Symptoms Of Orthostatic Intolerance Research Articles

Characterization of Autonomic Dysfunction Among Migraineurs With and Without Complaints of Orthostatic Intolerance

Purpose and Hypothesis: To identify and distinguish central autonomic dysfunction from peripheral autonomic dysfunction (or both) in migraineurs suffering from orthostatic intolerance (OI) compared to migraineurs not suffering from OI. We hypothesize that OI manifests from a predominantly central autonomic component. Methods: We studied two populations of migraineurs, one group complaining of symptoms of OI for 6 months or longer and a group without OI symptoms, using a 70-degree, 45-minute passive head-up tilt-table test (HUT), R-R interval measurements during deep breathing, blood pressure and heart rate monitoring during Valsalva maneuver and release, Quantitative Sudomotor Axon Reflex Test (QSART), and skin biopsy for intraepidermal nerve fiber density. Categorical differences between the two populations were compared using exact likelihood ratio chi-square tests, and 95% confidence intervals for sensitivity, specificity, positive and negative predictive values were calculated. Results: Thirty-seven migraineurs with OI (Group 1) and 22 migraineurs without (Group 2) were studied and were demographically similar except for a greater representation of migraines with brainstem auras in Group 1 (27% v 5%; p= 0.032). Ninety-seven percent of Group 1 patients, versus 68% Group 2, manifested abnormal 45-minutes HUT, a significant difference (p=0.020, Fisher’s exact test). The first 5-minute evaluation of the HUT exhibited high specificity (1.00; 95% CI: 0.85-1.00) for the diagnosis of postural tachycardia syndrome (POTS) with a positive predictive value of 1.00 (0.59, 1.00; p=0.037). The HUT extended to 45-minutes however showed greater sensitivity compared with the 10-minute HUT (0.95; 95% CI:0.82-0.99; p=0.020). We found no differences between groups in autonomic laboratory or skin biopsy findings. Fifty-seven percent of Group 1 and 50% of Group 2 exhibited biopsy-proven small fiber neuropathy (SFN), a difference that did not reach statistical significance. Conclusions: We failed to confirm our hypothesis that OI is a manifestation of a central autonomic dysfunction in migraineurs. The finding of SFN in a majority of subjects points to peripheral autonomic contributions and raises the possibility of an underlying systemic disorder. Extending HUT table testing to 45-minutes increases diagnostic sensitivity and better reflects life events. Funding Statement: This study was supported by a grant from the Bakken Heart-Brain Institute, Cleveland Clinic, Cleveland, Ohio, USA. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The study was approved by the Cleveland Clinic’s Institutional Review Board. Informed consent was obtained from all participants in the study.

Postural orthostatic tachycardia syndrome in patients of orthostatic intolerance symptoms: an ambispective study.

BackgroundA Postural orthostatic tachycardia syndrome (POTS) is infrequently diagnosed in routine practice because of the variable range of symptoms that could be seen in cardiac rhythm disorders, vertigo, chronic fatigue syndrome and anxiety panic disorder. POTS is a chronic debilitating condition that affects day to day efficient working of an individual. We have planned a study to look for POTS in patients who are having orthostatic intolerance symptoms and underwent a head-up tilt table test (HUTT).AimTo study the prevalence of POTS in patients of orthostatic intolerance (OI) symptoms and to analyze symptomatology, its association with neurocardiogenic syncope (NCS), and its outcome.MethodsWe reviewed the medical records of 246 patients presented with symptoms of OI seen at our centre from January 2010 till March 2019. Out of them, 40 patients included, those qualifying the criteria for POTS on HUTT.ResultsThe mean age of the cohort was 25.90 ± 10.33 years with a range of 15 to 55 years, and males comprised 52.5% (21/40) of total patients. The most frequent presenting orthostatic symptoms of POTS patients are loss of consciousness (77.5%), lightheadedness (75%), and palpitation (67.5%). A total of 18 patients (45%) had coexisting neurocardiogenic syncope.ConclusionPOTS is a prevalent condition and have a significant impact on the quality of life, and the majority of patients may not present with OI symptoms during HUTT. We have to keep this possibility in young patients of transient loss of consciousness because it may coexist with NCS.

Downregulation of growth hormone in postural orthostatic tachycardia syndrome: insights from the SYSTEMA cohort

Abstract Background Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular autonomic disorder occurring predominantly in young women. POTS is characterized by an excessive heart rate increase when assuming upright posture accompanied by symptoms of orthostatic intolerance. The pathophysiology of POTS has not been fully established and is believed to be multifactorial. Purpose We aimed to investigate the alterations in circulating growth hormone level in POTS. Methods We conducted an age-matched case-control study enrolling 42 patients with POTS (age 31±9 years; 36 women) verified by positive head-up tilt testing and cardiovascular autonomic tests, and 46 controls (32±9 years; 35 women) with negative active standing test and no history of syncope, orthostatic intolerance and endocrine disease. We measured plasma levels of growth hormone using a high-sensitivity chemiluminescence immunoassay in relation to presence of POTS diagnosis. All study participants completed the validated Orthostatic Hypotension Questionnaire (OHQ), consisting of two components: the symptoms assessment scale (OHSA) and daily activity scale (OHDAS) to evaluate the burden of symptoms. We applied standard statistical tests for group differences. Growth hormone values were log-transformed and standardized before the group comparison. Results POTS patients had significantly lower plasma levels of growth hormone (ng/mL) (median=0.53, IQR, 0.10–2.83 vs. median=2.33, IQR, 0.26–7.2, p=0.04) than controls. Levels of growth hormone were reversely related to OHDAS (p=0.049) among POTS patients. Supine heart rate was significantly higher in POTS patients (69.0±11.1 beats/min vs. 63.3±10.8 beats/min, p=0.02), as well as diastolic blood pressure (72.9±9.1 mmHg vs. 69.0±8.5 mmHg, p=0.04). We observed no significant difference in supine systolic blood pressure (116.6±13.3 mmHg vs. 115.2±10.0 mmHg, p=0.60). POTS patients had a significantly higher composite OHQ score than controls (60.0±18.6 vs. 4.2±7.5, p<0.001), as well as OHSA (36.2±10.0 vs. 3.6±6.4, p<0.001) and OHDAS (23.8±9.7 vs. 0.6±1.3, p<0.001). Conclusion(s) Our study shows that patients with POTS have significantly reduced plasma levels of circulating growth hormone. Lower growth hormone levels among POTS patients are associated with increased impairment of daily life activities. Further studies are necessary to confirm our findings in the independent populations and explain the mechanisms behind this alteration. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Crafoord Foundation, Swedish Heart and Lung Foundation

Regional analysis of cerebral hemodynamic changes during the head-up tilt test in Parkinson's disease patients with orthostatic intolerance.

.Significance: Cerebral oxygenation changes in the superior, middle, and medial gyri were used to elucidate spatial impairments of autonomic hemodynamic recovery during the head-up tilt table test (HUTT) in Parkinson’s disease (PD) patients with orthostatic intolerance (OI) symptoms.Aim: To analyze dynamic oxygenation changes during the HUTT and classify PD patients with OI symptoms using clinical and oxygenation features.Approach: Thirty-nine PD patients with OI symptoms [10: orthostatic hypotension (PD-OH); 29: normal HUTT results (PD-NOR)] and seven healthy controls (HCs) were recruited. Prefrontal oxyhemoglobin (HbO) changes during the HUTT were reconstructed with diffuse optical tomography and segmented using the automated anatomical labeling system. Decision trees were used for classification.Results: HCs and PD-NOR patients with positive rates of HbO change (PD-POS) showed the greatest HbO recovery in the superior frontal gyrus (SFG) during tilt. PD-OH and PD-NOR patients with negative rates of HbO change (PD-NEG) showed asymmetric reoxygenation. The classification accuracy was 89.4% for PD-POS versus PD-NEG, 71% for PD-NOR versus PD-OH, and 55.8% for PD-POS versus PD-NEG versus PD-OH. The oxygenation features were more discriminative than the clinical features.Conclusions: PD-OH showed decreased right SFG function, which may be associated with impaired compensatory autonomic responses to orthostatic stress.

Reductions in Cerebral Blood Flow Can Be Provoked by Sitting in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients.

Introduction: In a large study with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients, we showed that 86% had symptoms of orthostatic intolerance in daily life and that 90% had an abnormal reduction in cerebral blood flow (CBF) during a standard tilt test. A standard head-up tilt test might not be tolerated by the most severely affected bed-ridden ME/CFS patients. Sitting upright is a milder orthostatic stress. The present study examined whether a sitting test, measuring cerebral blood flow by extracranial Doppler, would be sufficient to provoke abnormal reductions in cerebral blood flow in severe ME/CFS patients. Methods and results: 100 severe ME/CFS patients were studied, (88 females) and were compared with 15 healthy controls (HC) (13 females). CBF was measured first while seated for at least one hour, followed by a CBF measurement in the supine position. Fibromyalgia was present in 37 patients. Demographic data as well as supine heart rate and blood pressures were not different between ME/CFS patients and HC. Heart rate and blood pressure did not change significantly between supine and sitting both in patients and HC. Supine CBF was not different between patients and HC. In contrast, absolute CBF during sitting was lower in patients compared to HC: 474 (96) mL/min in patients and 627 (89) mL/min in HC; p < 0.0001. As a result, percent CBF reduction while seated was −24.5 (9.4)% in severe ME/CFS patients and −0.4 (1.2)% in HC (p < 0.0001). In the ten patients who had no orthostatic intolerance complaints in daily life, the CBF reduction was −2.7 (2.1)%, which was not significantly different from HC (p = 0.58). The remaining 90 patients with orthostatic intolerance complaints had a −26.9 (6.2)% CBF reduction. No difference in CBF parameters was found in patients with and without fibromyalgia. Patients with a previous diagnosis of postural orthostatic tachycardia syndrome (POTS) had a significantly larger CBF reduction compared with those without POTS: 28.8 (7.2)% vs. 22.3 (9.7)% (p = 0.0008). Conclusions: A sitting test in severe ME/CFS patients was sufficient to provoke a clinically and statistically significant mean CBF decline of 24.5%. Patients with a previous diagnosis of POTS had a larger CBF reduction while seated, compared to patients without POTS. The magnitude of these CBF reductions is similar to the results in less severely affected ME/CFS patients during head-up tilt, suggesting that a sitting test is adequate for the diagnosis of orthostatic intolerance in severely affected patients.

Baroreflex function in Parkinson's disease: insights from the modified-Oxford technique.

Nonmotor symptoms are common in Parkinson's disease (PD) and they include dysregulation of cardiovascular system, which adversely affects quality of life. Recent studies provide indirect evidence that baroreflex dysfunction may be one of the mechanisms of cardiovascular dysregulation in PD. Herein, we tested the hypothesis that the baroreflex gain, assessed across an extensive range of the reflex arc by eliciting rapid changes in blood pressure (BP) induced by sequential boluses of vasoactive drugs (modified-Oxford technique) would be attenuated in middle-aged patients with PD. Beat-to-beat heart rate (electrocardiography) and BP (finger photoplethysmography) were obtained during 10 min of supine rest preceding the modified-Oxford (bolus of nitroprusside followed by phenylephrine 1 min afterward) in 11 patients with PD (51 ± 6 yr) and 7 age-matched controls (47 ± 6 yr). The resulting systolic BP and R-R interval responses were plotted and fitted with segmental linear regression and symmetric sigmoid model. Spontaneous indices obtained via sequence technique were also used to estimate baroreflex gain. Compared with controls, the estimated gains measured by segmental linear regression (patients: 3.83 ± 2.6 ms/mmHg versus controls: 7.78 ± 1.7 ms/mmHg; P = 0.003) and symmetric sigmoid model (patients: 12.36 ± 6.9 ms/mmHg versus controls: 32.02 ± 19.0 ms/mmHg; P = 0.009) were lower in patients with PD. The operating range of BP was larger in patients with PD compared with controls (13 ± 7 mmHg versus controls: 7 ± 3 mmHg; P = 0.032). Of note, the gain obtained from spontaneous indices was similar between groups. These data indicate that baroreflex gain was reduced by >50% in PD, thereby providing clear and direct evidence that cardiovagal baroreflex dysfunction occurs in PD.NEW & NOTEWORTHY Attenuated baroreflex gain may contribute to adverse cardiovascular outcomes, including orthostatic intolerance symptoms typically observed in patients with Parkinson's disease. We found that the baroreflex gain (assessed by the modified-Oxford technique) is attenuated and accompanied by an increased operating range in patients with Parkinson's disease. These findings highlight that cardiovascular perturbations are required to detect baroreflex impairments and that spontaneous indices do not reveal cardiovagal-baroreflex dysfunction in a middle-aged group of patients with Parkinson's disease.

Postural Tachycardia Syndrome in Children and Adolescents: Pathophysiology and Clinical Management.

Postural tachycardia syndrome (POTS), characterized by chronic (≥6 months) orthostatic intolerance symptoms with a sustained and excessive heart rate increase while standing without postural hypotension, is common in children and adolescents. Despite the unclear pathogenesis of POTS, the present opinion is that POTS is a heterogeneous and multifactorial disorder that includes altered central blood volume, abnormal autonomic reflexes, “hyperadrenergic” status, damaged skeletal muscle pump activity, abnormal local vascular tension and vasoactive factor release, mast cell activation, iron insufficiency, and autoimmune dysfunction. A number of pediatric POTS patients are affected by more than one of these pathophysiological mechanisms. Therefore, individualized treatment strategies are initiated in the management of POTS, including basal non-pharmacological approaches (e.g., health education, the avoidance of triggers, exercise, or supplementation with water and salt) and special pharmacological therapies (e.g., oral rehydration salts, midodrine hydrochloride, and metoprolol). As such, the recent progress in the pathogenesis, management strategies, and therapeutic response predictors of pediatric POTS are reviewed here.

Hemodynamics during the 10-minute NASA Lean Test: evidence of circulatory decompensation in a subset of ME/CFS patients

BackgroundLightheadedness, fatigue, weakness, heart palpitations, cognitive dysfunction, muscle pain, and exercise intolerance are some of the symptoms of orthostatic intolerance (OI). There is substantial comorbidity of OI in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome). The 10-minute NASA Lean Test (NLT) is a simple, point-of-care method that can aid ME/CFS diagnosis and guide management and treatment of OI. The objective of this study was to understand the hemodynamic changes that occur in ME/CFS patients during the 10-minute NLT.MethodsA total of 150 ME/CFS patients and 75 age, gender and race matched healthy controls (HCs) were enrolled. We recruited 75 ME/CFS patients who had been sick for less than 4 years (< 4 ME/CFS) and 75 ME/CFS patients sick for more than 10 years (> 10 ME/CFS). The 10-minute NLT involves measurement of blood pressure and heart rate while resting supine and every minute for 10 min while standing with shoulder-blades on the wall for a relaxed stance. Spontaneously reported symptoms are recorded during the test. ANOVA and regression analysis were used to test for differences and relationships in hemodynamics, symptoms and upright activity between groups.ResultsAt least 5 min of the 10-minute NLT were required to detect hemodynamic changes. The < 4 ME/CFS group had significantly higher heart rate and abnormally narrowed pulse pressure compared to > 10 ME/CFS and HCs. The < 4 ME/CFS group experienced significantly more OI symptoms compared to > 10 ME/CFS and HCs. The circulatory decompensation observed in the < 4 ME/CFS group was not related to age or medication use.ConclusionsCirculatory decompensation characterized by increased heart rate and abnormally narrow pulse pressure was identified in a subgroup of ME/CFS patients who have been sick for < 4 years. This suggests inadequate ventricular filling from low venous pressure. The 10-minute NLT can be used to diagnose and treat the circulatory decompensation in this newly recognized subgroup of ME/CFS patients. The > 10 ME/CFS group had less pronounced hemodynamic changes during the NLT possibly from adaptation and compensation that occurs over time. The 10-minute NLT is a simple and clinically useful point-of-care method that can be used for early diagnosis of ME/CFS and help guide OI treatment.

Heart Rate Variability in Head-Up Tilt Tests in Adolescent Postural Tachycardia Syndrome Patients.

Introduction: Postural tachycardia syndrome (POTS) is a suspected dysautonomia with symptoms of orthostatic intolerance and abnormally increased heart rate while standing. We aimed to study cardiac autonomic nervous system functioning in head-up tilt (HUT) in adolescents with POTS to find out if parasympathetic tone is attenuated in the upright position.Methods: We compared characteristics of a group of 25 (females 14/25; 56%) adolescents with POTS and 12 (females 4/12; 34%) without POTS aged 9–17 years. We compared heart rate variability with high- and low-frequency oscillations, and their temporal changes in HUT.Results: The high-frequency oscillations, i.e., HF, attenuated in both groups during HUT (p < 0.05), but the attenuation was bigger in POTS (p = 0.04). In the beginning of HUT, low-frequency oscillations, i.e., LF, increased more in POTS (p = 0.01), but in the end of HUT, an attenuation in LF was seen in the POTS group (p < 0.05), but not in the subjects without POTS. There were no associations of previous infections or vaccinations with POTS. Subjects with POTS were sleepier and their overall quality of life was very low.Conclusion: The results imply to an impaired autonomic regulation while standing in POTS, presenting as a lower HF and higher LF in the beginning of HUT and an attenuated LF in the prolonged standing position.

Differential diagnosis of orthostatic hypotension.

Orthostatic hypotension (OH) is a common clinical manifestation characterized by a significant fall in blood pressure with postural change and is frequently accompanied by debilitating symptoms of orthostatic intolerance. The reported prevalence of OH ranges between 5 and 10% in middle-aged adults with a burden that increases concomitantly with age; in those over 60years of age, the prevalence is estimated to be over 20%. Unfortunately, the clinical course of OH is not necessarily benign. OH patients are at an increased risk of adverse clinical outcomes including death, falls, cardiovascular and cerebrovascular events, syncope, and impaired quality of life. The differential diagnosis of OH is broad and includes acute precipitants as well as chronic underlying medical conditions, especially of neurological origin. Appropriate diagnosis relies on a systematic history and physical examination with particular attention to orthostatic vital signs, keeping in mind that ambient conditions during diagnostic testing may affect OH detection due to factors such as diurnal variation.

Orthostatic Hypertension in Children: An Update.

The concept of orthostatic hypertension in children was first proposed in 2012. The pathogenesis is not clear by now. Orthostatic hypertension is one of the important causes of orthostatic intolerance in children and is related to the development of essential hypertension in the future. It is commonly seen in older children, with dizziness and syncope as their main clinical manifestations. Non-drug therapy is the commonly used treatment strategy, which is effective to improve the orthostatic intolerance symptoms. In this paper, we reviewed the clinical studies on the pathogenesis, clinical characteristics, diagnostic criteria, and treatment of orthostatic hypertension in children, aiming to provide new insights for the future studies on pediatric orthostatic hypertension.

Short-term efficacy of ORS formulation and propranolol regimen in children with POTS

BackgroundTo evaluate the short-term effectiveness of reduced-osmolarity oral rehydration salt formulation (ORS) and propranolol in children diagnosed with postural orthostatic tachycardia syndrome (POTS) in head-up tilt testing (HUTT). MethodsChildren were admitted with symptoms of orthostatic intolerance (OI) occurring in a standing position and disappearing in the supine position. Patients with heart rate increments of ≥40bpm and symptoms of OI constituted the pediatric POTS group in HUTT. A total of 70 pediatric patients with POTS were included in the study. POTS patients were divided into two groups based on whether they were prescribed reduced-osmolarity ORS and propranolol or not. The study group comprised patients on a regimen of reduced-osmolarity ORS and propranolol (n=34), while the control group comprised patients who were not prescribed any medication (n=36). The frequency of symptoms and standardized symptom scores were analyzed before and after 3 months of treatment in both groups. ResultsThe post-treatment frequency of syncopal attacks was significantly reduced in both groups (P<0.01 for both groups), but the post-treatment standardized symptom scores were significantly reduced in the pediatric study group compared with the control group (P<0.01). ConclusionThe frequency of syncopal attacks was significantly reduced and the symptom scores for OI were improved in the study group. The improvement in OI symptom scores was better in the treatment group than in the control group. The control group symptoms persisted and caused extreme difficulty in their daily activities. In view of its clinical efficacy, we strongly advocate the use of combined treatment of reduced-osmolarity ORS and low-dose propranolol in pediatric patients with POTS.

Symptom Score: A New Instrument to Assess Orthostatic Intolerance in Children and Adolescents.

To develop an orthostatic intolerance symptom scoring system to assess orthostatic intolerance and then to compare the symptom score among different head-up tilt test responses. 272 subjects (5-18 years) presenting with orthostatic intolerance symptoms finished questionnaire and head-up tilt test. According to head-up tilt test hemodynamic responses, the subjects were divided into head-up tilt test negative, vasovagal syncope, and postural tachycardia syndrome groups. We built up a symptom score according to the frequency of dizziness, headache, blurred vision, palpitations, chest discomfort, gastrointestinal symptoms, profuse perspiration, and syncope. The median score in postural tachycardia syndrome subjects was highest. A score of 2.5 for predicting vasovagal syncope yielded a sensitivity of 75.0% and specificity of 50.3%, a score of 5.5 for predicting postural tachycardia syndrome yielded a sensitivity of 69.7% and specificity of 72.0%. Furthermore, the median score in postural tachycardia syndrome subjects was significantly higher than that in head-up tilt test negative subjects with heart rate increment of 30-39 beats/min (P < .01). This suggests that the symptom score has some predictive value in head-up tilt test results, which can be served as a preliminary assessment instrument.

Increased Salt Intake for Orthostatic Intolerance Syndromes: A Systematic Review and Meta-Analysis

BackgroundGuidelines recommend increased salt intake as a first-line recommendation in the management of symptomatic orthostatic hypotension and recurrent syncope. There have been no systematic reviews of this intervention. We sought to summarize the evidence for increased salt intake in patients with orthostatic intolerance syndromes. MethodsWe conducted a systematic review and meta-analysis of studies in PubMed, EMBASE, and CINAHL. Interventional studies that increased salt intake in individuals with orthostatic intolerance syndromes were included. Primary outcome measures included incidence of falls and injuries, and rates of syncope and presyncope. Secondary outcome measures included other orthostatic intolerance symptoms, blood pressure, and heart rate. ResultsA total of 14 studies were eligible, including participants with orthostatic hypotension, syncope, postural orthostatic tachycardia syndrome, and idiopathic orthostatic tachycardia (n = 391). Mean age was 35.6 (± 15) years. All studies were small and short-term (<60 mins-90 days). No study reported on the effect of increased salt intake on falls or injuries. Meta-analysis demonstrated that during head-up tilt, mean time to presyncope with salt intake increased by 1.57 minutes (95% confidence interval [CI], 1.26-1.88), mean systolic blood pressure increased by 12.27 mm Hg (95% CI, 10.86-13.68), and mean heart rate decreased by −3.97 beats per minute (95% CI, −4.08 to −3.86), compared with control. Increased salt increased supine blood pressure by 1.03 mm Hg (95% CI, 0.81 to 1.25). Increased salt intake resulted in an improvement or resolution of symptoms in 62.3% (95% CI, 51.6 to 72.6) of participants in short-term follow-up studies (mean follow-up of 44.3 days, 6 studies; n=91). Methodological quality of studies were low with high statistical heterogeneity in all meta-analyses. ConclusionsOur meta-analysis provides low-quality evidence of a short-term improvement in orthostatic intolerance with increased salt intake. There were no clinical trials demonstrating the efficacy and safety of increased salt intake on long-term clinical outcomes. Overall, there is a paucity of clinical trial evidence to support a cornerstone recommendation in the management of orthostatic intolerance syndromes.

Cerebral Blood Flow Is Reduced in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients During Mild Orthostatic Stress Testing: An Exploratory Study at 20 Degrees of Head-Up Tilt Testing.

Introduction: In a study of 429 adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), we demonstrated that 86% had symptoms of orthostatic intolerance in daily life. Using extracranial Doppler measurements of the internal carotid and vertebral arteries during a 30-min head-up tilt to 70 degrees, 90% had an abnormal reduction in cerebral blood flow (CBF). A standard head-up tilt test of this duration might not be tolerated by the most severely affected bed-ridden ME/CFS patients. This study examined whether a shorter 15-min test at a lower 20 degree tilt angle would be sufficient to provoke reductions in cerebral blood flow in severe ME/CFS patients. Methods and results: Nineteen severe ME/CFS patients with orthostatic intolerance complaints in daily life were studied: 18 females. The mean (SD) age was 35(14) years, body surface area (BSA) was 1.8(0.2) m2 and BMI was 24.0(5.4) kg/m2. The median disease duration was 14 (IQR 5–18) years. Heart rate increased, and stroke volume index and end-tidal CO2 decreased significantly during the test (p ranging from <0.001 to <0.0001). The cardiac index decreased by 26(7)%: p < 0.0001. CBF decreased from 617(72) to 452(63) mL/min, a 27(5)% decline. All 19 severely affected ME/CFS patients met the criteria for an abnormal CBF reduction. Conclusions: Using a less demanding 20 degree tilt test for 15 min in severe ME/CFS patients resulted in a mean CBF decline of 27%. This is comparable to the mean 26% decline previously noted in less severely affected patients studied during a 30-min 70 degree head-up tilt. These observations have implications for the evaluation and treatment of severely affected individuals with ME/CFS.

Update of Individualized Treatment Strategies for Postural Orthostatic Tachycardia Syndrome in Children.

Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous disease that predominantly affects children and adolescents. There is a great difference between children and adults in the diagnosis and treatment of POTS patients. POTS in children and adolescents is marked by chronic symptoms of orthostatic intolerance with a heart rate (HR) rise of ≥40 bpm, or heart rate exceeding 130 bpm for 6–12-years-old children and exceeding 125 bpm for those 13–18 years old without orthostatic hypotension, which is different from adult patients. The three major clinical forms of POTS include hypovolemic POTS, neuropathic POTS, and hyperadrenergic POTS; these are distinguished by their major mechanisms. The different subtypes of POTS in children and adolescents each have their own clinical characteristics and biomarkers. Based on these, we propose individualized treatment strategies. Individualized management strategies based on different subtypes of POTS would largely improve the curative effects of drugs for children with POTS. However, a further clinical investigation is still required to better understand the pathophysiology and treatment options.

Cerebral hemodynamic monitoring of Parkinson's disease patients with orthostatic intolerance during head-up tilt test.

.Significance: Monitoring of cerebral perfusion rather than blood pressure changes during a head-up tilt test (HUTT) is proposed to understand the pathophysiological effect of orthostatic intolerance (OI), including orthostatic hypotension (OH), in Parkinson’s disease (PD) patients.Aim: We aim to characterize and distinguish the cerebral perfusion response to a HUTT for healthy controls (HCs) and PD patients with OI symptoms.Approach: Thirty-nine PD patients with OI symptoms [10 PD patients with OH (PD-OH) and 29 PD patients with normal HUTT results (PD-NOR)], along with seven HCs participated. A 108-channel diffuse optical tomography (DOT) system was used to reconstruct prefrontal oxyhemoglobin (HbO), deoxyhemoglobin (Hb), and total hemoglobin (HbT) changes during dynamic tilt (from supine to 70-deg tilt) and static tilt (remained tilted at 70 deg).Results: HCs showed rapid recovery of cerebral perfusion in the early stages of static tilt. PD-OH patients showed decreasing HbO and HbT during dynamic tilt, continuing into the static tilt period. The rate of HbO change from dynamic tilt to static tilt is the distinguishing feature between HCs and PD-OH patients. Accordingly, PD-NOR patients were subgrouped based on positive-rate and negative-rate of HbO change. PD patients with a negative rate of HbO change were more likely to report severe OI symptoms in the COMPASS questionnaire.Conclusions: Our findings showcase the usability of DOT for sensitive detection and quantification of autonomic dysfunction in PD patients with OI symptoms, even those with normal HUTT results.

Pediatric-Onset Postural Orthostatic Tachycardia Syndrome in a Single Tertiary Care Center.

We characterize the pediatric postural orthostatic tachycardia syndrome (POTS) population seen at a single tertiary care referral center. Retrospective chart review of all pediatric POTS patients seen in our center between 2015 and 2017. Pediatric POTS was defined as chronic, at least 3 months, symptoms of orthostatic intolerance associated with excessive orthostatic tachycardia as determined by tilt table testing with orthostatic heart rate increment of ≥40 bpm within 5 minutes of head-up tilt or absolute orthostatic heart rate ≥130 bpm for patients 13 years old and younger and ≥120 bpm for those 14 years and older. We looked at demographics, presenting symptoms, comorbidities, examination findings, investigation findings, treatment, and patient reported outcomes. Outcome measures were separated by patient report and group comparisons were made using 2-sample t tests or Mann-Whitney U tests for continuous variables and Fisher exact tests for categorical variables. One hundred thirty-four patients with pediatric onset POTS were identified. The mean age was 15 years. Seventy-nine percent of patients were female and 90% were white. The most common presenting symptoms included dizziness/lightheadedness (88%), syncope (54%), and palpitations (40%). Many patients had significant comorbidities attributable to numerous bodily systems, most commonly headache syndromes (migraine 43%, nonspecific headache 22%, chronic daily headache 14%, and new daily persistent headache 5%) and chronic fatigue (60%). Low vitamin D and insufficient iron stores were commonly seen. The majority of patients improved or had resolution of symptoms following treatment (70%). When separated by outcome, statistically significant differences were found for glucose (patients whose symptoms resolved had higher median glucose), palpitations (patients whose symptoms resolved were less likely to have palpitations), constipation (patients whose symptoms were stable/worsened were more likely to have constipation), and unexplained pain (patients whose symptoms were stable/worsened were more likely to have unexplained pain). Pediatric POTS is a chronic condition with a fairly good prognosis following appropriate treatment. It is associated with numerous comorbidities that necessitate multidisciplinary expert care.

INTERPRETING MULTIPLE MEASUREMENTS OF FUNCTIONAL STATUS IN CONTROLLED POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME (POTS) USING 6 MINUTE WALK TEST (6MWT)

POTS manifests as chronic symptoms of orthostatic intolerance accompanied by an exaggerated HR response. Symptoms can be cardiac, non-cardiac, physically and mentally debilitating which can persistently interfere with an individual's functional capacity to cope with minimal exertions and demands of

Transient Orthostatic Hypertension During Head-Up Tilt Test in Young Adults: A Phenotype of Blood Pressure Variability.

The mechanisms underlying orthostatic hypertension (OHT) remain poorly understood. The authors evaluated the cardiovascular, cerebrovascular dynamics, and autonomic response to head-up tilt test (HUTT) in young adults with symptoms of orthostatic intolerance and transient OHT. Forty-four female subjects were included (34 ± 13 years old) and categorized in three groups after a 30-minute 70° passive HUTT: symptomatic patients with OHT (surge of systolic blood pressure ≥20 mm Hg for at least 5 minutes at any given time during HUTT), orthostatic intolerance (symptomatic patients without orthostatic blood pressure changes), and healthy asymptomatic control subjects. At baseline, OHT patients had lower systolic blood pressure than orthostatic intolerance patients (103 ± 8 vs. 116 ± 10 mm Hg, p < 0.01) and lower baroreflex sensitivity than control subjects (15.8 ± 8.3 vs. 27.1 ± 11.7 ms/mm Hg, p = 0.01). On tilt, cardiac output decreased in OHT patients from 6.1 ± 1.4 L/minute during baseline to 5.2 ± 0.8 L/minute after 10 minutes of HUTT (p = 0.01). In OHT patients at 30 minutes of HUTT, sympathetic efferent heart activity was higher (77.4 ± 14.9 normalized units or nu) than orthostatic intolerant patients (63.5 ± 11.8 nu, p = 0.02) and control subjects (65.8 ± 11.2 nu, p = 0.05). Cerebrovascular resistance in OHT was higher than control subjects after 30 minutes (2.2 ± 0.8 vs. 1.6 ± 0.3 cm/second, respectively, p = 0.02). This study demonstrates that transient OHT can occur at any given time during HUTT. These patients exhibit a decrease in cardiac output and a hyperadrenergic response to tilt.