Postural orthostatic tachycardia syndrome (POTS) is a chronic form of orthostatic intolerance that primarily impacts female patients of childbearing age. The role of sex differences in POTS is not well understood. We sought to identify sex differences in diagnosis, symptoms, comorbidities, and treatments in female and male patients diagnosed with POTS. A comprehensive survey was designed in partnership by Dysautonomia International (East Moriches, NY) and Vanderbilt University Medical Center (Nashville, TN). Patients were recruited through Dysautonomia International's website and social media channels. The survey was delivered online through a secure research data capture database. Responses were analyzed according to biological sex. Continuous variables are presented as median (25th percentile-75th percentile), and categorical variables are presented as number and proportion of participants. A total of 8919 patients reported a physician diagnosis of POTS and were included in this analysis. The majority of respondents were female (93.7%). Female and male patients experienced misdiagnosis at similar rates (76.2% vs 74.9%,  = 0.5) and saw a similar number of doctors before diagnosis (5 [3-8] vs 5 [3-8],  = 0.9). Despite these similarities, diagnostic delay was longer for female, compared with male, patients (1.50 [0.25-5.25] years vs 0.92 [0.08-2.91] years, < 0.001). Despite the primarily female demographic of POTS patients, female patients experience more challenges with diagnosis than male patients. Increased awareness and recognition of POTS may help to reduce the diagnostic challenges in both female and male patients, and improve treatment and management for individuals living with this debilitating disorder.

In this paper we highlight the presence of tachycardia in post-acute COVID-19 syndrome by introducing a new label for this phenomenon-post-COVID-19 tachycardia syndrome-and argue that this constitutes a phenotype or sub-syndrome in post-acute COVID-19 syndrome. We also discuss epidemiology, putative mechanisms, treatment options, and future research directions in this novel clinical syndrome.

: Symptoms and hemodynamic findings during orthostatic stress have been reported in both long-haul COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but little work has directly compared patients from these two groups. To investigate the overlap in these clinical phenotypes, we compared orthostatic symptoms in daily life and during head-up tilt, heart rate and blood pressure responses to tilt, and reductions in cerebral blood flow in response to orthostatic stress in long-haul COVID-19 patients, ME/CFS controls, and healthy controls. : We compared 10 consecutive long-haul COVID-19 cases with 20 age- and gender-matched ME/CFS controls with postural tachycardia syndrome (POTS) during head-up tilt, 20 age- and gender-matched ME/CFS controls with a normal heart rate and blood pressure response to head-up tilt, and 10 age- and gender-matched healthy controls. Identical symptom questionnaires and tilt test procedures were used for all groups, including measurement of cerebral blood flow and cardiac index during the orthostatic stress. : There were no significant differences in ME/CFS symptom prevalence between the long-haul COVID-19 patients and the ME/CFS patients. All long-haul COVID-19 patients developed POTS during tilt. Cerebral blood flow and cardiac index were more significantly reduced in the three patient groups compared with the healthy controls. Cardiac index reduction was not different between the three patient groups. The cerebral blood flow reduction was larger in the long-haul COVID-19 patients compared with the ME/CFS patients with a normal heart rate and blood pressure response. : The symptoms of long-haul COVID-19 are similar to those of ME/CFS patients, as is the response to tilt testing. Cerebral blood flow and cardiac index reductions during tilt were more severely impaired than in many patients with ME/CFS. The finding of early-onset orthostatic intolerance symptoms, and the high pre-illness physical activity level of the long-haul COVID-19 patients, makes it unlikely that POTS in this group is due to deconditioning. These data suggest that similar to SARS-CoV-1, SARS-CoV-2 infection acts as a trigger for the development of ME/CFS.

Brain fog is a common and highly disturbing symptom for patients with neuropathic postural tachycardia syndrome (POTS). Cognitive deficits have been measured exclusively in the upright body position and mainly comprised impairments of higher cognitive functions. The cause of brain fog is still unclear today. This study aimed to investigate whether increased autonomic activation might be an underlying mechanism for the occurrence of brain fog in neuropathic POTS. We therefore investigated cognitive function in patients with neuropathic POTS and a healthy control group depending on body position and in relation to catecholamine release as a sensitive indicator of acute stress. The second aim was to test the effect of water intake on cardiovascular regulation, orthostatic symptoms, cognitive function and catecholamine release. Thirteen patients with neuropathic POTS and 15 healthy control subjects were included. All participants completed a total of four rounds of cognitive testing: two before and two after the intake of 500 ml still water, each first in the supine position and then during head-up tilt. At the end of each cognitive test, a blood sample was collected for determination of plasma catecholamines. After each head-up tilt phase participants were asked to rate their current symptoms on a visual analogue scale. Working memory performance in the upright body position was impaired in patients, which was associated with self-reported symptom severity. Patients had elevated plasma norepinephrine independent of body position and water intake that increased excessively in the upright body position. The excessive increase of plasma norepinephrine was related to heart rate and symptom severity. Water intake in patients decreased norepinephrine concentrations and heart rate, and improved symptoms as well as cognitive performance. Brain fog and symptom severity in neuropathic POTS are paralleled by an excessive norepinephrine secretion. Bolus water drinking down-regulates norepinephrine secretion and improves general symptom severity including brain fog.

The aim of the study was to establish whether whole-blood microRNA (miRNA) profiles differ between postural tachycardia syndrome (POTS) sufferers and control subjects and to identify the miRNA that regulates plasma HS. High-throughput sequencing was used to obtain whole-blood miRNA expression profiles for 20 POTS sufferers and 20 normal children.The thresholds for defining differentially expressed miRNAs (DEmiRNAs) were an adjusted DESeq of <0.05 and a log2 fold variation of ≥3. The DEmiRNA target genes were identified using RNAhybrid and miRanda, and only those identified by both were considered. The combined effects of the DEmiRNAs were determined using KEGG pathway analysis. Another 40 POTS and 20 normal patients were used as validation subjects. Plasma HS was determined with a sulfide electrode, and flow-mediated vasodilation (FMD) was performed with a color Doppler ultrasound system. miRNAs were analyzed using qRT-PCR. Totally, 13 DEmiRNAs were identified through high-throughput sequencing. In the 60-member validation group, the 13 miRNAs were verified again, and it turned out that miR-21 was significantly elevated and could diagnose POTS with a 100% specificity and 92.5% sensitivity. Overall, 198 and 481 genes, respectively, were shown to be targeted by the 13 DEmiRNAs when values of 0.01 and 0.05 were used. The target gene of hsa-miR-21-5p was SP1 when the -value is <0.01. DEmiRNAs were significantly enriched in 36 pathways ( < 0.05), in which PI3K/Akt signaling was closely related to vascular function. In the validation subjects, the plasma HS and FMD were higher in the POTS sufferers ( < 0.05). Elevated whole-blood miR-21 levels serve as an indicator for POTS and may explain the increased plasma HS observed in POTS sufferers.

There is emerging evidence that a proportion of patients who develop long (post)-COVID-19 have abnormalities in the regulation of their autonomic nervous system manifesting as postural tachycardia syndrome (PoTS). We report a series of 14 patients who developed symptoms and signs compatible with PoTS following clinically diagnosed COVID-19 infection. Their symptoms and clinical findings were consistent with those of patients with non-COVID-related PoTS. The authors recommend an active stand test for patients who present after COVID-19 infection with cardiovascular symptoms including chest pain, palpitations, lightheadedness and breathlessness that are worse with the upright posture. They further recommend training of clinicians and investment in health services to provide for the anticipated significant increase in patients presenting with PoTS and other forms of autonomic dysfunction due to the COVID-19 pandemic.

To investigate the predictive value of heart rate (HR) and blood pressure (BP) on the prognosis of postural tachycardia syndrome (POTS) in children. 53 cases of children aged 5 to 15 years who visited in the Pediatric Syncope Specialist Clinic of The Second Xiangya Hospital of Central South University for unexplained syncope or syncope precursor were diagnosed with POTS by head-up tilt test (HUTT) as the POTS group. 38 healthy children aged 5 to 16 years who underwent physical examination at the Child Health Care Clinic of the hospital in the same period were matched as controls (control group). The children with POTS were followed up after 3 months of treatment and were divided into good prognosis group (40 cases) and poor prognosis group (13 cases) according to the results of HUTT re-examination and whether the symptoms improved or not. HR and BP indicators were collected from each group at baseline and during HUTT. There were 91 research subjects, of which 45 are males, with a mean age of 11.52 ± 2.13 years. (1) HR at 5 and 10 min (HR 5 and HR 10, respectively), HR difference at 5 and 10 min (HRD 5 and HRD 10, respectively), and HR and BP product at 5 and 10 min (RPP 5 and RPP 10, respectively) were greater in the POTS group than in the control group ( < 0.01). (2) HR 5, HR 10, HRD 5, HRD 10, and RPP 10 in children with POTS were smaller in the good prognosis group than the poor prognosis group ( < 0.01). (3) The area under curve was 0.925 on the four combined indicators (HR 5, HR 10, HRD 5, and HRD 10), predicting a good prognosis of POTS, sensitivity of 99.99%, and specificity of 75.00%. HR 5, HR 10, HRD 5, HRD 10, and RPP 10 and the four combined indicators (HR 5, HR 10, HRD 5, and HRD 10) had predictive value for the POTS prognosis in children. The predictive value of the four combined indicators for the POTS prognosis was better than that of the single HR 5, HRD 5, and RPP 10.

To explore the role of the Poincaré plot derived from a 24-hour Holter recording in distinguishing vasovagal syncope (VVS) from postural tachycardia syndrome (POTS) in pediatric patients. Pediatric patients with VVS or POTS, hospitalized in Peking University First Hospital between January 2012 and December 2018, were included in a derivation study. The transverse axis (T), longitudinal axis (L), T/L ratio, product T × L, distance between the origin and the proximal end of the longitudinal axis (pro-D), and distance between the origin and distal end of the longitudinal axis (dis-D) of the Poincaré plot were compared between the VVS and POTS groups, and the differential diagnostic performance of the above-mentioned graphic parameters was evaluated using receiver operating characteristic curve analysis. A validation study was conducted in pediatric patients hospitalized between January 2019 and December 2020. In school-aged children, the T, L, T/L, T × L, and dis-D values of patients with VVS were greater than those of patients with POTS; in adolescents, the T, T/L, T × L, and pro-D values of patients with VVS were greater than those of patients with POTS. Using a T/L cut-off value of 0.3 to distinguish between the two diseases, the sensitivity and specificity were 91.0 and 90.5%, respectively, for the total participants; 91.6 and 88.9%, respectively, for the school-aged children; and 82.1 and 95.7%, respectively, for the adolescents. In the validation study, a T/L cut-off value of 0.3 yielded an accuracy, sensitivity, and specificity of 81.8, 87.2, and 77.6%, respectively, in the total participants; 76.5, 82.6, and 71.4%, respectively, in the school-aged children; and 89.2, 93.8, and 85.7%, respectively, in the adolescents, in distinguishing VVS from POTS validated by clinical diagnosis. The graphic parameters of the Poincaré plot are significantly different between VVS and POTS in pediatric patients, and the T/L of the Poincaré plot may be a useful measure to help differentiate VVS from POTS in children and adolescents.

The study was designed to explore the risk factors for sitting-induced tachycardia syndrome (STS) in children and adolescents. In this case-control study, 46 children with STS and 184 healthy children and adolescents were recruited. Demographic characteristics, lifestyle habits, allergy history, and family history were investigated using a questionnaire. The changes in heart rate and blood pressure from supine to sitting were monitored using a sitting test. The possible differences between STS patients and healthy children were analyzed using univariate analysis. Logistic regression analysis was used to explore the independent risk factors for STS. Univariate analysis showed that the daily sleeping time of the STS children were significantly shorter than that of the control group [(8.8 ± 1.2) hours/day vs. (9.3 ± 1.0) hours/day, P = 0.009], and the proportion of positive family history of syncope in the STS patients was higher than the controls (4/42 vs. 3/181, P = 0.044). Multivariate logistic regression studies showed that reduced daily sleeping time was an independent risk factor of STS in children (P = 0.006). Furthermore, when daily sleeping time was prolonged by 1 h, the risk of STS was decreased by 37.3%. Reduced daily sleeping was an independent risk factor for STS in children and adolescents.

Postural tachycardia syndrome (POTS) is a form of autonomic dysregulation. There is increasing evidence that the etiology may be immune-mediated in a subgroup of patients. Patients with POTS often experience an exacerbation of their symptoms associated with (viral) infections and often fear the same symptom aggravation after vaccination. In this report we describe the tolerability of messenger ribonucleic acid (mRNA) vaccines against coronavirus disease 19 (COVID-19) and the consequences of a COVID-19 infection on POTS symptoms in our cohort of patients with neuropathic POTS. We conducted a standardized, checklist-based interview with 23 patients and recorded the acute side effects of mRNA vaccination, acute symptoms of COVID-19 infection as well as the effects of vaccination and COVID-19 infection on POTS symptoms. : Of all included patients, 20 patients received two mRNA vaccines without having had a previous COVID-19 infection, and five patients in total had suffered a COVID-19 infection. Of these, three had COVID-19 without and two after being vaccinated. No increased frequency of side effects after both doses of mRNA vaccines was observed. Six patients reported a mild and short-term aggravation of their POTS symptoms beyond the duration of acute vaccine side effects. All five patients who suffered a COVID-19 infection subsequently reported a pronounced and persistent exacerbation of POTS symptoms. Our observations suggest that mRNA vaccines are not associated with a higher frequency of acute side effects in patients with POTS. Symptom exacerbation as a consequence of mRNA vaccination seems to be less frequent and of shorter duration compared to patients who suffered a COVID-19 infection.

To compare the levels of cortisol in patients of vasovagal syncope (VVS) and postural tachycardia syndrome (POTS). A cross-sectional analytical study was conducted at Islamic International Medical College, Rawalpindi and Electrophysiology Department at (AFIC). This study included 80 subjects, comprising of 35 patients in each group of vasovagal syncope and postural tachycardia syndrome and 10 healthy subjects. Patients with complaint of syncope was evaluated for vasovagal syncope and postural tachycardia syndrome using Head Up Tilt Test (HUTT. Blood samples of all the participants were taken and serum cortisol was analyzed using ELISA method. Results were analyzed on SPSS Statistics 21 using ANOVA with a p value of ≤0.05 regarded as significant. Hormonal analysis shows that cortisol levels in the vasovagal, postural tachycardia syndrome and in control group was 153±16.7pg/ml, 160.17±pg/ml, and 69.65± 5.8pg/ml respectively. Cortisol levels were significantly higher in both vasovagal and POTS groups as compared to controls with a p-value of 0.04 and 0.023 respectively. However, there was no significant difference between vasovagal and POTS patients with p value 0.570. It is concluded from the study that cortisol responses of VVS and POTS were positive.

Postural orthostatic tachycardia syndrome is an underdiagnosed disorder of the autonomic nervous system. The median time to achieve correct diagnosis is 2 years and may take more than 10 years for some patients. Symptoms can be devastating to the daily life of patients and can result in long-term disability. Treatment availability is limited due to the need for further studies.

Salt supplementation is a common non-pharmacological approach to the management of recurrent orthostatic syncope or presyncope, particularly for patients with vasovagal syncope (VVS) or postural orthostatic tachycardia syndrome (POTS), although there is limited consensus on the optimal dosage, formulation and duration of treatment. Accordingly, we reviewed the evidence for the use of salt supplementation to reduce susceptibility to syncope or presyncope in patients with VVS and POTS. We found that short-term (~3 months) salt supplementation improves susceptibility to VVS and associated symptoms, with little effect on supine blood pressure. In patients with VVS, salt supplementation is associated with increases in plasma volume, and an increase in the time taken to provoke a syncopal event during orthostatic tolerance testing, with smaller orthostatic heart rate increases, enhanced peripheral vascular responses to orthostatic stress, and improved cerebral autoregulation. Responses were most pronounced in those with a baseline sodium excretion <170 mmol/day. Salt supplementation also improved symptoms, plasma volume, and orthostatic responses in patients with POTS. Salt supplementation should be considered for individuals with recurrent and troublesome episodes of VVS or POTS without cardiovascular comorbidities, particularly if their typical urinary sodium excretion is low, and their supine blood pressure is not elevated. The efficacy of the response, in terms of the improvement in subjective and objective markers of orthostatic intolerance, and any potential deleterious effect on supine blood pressure, should be routinely monitored in individuals on high salt regimes.

Postural Orthostatic Tachycardia Syndrome (POTS) is a disorder of the autonomic nervous system most commonly affecting women of reproductive age. Studies on POTS and pregnancy are limited, and there is a lack of clinical guidelines regarding assessment and management of pregnant women with POTS. The purpose of this review is to summarize data from the available studies on the topic of pregnancy in POTS and common comorbid conditions and to provide the clinical recommendations regarding evaluation and treatment of POTS in pregnant women, based on the available studies and clinical experience. We conclude that pregnancy appears to be safe for women with POTS and is best managed by a multi-disciplinary team with knowledge of POTS and its various comorbidities. Importantly, large, prospective studies are needed to better delineate the course and outcomes of pregnancy, as well as possible pregnancy-related complications in women with POTS. Clinicians should be aware of the clinical presentation, diagnostic criteria, and treatment options in pregnant women with POTS to optimize outcomes and improve medical care during pregnancy and post-partum period.

A primigravida presented to our institution in established labour. Her past medical history included joint hypermobility, postural orthostatic tachycardia syndrome, Raynaud's syndrome, fibromyalgia and gastroparesis. Two technically uneventful lumbar epidurals with bupivacaine and fentanyl provided no analgesia. The spinal element of a planned combined spinal and epidural was also ineffective, so alternative analgesia was offered. While this was being prepared, the obstetric team recommended an instrumental delivery. An attempted pudendal nerve block with lidocaine had no effect, and general anaesthesia was therefore provided for a lower segment caesarean delivery. We believe this is the first report of local anaesthetic resistance via three distinct routes of administration in a single patient. Resistance to local anaesthetics is unusual and is more common in patients with hypermobility spectrum disorders. This case demonstrates the unique experience of a patient with a hypermobility condition who had failed epidural, spinal and pudendal local anaesthetic. We suggest that patients with a hypermobility condition should be specifically assessed for local anaesthetic resistance as part of anaesthetic pre-assessment, to enable early planning.

Postural orthostatic tachycardia syndrome (POTS) has been observed following SARS-CoV-2 infection. In this study, we observed occurences of POTS following COVID-19 vaccination, albeit at a lower rate than following COVID-19 infection.

Syncope is the primary cause of transient loss of consciousness, which causes severe physical and mental burdens to children and adolescents. The study was designed to analyze the spectrum of underlying diseases of syncope and treatment options for neurally-mediated syncope (NMS) in Chinese children and adolescents. Medical records including history, physical examination, blood biochemistry, standing test, head-up tilt (HUTT), sitting-up test, electroencephalogram (EEG), electrocardiogram (ECG), and echocardiography were retrospectively studied in children and adolescents admitted to the National Pediatric Syncope Center, Department of Pediatrics, Peking University First Hospital between 1992 and 2021. All the data were collected from the Beijing Kaihua Medical Management System (Kaihua, Beijing, China). Children who met the syncope diagnostic criteria were enrolled in the study. The spectrum of the underlying diseases of syncope in children and adolescents and the treatment options of NMS were analyzed. A total of 1,947 children and adolescents with syncope were admitted, including 869 males (44.63%) and 1,078 females (55.37%) aged 1-18 years, with an average age of 11.1 ± 3.1 years. The number of children and adolescents with syncope displayed a gradually increasing trend between 1992 and 2021 except after 2020. NMS proportion increased, and the proportion of unexplained syncope decreased (χ = 128.839, < 0.01). The treatment options of NMS mainly included autonomic nervous function exercise (549, 34.46%), oral rehydration salt (ORS; 445, 27.94%), metoprolol (219, 13.75%), midodrine (120, 7.53%), ORS plus metoprolol (139, 8.73%), ORS plus midodrine (120, 7.53%), and pacemakers (1, 0.06%). Patients with vasovagal syncope (VVS) coexisting with postural orthostatic tachycardia syndrome (POTS) were more likely to take pharmacological treatments than those with VVS or POTS only (χ = 41.696, < 0.01). The number of children with syncope displayed an increasing trend before 2020, and the proportion of unexplained syncope decreased. Autonomic nervous function exercise was the most common treatment for children and adolescents with NMS. Children with VVS coexisting with POTS were more likely to receive pharmacological treatments than those with either.

Physical counter pressure maneuvers (CPM) are movements that are recommended to delay or prevent syncope (fainting) by recruiting the skeletal muscle pump to augment cardiovascular control. However, these recommendations are largely based on theoretical benefit, with limited data evaluating the efficacy of CPM to prevent syncope in the real-world setting. We conducted a semi-systematic literature review and meta-analysis to assess CPM efficacy, identify literature gaps, and highlight future research needs. Articles were identified through a literature search (PubMed, April 2022) of peer-reviewed publications evaluating the use of counter pressure or other lower body maneuvers to prevent syncope. Two team members independently screened records for inclusion and extracted data. From 476 unique records identified by the search, 45 met inclusion criteria. Articles considered various syncopal conditions (vasovagal = 12, orthostatic hypotension = 8, postural orthostatic tachycardia syndrome = 1, familial dysautonomia = 2, spinal cord injury = 1, blood donation = 10, healthy controls = 11). Maneuvers assessed included hand gripping, leg fidgeting, stepping, tiptoeing, marching, calf raises, postural sway, tensing (upper, lower, whole body), leg crossing, squatting, "crash" position, and bending foreword. CPM were assessed in laboratory-based studies ( = 28), the community setting ( = 4), both laboratory and community settings ( = 3), and during blood donation ( = 10). CPM improved standing systolic blood pressure (+ 14.8 ± 0.6 mmHg, < 0.001) and heart rate (+ 1.4 ± 0.5 bpm, = 0.006), however, responses of total peripheral resistance, stroke volume, or cerebral blood flow were not widely documented. Most patients experienced symptom improvement following CPM use (laboratory: 60 ± 4%, community: 72 ± 9%). The most prominent barrier to employing CPM in daily living was the inability to recognize an impending faint. Patterns of postural sway may also recruit the skeletal muscle pump to enhance cardiovascular control, and its potential as a discrete, proactive CPM needs further evaluation. Physical CPM were successful in improving syncopal symptoms and producing cardiovascular responses that may bolster against syncope; however, practical limitations may restrict applicability for use in daily living.

To determine if the baseline baroreflex sensitivity (BRS) could be a useful predictor for the metoprolol therapeutic efficacy on postural orthostatic tachycardia syndrome (POTS) in children. In this retrospective case-control study, 54 children suffering from POTS treated with metoprolol were recruited from the pediatric department of Peking University First Hospital. After 2-3 months of metoprolol treatment, all subjects were divided into responders and non-responders based on whether the symptom score (SS) was decreased by over 50% after metoprolol treatment at the follow-up. The baseline demographic parameters and the supine BRS during the head-up tilt test (HUTT) obtained by Finapres Medical System (FMS) were compared between the two groups. The value of BRS to predict the effectiveness of POTS was analyzed by a receiver-operating characteristic (ROC) curve. The age, sex, height, weight, body mass index (BMI), course of the disease, baseline SS, medication time, metoprolol dose, and follow-up time of the subjects were not statistically different between the responders and non-responders ( > 0.05). The decline in symptom scores (ΔSS) of the responders was more obvious than that of the non-responders ( < 0.01). The supine BRS, BRS at maximum HR, supine heart rate (HR), and maximum HR were different between responders and non-responders ( < 0.01, = 0.022, < 0.01, = 0.047). The binary multivariable analysis showed that baseline supine BRS was significantly associated with the response to metoprolol therapy [OR: 2.079, 95% CI: (1.077, 4.015), = 0.029]. According to the ROC curve, the area under the curve (AUC) of baseline BRS was 0.912 (95% CI, 0.840-0.984), with a cut-off value of 8.045 ms/mmHg, yielding a sensitivity and specificity of 75.8% and 95.2%, respectively, in predicting the effectiveness of POTS. The baseline supine BRS level > 8.045 ms/mmHg can predict a good therapeutic response to metoprolol and the results would assist in guiding the individualized β-adrenoceptor blocker use in pediatric patients suffering from POTS.

Some patients with acute COVID-19 are left with persistent, debilitating fatigue, cognitive impairment ("brain fog"), orthostatic intolerance (OI) and other symptoms ("Long COVID"). Many of the symptoms are like those of other post-infectious fatigue syndromes and may meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Common diagnostic laboratory tests are often unrevealing. We evaluated whether a simple, standardized, office-based test of OI, the 10-min NASA Lean Test (NLT), would aggravate symptoms and produce objective hemodynamic and cognitive abnormalities, the latter being evaluated by a simple smart phone-based app. People with Long COVID ( = 42), ME/CFS ( = 26) and healthy control subjects ( = 20) were studied just before, during, immediately after, 2 and 7 days following completion of the NLT. The NLT provoked a worsening of symptoms in the two patient groups but not in healthy control subjects, and the severity of all symptoms was similar and significantly worse in the two patient groups than in the control subjects ( < 0.001). In the two patient groups, particularly those with Long COVID, the NLT provoked a marked and progressive narrowing in the pulse pressure. All three cognitive measures of reaction time worsened in the two patient groups immediately following the NLT, compared to the healthy control subjects, particularly in the Procedural Reaction Time ( < 0.01). A test of orthostatic stress easily performed in an office setting reveals different symptomatic, hemodynamic and cognitive abnormalities in people with Long COVID and ME/CFS, compared to healthy control subjects. Thus, an orthostatic challenge easily performed in an office setting, and the use of a smart phone app to assess cognition, can provide objective confirmation of the orthostatic intolerance and brain fog reported by patients with Long COVID and ME/CFS.

Postural orthostatic tachycardia syndrome (POTS) is a devastating chronic form of orthostatic intolerance associated with excessive heart rate increase without hypotension during upright posture. POTS patients exhibit increased circulating norepinephrine levels with exaggerated sympathetic nervous system response upon standing. Emerging evidence suggests a role for the gut microbiome in cardiovascular disorders. However, the etiology of POTS and whether the gut microbiome plays a role are not fully elucidated. We assessed whether the gut microbiome and fecal short-chain fatty acids were different in POTS patients ( = 25) compared to healthy control ( = 23) women. Patients underwent hemodynamic measurements while supine and upon standing. Fecal samples were collected and analyzed using shotgun sequencing and Liquid Chromatography-High Resolution Mass Spectrometry and dietary habits were measured with a fitness application. We found that POTS patients in the standing position had higher circulating norepinephrine and epinephrine levels and increased heart rate. There were no differences in diet composition between groups. Of note dietary salt intake was also similar despite the fact that these patients are advised to consume a high salt diet. Alpha and beta diversity were similar between groups. We observed no differences in bacteria at the phylum levels or Firmicutes to Bacteroidetes ratio. We found no significant differences at the genus level, but observed trends in certain bacteria. genus were higher in POTS when compared to the control group. On the other hand, and , were lower in POTS patients compared to controls. Although our KEGG metabolic pathways indicated differences related to short-chain fatty acids (SCFAs), we found that both POTS patients and healthy controls had similar levels of SCFAs. These results suggest POTs per se may have limited effects on gut microbiota composition and derived SCFAs. Further studies are needed to assess the role of the alterations observed at the genus level.

On March 11, 2020, the World Health Organization sounded the COVID-19 pandemic alarm. While efforts in the first few months focused on reducing the mortality of infected patients, there is increasing data on the effects of long-term infection (Post-COVID-19 condition). Among the different symptoms described after acute infection, those derived from autonomic dysfunction are especially frequent and limiting. To conduct a narrative review synthesizing current evidence of the signs and symptoms of dysautonomia in patients diagnosed with COVID-19, together with a compilation of available treatment guidelines. Autonomic dysfunction associated with SARS-CoV-2 infection occurs at different temporal stages. Some of the proposed pathophysiological mechanisms include direct tissue damage, immune dysregulation, hormonal disturbances, elevated cytokine levels, and persistent low-grade infection. Acute autonomic dysfunction has a direct impact on the mortality risk, given its repercussions on the respiratory, cardiovascular, and neurological systems. Iatrogenic autonomic dysfunction is a side effect caused by the drugs used and/or admission to the intensive care unit. Finally, late dysautonomia occurs in 2.5% of patients with Post-COVID-19 condition. While orthostatic hypotension and neurally-mediated syncope should be considered, postural orthostatic tachycardia syndrome (POTS) appears to be the most common autonomic phenotype among these patients. A review of diagnostic and treatment guidelines focused on each type of dysautonomic condition was done. Symptoms deriving from autonomic dysfunction involvement are common in those affected by COVID-19. These symptoms have a great impact on the quality of life both in the short and medium to long term. A better understanding of the pathophysiological mechanisms of Post-COVID manifestations that affect the autonomic nervous system, and targeted therapeutic management could help reduce the sequelae of COVID-19, especially if we act in the earliest phases of the disease.

Orthostatic tachycardia (OT) affects some patients after concussion/mild traumatic brain injury (mTBI). In this study, we sought to identify the factors associated with increased risk for OT in patients with mTBI. We conducted a retrospective review of 268 patients (8-25 years) with mTBI/concussion to determine the prevalence of OT, defined as orthostatic heart rate change ≥40 bpm for those ≤19 years of age and ≥30 bpm on active standing test for those >19 years of age. Among the study population, 7% (n = 19) exhibited post-concussive OT. The only significant difference between OT and non-OT groups was that history of prior concussion was more prevalent in the OT group. A substantial subset (7%) of concussion clinic patients exhibit OT. While POTS literature describes female and adolescent predominance, post-concussive OT had similar prevalence across age and gender groups in this study, suggesting that it may be distinct from POTS.

Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by an abrupt-onset of severe psychiatric symptoms including OCD, anxiety, cognitive difficulties, and sleep issues which is thought to be a post-infection brain inflammatory disorder. We observed postural orthostatic tachycardia syndrome (POTS) which resolved with immunomodulation in a patient with Pediatric acute-onset neuropsychiatric syndrome (PANS). Here, we aim to present a case of POTS and to examine the prevalence of (POTS) in our PANS cohort, and compare the clinical characteristics of patients with and without POTS. We conducted this cohort study of patients meeting PANS criteria who had at least three clinic visits during the study period. We included data from prospectively collected questionnaires and medical record review. We present a case followed by statistical comparisons within our cohort and a Kaplan-Meier analysis to determine the time-dependent risk of a POTS diagnosis. Our study included 204 patients: mean age of PANS onset was 8.6 years, male sex (60%), non-Hispanic White (78%). Evidence of POTS was observed in 19/204 patients (9%) with 5/19 having persistent POTS defined as persistent abnormal orthostatic vitals, persistent POTS symptoms, and/or continued need for pharmacotherapy for POTS symptoms for at least 6 months). In this PANS cohort, patients with POTS were more likely to have comorbid joint hypermobility (63 vs 37%, = 0.04), chronic fatigue (42 vs 18%, = 0.03), and a family history of chronic fatigue, POTS, palpitations and syncope. An unadjusted logistic regression model showed that a PANS flare (abrupt neuropsychiatric deterioration) was significantly associated with an exacerbation of POTS symptoms (OR 3.3, 95% CI 1.4-7.6, < 0.01). Our study describes a high prevalence of POTS in patients with PANS (compared to the general population) and supports an association between POTS presentation and PANS flare within our cohort.

Bier anemic spots, cyanosis, and urticaria-like eruption (BASCULE) syndrome is an underreported pediatric vascular disorder from the group of acrosyndromes. In children, these include paroxysmal acrosyndromes (Raynaud's phenomenon and chilblain-like lesions), permanent acrosyndromes (acrocyanosis), and transient acrosyndromes, in which their pathogeneses are associated with virus infections, Epstein-Barr virus, and, more recently, SARS-CoV-2, respectively. We reported a case of BASCULE syndrome associated with postural orthostatic tachycardia syndrome (POTS) and provided a narrative review of case reports describing the BASCULE syndrome in children. Moreover, we presented the results of a prospective practice survey that we performed in the French medical community. A 14-years-old boy reported pruritic erythrocyanic lesions on the lower limbs, which occurred whenever he was in a standing position and fully resolved when he laid down. He reported asthenia and cramps. He presented a typical BASCULE syndrome associated with POTS confirmed by a tilt-test. Physical and vascular examinations were within the normal range. We identified 12 case reports, describing 21 pediatric cases since 2016. Most patients were adolescents between 12 and 19 years of age or were newborns. Furthermore, 20% of cases in the literature have presented POTS or orthostatic intolerance. Our survey among 95 French physicians confirmed that BASCULE syndrome is an underdiagnosed and under recognized disease in the general pediatric practice, at least in France. Among these physicians, 65% had already encountered patients with similar symptoms, but only 30% declared that they had knowledge of the BASCULE syndrome. The under-recognition of the clinical manifestations leads the patients to consult emergency rooms, with multiple unnecessary investigations performed. Therefore, we suggest that the diagnosis of BASCULE syndrome is based on clinical observations, without the need for laboratory tests, to avoid unnecessary health costs. We suggest physicians to perform a tilt-test when POTS is suspected.