Orthostatic Intolerance Syndromes Research Articles

Validation of the Chinese orthostatic discriminant and Severity Scale (ODSS) for detection of orthostatic intolerance syndrome

BackgroundOrthostatic intolerance (OI) is the inability to tolerate orthostatic stress during any postural change. The etiology of OI varies, and methods to obtain a specific diagnosis and plan appropriate treatment are important. The tools available within the Chinese context to swiftly identify orthostatic intolerance syndrome (OIS) are currently limited. MethodsPatients with OI symptoms were included in this study and categorized into two groups based on the results of the supine-to-stand test. Those with abnormal test results were assigned to the OIS group, while those with normal test results were placed in the non-OIS group. We evaluated the internal consistency and predictive value of the Chinese Orthostatic Discriminant and Severity Scale (ODSS) by comparing patients’ scores with their physiological measurements collected during orthostatic stress tests and the results of other available questionnaires, including the orthostatic Symptom Questionnaire and Orthostatic Grading Scale (OGS). ResultsPatients with OIS scored significantly higher on all three questionnaires and showed significant differences in autonomic responses during orthostatic stress tests compared with non-OIS patients. Receiver operating characteristic curve analysis showed that the orthostatic score from the ODSS had moderate predictive value for the supine test (area under the curve [AUC] = 0.754). Further subgroup analysis revealed that the orthostatic score from the ODSS had uniquely high specificity and sensitivity for identifying patients with orthostatic hypotension with abnormal cerebral blood flow (OH–U, AUC = 0.919). ConclusionsWe conclude that the Chinese version of the ODSS has sufficient reliability and validity to distinguish patients with OIS and could possibly be used as a diagnostic tool for OH–U patients. Thus, the Chinese ODSS offers a beneficial screening tool for quickly assessing whether patients have OIS that requires further clinical assessment.

Postural Orthostatic Tachycardia Syndrome (POTS) of Autoimmune Origin - Case and Review

Introduction: Postural Orthostatic Tachycardia Syndrome (POTS) belongs to a group of orthostatic intolerance syndromes. It is defined by the increase in heart rate ≥30 bpm or heart rate higher than 120/min during first 10 minutes after standing, without significant decrease in blood pressure. It is a rare disease, typically affecting younger females. The dysregulation of autonomic nervous system plays a key role in the pathogenesis. The autonomic dysbalance can be caused by various neurohumoral mechanisms, receptor hypersensitivity, hypovolemia, mast cell dysregulation and last but not least, autoimmunity. The presence of autoantibodies targeted against various adrenergic and muscarinic receptors, as well, as angiotensin or endothelin receptors, has been identified in some but not all patients with POTS. Case Description: We present a case of a young patient with an overlap syndrome of POTS and vasovagal vasodepressoric syncope diagnosed with the head up tilt test, without any identified trigger. The laboratory investigation documented the presence of anti-alpha-1, beta-1 and beta-2 adrenergic receptor antibodies, antimuscarinic receptor 3 antibodies and antibodies against angiotensin II type 1 receptor. MIBG (metaiodobenzylguanidine) scan has not revealed any changes in the sympathetic inervation of the heart. The initial treatment by betablockers, as well as by ivabradine failed. On midodrine medication, the symptoms of postural tachycardia and the reflex syncope improved. Conclusion: The role of autoimmunity in POTS is currently studied, though the role of autoantibodies against autonomic nervous system in the pathogenesis of vasovagal syncope remains unclear.

Autoimmunity in Syndromes of Orthostatic Intolerance: An Updated Review.

Orthostatic intolerance is a broad term that represents a spectrum of dysautonomic disorders, including postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH), as manifestations of severe autonomic failure. While the etiology of orthostatic intolerance has not yet fully been uncovered, it has been associated with multiple underlying pathological processes, including peripheral neuropathy, altered renin-aldosterone levels, hypovolemia, and autoimmune processes. Studies have implicated adrenergic, cholinergic, and angiotensin II type I autoantibodies in the pathogenesis of orthostatic intolerance. Several case series have demonstrated that immunomodulation therapy resulted in favorable outcomes, improving autonomic symptoms in POTS and OH. In this review, we highlight the contemporary literature detailing the association of autoimmunity with POTS and OH.

Small fiber neuropathy in children, adolescents, and young adults with chronic orthostatic intolerance and postural orthostatic tachycardia syndrome: A retrospective study

PurposeTo determine in children, adolescent and young adult (CAYA) patients presenting with Orthostatic Intolerance (OI) or Postural Orthostatic Tachycardia Syndrome (POTS) associated with the additional symptoms of neuropathic discomfort (pain, paresthesia and/or allodynia): 1) the incidence of small fiber neuropathy, and 2) assess if there was serologic evidence for an underlying inflammatory or autoimmune state. MethodsA cohort of 109 CAYA patients with the above symptoms underwent epidermal skin biopsy for nerve fiber density. Blood biomarkers for inflammation were tested (CRP, ESR, ANA, complement (C3), thyroid function testing with antibodies (thyroid peroxidase antibody and thyroglobulin antibody), and cytokine panel 13). Patients completed a Quality of Health questionnaire. Statistical analysis was performed using Wilcoxon rank sum tests. ResultsIn CAYA patients with OI or POTS and neuropathic symptoms, skin biopsy for small fiber neuropathy was abnormal in 53 %. The sample population was predominantly female and Caucasian with moderately decreased perceived quality of health. OI /POTS patients with small fiber neuropathy had a 3-fold probability of having a positive ANA or anti-thyroid antibody, suggesting an underlying autoimmune or inflammatory process. ConclusionOur data suggest a link between OI and POTS and small fiber neuropathy. Small fiber neuropathy was found by skin biopsy in over half of the patients tested. OI and Postural orthostatic tachycardia patients with small fiber neuropathy expressed multiple markers suggesting an underlying autoimmune or inflammatory process. Future research will be done to evaluate the symptomatic implication of SFN and whether immune or pharmacologic manipulation can alter patient symptoms.

Cardiovascular, autonomic symptoms and quality of life in children with hypermobile Ehlers-Danlos syndrome.

Hypermobile Ehlers-Danlos syndrome is a connective tissue disorder characterized by joint hypermobility and other systemic manifestations. Cardiovascular, autonomic symptoms and dysautonomia are frequently reported in adults with hypermobile Ehlers-Danlos syndrome and have been shown to have a negative impact on quality of life. However, there is scant literature on autonomic symptoms in pediatric patients with hypermobile Ehlers-Danlos syndrome. This study aims to characterize cardiovascular symptoms and diagnoses in pediatric patients with hypermobile Ehlers-Danlos syndrome and evaluate the impact of autonomic symptoms on quality of life. As part of a longitudinal study, a consecutive sample of 70 patients with Ehlers-Danlos syndromes were recruited at routine clinical care visits. Medical history was reviewed, demographics were obtained, and patient-reported outcomes were completed by the patients. The average age of 70 patients was 15.8 years, and the majority were females (89%) and Caucasian (89%). The most common cardiovascular diagnoses were orthostatic intolerance (59%), dysautonomia (47%), and postural orthostatic tachycardia syndrome (21%). Most patients had an echocardiogram (77%), that was normal (82%). No patients had mitral valve prolapse, and only one patient had mild aortic root dilation (2%). Patient-reported outcomes revealed decreased quality of life associated with autonomic symptoms. This study shows that most children with hypermobile Ehlers-Danlos syndrome have cardiovascular and autonomic symptoms, which have a negative impact on quality of life. Few patients with hypermobile Ehlers-Danlos syndrome have structural abnormalities on echocardiogram, which suggests that the cardiovascular symptoms experienced by patients are not due to structural cardiovascular disease and possibly reflective of autonomic pathology, though further studies will need to confirm this. This study confirms that cardiovascular and symptoms are prevalent and have a dramatic impact on quality of life in pediatric and young adult patients diagnosed with hypermobile Ehlers-Danlos syndrome.

Evaluation of the relationship between mast cell activation and postural orthostatic tachycardia syndrome in children and adolescents.

Postural orthostatic tachycardia syndrome (POTS) is one of the orthostatic intolerance syndromes that are common in young adolescents and impair quality of life. POTS is a multi-systemic disease. Many mechanisms have been defined in POTS etiology, such as autonomic denervation, hypovolemia, hyperadrenergic stimulation, low condition, and hypervigilance. Recently, mast cell activation (MCA) has also been on the agenda in etiology. There are few studies in the literature on the relationship between MCA and POTS in adulthood. However, data on children and adolescents is limited. In light of this information, we aimed to evaluate the relationship between POTS and MCA by measuring serum tryptase levels, a specific marker for MCA. This prospective study included patients who were admitted to Kocaeli University Faculty of Medicine Hospital Pediatric Cardiology outpatient clinic for syncope-presyncope between November 2018 and August 2019. Patients who underwent the TILT-table test were enrolled in the study. Patients with structural heart disease or chronic heart disease were not included in this study. Serum tryptase levels were obtained from all patients before the TILT-table test, and serum tryptase levels were re-studied after the test was terminated in patients with positive TILT-table tests for POTS. Patients diagnosed with POTS were classified as Group 1, and other patients were classified as Group 2. Twenty-eight of the 58 patients included in the study (mean: 14.4±2.0 years; 38 girls, 20 boys) were diagnosed with POTS. The remaining 30 patients were diagnosed with vasovagal syncope and included in Group 2. The increase in mean heart rate during the test was 38±6 beats/min and 47.05%±15.65% in patients with POTS. Basal serum tryptase levels were not different between groups (3.2±1.3 ng/ml and 3.84±1.78 ng/ml, respectively; p=0.129), while serum tryptase levels (both baseline and after 45-60 min of the TILT-table test) were higher in patients presenting with symptoms related to MCA compared to others. In the literature, MCA was considered to be one of the mechanisms leading to POTS. Although other mechanisms, such as neuropathic and hypovolemic POTS, may be active in the patients, the symptoms of MCA in these patients should be routinely questioned.

Selected biomarkers of orthostatic intolerance.

Orthostatic intolerance (OI) is defined as a group of diseases which symptoms are typically manifested in a standing position. These symptoms result from cerebral hypoperfusion and disappear in the supine position. We include postural orthostatic intolerance syndrome (POTS), orthostatic hypotension (OH) and vasovagal orthostatic syncope in this group of diseases. Each of them have similar clinical presentation (blurred vision, weakness, dizziness, nausea, headaches, fatigue). However, they vary from each other in biochemical, autonomic and hemodynamic characteristics. The aim of the work is to provide an overview of humoral and non-human markers that are involved in the etiopathogenesis of orthostatic intolerance.

Hypocapnic Orthostatic Intolerance with (POTS) and without (HYCH) Tachycardia Represent a Spectrum of the Same Disorder (S43.003)

<h3>Objective:</h3> To compare postural tachycardia syndrome (POTS) with hypocapnic cerebral hypoperfusion (HYCH). <h3>Background:</h3> Several chronic orthostatic intolerance syndromes are associated with hypocapnia-driven cerebral hypoperfusion. Common syndromes are POTS where orthostatic tachycardia is present, and HYCH, where orthostatic tachycardia is absent. <h3>Design/Methods:</h3> This retrospective study evaluated consecutive patients with POTS and HYCH. Analyzed data included surveys (autonomic and sensory), autonomic (Valsalva maneuver, deep breathing, sudomotor and tilt tests), cerebrovascular (cerebral blood flow velocity (CBFv) monitoring in the middle cerebral artery), respiratory (capnography), neuropathic (skin biopsies for assessment of small fibers) testing and metabolic/inflammatory/autoimmune markers. <h3>Results:</h3> Eighty-one POTS and seventy-two HYCH patients were evaluated and they were compared to 25 healthy controls. POTS and HYCH patients had similar ages, gender, disease duration, and survey scores. Orthostatic CBFv was reduced in HYCH (−22.1±9.4%) and POTS (−23.3±12.0%) compared to controls (−4.4±7.1%,p&lt;0.001). Orthostatic end-tidal CO₂ was reduced in HYCH (27.9±5.6 mmHg) and POTS (27.1±5.6 mmHg) compared to controls (35.3±4.8 mmHg, p&lt;0.001). Orthostatic heart rate was higher in POTS (117±19.3 BPM) compared to HYCH (88.5±15.0 BPM, p&lt;0.001). Mild autonomic failure was present in 91.7% of HYCH and 82.7% of POTS patients. Compared HYCH with POTS, there was no significant difference in the following QASAT scores: sympathetic sudomotor (1.7±1.6/1.3±1.8, HYCH/POTS), parasympathetic cardiovagal (0.4±0.7/0.3±0.6), sympathetic adrenergic (1.2±0.9/1.1±1.0), epidermal fiber density (EFD, 1.8±2.1/1.9/2.4) and sweat gland fiber density (SGF, 1.4±2.0/1.5±2.3). EFD/SGF was abnormal in 63.4%/41.5% of HYCH and 55.8%/43.1% of POTS. Autoimmune markers were positive in 75% of HYCH and 81.5% of POTS. There was no significant difference in supine and orthostatic norepinephrine in both conditions. <h3>Conclusions:</h3> POTS and HYCH have similar abnormalities on subjective and objective measures except for the presence of tachycardia in POTS. Considering that the POTS-grade orthostatic tachycardia (≥30 BPM) can be seen in healthy subjects, these results suggest that HYCH and POTS represent a spectrum of the same disorder. <b>Disclosure:</b> Dr. Novak has received personal compensation for serving as an employee of Dysimmune Disease Foundation. Dr. Novak has stock in Pfeizer. Dr. Novak has stock in Moderna. Dr. Novak has stock in Novavax. Dr. Novak has stock in Editas Medicine. Dr. Novak has stock in Prothena. Dr. Novak has received publishing royalties from a publication relating to health care. Miss Marciano has nothing to disclose.

Autoimmunity in Long Covid and POTS.

Orthostatic intolerance and other autonomic dysfunction syndromes are emerging as distinct symptom clusters in Long Covid. Often accompanying these are common, multi-system constitutional features such as fatigue, malaise and skin rashes which can signify generalized immune dysregulation. At the same time, multiple autoantibodies are identified in both Covid-related autonomic disorders and non-Covid autonomic disorders, implying a possible underlying autoimmune pathology. The lack of specificity of these findings precludes direct interpretations of cause and association, but their prevalence with its supporting evidence is compelling.

ODP291 A Series of COVID Reinfections in a Vaccinated Patient leading to Development of Neurogenic Orthostatic Hypotension and Postural Orthostatic Tachycardia

Abstract The recently recognized 'long COVID' syndrome, encompasses symptoms of shortness of breath, chest pain, palpitations and orthostatic intolerance which can last for weeks or more following even mild illness. 'Long COVID' is postulated to be related to a virus- or immune-mediated disruption of the autonomic nervous system resulting in orthostatic intolerance syndromes. We report a 32-yr old female nurse who presented to the endocrinology clinic for symptoms of orthostatic hypotension following two COVID 19 infections. She had received 1 dose of Moderna vaccine in February and March of 2021 respectively. She was hospitalized for COVID June and September of 2021. Following the first hospitalization, she developed severe orthostatic hypotension, chest pain, shortness of breath, fatigue, anxiety, memory, concentration and word finding difficulty. Blood pressure ranged from 110/78 to 124/82 while lying and from 85/45 to 103/59 while standing. HR ranged from 88 to 96 while lying and from 130 to 42 while standing. She was started on midodrine 10 mg three times daily which was discontinued due to patient intolerance. She followed a regimen of adequate hydration, adequate salt intake, fall precautions, physical and speech therapy and high protein/low carb diet with frequent snacks, which improved her symptoms of dizziness and orthostasis, but without complete resolution. However, symptoms of anxiety, dizziness, chest pain and palpitations became even worse after the second hospitalization. She was started on Propranolol 20 mg 2-3 times daily depending on symptoms, and she felt better with this intervention. Evaluation for secondary causes of hypotension were all negative [Cortisol of 19 ug/dL (n=5.3-22.5); ACTH 20 pg/mL (n=0-47); TSH 2.36 uIU/mL (n=0.358 -3.74); Free T4 0.97 ng/dL (n=0.76-1.46); B12 480 pg/mL (n=193-986); Hba1c 4.9%; 25 OH Vitamin D 24.3 ng/mL; tryptase 3.7 mcg/L (n= &amp;lt;11); Sed rate 4 mm/HR (n=0-20). CBC, CMP, TPO and Tg abs, troponin levels, iron studies, ANA panel, Rheumatoid factor, anti-CCP abs, myasthenia gravis panel], CT head and MRI brain, EKG and QTc interval. Echocardiogram= small PFO. 'Post-acute COVID' refers to persistent symptoms 3 weeks after COVID-19 infection, while 'Chronic COVID' describes symptoms lasting more than 12 weeks. Symptoms include fatigue, dyspnea, chest pain, palpitations, dizziness, body aches, presyncope and orthostatic intolerance. Individuals may even develop post-traumatic stress disorder, panic attacks and irritable bowel syndrome. Orthostatic intolerance occurs due to release of epinephrine and norepinephrine leading to development of palpitations, breathlessness, and chest pain. It has been well described that orthostatic intolerance is preceded by viral infections and is associated with the development of autoantibodies α-/β-adrenoceptors and muscarinic receptors. COVID 19 itself can affect the autonomic nervous system through the release of a cytokine storm leading to sympathetic activation. It is crucial to consider the diagnosis of orthostatic intolerance syndromes post COVID infection. Presentation: No date and time listed

A UNIQUE CASE OF CONCURRENT EHLERS DANLOS SYNDROME (EDS) AND POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME (POTS) ASSOCIATED WITH ORTHOSTATIC HYPERTENSION RESPONDING TO IV FLUIDS

A UNIQUE CASE OF CONCURRENT EHLERS DANLOS SYNDROME (EDS) AND POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME (POTS) ASSOCIATED WITH ORTHOSTATIC HYPERTENSION RESPONDING TO IV FLUIDS

Sympathetic toggled sinus rate acceleration as a mechanism of sustained sinus tachycardia in chronic orthostatic intolerance syndrome

The role of sympathetic nerve activity to maintain sinus rate acceleration remains unclear. The purpose of this study was to test the hypothesis that sustained (>30 seconds) sinus rate acceleration can be associated with either a sympathetic driven or a sympathetic toggled mechanism. We used a patch monitor to record skin sympathetic nerve activity (SKNA) and electrocardiogram over 24 hours. Study 1 included chronic orthostatic intolerance (OI) (n = 18), atrial fibrillation (n = 7), and asymptomatic normal control (n = 19) groups. Study 2 included 17 participants with chronic OI not treated with ivabradine, pyridostigmine, or β-blockers. While a majority of sinus rate acceleration was driven by persistent SKNA in study 1, some episodes were toggled on and off by SKNA bursts without persistent SKNA elevation. The sympathetic toggled sinus rate acceleration episodes were found in 7 of 18 participants with chronic OI (39%), 2 of 7 participants with atrial fibrillation (29%), and 6 of 19 normal control participants (32%) (P = .847) and were faster and longer in the chronic OI group than in other groups. In study 2, there were a total of 11 episodes of sinus rate acceleration that persisted for >200 seconds. Among these episodes, 6 (35%) were toggled on and off by SKNA bursts. Sustained sinus rate acceleration (may be toggled on or off) is associated with SKNA bursts in participants with chronic OI, participants with atrial fibrillation, and normal controls. Patients with OI had more frequent and longer episodes than did other groups.

İnsülin Duyarlılığı ve Vücut Kitle İndeksinin Ortostatik İntolerans Üzerine Etkileri

Objective: To assess the effects of insulin sensitivity and anthropometric measurements on orthostatic intolerance syndromes. Methods: This is a retrospective study. Patients with history of syncope aged between 7-18 years were analyzed according to insulin sensitivity index and anthropometric measurements. Patients were grouped according to the head-up tilt test results (test positive and test negative). Also, patients who had positive tilt tests were divided into four subgroups such as vasodepressor vasovagal syncope (VVS), cardioinhibitory VVS, mixed VVS, and postural orthostatic tachycardia syndrome. Results: A total of 509 patients were included in the study. The mean age was 13.45 ± 2.82 years, and %64.4 were girls. The tilt test was positive in 214 patients and negative in 295. With the tilt test results, 173 patients were diagnosed with VVS and 41 patients (19 %) with POTS. There were no statistically significant difference between the groups according to the insulin sensitivity indices. In anthropometric measurements, a significant difference was observed between the two groups in height, height standard deviation score (SDS), BMI SDS and BMI p (p =0.008, p= 0.02, p=0.036, p=0.03, respectively). Conclusion: In our study, while the low BMI and being tall were the predisposing factors for VVS episodes especially in young girls, there was no relationship between the insulin sensitivity indices and positive head-up tilt test result. Providing appropriate treatment by shedding light on factors that cause recurrent syncope can contribute to the quality of life of patients.

A Novel Methodology for the Synchronous Collection and Multimodal Visualization of Continuous Neurocardiovascular and Neuromuscular Physiological Data in Adults with Long COVID.

Background: Reports suggest that adults with post-COVID-19 syndrome or long COVID may be affected by orthostatic intolerance syndromes, with autonomic nervous system dysfunction as a possible causal factor of neurocardiovascular instability (NCVI). Long COVID can also manifest as prolonged fatigue, which may be linked to neuromuscular function impairment (NMFI). The current clinical assessment for NCVI monitors neurocardiovascular performance upon the application of orthostatic stressors such as an active (i.e., self-induced) stand or a passive (tilt table) standing test. Lower limb muscle contractions may be important in orthostatic recovery via the skeletal muscle pump. In this study, adults with long COVID were assessed with a protocol that, in addition to the standard NCVI tests, incorporated simultaneous lower limb muscle monitoring for NMFI assessment. Methods: To conduct such an investigation, a wide range of continuous non-invasive biomedical sensing technologies were employed, including digital artery photoplethysmography for the extraction of cardiovascular signals, near-infrared spectroscopy for the extraction of regional tissue oxygenation in brain and muscle, and electromyography for assessment of timed muscle contractions in the lower limbs. Results: With the proposed methodology described and exemplified in this paper, we were able to collect relevant physiological data for the assessment of neurocardiovascular and neuromuscular functioning. We were also able to integrate signals from a variety of instruments in a synchronized fashion and visualize the interactions between different physiological signals during the combined NCVI/NMFI assessment. Multiple counts of evidence were collected, which can capture the dynamics between skeletal muscle contractions and neurocardiovascular responses. Conclusions: The proposed methodology can offer an overview of the functioning of the neurocardiovascular and neuromuscular systems in a combined NCVI/NMFI setup and is capable of conducting comparative studies with signals from multiple participants at any given time in the assessment. This could help clinicians and researchers generate and test hypotheses based on the multimodal inspection of raw data in long COVID and other cohorts.

Orthostatic intolerance: a frailty marker for older adults.

Frailty, orthostatic blood pressure changes (OBPC), and orthostatic intolerance syndrome (OIS) are common in geriatric patients. However, the results of the studies evaluating the relationship between these entities are discordant. We aimed to investigate the association between frailty and OIS with or without OBPC. Comprehensive geriatric assessment (CGA), frailty assessment, OBPC evaluations in the active-standing test (1st, 3rd, 5th, and 10th min), OIS investigation both in history before the test (self-reported OIS) and emerged during the active-standing test, and sarcopenia assessment via BIA and handgrip strength (HGS) were performed in 102 geriatric outpatients. Patients were divided into three categories according to their frailty status (non-frail, prefrail, and frail) by Modified Fried Frailty Index (FFI) and Clinical Frailty Scale (CFS). Prevalence of self-reported OIS and OIS during the test were statistically higher in the frail group assessed by both frailty scales (P value: 0.001 for CFS, P value < 0.0001 for FFI, and P value: 0.001 for CFS, P value: 0.007 for FFI, respectively). Logistic regression analysis showed that OIS significantly increased frailty assessed both by FFI and CFS, when adjusted for age, sex, comorbidities, CGA, and sarcopenia (For FFI, OR: 19.37; 95% CI: 2.38-157.14; P value: 0.006 and for CFS OR: 4.32; 95% CI: 1.184-11.47; P value: 0.003, respectively). To the best of our knowledge, this is the first study defining OIS as symptoms both self-reported and provoked during the test, and showed a strong correlation between OIS and frailty. OIS may be defined as a multifactorial and independent marker for frailty, regardless of OBPC. Further prospective investigations are warranted to support the relationships between OIS and frailty.

Salt: The paradoxical philosopher's stone of autonomic medicine.

Sodium chloride, or common table salt, for millennia has played a prominent role in human affairs. Salt is also a key molecule for regulating intravascular fluid volume in patients with orthostatic disorders. In this first article of a special issue of the journal focusing on salt and the autonomic nervous system, the historical and physiologic significance of salt is reviewed, highlighting its importance to society and to medicine. The relevance of salt both for civilization and for autonomic physiology penetrates into nearly every aspect of life and health. Replacing salt that has been depleted or administering salt to expand intravascular volume is considered standard treatment for patients with orthostatic hypotension and syndromes of orthostatic intolerance. The potential longterm effects of added salt, including effects unrelated to intravascular volume, have been insufficiently studied in patients with autonomic disorders. A salient concern is the potential increased risk of developing hypertension. Underappreciated aspects of salt include its ability to increase anxiety and through nonosmotic mechanisms to contribute to local tissue inflammation. Salt may be either salubrious or detrimental, or possibly both at the same time, depending on the clinical conditions. Reconciling these opposite effects in clinical practice requires weighing benefits against potential risks, assessing what is known alongside what is uncertain, and titrating treatment decisions to the particular needs of each individual patient.

Orthostatic intolerance syndromes after hematopoietic cell transplantation: clinical characteristics and therapeutic interventions in a single-center experience

BackgroundHematopoietic cell transplantation (HCT) is an established and potentially curative therapeutic option for hematologic cancers. HCT survivors are at risk of developing long-term complications impacting on morbidity and mortality. Orthostatic hypotension (OH) and postural tachycardia syndrome (POTS) have been anecdotally described after HCT. However, the incidence and clinical characteristics of patients with OH and POTS after HCT has not been well defined.MethodsThis retrospective study included 132 patients who had HCT between March 2011 and July 2018 and were referred to Cardio-oncology clinic. Patients were screened for OH and POTS. Using logistic regression analysis we evaluated the association between clinical factors and the incidence of OH and POTS.ResultsMedian age was 58 (47–63) years, 87 (66%) patients were male, 95 (72%) were Caucasian. OH was diagnosed in 30 (23%) subjects and POTS in 12 (9%) after the HCT. No significant differences in demographic characteristics were found when comparing patients with and without OH or POTS. The two groups did not differ for cardiovascular diseases prevalence nor for the prior use of antihypertensive drugs. Previous radiotherapy and treatment with specific chemotherapy drugs were found to be associated with the incidence of OH or POTS, but none of the factors maintained the significance in the multivariate model. Pharmacological therapy was required in 38 (91%) cases, including a b-adrenergic blocker (n = 24, 57%), midodrine (n = 24, 57%) and fludrocortisone (n = 7, 18%).ConclusionOrthostatic intolerance syndromes are commonly diagnosed in patients referred to the cardiologist after HCT, involving approximately 1/3 of patients and requiring pharmacological therapy to cope with symptoms in the majority of cases. Risk factors specific to this population are identified but cannot fully explain the incidence of POTS and OH after HCT.

Cutaneous manifestations of orthostatic intolerance syndromes.

Dysautonomia refers to a group of autonomic nervous system disorders that affect nearly 70 million people worldwide. One subset of dysautonomia includes syndromes of orthostatic intolerance (OI), which primarily affect adolescents and women of childbearing age. Due to the variability in disease presentation, the average time from symptom onset to diagnosis of dysautonomia is 6 years. In general, there is a paucity of dermatological research articles describing patients with dysautonomia. The objective of this review is to summarize the existing literature on cutaneous manifestations in dysautonomia, with an emphasis on syndromes of OI. A PubMed database of the English-language literature (1970–2020) was searched using the terms “dysautonomia”, “orthostatic intolerance”, “cutaneous”, “skin”, “hyperhidrosis”, “hypohidrosis”, “sweat”, and other synonyms. Results showed that cutaneous manifestations of orthostatic intolerance are common and varied, with one paper citing up to 85% of patients with OI having at least one cutaneous symptom. Recognition of dermatological complaints may lead to an earlier diagnosis of orthostatic intolerance, as well as other comorbid conditions.

It's not over till it's over: a narrative review of Long COVID

Viral persistence following acute COVID infection is increasingly being reported by patients and gradually being recognized as a medical syndrome. Like much about COVID, this so-called Long COVID is perplexing. It is associated with numerous symptoms, foremost among them profound fatigue, and often occurs in a relapsing/remitting pattern. There is one “living” guideline for managing Long COVID and even terminology and definitions of the syndrome are in flux. Long COVID occurs in patients who have recovered from the acute infection and this may be viral persistence, a form of autoimmunity, or the long-term results of organ damage sustained during the acute infection. Symptoms have been reported up to six months after acute infection with no clear association between the severity of the acute infection and the presence or absence of Long COVID. The symptoms of the acute illness do not necessarily align with the symptoms of Long COVID. Disruptions to the autonomic function in Long COVID are particularly puzzling, including orthostatic intolerance syndrome (which may not have occurred during the acute infection). Loss of the sense of smell and taste is one symptom that appears common in both acute and Long COVID; on the other hand, fever is more prevalent in acute than Long COVID. Research is urgently needed to better understand Long COVID, for example: what is the role of elevated biomarkers such as D-dimer and C-reactive protein in Long COVID? Is Long COVID one or more than one syndrome? How can patients with Long COVID be appropriately treated?

Autonomic dysfunction in ‘long COVID’: rationale, physiology and management strategies

The SARS-CoV-2 (COVID-19) pandemic has caused unprecedented morbidity, mortality and global disruption. Following the initial surge of infections, focus shifted to managing the longer-term sequelae of illness in survivors. 'Post-acute COVID' (known colloquially as 'long COVID') is emerging as a prevalent syndrome. It encompasses a plethora of debilitating symptoms (including breathlessness, chest pain, palpitations and orthostatic intolerance) which can last for weeks or more following mild illness. We describe a series of individuals with symptoms of 'long COVID', and we posit that this condition may be related to a virus- or immune-mediated disruption of the autonomic nervous system resulting in orthostatic intolerance syndromes. We suggest that all physicians should be equipped to recognise such cases, appreciate the symptom burden and provide supportive management. We present our rationale for an underlying impaired autonomic physiology post-COVID-19 and suggest means of management.