The antimalarial agent mefloquine has been reported to cause a number of possible side effects. Here we describe a case demonstrating a previously unreported complication, the postural orthostatic tachycardia syndrome (POTS). A 44-year-old woman presented with symptoms of severe orthostatic intolerance (palpitations and dizziness) in combination with postural tachycardia (but no fall in blood pressure) following the use of mefloquine prophylaxis. Investigations revealed evidence of autonomic dysfunction (with loss of ECG R-R interval variation) consistent with POTS. Her symptoms responded well to beta-blockade with propranolol. The possibility of POTS should be considered in patients presenting with symptoms of palpitations, dizziness, presyncope or other features suggestive of autonomic dysfunction following the use of mefloquine.

Some patients with functional abdominal pain report worsening of symptoms in the upright position. Many of these have a postural tachycardia syndrome (POTS). We investigated whether the electrical activity of the stomach changes during the upright portion of a tilt table test in patients with and without POTS. All of the children undergoing autonomic testing were offered enrollment in this institutional review board-approved prospective study between October 2007 and January 2009. Electrogastrography was recorded 10 minutes in the supine position and during the entire upright portion of tilt. Children were divided into 2 groups: POTS and No-POTS. Findings were correlated with this grouping using Fisher exact test and either Student t test or Wilcoxon rank sum test as appropriate. Forty-nine patients participated (35 girls), with a mean age of 14.7 + 3.5 years, 25 with POTS and 24 without. The POTS and No-POTS groups did not differ in baseline normal gastric activity. The change from supine to standing showed a significant difference in the electrogastrographic tracing between the POTS and No-POTS groups (P < 0.04-0.09), best seen in channels 1 and 4. In particular, gastric activity became more abnormal in the upright position in the POTS group, whereas the opposite occurred in the No-POTS group. The electrical activity of the stomach changes during the upright position in children with POTS, but not in children without this diagnosis. These changes could relate to their report of worsening pain in the upright position.

Autonomic dysfunction presenting as inappropriate sinus tachycardia has been reported to occur following slow pathway ablation for atrioventricular node tachycardia. We report on a series of patients who developed new onset postural orthostatic tachycardia syndrome (POTS) following successful radiofrequency ablation of atrioventricular nodal reentrant tachycardia (AVNRT). The study was a retrospective analysis that was approved by our Institutional Review Board. Patients were identified from those seen at our Syncope and Autonomic Disorders Clinic. A total of six patients were identified who were previously healthy except for supraventricular tachycardia. Each was found to have AVNRT during electrophysiology study and each underwent successful radiofrequency modification of the slow atrioventricular nodal pathway. Following ablation each patient developed the new onset of symptoms of orthostatic intolerance consistent with POTS. After an initial symptom-free period (3-6 weeks) post ablation each patient began to experience symptoms of orthostatic intolerance. All six patients began to experience progressive severe fatigue. Orthostatic tachycardia was reported by five patients, syncope by three patients, and presyncope by all six patients. Each patient reported the occurrence of symptom while upright that were relieved by becoming supine. Each patient had experienced symptoms for greater than 6 months prior to being seen at our center. Three patients reported such severe symptoms of orthostatic tachycardia that they underwent repeat electrophysiology study; however, none had evidence of AVNRT. Each patient demonstrated a POTS response within the first 10 min of upright tilt with reproduction of their clinical symptoms that had occurred post ablation. POTS may be a complication of radiofrequency ablation of AVNRT.

Rapid water ingestion improves orthostatic intolerance (OI) in multiple system atrophy (MSA) and postural tachycardia syndrome (PoTS). We compared haemodynamic changes after water and clear soup intake, the latter being a common treatment strategy for OI in daily practice. Seven MSA and seven PoTS patients underwent head-up tilt (HUT) without fluid intake and 30 min after drinking 450 ml of water and clear soup, respectively. All patients suffered from moderate to severe OI because of neurogenic orthostatic hypotension (OH) and excessive orthostatic heart rate (HR) increase, respectively. Beat-to-beat cardiovascular indices were measured non-invasively. In MSA, HUT had to be terminated prematurely in 2/7 patients after water, but in 6/7 after clear soup. At 3 min of HUT, there was an increase in blood pressure of 15.7(8.2)/8.3(2.3) mmHg after water, but a decrease of 11.6(18.9)/8.1(9.2) mmHg after clear soup (P < 0.05). In PoTS, HUT could always be completed for 10 min, but OI subjectively improved after both water and clear soup. The attenuation of excessive orthostatic HR increase did not differ significantly after water and clear soup drinking. In MSA, clear soup cannot substitute water for eliciting a pressor effect, but even worsens OI after rapid ingestion. In PoTS, acute water and clear soup intake both result in improvement of OI. These findings cannot solely be explained by difference in osmolarity but may reflect some degree of superimposed postprandial hypotension in widespread autonomic failure in MSA compared to the mild and limited autonomic dysfunction in PoTS.

Dysfunction of the autonomic nervous system, or dysautonomia, is an uncommon disease. Postural orthostatic tachycardia syndrome is one of the several types of dysautonomia. Postural orthostatic tachycardia syndrome, also known as chronic orthostatic intolerance, is the most common but least severe of the dysautonomic disorders; it will serve as the model for evaluation and management of the other dysautonomias. Overall, these patients can have variable dysfunction of the autonomic nervous system that is more severe than that observed in typical neurocardiogenic syncope. Frequently, providers are not familiar with either the evaluation or the management of this syndrome, or are just not interested in doing so. This article attempts to describe strategies for evaluation and management of postural orthostatic tachycardia syndrome. The diagnosis of postural orthostatic tachycardia syndrome is made by the finding of orthostatic intolerance associated with a pulse greater than 120 beats per minute in the first 10 minutes of upright position or an elevation in pulse greater than 30 beats per minute in the first 10 minutes of upright position. Overall, these patients can have variable dysfunction of the autonomic nervous system that is more severe than that seen in typical neurocardiogenic syncope. A wide variety of associated symptoms may exist and these symptoms can have tremendous impact on the lives of the patients and their families. Management of these patients can be difficult as well as rewarding. It is helpful to perform an extensive education up front with these patients and their families. Interventions for patients with postural orthostatic tachycardia syndrome typically fall into two broad categories: non-pharmacological and pharmacological. Non-pharmacological therapies are varied, but are based primarily on ensuring adequate status of intravascular fluid. Polypharmacy may be required to control symptoms associated with postural orthostatic tachycardia syndrome. On account of the severity of their symptoms, these patients frequently have difficulty in completing their school assignments. The physician may need to help support the attempts of the family to work with the school to help the patient stay in school. As postural orthostatic tachycardia syndrome is underdiagnosed and poorly understood, it is a disease that provides an excellent opportunity to perform research. The most important studies would be those that aim to elucidate an aetiology and a pathophysiology of postural orthostatic tachycardia syndrome. In the final analysis, the role of the cardiologist in the evaluation and management of a patient with dysautonomia is to help a patient with severe disability to feel as if they are normal, or much closer to it.

A 26-year-old woman experienced syncope on standing 2-3 times a year for more than 15 years. The attack was typically associated with palpitations and frequently accompanied by a feeling of intense fear. The patient underwent head-up tilt table testing at 70° for 40 min to determine the cause of the syncope. The tilt test results suggested that the etiology of the syncope was orthostatic tachycardia syndrome complicated by panic attack-associated hypocapnic hyperventilation, which presumably caused a greater degree of deep cerebral hypoperfusion than would be expected with orthostatic tachycardia syndrome alone, ultimately leading to the patient's symptoms, including syncope. In conclusion, monitoring the ventilation and/or arterial CO(2) level during head-up tilt table testing is occasionally required when evaluating patients with postural syncope.

We present our single center experience of 27 patients of hyperadrenergic postural orthostatic tachycardia syndrome (POTS). In a retrospective analysis, we reviewed the charts of 300 POTS patients being followed at our autonomic center from 2003 to 2010, and found 27 patients eligible for inclusion in this study. POTS was defined as symptoms of orthostatic intolerance (of greater than six months' duration) accompanied by a heart rate increase of at least 30 bpm (or a rate that exceeds 120 bpm) that occurs in the first 10 min of upright posture or head up tilt test (HUTT) occurring in the absence of other chronic debilitating disorders. Patients were diagnosed as having the hyperadrenergic form based on an increase in their systolic blood pressure of ≥ 10 mm Hg during the HUTT (2) with concomitant tachycardia or their serum catecholamine levels (serum norepinephnrine level ≥ 600 pg/mL) upon standing. Twenty seven patients, aged 39 ± 11 years, 24, (89%) of them female and 22 (82%) Caucasian were included in this study. Most of these patients were refractory to most of the first and second line treatments, and all were on multiple combinations of medications. Hyperadrenergic POTS should be identified and differentiated from neuropathic POTS. These patients are usually difficult to treat and there are no standardized treatment protocols known at this time for patients with hyperadrenergic POTS.

Postural orthostatic tachycardia syndrome (POTS) is an autonomic disorder characterized by an exaggerated increase in heart rate that occurs during standing, without orthostatic hypotension. Women are most frequently affected, and may present with palpitations, chest discomfort, shortness of breath, weakness, exercise intolerance, lightheadedness, presyncope, and syncope. We present three cases of POTS in otherwise healthy women, and discuss the clinical management of different types of this orthostatic intolerance. The diagnosis was established with a tilt-table test in 1 patient who became symptom-free with β-blockade and nonpharmacologic treatment, including fluid therapy, liberal sodium intake, support hose, and a reconditioning exercise program. The other 2 were diagnosed through a standing test, serum norepinephrine levels, and red-cell volumes. One patient had neuropathic POTS and partially responded to b-blockade and nonpharmacotherapy. The other patient had hyperadrenergic POTS and responded well to nonpharmacotherapy, a dualacting b-blocker, and a vasoconstrictor agent. Postural orthostatic tachycardia syndrome is not an uncommon clinical entity and making a correct diagnosis is crucial in providing appropriate treatment to restore patients' functional capability and quality of life.

A subgroup of patients suffering from Lyme disease (LD) may initially respond to antibiotics only to later develop a syndrome of fatigue, joint pain and cognitive dysfunction referred to as 'post treatment LD syndrome'. We report on a series of patients who developed autonomic dysfunction in the form of postural orthostatic tachycardia syndrome (POTS). All of the patients in this report had suffered from LD in the past and were successfully treated with antibiotics. All patients were apparently well, until years later when they presented with fatigue, cognitive dysfunction and orthostatic intolerance. These patients were diagnosed with POTS on the basis of clinical features and results of the tilt table (HUTT) testing. Five patients (all women), aged 22-44 years, were identified for inclusion in this study. These patients developed symptoms of fatigue, cognitive dysfunction, orthostatic palpitations and either near syncope or frank syncope. The debilitating nature of these symptoms had resulted in lost of the employment or inability to attend school. Three patients were also suffering from migraine, two from anxiety and depression and one from hypertension. All patients demonstrated a good response to the employed treatment. Four of the five were able to engage in their activities of daily living and either resumed employment or returned to school. In an appropriate clinical setting, evaluation for POTS in patients suffering from post LD syndrome may lead to early recognition and treatment, with subsequent improvement in symptoms of orthostatic intolerance.

The study was carried out to examine the effect of selective α1 adrenoceptor agonist midodrine hydrochloride vs. β-adrenergic blockade metoprolol in the treatment of children with postural orthostatic tachycardia syndrome (POTS). Fifty-three children with POTS were divided into group I (midodrine hydrochloride plus conventional therapy), group II (metoprolol plus conventional therapy) and group III (conventional therapy). Standing test was conducted for all participants. The cure rate, improvement rate, effective rate and score of symptoms were compared among the 3 groups. A Kaplan-Meier survivorship curve was used to describe the proportion of symptom-free cases during a long term follow-up. The cure rate and effective rate at the end of short term follow-up in group I were significantly higher than those of group II and group III (68.42% vs. 42.11% vs. 20.00%, P<0.05; 89.47% vs. 57.89% vs. 53.33%, P<0.05). After treatment, the symptom score in group I was significantly lower than group II and group III, respectively (1.1±2.2 vs. 2.8±2.4 vs. 3.7±2.0, P<0.05), and it also had significant difference between group II and group III (P<0.05). The symptom recurrent rate in group I was significantly lower than that of group II and group III, respectively (P<0.05), but it did not differ between group II and group III (P>0.05). Midodrine hydrochloride is effective in the treatment of children with POTS.

To test the hypothesis that excessive postural tachycardia is associated with deconditioning rather than merely being an independent sign of autonomic dysfunction in patients with postural orthostatic tachycardia syndrome (POTS). We retrospectively analyzed records from 202 adolescents who underwent both head up-tilt and maximal exercise testing. Patients were classified as POTS if they had ≥ 30 min(-1) rise in heart rate (HR) after tilt-table test; and deconditioned if peak O(2) uptake was < 80% predicted. Changes in HR during exercise and recovery were compared between groups. Two-thirds of patients were deconditioned, irrespective of whether they fulfilled diagnostic criteria for POTS, but peak O(2) uptake among patients with POTS was similar to patients without POTS. HR was higher at rest and during exercise; whereas stroke volume was lower during exercise, and HR recovery was slower in patients with POTS compared with patients without POTS. Most patients who presented with chronic symptoms of dizziness, fatigue, or pre-syncope, were deconditioned, but, because the proportion of deconditioned patients was similar in POTS vs non-POTS groups, we conclude that HR changes in POTS are not solely because of inactivity resulting in deconditioning.

To investigate the frequency of various nonorthostatic complaints in children with postural orthostatic tachycardia syndrome (POTS). We used our autonomic laboratory database to identify all pediatric patients with traditionally defined POTS who had completed the Ohio Dysautonomia Survey (ODYSA). The responses of the patients to questions targeting various autonomic complaints, including syncope, gastrointestinal symptoms, sleep disturbances, headaches, urinary symptoms, chronic pain, and Raynaud-like symptoms, were collected and analyzed. A total of 53 pediatric patients completed the ODYSA questionnaire. The participants reported high frequencies of sleep abnormalities, chronic pain, Raynaud-like symptoms, and gastrointestinal abnormalities, with lower rates of headaches, syncope, and urinary complaints. Our findings demonstrate the occurrence of various nonorthostatic symptoms in pediatric patients with POTS. These findings suggest the need for an interdisciplinary approach to the treatment and management of POTS, as well as for further investigation into the mechanisms that lead to the concurrent presentation of both orthostatic and nonorthostatic symptoms in these patients.

The aim of this study was to assess cardiac ventricular repolarization in patients with postural tachycardia syndrome (POTS) and further the possible link between ventricular repolarization and sympathetic nervous system activity. We recorded body surface ECGs together with plasma noradrenaline (NE) spillover, and muscle sympathetic nerve activity (MSNA) in twelve healthy control subjects (CON; 5 males; age: 23±2 yrs) and 13 subjects with postural tachycardia syndrome (POTS; 4 males; 32±13 yrs) during graded head-up tilt (0°-20°-30°-40°). Ventricular repolarization was assessed by computing various measures of beat-to-beat QT interval variability and T wave amplitude. In patients with POTS, baseline heart rates were higher and MSNA increases during tilt were more pronounced than in CON. None of the QT variability measures was significantly affected by tilt or different between CON and POTS when corrected for heart rate. Contrary, the T wave amplitude flattened due to tilt (p<0.001) and this effect was significantly more pronounced in POTS (32% at 40°) than in CON (21% at 40°; p=0.03). Beat-to-beat variability of the QT interval is normal in patients with POTS. However, significantly more attenuated T waves during head-up tilt together with elevated MSNA levels suggest increased sympathetic outflow to the ventricular myocardium in patients with POTS. Monitoring of the T wave during tilt test may provide a non-invasive tool for assessing excessive sympathetic outflow to the ventricular myocardium.

Postural tachycardia syndrome (POTS) is a disorder characterized by excessive orthostatic tachycardia and significant functional disability. We previously reported that POTS patients have low blood volume and inappropriately low plasma renin activity (PRA) and aldosterone. In this study, we sought to more fully characterize the renin-angiotensin-aldosterone system (RAAS) to gain a better understanding of the pathophysiology of POTS. The purpose of this study was to prospectively assess the plasma levels of angiotensin (Ang) peptides and their relationship to other RAAS components in patients with POTS compared with healthy controls. Heart rate, PRA, Ang I, Ang II, Ang (1-7), and aldosterone were measured in POTS patients (n = 38) and healthy controls (n = 13) while they were consuming a sodium-controlled diet. POTS patients had larger orthostatic increases in heart rate than did controls (52 ± 3 [mean ± SEM] bpm vs 27 ± 6 bpm, P = .001). Plasma Ang II was significantly higher in POTS patients (43 ± 3 pg/mL vs 28 ± 3 pg/mL, P = .006), whereas plasma Ang I and angiotensin 1-7 [Ang-(1-7)] were similar between groups. Despite the twofold increase of Ang II, POTS patients trended to lower PRA levels than did controls (0.9 ± 0.1 ng/mL/h vs 1.6 ± 0.5 ng/mL/h, P = .268) and lower aldosterone levels (4.6 ± 0.8 pg/mL vs 10.0 ± 3.0 pg/mL, P = .111). Estimated angiotensin-converting enzyme-2 (ACE2) activity was significantly lower in POTS patients than in controls (0.25 ± 0.02 vs 0.33 ± 0.03, P = .038). Some patients with POTS have inappropriately high plasma Ang II levels, with low estimated ACE2 activity. We propose that these abnormalities in Ang regulation may play a key role in the pathophysiology of POTS in some patients.

Orthostatic and non-orthostatic headache spectrum was prospectively studied in 24 consecutive patients with postural orthostatic tachycardia syndrome (POTS). Patients were interviewed about clinical aspects of headache and its precipitation during head-up tilt (HUT). Autonomic functions were assessed using a standard battery of tests. The relationship of orthostatic headache to cardiovascular variables was examined using unpaired two-tailed t-test. Orthostatic headache occurred during daily activity in 14 patients (58.3%) and during HUT in 15 patients (62.5%). Age under 30 years and increasing duration of tilt were predictive for orthostatic headache. Of the 24 patients, 23 (95.8%) had non-orthostatic headache fitting the criteria of migraine or probable migraine. Orthostatic headache affected two-thirds of POTS patients, especially those under age 30. Patients with orthostatic headache should be clinically assessed for POTS and informed of this association to reduce short-term morbidity. Migraine afflicted almost all POTS patients. This co-morbidity should be considered in management of POTS.

Postural orthostatic tachycardia syndrome (POTS) is associated with tachycardia on orthostasis. Patients frequently report palpitations, presyncope, and fatigue. Conventional therapy is effective in less than 60%. Case reports suggest ivabradine (a selective sinus node blocker, with no effect on blood pressure) may alleviate POTS-related symptoms. This is a retrospective case-series. Postural orthostatic tachycardia syndrome patients prescribed ivabradine were identified from the pharmacy database. Case notes were reviewed and participants completed a symptom assessment tool. Twenty-two patients were identified. Data were available from 20. Eight patients reported reduced tachycardia and fatigue and four reported only reduced tachycardia. The most common reason for discontinuing ivabradine was lack of efficacy (n = 6). Five patients reported side-effects resulting in two discontinuing treatment. This retrospective case series indicates that 60% of patients treated with ivabradine report a symptomatic improvement. A randomized controlled trial accessing the efficacy of ivabradine in POTS is indicated, particularly in patients resistant to, or intolerant of, conventional therapy.

Vasospastic disorders affecting the lower extremities are unusual entities. Two cases of asymptomatic foot discoloration with lower extremity dependency are presented. In the first case, an elderly gentleman was admitted to the hospital with a contralateral foot infection. His physical exam revealed pulse examination within normal limits and his blood work failed to identify any known causes for vasospasm. His foot infection was successfully treated with sensitivity-directed antibiotics. The second case is that of a young man with a history of quadriplegia secondary to a remote diving accident, who presented with a three-month history of foot discoloration while sitting up in his wheelchair, which resolved with recumbent leg positioning. A review of the possible diagnoses for these patients' presentation is presented herein.

The exact incidence of dizziness and vertigo during adolescence is not known. For those few adolescents who seek outpatient evaluation for these complaints, the majority are diagnosed with migraine headache. The authors provide a discussion of the differential diagnosis, evaluation, and management of vertigo and dizziness in the adolescence with emphasis on migraine headaches, chronic daily headaches, postural orthostatic tachycardia syndrome, and presentations that may require head imaging.

Orthostatic tachycardia (POTS) can occur after space flights. We determined orthostatic heart rate responses in 18 cosmonauts before and 3-5 days after long-term space missions. Cosmonauts undergoing a cardiovascular training program in space experienced only moderate POTS after their return to earth. Cardiovascular countermeasures may have attenuated POTS. Another possible interpretation is that cardiovascular deconditioning is not sufficient to elicit full blown POTS in the absence of additional genetic or environmental factors.

Postural orthostatic tachycardia syndrome (POTS) is characterized by excessive tachycardia in the upright position. To test the hypothesis that patients with POTS have impaired arterial-cardiac baroreflex function, while exercise training normalizes the baroreflex function in these patients. Seventeen POTS patients aged 27 ± 9 (mean ± SD) years underwent an exercise training program for 3 months. Arterial-cardiac baroreflex function was assessed by spectral and transfer function analysis of beat-to-beat R-R interval (RRI) and systolic blood pressure (SBP) variability in the supine position and at 60° upright tilt during spontaneous breathing before and after training. Data were compared with 17 healthy sedentary controls. Even though upright heart rate (HR) was greater in patients than controls, indexes of RRI variability did not differ between groups. Transfer function gain (SBP to RRI), used as an index of arterial-cardiac baroreflex sensitivity was similar between patients and controls in both low- (LF, P = 0.470) and high-frequency (HF, P = 0.663) ranges. Short-term exercise training decreased upright HR and increased RRI variability in POTS patients. LF baroreflex gain increased significantly in the supine position and during upright tilt [analysis of variance (ANOVA), P = 0.04 for training], while HF gain increased modestly after training (ANOVA, P = 0.105 for training) in these patients; however, the baroreflex gains remained within the normal ranges when compared with healthy controls. These data suggest that patients with POTS have normal arterial-cardiac baroreflex function in both supine and upright postures. Short-term exercise training increases the baroreflex sensitivity in these patients, associated with a decrease in upright heart rate.

Patients with postural tachycardia syndrome (POTS) commonly complain of fatigue, unrefreshing sleep, daytime sleepiness, and diminished quality of life. This study's objective was to assess the sleep quality and health-related quality of life in patients with POTS as compared with healthy control subjects. Patients with POTS (n = 44) and healthy control subjects (n = 46) completed a battery of questionnaires including Medical Outcomes Study (MOS) Sleep Survey and the Epworth Sleepiness Scale to assess sleep, fatigue visual analogue scale (VAS) to assess fatigue, and the RAND-36 and EuroQol (EQ-5D) surveys to assess health-related quality of life. Compared with healthy control subjects, patients with POTS have more sleep problems (58 ± 18 vs. 20 ± 13; p < 0.0001) and excessive daytime sleepiness (10.2 ± 5.7 vs. 6.2 ± 3.2; p < 0.0001), higher fatigue levels (7.5 ± 2.0 vs. 2.8 ± 2.5; p < 0.0001), and poor health-related quality of life (EQ-5D health thermometer 53 ± 17 vs. 89 ± 7; p < 0.0001). There were strong correlations between MOS Sleep Survey index and the fatigue VAS (Rs = 0.73; R(2) = 0.53; p < 0.0001) and the RAND-36 physical health composite scores (Rs = -0.70; R(2) = 0.53; p < 0.0001) Patients with POTS have higher subjective daytime sleepiness, fatigue, and worse sleep and health related quality of life. The sleep problems contribute significantly to the diminished quality of life: ∼ 50% of the variability in HRQL can be explained by the variability in sleep problems. Further objective studies are needed to delineate the specific nature of the sleep problems in patients with POTS.

The combination of functional brain imaging with measurement of peripheral autonomic responses in humans can provide insight into the embodiment of mental processes and the integration of cognition and emotion with changes in somatic physiology. Initial studies in healthy people and patents validate inferences from more detailed animal experiments regarding the organization of central autonomic control. In particular these have illustrated the coupling of behaviour with sympathetic arousal. Over the last two decades, the growth of emotional neuroscience alongside advances in functional brain imaging has fuelled investigations of relationships between perception, feeling states, somatic and autonomic bodily reactions. These studies have driven a more mechanistic understanding of brain systems through which bodily state is regulated and modified to support adaptive behaviour. In parallel, they have enabled the application of human neuroimaging to autonomic neuroscience. Specific methodological challenges are posed by combining physiological recordings with neuroimaging techniques, particularly functional magnetic resonance brain imaging, which are nevertheless addressable. Using such methods, the neural correlates of dynamic autonomic control has been systematically examined in studies of healthy individuals and patients with specific autonomic dysfunction (including autonomic failure, autonomic (neurally) mediated syncope and the postural tachycardia syndrome). These studies reveal antagonistic interaction of systems underpinning autonomic cardiovascular control (involving mid and subgenual cingulate cortices) and partial organ-specificity of other axes of autonomic response. Current and anticipated technical advances, including the integration of autonomically-focused microneurography and neural stimulation with advanced neuroimaging, will continue to provide detailed insight into dynamics of autonomic control. Translating these insights into clinical benefits remains a priority.

There is anecdotal evidence that one or more forms of orthostatic intolerance (OI) subgroups may coexist in the same patients. However, there is a paucity of published data on the clinical features and management of patients who suffer from coexisting features of postural tachycardia syndrome (POTS) and neurocardiogenic syncope (NCS). We herein present our experience of 18 patients who we found displayed evidence of coexisting NCS and POTS. We reviewed charts of 300 POTS patients seen at the University of Toledo Syncope and Autonomic Disorders Center from 2003 to 2010 and found 18 patients eligible for inclusion in this study. Patients were included in this study if they reported clinical symptoms consistent with both POTS and NCS and then demonstrated a typical POTS pattern (a rise in heart rate without change in blood pressure [BP]) on head up tilt table (HUTT) within the first 10 minutes of upright posture followed by a neurocardiogenic pattern (a sudden fall in heart rate and/or fall in blood pressure) reproducing symptoms that were similar to the patients spontaneous episodes. We found 18 patients, mean age (30 ± 12), with 15 (84%) women and three (16%) men, who met the inclusion criterion for this study. Each of these 18 patients demonstrated a typical POTS pattern within the first 10 minutes on initial physical exam and on a HUTT. Continued tilting beyond 10 minutes resulted in a sudden decline in heart rate (which in some patients manifested as an asystole that lasted anywhere between 10 and 32 seconds [mean of 18 seconds]) and/or a fall in BP in each of these patients demonstrating a pattern consistent with neurocardiogenic subtype of OI. The mean time to the NCS pattern of a fall in BP and heart was 15 minutes with a range of 13-20 minutes. This group of patients was highly symptomatic and reported frequent clinical symptoms that were suggestive of OI. Recurrent presyncope, syncope, orthostatic palpitations, exercise intolerance, and fatigue were the principal symptoms reported. NCS may coexist with POTS in a subgroup of patients suffering from OI.

The long-term efficacy of pyridostigmine, a reversible acetyl cholinesterase inhibitor, in the treatment of postural orthostatic tachycardia syndrome (POTS) patients remains unclear. We report our retrospective, single-center, long-term experience regarding the efficacy and adverse effect profile of pyridostigmine in the treatment of POTS patients. This retrospective study included an extensive review of electronic charts and data collection in regards to patient demographics, orthostatic parameters, side-effect profile, subjective response to therapy, as well as laboratory studies recorded at each follow-up visit to our institution's Syncope and Autonomic Disorders Center. The response to pyridostigmine therapy was considered successful if patient had both symptom relief in addition to an objective response in orthostatic hemodynamic parameters (heart rate [HR] and blood pressure). Three hundred patients with POTS were screened for evaluation in this study. Of these 300, 203 patients with POTS who received pyridostigmine therapy were reviewed. Of these 203 patients, 168 were able to tolerate the medication after careful dose titration. The mean follow-up duration in this group of patients was 12 ± 3 (9-15) months. Pyridostigmine improved symptoms of orthostatic intolerance in 88 of 203 (43%) of total patients or 88 of 172 (51%) who were able to tolerate the drug. The symptoms that improved the most included fatigue (55%), palpitations (60%), presyncope (60%), and syncope (48%). Symptom reduction correlated with a statistically significant improvement in upright HR and diastolic blood pressure after treatment with pyridostigmine as compared to their baseline hemodynamic parameters (standing HR 94 ± 19 vs 82 ± 16, P < 0.003, standing diastolic blood pressure 71 ± 11 vs 74 ± 12, P < 0.02). Gastrointestinal problems were the most common adverse effects (n = 39, 19%) reported. The overall efficacy of pyridostigmine in our study was seen in 42% of total patients or 52% of patients who could tolerate taking the drug. The subgroup of POTS patients who can tolerate oral pyridostigmine may demonstrate improvement in their standing HR, standing diastolic blood pressure, and clinical symptoms of orthostatic intolerance.

Syncope accounts for about 1-2% of emergency department visits, but the etiology in many patients with syncope is unclear. Recently, with the use of the head-up tilt test (HUT), the number of patients with unexplained syncope (UPS) has been decreasing; however, the spectrum of underlying diseases of syncope in children is unclear. This retrospective study aimed to analyze the spectrum of underlying diseases in children with syncope. This multi-center clinical study consisted of 888 children (417 males, 471 females, aged 5-18 yrs, median age 12.0±3.0 yrs) with syncope who came from Beijing city, Hunan province, Hubei province and Shanghai from August 1999 to March 2009. The clinical and laboratory data of children were studied and the spectrum of underlying diseases in children with syncope was analyzed. In 888 children with syncope, 175 (19.7%) had vasovagal syncope (VVS) with vasoinhibitory response, 35 (3.9%) had VVS with cardioinhibitory response, 73 (8.2%) had VVS with mixed response, 286 (32.2%) had postural orthostatic tachycardia syndrome (POTS), 19 (2.1%) had orthostatic hypotension, 7 (0.9%) had situational syncope, 13 (1.5%) had cardiogenic syncope, and 280 (31.5%) had unexplained syncope. The data suggest that neurally-mediated syncope was the most common cause in children with syncope. POTS and VVS were the most common hemodynamic patterns of neurally-mediated syncope.