO-induced vasodilation, which could contribute to orthostatic intolerance, have been reported in POTS. In protocol 1, 13 healthy volunteers (33 ± 3 years) underwent autonomic blockade with trimethaphan and were administered equipressor doses of Nω-monomethyl-L-arginine (L-NMMA, a NO synthase inhibitor) and phenylephrine to determine the direct chronotropic effects of NO (independent of baroreflex modulation). In protocol 2, we compared the effects of L-NMMA in 9 POTS patients (31 ± 3 years) and 14 healthy (32 ± 2 years) volunteers, during autonomic blockade. During autonomic blockade, L-NMMA and phenylephrine produced similar increases in systolic blood pressure (27 ± 2 versus 27 ± 3 mm Hg). Phenylephrine produced only minimal heart rate changes, whereas L-NMMA produced a modest, but significant, bradycardia (-0.8 ± 0.4 versus -4.8 ± 1.2 bpm; P=0.011). There were no differences between POTS and healthy volunteers in the systolic blood pressure increase (22 ± 2 and 28 ± 5 mm Hg) or heart rate decrease (-6 ± 2 and -4 ± 1 bpm for POTS and controls, respectively) produced by L-NMMA. In the absence of baroreflex buffering, inhibition of endogenous NO synthesis results in a significant bradycardia, reflecting direct tonic modulation of heart rate by NO in healthy individuals. We found no evidence of a primary alteration in NO function in POTS. If NO dysfunction plays a role in POTS, it is through its interaction with the autonomic nervous system.

Most patients who present to a cardiologist with syncope have vasovagal (reflex) syncope. A busy syncope practice often also sees patients with postural tachycardia syndrome, often presenting with severe recurrent presyncope. Recognition of this syncope confounder might be difficult without adequate knowledge of their presentation, and this can adversely affect optimal management. Postural tachycardia syndrome can often be differentiated from vasovagal syncope by its hemodynamic pattern during tilt table test and differing clinical characteristics. This article reviews the presentation of postural tachycardia syndrome and its putative pathophysiology and presents an approach to nonpharmacologic and pharmacologic management.

Inappropriate sinus tachycardia (IST) is a syndrome in which the sinus heart rate is inexplicably faster than expected and associated symptoms are present. The heart rate at rest, even in a supine position, can exceed 100 beats/min; minimal activity accelerates the rate rapidly and substantially. Patients with IST may require restriction from physical activity. Mechanisms responsible for IST are understood incompletely. It is important to distinguish IST from so-called appropriate sinus tachycardia and from postural orthostatic tachycardia syndrome, with which overlap may occur. Because the long-term outcome seems to be benign, treatment may be unnecessary or may be as simple as physical training. However, for patients with intolerable symptoms, therapeutic measures are warranted. Even at high doses, β-adrenergic blockers, the first-line therapy, often are ineffective; the same is true for most other medical therapies. In rare instances, catheter- or surgically- based right atrial or sinus node modification may be helpful, but even this is fraught with limited efficacy and potential complications. Overtreatment, in an attempt to reduce symptoms, can be difficult to avoid, but is discouraged.

Functional gastrointestinal disorders (FGIDs) are currently classified under the Rome criteria based on symptoms and absence of organic disease. Preliminary studies have shown that FGIDs are probably not restricted to the GI tract, but may represent a systemic disorder with comorbidities affecting other parts of the body, including migraine, fatigue, aches and pains, etc. The autonomic nervous system (ANS) provides the extrinsic control of GI motility, secretions, and even immune response. The role of the ANS in the development of FGIDs and comorbidities is still unclear. Limited data demonstrate orthostatic intolerance such as reflex syncope and postural tachycardia syndrome in a large subset of subjects with FGIDs. Some studies have found improvement in the GI symptoms with treatment of the orthostatic intolerance it produces. Prospective studies are needed to determine the chronology of the development of the comorbidities, the triggers that induce these syndromes, and effective treatments. This chapter aims to review current understanding of the role of the ANS in FGIDs.

Postural tachycardia syndrome is a chronic condition with frequent symptoms of orthostatic intolerance or sympathetic activation and excessive tachycardia while standing, without significant hypotension. Orthostatic symptoms include dizziness, lightheadedness, blurring of vision, near faints, weakness in legs, poor concentration, nausea, and headaches. Somatic symptoms include fatigue, sleep disorder, widespread pain, abdominal pain, and menstrual irregularities. Psychological problems may overlap with physical complaints. This review discusses the normal physiology of orthostatic change, different pathophysiological mechanisms of postural tachycardia syndrome, including hypovolemia, venous pooling, autonomic neuropathy, and hyperadrenergic responses. In addition, an outline for management tailored to the patient's clinical syndrome is presented, along with concluding thoughts on future research needs.

Vasovagal syncope is an acute manifestation of autonomic nervous system dysfunction. This type of syncope is often associated with other dysautonomic expressions such as migraine, gastroparesis, or postural tachycardia syndrome. Autonomic nervous system dysfunction has been proposed as a key element in the pathogenesis of fibromyalgia. The objectives of this study were to estimate the frequency of fibromyalgia in a sample of patients with vasovagal syncope and also to correlate the presence of syncope and fibromyalgia with different dysautonomic manifestations. We studied 50 consecutive patients with vasovagal syncope seen at the Syncope Unit of the National Cardiology Institute of Mexico between June 2009 and June 2012. All individuals filled out the Composite Autonomic Symptoms and Signs questionnaire and the Fibromyalgia Impact Questionnaire. All cases underwent a head-up tilt test. A rheumatologist examined all participants to assess the presence of fibromyalgia. The median age of the studied population was 21 years. Sixty-eight percent of participants were women. Eight cases (16%) had concomitant fibromyalgia. Significantly, all fibromyalgia cases were female. This subgroup of fibromyalgia subjects had more secretomotor complaints (mainly dry eyes and dry mouth) and more bowel constipation than the remainder of the group. Also in this subgroup of fibromyalgia subjects, several significant associations were found between age, blood pressure, number of syncopal episodes, constipation, insomnia, pupillomotor impairment, and disability. In contrast, no correlations were found in the subgroup of fainters without fibromyalgia. Fibromyalgia was relatively frequent in these women with vasovagal syncope and could be associated with dysautonomic symptoms. Therefore, it seems important to search for dysautonomic comorbidities in patients with vasovagal syncope and/or fibromyalgia, to provide a patient-centered holistic approach, instead of the often currently used therapeutic partition.

Orthostatic hypotension (OH) is a relatively common heterogenous and multifactorial disorder, traditionally classified as neurogenic (less common but often more severe) or nonneurogenic (more common, with no direct signs of autonomic nervous system disease). The different clinical variants of orthostatic intolerance include initial, classical and delayed OH as well as postural tachycardia syndrome. Orthostatic instability may induce syncopal attacks either alone or in combination with other mechanisms, and is often dismissed as a precipitating factor. Moreover, prevalent OH is an independent risk factor for all-cause mortality and cardiovascular morbidity, and the majority of patients with OH are asymptomatic or have few nonspecific symptoms. Management of symptomatic orthostatic intolerance includes both nonpharmacological and pharmacological methods, but it is not always successful and may lead to complications. Future studies of OH should focus on mechanisms that lead to neurogenic and nonneurogenic OH, novel diagnostic methods and more effective therapeutic modalities.

Postural tachycardia syndrome (PoTS) is an important cause of orthostatic intolerance resulting from cardiovascular autonomic dysfunction. In addition to postural symptoms, PoTS patients may have allied features, including gastrointestinal (GI) symptoms, which have not yet been thoroughly investigated. We evaluated gastric myoelectrical activity in PoTS patients. Using cutaneous electrogastrography (EGG), we recorded gastric myoelectrical activity before and after standard liquid meal ingestion in 15 PoTS patients (age 27 ± 4 years); including 7 with and 8 without GI symptoms, and in 11 healthy individuals (age 23 ± 7 years). We performed spectral analysis of EGG recordings to obtain the dominant frequency of gastric pacemaker rhythm (DF), instability coefficient of DF (ICDF), and low (LFR%), normal (NFR%), and high (HFR%) range power percentages of the total power. Instability coefficient of DF, an index of variability of gastric pacemaker rhythm, was significantly elevated both pre- and post-prandially (30-45 min after the meal) in the PoTS group (8.8 ± 6, 10.0 ± 8 %) compared with controls (4.0 ± 3, 4.0 ± 3 %; both p < 0.05). Patients with GI symptoms had significantly higher post-prandial ICDF (15.0 ± 5 %) than those without GI symptoms (5.6 ± 4 %; p < 0.05). There were no significant differences in DF, LFR%, NFR% and HFR% before and after the meal between the PoTS and control groups, or between PoTS patients with and without GI symptoms. Our study revealed increased variability of gastric pacemaker rhythm in PoTS, and these findings might be related to pathophysiology of functional GI symptoms in PoTS.

The autonomic nervous system, adequate blood volume, and intact skeletal and respiratory muscle pumps are essential components for rapid cardiovascular adjustments to upright posture (orthostasis). Patients lacking sufficient blood volume or having defective sympathetic adrenergic vasoconstriction develop orthostatic hypotension (OH), prohibiting effective upright activities. OH is one form of orthostatic intolerance (OI) defined by signs, such as hypotension, and symptoms, such as lightheadedness, that occur when upright and are relieved by recumbence. Mild OI is commonly experienced during intercurrent illnesses and when standing up rapidly. The latter is denoted "initial OH" and represents a normal cardiovascular adjustment to the blood volume shifts during standing. Some people experience episodic acute OI, such as postural vasovagal syncope (fainting), or chronic OI, such as postural tachycardia syndrome, which can significantly reduce quality of life. The lifetime incidence of ≥1 fainting episodes is ∼40%. For the most part, these episodes are benign and self-limited, although frequent syncope episodes can be debilitating, and injury may occur from sudden falls. In this article, mechanisms for OI having components of adrenergic hypofunction, adrenergic hyperfunction, hyperpnea, and regional blood volume redistribution are discussed. Therapeutic strategies to cope with OI are proposed.