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Concept: Orthostatic intolerance


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.

Concepts: Medical terms, Cardiology, Symptoms, Symptom, Orthostatic hypotension, Post-concussion syndrome, Postural orthostatic tachycardia syndrome, Orthostatic intolerance


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.

Concepts: Psychology, Cognitive psychology, Cognition, Neurology, Perception, Mind, Postural orthostatic tachycardia syndrome, Orthostatic intolerance


Infections with human papilloma virus (HPV) can result in cervical, oropharyngeal, anal, and penile cancer and vaccination programs have been launched in many countries as a preventive measure. We report the characteristics of a number of patients with a syndrome of orthostatic intolerance, headache, fatigue, cognitive dysfunction, and neuropathic pain starting in close relation to HPV vaccination.

Concepts: Immune system, Cancer, Human papillomavirus, Cervical cancer, HPV vaccine, Anal cancer, Postural orthostatic tachycardia syndrome, Orthostatic intolerance


Postural tachycardia syndrome (POTS) is defined by a heart rate increment of 30 beats/min or more within 10 minutes of standing or head-up tilt in the absence of orthostatic hypotension; the standing heart rate is often 120 beats/min or higher. POTS manifests with symptoms of cerebral hypoperfusion and excessive sympathoexcitation. The pathophysiology of POTS is heterogeneous and includes impaired sympathetically mediated vasoconstriction, excessive sympathetic drive, volume dysregulation, and deconditioning. POTS is frequently included in the differential diagnosis of chronic unexplained symptoms, such as inappropriate sinus tachycardia, chronic fatigue, chronic dizziness, or unexplained spells in otherwise healthy young individuals. Many patients with POTS also report symptoms not attributable to orthostatic intolerance, including those of functional gastrointestinal or bladder disorders, chronic headache, fibromyalgia, and sleep disturbances. In many of these cases, cognitive and behavioral factors, somatic hypervigilance associated with anxiety, depression, and behavioral amplification contribute to symptom chronicity. The aims of evaluation in patients with POTS are to exclude cardiac causes of inappropriate tachycardia; elucidate, if possible, the most likely pathophysiologic basis of postural intolerance; assess for the presence of treatable autonomic neuropathies; exclude endocrine causes of a hyperadrenergic state; evaluate for cardiovascular deconditioning; and determine the contribution of emotional and behavioral factors to the patient’s symptoms. Management of POTS includes avoidance of precipitating factors, volume expansion, physical countermaneuvers, exercise training, pharmacotherapy (fludrocortisone, midodrine, β-blockers, and/or pyridostigmine), and behavioral-cognitive therapy. A literature search of PubMed for articles published from January 1, 1990, to June 15, 2012, was performed using the following terms (or combination of terms): POTS; postural tachycardia syndrome, orthostatic; orthostatic; syncope; sympathetic; baroreceptors; vestibulosympathetic; hypovolemia; visceral pain; chronic fatigue; deconditioning; headache; Chiari malformation; Ehlers-Danlos; emotion; amygdala; insula; anterior cingulate; periaqueductal gray; fludrocortisone; midodrine; propranolol; β-adrenergic; and pyridostigmine. Studies were limited to those published in English. Other articles were identified from bibliographies of the retrieved articles.

Concepts: Hypertension, Cardiology, Orthostatic hypotension, Vasoconstriction, Postural orthostatic tachycardia syndrome, Ehlers-Danlos syndrome, Arnold-Chiari malformation, Orthostatic intolerance


This study aimed at examining three tilt angle-based positive responses and the time to positive response in a head-up tilt test for children with orthostatic intolerance, and the psychological fear experienced at the three angles during head-up tilt test. A total of 174 children, including 76 boys and 98 girls, aged from 4 to 18 years old (mean 11.3±2.8 years old), with unexplained syncope, were randomly divided into three groups, to undergo head-up tilt test at the angles of 60°, 70° and 80°, respectively. The diagnostic rates and times were analysed, and Wong-Baker face pain rating scale was used to access the children’s psychological fear. There were no significant differences in diagnostic rates of postural orthostatic tachycardia syndrome and vasovagal syncope at different tilt angles during the head-up tilt test (p>0.05). There was a significant difference, however, in the psychological fear at different tilt angles utilising the Kruskal-Wallis test (χ2=36.398, p<0.01). It was mildest at tilt angle 60° utilising the Kolmogorov-Smirnov test (p<0.01). A positive rank correlation was found between the psychological fear and the degree of tilt angle (rs=0.445, p<0.01). Positive response appearance time was 15.1±14.0 minutes at 60° for vasovagal syncope children. There was no significant difference in the time to positive response, at different tilt angles during the head-up tilt test for vasovagal syncope or for postural orthostatic tachycardia syndrome. Hence, it is suggested that a tilt angle of 60° and head-up tilt test time of 45 minutes should be suitable for children with vasovagal syncope.

Concepts: Statistical tests, Cardiology, Statistical significance, Non-parametric statistics, Difference, Orthostatic hypotension, Postural orthostatic tachycardia syndrome, Orthostatic intolerance


Postural tachycardia syndrome (POTS) is characterized by symptoms of orthostatic intolerance. Antibodies of acetylcholine receptor (AChR-ab) affect acetylcholine transmission between the ganglia and result in imbalance of the autonomic nervous system in POTS. This study was designed to analyze the clinical characteristics of POTS patients with AChR-ab positive and explore the value of AChR-ab in children with POTS. In 82 children with POTS, twenty patients (24.39 %) were found as AChR-ab positive. Their clinical characteristics and hemodynamic responses to orthostatic changes were compared with the remaining 60 patients with negative AChR-ab. Symptoms of POTS children with AChR-ab positive were significantly severe than those of AChR-ab negative patients (p = 0.001). Preceding infection was predominant in patients with AChR-ab positive compared with that of patients with AChR-ab negative (p < 0.001). Syncope and fatigue were more common in the AChR-ab positive patients (p < 0.05). The change of upright heart rate was increased significantly in AChR-ab positive patients compared with AChR-ab negative cases (p = 0.013). Multiple logistic regression analysis revealed that preceding infection (OR 22.356, 95 % CI 2.151-34.920), syncope (OR 11.570, 95 % CI 2.098-63.810), and fatigue (OR 11.145, 95 % CI 1.658-74.911) were independent risk factors for POTS with AChR-ab positive. In conclusion, POTS with positive AChR-ab was a heterogeneous disorder. Preceding infection, syncope and fatigue were their main clinical characteristics.

Concepts: Nervous system, Regression analysis, Logistic regression, Cardiology, Acetylcholine, Orthostatic hypotension, Postural orthostatic tachycardia syndrome, Orthostatic intolerance


The postural tachycardia syndrome (POTS) is a heterogeneous group of disorders that results in symptoms of orthostatic intolerance. Excess blood pooling has been observed to cause low effective circulating volume in the central vasculature. Consequently, acute volume loading with IV saline has emerged as a potential strategy for clinical intervention. We evaluated the impact of acute volume loading on both the signs and symptoms of patients suffering from POTS.

Concepts: Cardiology, The Canon of Medicine, Effectiveness, Neurology, Syndromes, Orthostatic hypotension, Postural orthostatic tachycardia syndrome, Orthostatic intolerance


The prevalence of postural orthostatic tachycardia syndrome (POTS) in adolescents and young adults has been increasing during the past decade. Despite this increase, documentation regarding treatment of these patients is just beginning to emerge. In addition, despite a call for a multidisciplinary or interdisciplinary approach, no studies have examined the efficacy of such an approach to treatment. This paper describes a case study of a 19-year-old male with debilitating POTS seen at a tertiary clinic for evaluation and subsequent intensive interdisciplinary treatment. The treatment approach is described and outcomes are presented.

Concepts: Evaluation methods, Case study, Cultural studies, Orthostatic hypotension, Postural orthostatic tachycardia syndrome, Interdisciplinarity, Multidisciplinarity, Orthostatic intolerance


While strongly implicated in postural tachycardia syndrome (POTS), considerable controversy exists regarding norepinephrine transporter (NET) loss of function. POTS is characterized by the clinical symptoms of orthostatic intolerance, lightheadedness, tachycardia, and syncope or near syncope with upright posture. Abnormal sympathetic nervous system activity is typical, of a type which suggests dysfunction of the NET, with evidence that the gene responsible is under tight epigenetic control. Using RNA of isolated chromatin combined with massive parallel sequencing (RICh-seq) we show that let-7i miRNA suppresses NET by methyl-CpG-binding protein 2 (MeCP2). Vorinostat restores epigenetic control and NET expression in leukocytes derived from POTS participants.

Concepts: DNA, Gene, Cardiology, Epinephrine, Orthostatic hypotension, Norepinephrine, Postural orthostatic tachycardia syndrome, Orthostatic intolerance


Both the adrenergic and renin-angiotensin systems contribute to orthostatic circulatory homeostasis, which is impaired in postural orthostatic tachycardia syndrome (POTS). Activating autoantibodies to the α1-adrenergic and β1/2-adrenergic receptors have previously been found in sera from patients with POTS. We hypothesized that patients with POTS might also harbor activating autoantibodies to the angiotensin II type 1 receptor (AT1R) independently of antiadrenergic autoimmunity. This study examines a possible pathophysiological role for AT1R autoantibodies in POTS.

Concepts: Endocrinology, Angiotensin, Postural orthostatic tachycardia syndrome, Orthostatic intolerance