A significant proportion of patients with chronic fatigue syndrome (CFS) also have postural orthostatic tachycardia syndrome (POTS). We aimed to characterize these patients and differentiate them from CFS patients without POTS in terms of clinical and autonomic features. A total of 179 patients with CFS (1994 Centers for Disease Control and Prevention criteria) attending one of the largest Department of Health-funded CFS clinical services were included in this study. Outcome measures were as follows: (i) symptom assessment tools including the fatigue impact scale, Chalder fatigue scale, Epworth sleepiness scale (ESS), orthostatic grading scale (OGS) and hospital anxiety and depression scale (HADS-A and -D, respectively), (ii) autonomic function analysis including heart rate variability and (iii) haemodynamic responses including left ventricular ejection time and systolic blood pressure drop upon standing. CFS patients with POTS (13%, n = 24) were younger (29 ± 12 vs. 42 ± 13 years, P < 0.0001), less fatigued (Chalder fatigue scale, 8 ± 4 vs. 10 ± 2, P = 0.002), less depressed (HADS-D, 6 ± 4 vs. 9 ± 4, P = 0.01) and had reduced daytime hypersomnolence (ESS, 7 ± 6 vs. 10 ± 5, P = 0.02), compared with patients without POTS. In addition, they exhibited greater orthostatic intolerance (OGS, 11 ± 5; P < 0.0001) and autonomic dysfunction. A combined clinical assessment tool of ESS ≤9 and OGS ≥9 identifies accurately CFS patients with POTS with 100% positive and negative predictive values. The presence of POTS marks a distinct clinical group of CFS patents, with phenotypic features differentiating them from those without POTS. A combination of validated clinical assessment tools can determine which CFS patients have POTS with a high degree of accuracy, and thus potentially identify those who require further investigation and consideration for therapy to control heart rate.

To determine the effect of low-dose propranolol on maximal exercise capacity in patients with postural tachycardia syndrome (POTS). We compared the effect of placebo vs a single low dose of propranolol (20 mg) on peak oxygen consumption (VO2max), an established measure of exercise capacity, in 11 patients with POTS and 7 healthy subjects in a randomized, double-blind study. Subjects exercised on a semirecumbent bicycle, with increasing intervals of resistance to maximal effort. Maximal exercise capacity was similar between groups following placebo. Low-dose propranolol improved VO2max in patients with POTS (24.5 ± 0.7 placebo vs 27.6 ± 1.0 mL/min/kg propranolol; p = 0.024), but not healthy subjects. The increase in VO2max in POTS was associated with attenuated peak heart rate responses (142 ± 8 propranolol vs 165 ± 4 bpm placebo; p = 0.005) and improved stroke volume (81 ± 4 propranolol vs 67 ± 3 mL placebo; p = 0.013). In a separate cohort of POTS patients, neither high-dose propranolol (80 mg) nor metoprolol (100 mg) improved VO2max, despite similar lowering of heart rate. These findings suggest that nonselective β-blockade with propranolol, when used at the low doses frequently used for treatment of POTS, may provide a modest beneficial effect to improve heart rate control and exercise capacity. This study provides Class II evidence that a single low dose of propranolol (20 mg) as compared with placebo is useful in increasing maximum exercise capacity measured 1 hour after medication.

To identify symptoms that may predict postural tachycardia syndrome (POTS) among adolescent patients with headache and lightheadedness referred for tilt table testing. Individuals with POTS can have a variety of symptoms that impair quality of life. The specific symptoms that help to distinguish the POTS patient in an adolescent headache population have not been determined. A group of symptoms was compared among 70 adolescent patients with headache and lightheadedness referred to a pediatric headache clinic for tilt table testing. Every patient completed a symptom questionnaire prior to the tilt table test. The chi-square test was used to compare questionnaire responses between patients found to have POTS and those who did not have POTS. Thirteen symptoms were analyzed. Symptoms that differed statistically between groups were further assessed for sensitivity, specificity, and diagnostic predictive values. Thirty-seven (53%) patients met diagnostic criteria for POTS. Several symptoms differed between the patients found to have POTS and those without POTS. Headache type was not predictive. Vertigo and evening exacerbation of headaches had P values <.05 but did not meet significance after a statistical correction for multiple variables, P ≤ .004 (0.05/13). New-onset motion sickness, dizziness as a headache trigger, and orthostatic headaches had P values <.004 and were relatively sensitive and/or specific for the POTS diagnosis. While no single clinical symptom or headache type reliably establishes the POTS diagnosis, several symptoms can help to distinguish the POTS patient in an adolescent headache population.

The present study was designed to analyse the usefulness of a modified Calgary score system during differential diagnosis between cardiac syncope and postural orthostatic tachycardia syndrome-associated syncope through a large sample sized clinical investigation. The study included 213 children, including 101 boys and 112 girls, with cardiac syncope or postural orthostatic tachycardia syndrome-associated syncope in the age group of 2-19 years (mean 11.8 ± 2.9 years). A modified Calgary score was created, which was analysed to predict differential diagnoses between cardiac syncope and postural orthostatic tachycardia syndrome-associated syncope using a receiver operating characteristic curve. The median of modified Calgary scores for cardiac syncope was -5.0, which significantly differed from that of postural orthostatic tachycardia syndrome (0.0; p < 0.01). The sensitivity and specificity of a differentiation score of less than -2.5 was 96.3% and 72.7%, respectively. Owing to the fact that the modified Calgary score was an integer, when less than -3.0 the diagnosis could be considered as cardiac syncope. The modified Calgary score could be used to make an initial differential diagnosis between cardiac syncope and postural orthostatic tachycardia syndrome-associated syncope in the clinic.

We investigated a short pain-provoked head-up tilt (PP-HUT) and the Calgary Syncope Symptom Score in a group of patients with clinically diagnosed vasovagal syncope and group of neurological patients without transient loss of consciousness. We included 127 consecutive patients who were investigated in our laboratory. The group 1 included 56 patients who after appropriate investigations were diagnosed with vasovagal syncope. The group 2 included 70 neurological patients without transient loss of consciousness. The subjects were tilted to 70° for a maximum period of 10 min or until symptoms occurred. If there were no symptoms after initial 10 min, a painful stimulus with the insertion of 0.7 mm needle into the dorsum of hand subcutaneously for 30 s was performed with the patient in the tilted for further 5 min. Calgary Syncope Symptom Score was calculated for all patients. In the group 1, significantly higher number of patients had positive results on PP-HUT (36 vs. 6 patients, respectively; p < 0,001). There was no difference in the presence of orthostatic hypotension (8 vs. 15 patients, respectively; p = 0.36) or postural orthostatic tachycardia syndrome (3 vs. 1 patient, respectively; p = 0.32) between groups. PP-HUT had sensitivity of 65.9 % (95 % CI 0.49-0.79) and specificity of 89.7 % (95 % CI 0.75-0.97). The CSSS had sensitivity of 58.5 % (95 % CI 0.42-0.73) and specificity of 46.1 % (95 % CI 0.30-0.63). PP-HUT has a higher diagnostic rate than the CSSS and provides a rapid alternative to conventional methods.

Postural orthostatic tachycardia syndrome (POTS) is a common autonomic disorder of largely unknown etiology that presents with sustained tachycardia on standing, syncope and elevated norepinephrine spillover. Some individuals with POTS experience anxiety, depression and cognitive dysfunction. Previously, we identified a mutation, A457P, in the norepinephrine (NE; also known as noradrenaline) transporter (NET; encoded by SLC6A2) in POTS patients. NET is expressed at presynaptic sites in NE neurons and plays a crucial role in regulating NE signaling and homeostasis through NE reuptake into noradrenergic nerve terminals. Our in vitro studies demonstrate that A457P reduces both NET surface trafficking and NE transport and exerts a dominant-negative impact on wild-type NET proteins. Here we report the generation and characterization of NET A457P mice, demonstrating the ability of A457P to drive the POTS phenotype and behaviors that are consistent with reported comorbidities. Mice carrying one A457P allele (NET(+/P)) exhibited reduced brain and sympathetic NE transport levels compared with wild-type (NET(+/+)) mice, whereas transport activity in mice carrying two A457P alleles (NET(P/P)) was nearly abolished. NET(+/P) and NET(P/P) mice exhibited elevations in plasma and urine NE levels, reduced 3,4-dihydroxyphenylglycol (DHPG), and reduced DHPG:NE ratios, consistent with a decrease in sympathetic nerve terminal NE reuptake. Radiotelemetry in unanesthetized mice revealed tachycardia in NET(+/P) mice without a change in blood pressure or baroreceptor sensitivity, consistent with studies of human NET A457P carriers. NET(+/P) mice also demonstrated behavioral changes consistent with CNS NET dysfunction. Our findings support that NET dysfunction is sufficient to produce a POTS phenotype and introduces the first genetic model suitable for more detailed mechanistic studies of the disorder and its comorbidities.

Lipid rafts are specialized plasma membrane microdomains that serve as platforms for integrating cellular signal transductions. We have recently reported that autoantibodies against cardiac membrane proteins are present in patients with postural orthostatic tachycardia syndrome (POTS). In this study, we examined the presence of autoimmunoreactive IgGs against lipid raft proteins in these patients. IgGs were purified from the sera of 10 patients and 7 normal controls. Cardiac lipid raft preparations were isolated from normal human heart tissue. The lipid raft-associated proteins were resolved by 2-dimensional gel electrophoresis and immunoblotted against IgGs from each subject. Protein spots that reacted specifically with patient IgGs were identified by nano-liquid chromatography-mass spectrometry/mass spectrometry. Thirty-four such protein spots, and 72 unique proteins were identified. The targets of autoimmunoreactive IgGs include proteins associated with caveolae structure, adrenergic signaling, calcium signaling, cytostructures, chaperone and energy metabolism. Multiple pathways were involved including those that regulate caveolae-mediated signaling, oxidative phosphorylation, fatty acid metabolism, protein ubiquitination, and cardiac β-adrenergic signaling. Our results suggest that cardiac lipid raft-associated proteins are targets of autoimmunoreactive IgGs from patients with POTS. Autoimmunity may play a role in the pathogenesis of POTS.

Postural orthostatic tachycardia syndrome (POTS) refers to the presence of orthostatic intolerance with a heart rate (HR) increment of 30 beats per minute (bpm) or an absolute HR of 120 bpm or more. There are sporadic reports of the autonomic nervous system dysfunction in migraine and fibromyalgia. We report a case of POTS associated with migraine and fibromyalgia. The patient was managed with multidisciplinary therapies involving medication, education, and exercise which resulted in symptomatic improvement. We also review the literature on the association between POTS, migraine, and fibromyalgia.

Chronic symptoms of orthostatic intolerance occur in postural tachycardia syndrome (POTS) and patients with orthostatic intolerance (OI) without tachycardia. We recently reported that deconditioning is almost universal in both patient groups. In this study, we focussed on the question of how much dysautonomia, besides orthostatic tachycardia, is there in POTS vs. OI, and how the two groups compare in regards to clinical, autonomic, laboratory, and exercise variables. We retrospectively studied all patients referred for orthostatic intolerance at Mayo Clinic between January 2006 and June 2011, who underwent standardized autonomic and exercise testing. Eighty-four POTS and 100 OI fulfilled inclusion criteria, 89 % were females. The mean age was 25 and 32 years, respectively. Clinical presentation, autonomic parameters, laboratory findings, and degree of deconditioning were overall similar between the two groups, except for the excessive orthostatic heart rate (HR) rise and mild vasomotor findings observed in POTS but not in OI (slightly larger Valsalva ratio and incomplete blood pressure recovery during Valsalva). Both groups responded poorly to various medications. Severely deconditioned patients were similar to non-deconditioned patients, except for 24 h urine volume (1,555 vs. 2,417 ml), sweat loss on thermoregulatory sweat test (1.5 vs. 0.5 %), and few respiratory parameters during exercise, which are likely clinically insignificant. Though similar in clinical presentation, POTS and OI are different entities with greater, albeit still mild, dysautonomia in POTS. The clinical and pathophysiological relevance of minimal dysautonomia in the absence of orthostatic tachycardia as seen in OI remain uncertain.

We reported low iron storage in neurally mediated syncope (NMS). While reduced red cell mass indicative of anemia has been reported in POTS, iron indices and hemoglobin (Hb) data were not reported. We investigated whether POTS, like NMS, is associated with low iron storage and anemia. Thirty two children evaluated in 2007 and 2008 for probable POTS by a standing or tilt test or both at Texas Children's Hospital were included in a retrospective study. We measured serum ferritin (SF) and Hb values. We defined iron deficiency as SF < 12 μg/L, low iron storage as SF ≤ 25 μg/L, anemia as low Hb values for age and sex, and POTS as ≥2 symptoms of orthostatic intolerance >3 months and increased HR of >30 BPM or HR of >120 BPM within 10 min of standing or 70° tilt. Twenty four children had POTS, ages 12-18 years, 17 (71 %) were females. Value range (median) of SF 2-289 μg/L (25), Hb 11.5-14.6 (12.5) in females and 12-15.9 g/L (13.6) in males. Patients with POTS, when compared with normal US pediatric population had higher prevalence of low iron storage (50 vs. 14 %), iron deficiency (25 % of teenage girls vs. 9 %, and 16 % of teenage boys vs. 1 %), and anemia (18 % of teenage girls vs. 1.5 %, and 43 % of teenage boys vs. 0.1 %). Low iron storage and mild anemia are associated with POTS suggesting that low iron storage is a potentially pathophysiologic factor in both POTS and NMS.

Autonomic neuropathy is widely recognized to be associated with upper gastrointestinal symptoms and abnormal (i.e., rapid or slow) gastric emptying. While patients with postural orthostatic tachycardia syndrome (POTS) may also have gastrointestinal symptoms, our understanding of gastric-emptying disturbances in POTS is very limited. The objectives of this study were to evaluate the relationship between gastric-emptying disturbances and gastrointestinal symptoms in patients with POTS. We retrospectively reviewed the medical records of 22 well-characterized patients with POTS and upper gastrointestinal symptoms in whom autonomic (i.e., postganglionic sudomotor, cardiovagal, and adrenergic) functions and gastric emptying were evaluated using standardized techniques and scintigraphy, respectively. Medical records were reviewed retrospectively to assess clinical features, gastric emptying, and autonomic functions. Over 70 % of patients had nausea and/or vomiting, which was the most common GI symptom; other common symptoms were abdominal pain (59 %), bloating (55 %), and postprandial fullness/early satiety (46 %). Over one-third of patients had abnormal [i.e., rapid (27 %) or delayed (9 %)] gastric emptying. Gastric-emptying disturbances were not significantly associated with GI symptoms, autonomic symptoms or autonomic dysfunction. Over one-third of patients with POTS and gastrointestinal symptoms have abnormal, more frequently rapid than delayed gastric emptying. These findings need to be confirmed in a larger cohort of patients.

Reports have shown that younger individuals present with higher postural heart rate increments on head-up tilt (HUT). However, a correlation between the degree of heart rate increment and symptoms of orthostatic intolerance has not been determined. The objective of this study was to determine whether higher postural heart rate increments during HUT correlate with symptoms of orthostatic intolerance in healthy subjects. Postural heart rate increment on HUT did not differ between men and women (P = 0.48) but did show a significant decrease by age group (P < 0.0001). There was a significant negative correlation between heart rate increment on HUT and age [r = -0.63 (-0.73, -0.51), r(2) = 0.400; P < 0.0001]. There was a significant difference with respect to symptoms of orthostatic intolerance by sex (P = 0.03) but not age (P = 0.58). There was no significant correlation between either symptoms of orthostatic intolerance and age [r = -0.13 (-0.31, 0.06), r(2) = 0.017; P = 0.17] or heart rate increment on HUT and symptoms of orthostatic intolerance [r = 0.15 (-0.04, 0.33), r(2) = 0.022; P = 0.13]. The results demonstrate that higher postural heart rate increments in younger individuals do not result in an increase in orthostatic intolerance. This highlights the potential need for a reevaluation of the diagnostic criteria for postural orthostatic tachycardia syndrome in younger individuals.

Postural tachycardia syndrome (POTS) is a disorder of chronic orthostatic intolerance accompanied by excessive orthostatic tachycardia. Patients with POTS commonly have comorbid conditions such as attention deficit hyperactivity disorder, depression, or fibromyalgia that are treated with medications that inhibit the norepinephrine reuptake transporter (NRI). NRI medications can increase sympathetic nervous system tone, which may increase heart rate (HR) and worsen symptoms in POTS patients. We sought to determine whether NRI with atomoxetine increases standing tachycardia or worsens the symptom burden in POTS patients. Patients with POTS (n = 27) underwent an acute drug trial of atomoxetine 40 mg and placebo on separate mornings in a randomized, crossover design. Blood pressure (BP), HR, and symptoms were assessed while seated and after standing prior to and hourly for 4 hours following study drug administration. Atomoxetine significantly increased standing HR compared with placebo (121 ± 17 beats per minute versus 105 ± 15 beats per minute; P = 0.001) in POTS patients, with a trend toward higher standing systolic BP (P = 0.072). Symptom scores worsened with atomoxetine compared to placebo (+4.2 au versus -3.5 au; P = 0.028) from baseline to 2 hours after study drug administration. Norepinephrine reuptake inhibition with atomoxetine acutely increased standing HR and symptom burden in patients with POTS.

This study was designed to explore the value of flow-mediated vasodilation (FMD) as a predictor of therapeutic response to midodrine hydrochloride (MD) in children with postural orthostatic tachycardia syndrome (POTS). One hundred and eight children diagnosed with POTS and 20 healthy control children were enrolled. All children with POTS received MD and were followed up for 3 months. FMD of brachial artery for each participant was measured by vascular ultrasound. Symptom scores, FMD values, and head-up test (HUT)/head-up tilt test (HUTT) outcomes were investigated before and after treatment. A receiver operating characteristic curve was used to explore the value of FMD as a predictor. Baseline FMD (%) and increased heart rate (beats per minute) during HUT/HUTT were significantly greater in children with POTS compared with control children (FMD: 11 ± 3% vs 6 ± 2%, p <0.001; increased heart rate: 38 ± 9 vs 7 ± 7 beats/min, p <0.001, respectively). Before treatment, MD responders had greater FMD values than MD nonresponders (p <0.05). Symptom scores, excessive increases in heart rate during HUT, and increased FMD values were all reduced significantly after treatment (all p <0.05). The receiver operating characteristic curve for the predictive value of FMD showed the area under the curve to be 0.790 (95% confidence interval: 0.679 to 0.902; p <0.001) at 1-month and 0.803 (95% confidence interval: 0.669 to 0.936; p <0.01) at 3-month therapy. FMD of 9.85% had a high sensitivity (1-month therapy: 71.6%; 3-month therapy: 74.4%) and specificity (1-month therapy 77.8%; 3-month therapy: 80%). In conclusion, FMD is a predictor of the efficacy of MD for treating children with POTS.

Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous group of conditions characterised by autonomic dysfunction and an exaggerated sympathetic response to assuming an upright position. Up till recently, it was largely under-recognised as a clinical entity. There is now consensus about the definition of POTS as a greater than 30/min heart rate increase on standing from a supine position (greater than 40/min increase in 12-19-year-old patients) or an absolute heart rate of greater than 120/min within 10 min of standing from a supine position and in the absence of hypotension, arrhythmias, sympathomimetic drugs or other conditions that cause tachycardia. We present two cases of POTS, followed by a discussion of its pathogenesis, pathophysiology, epidemiology and management.

To evaluate the use of erythrocytic hydrogen sulfide (H2S) in predicting the therapeutic efficacy of midodrine hydrochloride for children with postural orthostatic tachycardia syndrome (POTS). Fifty-five children were included in this study, involving 28 children with POTS (POTS group) and 27 healthy children (control group). Children in the POTS group received midodrine hydrochloride treatment. Erythrocytic H2S production was measured; a receiver operating characteristic curve was used to assess if erythrocytic H2S could predict the therapeutic response to midodrine hydrochloride treatment. H2S production from erythrocytes was significantly higher in the POTS group than in the control group (P < .01). H2S production was also significantly higher in responders to midodrine hydrochloride than in non-responders (P < .05). The change in symptom score and baseline erythrocytic H2S production had a positive linear relationship (P < .01). There was also a positive correlation with the change in heart rate (P < .05). The receiver operating characteristic curve showed an area under curve value of 0.813. Erythrocytic H2S production yielded a sensitivity of 78.9% and a specificity of 77.8% in predicting the efficacy of midodrine hydrochloride therapy for children with POTS. Erythrocytic H2S could serve as a useful predictor of therapeutic response to midodrine hydrochloride in children with POTS.

Patients with postural tachycardia syndrome (POTS) commonly complain of fatigue, unrefreshing sleep, daytime sleepiness and diminished quality of life. The study objective was to assess sleep quality in POTS patients using wrist actigraphy. Prospective study with control group. Patients with POTS (n = 36) and healthy subjects (n = 36) completed a detailed sleep log and actigraphy for 7 days. Compared with healthy subjects, POTS patients have more self-reported problems including days with restless sleep (53 ± 30% vs. 21 ± 20%; P<0.001) and tiredness (75 ± 23% vs. 39 ± 27%; P<0.001). Using actigraphy, POTS patients have lower sleep efficiency (73 ± 13% vs. 79 ± 6%; P = 0.01). Actigraphy determined sleep onset latency (SOL) did not vary significantly in the two groups, but subjective SOL was higher in POTS patient (56 ± 66 min vs. 1 3 ± 9 min; P = 0.001). In POTS patients, there was a significant correlation between subjective complaints of tiredness and actigraphic sleep efficiency (Rs = -0.36; R(2) = 0.15; P = 0.01), significant correlations between actigraphic SOL and upright norepinephrine levels (P = 0.040), and between wake after sleep onset and standing heart rate (P = 0.02). POTS patients have more sleep-related symptoms and poor sleep efficiency. The pattern of subjective vs. objective SOL mismatch is suggestive of sleep-state misperception. High norepinephrine correlated with actigraphic SOL, and this activation of the stress system may contribute significantly to a hyperarousal state with consequent insomnia, poor mental and physical health in POTS patients.

Withdrawal of muscle sympathetic nerve activity (MSNA) may not be necessary for the precipitous fall of peripheral arterial resistance and arterial pressure (AP) during vasovagal syncope (VVS). We tested the hypothesis that the MSNA-AP baroreflex entrainment is disrupted before VVS regardless of MSNA withdrawal using the phase synchronization between blood pressure and MSNA during head-up tilt (HUT) to measure reflex coupling. We studied eight VVS subjects and eight healthy control subjects. Heart rate, AP, and MSNA were measured during supine baseline and at early, mid, late, and syncope stages of HUT. Phase synchronization indexes, measuring time-dependent differences between MSNA and AP phases, were computed. Directionality indexes, indicating the influence of AP on MSNA (neural arc) and MSNA on AP (peripheral arc), were computed. Heart rate was greater in VVS compared with control subjects during early, mid, and late stages of HUT and significantly declined at syncope (P = 0.04). AP significantly decreased during mid, late, and syncope stages of tilt in VVS subjects only (P = 0.001). MSNA was not significantly different between groups during HUT (P = 0.700). However, the phase synchronization index significantly decreased during mid and late stages in VVS subjects but not in control subjects (P < .001). In addition, the neural arc was significantly affected more than the peripheral arc before syncope. In conclusion, VVS is accompanied by a loss of the synchronous AP-MSNA relationship with or without a loss in MSNA at faint. This provides insight into the mechanisms behind the loss of vasoconstriction and drop in AP independent of MSNA at the time of vasovagal faint.

Postural orthostatic tachycardia syndrome (POTS) is a rare disease that is believed to be mediated by dysautonomia. Gastrointestinal complaints in POTS patients are common and disturbing but not well characterized. We hypothesized that gastrointestinal dysmotility may be contributory to these symptoms. We studied 12 POTS patients who presented with gastrointestinal symptoms to a tertiary referral center. Gastrointestinal symptoms were quantified using a previously validated symptom questionnaire. All patients underwent gastroduodenal manometry (GDM); select patients also underwent further testing including esophageal manometry (EM), anorectal manometry (ARM), plain abdominal radiography (AXR), abdominal computed tomography (CT), gastric emptying studies (GES), and colonic transit time (CTT) studies. The four most common symptoms were bloating, constipation, abdominal pain, and nausea/vomiting, all experienced by greater than 70 % of patients. On GDM testing, 93 % of patients demonstrated signs of neuropathy, and the most common abnormalities observed included bursts of uncoordinated phasic activity in both fasting (59 %) and post-prandial (42 %) states, low contractility in the post-prandial state (67 %), and lack of post-prandial pattern (42 %). A total of 67 % of patients undergoing EM and 86 % of those undergoing ARM demonstrated abnormalities consistent with dysmotility. On AXR or CT, 58 % demonstrated either dilated intestinal loops or air-fluid levels. On CTT 80 % demonstrated delayed colonic transit, while on GES 60 % demonstrated delayed gastric emptying. In this cohort of POTS patients with gastrointestinal symptoms, there is a high prevalence of abnormal manometric and radiographic findings suggestive of dysmotility.

Adolescents with postural tachycardia syndrome (POTS) often experience ill-defined cognitive impairment referred to by patients as "brain fog." The objective of this study was to evaluate the symptom of brain fog as a means of gaining further insight into its etiology and potential palliative interventions. Eligible subjects who reported having been diagnosed with POTS were recruited from social media web sites. Subjects were asked to complete a 38-item questionnaire designed for this study, and the Wood mental fatigue inventory (WMFI). Responses were received from 138 subjects with POTS (88 % female), ranging in age from 14 to 29 years; 132 subjects reported brain fog. WMFI scores correlated with brain fog frequency and severity (P < 0.001). The top ranked descriptors of brain fog were "forgetful," "cloudy," and "difficulty focusing, thinking and communicating." The most frequently reported brain fog triggers were fatigue (91 %), lack of sleep (90 %), prolonged standing (87 %), dehydration (86 %), and feeling faint (85 %). Although aggravated by upright posture, brain fog was reported to persist after assuming a recumbent posture. The most frequently reported interventions for the treatment of brain fog were intravenous saline (77 %), stimulant medications (67 %), salt tablets (54 %), intra-muscular vitamin B-12 injections (48 %), and midodrine (45 %). Descriptors for "brain fog" are most consistent with it being a cognitive complaint. Factors other than upright posture may play a role in the persistence of this symptom. Subjects reported a number of therapeutic interventions for brain fog not typically used in the treatment of POTS that may warrant further investigation.

We describe a 13-year-old female with abrupt onset urinary retention progressing rapidly to pandysautonomia with symptoms of postural orthostatic tachycardia syndrome, gastroparesis, anhidrosis, pupillary dysfunction, and abdominal pain. Pandysautonomia has been reported frequently in adults, but is less commonly described in children. Autonomic nervous system dysfunction usually has a self-limiting course with gradual near-complete or complete recovery. Most patients with pure pandysautonomia produce an antibody targeted against the ganglionic nicotinic acetylcholine receptor and titers have been shown to correlate with symptom severity. The clinical presentation described in this report is consistent with a progressive form of acute autoimmune autonomic neuropathy, but she was initially seronegative for known autoantibodies. She responded promptly to plasmapheresis. This case report emphasizes the importance of recognizing features of autonomic nervous system dysfunction and discusses the medical evaluation and treatment options for pediatric patients based on symptom severity.

Postural tachycardia syndrome (POTS) is prevalent in children and adolescents and has a great impact on health. But its risk factors have not been fully understood. This study aimed to explore possible risk factors for children and adolescents with POTS. 600 children and adolescents (test group) aged 7-18 (11.9 ± 3.0) years old, 259 males and 341 females, were recruited for identifying its risk factors. Another 197 subjects aged from 7 to 18 (11.3 ± 2.3) years old were enrolled in the validation group. Heart rate (HR) and blood pressure (BP) were monitored during upright test. Risk factors were analyzed and sensitivity and specificity for predicting POTS were tested via receiver operating characteristic curve. Among 600 subjects, 41 were confirmed with POTS patients (6.8%) based on clinical manifestation and upright test. The results showed a significant difference in daily water intake, the daily sleeping hours, supine HR, HR increment and maximum HR during upright test between POTS and the unaffected children (P<0.05). Likelihood of POTS would increase by 1.583 times if supine HR was increased by 10 beats/min (95%CI 1.184 to 2.116, P<0.01), by 3.877 times if a child's water intake was less than 800 ml/day (95%CI 1.937 to 7.760, P<0.001), or by 5.905 times (95%CI 2.972 to 11.733, P<0.001) if sleeping hours were less than 8 hours/day. Supine HR, daily water intake and sleeping hours showed the capability of predicting POTS in children and adolescents with an AUC of 83.9% (95% CI: 78.6%-89.1%), sensitivity of 80.5% and specificity of 75%. Furthermore, in validation group, predictive sensitivity and specificity were 73.3% and 72.5%. Faster supine HR, less water intake and shorter sleeping hours were identified as risk factors for POTS.

Orthostatic intolerance (OI) is a common disease at pediatric period which has a serious impact on physical and mental health of children. The purpose of this study was to investigate the effect of related factors on the prognosis of children with OI. The subjects were 170 children with OI, including 71 males (41.8%) and 99 females (58.2%) with age from 6 to 17 (12.0±2.6) years. The effect of related factors on the prognosis of children was studied by using univariate analysis. Then, the impact of children's age, symptom score, duration, disease subtype, and treatment on patient's prognosis was studied via analysis of COX proportional conversion model. Among 170 cases, 48 were diagnosed with vasovagal syncope, including 28 cases of vasoinhibitory type, 16 cases of mixed type, and 4 cases of cardioinhibitory type; 115 cases were diagnosed with postural tachycardia syndrome and 7 cases with orthostatic hypotension. By using univariate analysis of Cox regression, the results showed that symptom score had a marked impact on the time of symptoms improvement of children after taking medication (P < 0.05), while other univariates had no impact (P > 0.05). Multivariate analysis using Cox proportional hazards regression model showed that the symptom score at diagnosis had a significant effect on holding time of symptoms improvement of children after taking medication (P < 0.05). Kaplan-Meier curve showed that symptom-free survival was higher in children with symptom score equal to 1 than children with symptom score equal to or greater than 2 during follow-up (P < 0.05). Symptom score is an important factor affecting the time of symptom improvement after treatment for children with OI.

The incidence of postural tachycardia syndrome (POTS) has been increasing in children and adolescents, while clinical characteristics of POTS in the pediatric population are not fully understood. An observational study was performed in 150 pediatric patients aged between 5 and 18 years who underwent head-up tilt test (HUTT) with the diagnosis of POTS at Peking University First Hospital from March 2008 to August 2013. Demographic data, clinical presentation, autonomic parameters, laboratory findings, and treatments were recorded. POTS in children commonly occurred in the age of 7-14 years. Dizziness (84.00%) was the most common symptom, followed by weakness (72.00%) and orthostatic syncope (62.67%). Positive family history of orthostatic intolerance (OI) was found in 24.64% of children with POTS. And 33.09% of them had preceding infection history as precipitating events. Ten percent of them suffered from orthostatic hypertension. Hyperadrenergic status was documented in 51.28% of 39 patients who were tested for the standing norepinephrine levels. More than half of POTS patients, with 24-hour urinary sodium level <124 mmol/24 hours, were suitable for treatment of salt supplementation. At least 25.74% of POTS patients were of positive acetylcholine receptor (AChR) antibody. Low iron storage in children with POTS was relatively rare. Most patients responded well to treatments, 43.51% of patients recovered, while 7.63% of them had relapse after symptoms disappeared. POTS is a relatively common condition with complex pathophysiology and heterogeneous clinical manifestation. A comprehensive therapeutic regimen is recommended for the treatment.

Many patients with postural tachycardia syndrome (PoTS) suffer from fatigue, daytime sleepiness, and sleeping disturbances. The objective of this study was to compare subjective and objective sleep quality of PoTS patients with a group of healthy controls. All patients completed a Pittsburgh Sleep Quality Index questionnaire and the Epworth Sleepiness Scale. The patients sleep architecture, heart rate, and heart rate variability (HRV) measurements were taken during one night at the sleep laboratorium. All data was collected at the Sleep Unit, at Helios Klinikum Wuppertal. Thirty-eight patients diagnosed with PoTS were compared to 31 healthy controls, matched in age and gender. Patients with PoTS reached significantly higher scores in sleep questionnaires, which means that they were more sleepy and had a lower sleep quality. Polysomnography showed a significantly higher proportion of stage 2 sleep. The results of HRV analysis in different sleep stages confirmed changes in autonomic activity in both groups. PoTS patients, however, showed a diminished variability of the low-frequency (LF) band, high-frequency (HF) band, and LF/HF ratio in different sleep stages. It can therefore be gathered that PoTS could be considered as potential differential diagnosis for sleep disturbances since PoTS patients had a subjective diminished sleep quality, reached higher levels of daytime sleepiness, and showed a higher proportion of stage 2 sleep. PoTS patients showed furthermore a reduction of LF/HF ratio variability in different sleep stages.