Complete remission with histamine blocker in a patient with intractable hyperadrenergic postural orthostatic tachycardia syndrome secondary to long coronavirus disease syndrome.

The COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has emerged as a global public health concern and its sequels have barely started to outcrop. A good percentage of patients who suffered from COVID-19 are prone to develop long-COVID or post-COVID condition (PCC), a multisystemic, heterogeneous, chronic disorder. Patients with PCC may experience diverse manifestations, of which cardiovascular and neurological symptoms are among the most frequently reported. Indeed, dysautonomia presented as orthostatic intolerance has gained room following recent reports linking postural orthostatic tachycardia syndrome (POTS) with PCC. Disturbances in heart rate (HR) and blood pressure (BP) during postural changes are the cornerstones of orthostatic intolerance seen in patients suffering from PCC. A subtype of POTS, hyperadrenergic POTS, has been widely studied because of its association with mast cell activation syndrome (MCAS). Although a causative relationship between PCC, hyperadrenergic POTS, and MCAS remains unrevealed, these syndromes can overlap. We want to propose here a correlation produced by a close-loop mechanism with positive feedback established after SARS-CoV-2 infection in a previously healthy young patient.

Prevalence of orthostatic intolerance in long covid clinic patients and healthy volunteers: A multicenter study.

Orthostatic intolerance (OI), including postural orthostatic tachycardia syndrome (PoTS) and orthostatic hypotension (OH), are often reported in long covid, but published studies are small with inconsistent results. We sought to estimate the prevalence of objective OI in patients attending long covid clinics and healthy volunteers and associations with OI symptoms and comorbidities. Participants with a diagnosis of long covid were recruited from eight UK long covid clinics, and healthy volunteers from general population. All undertook standardized National Aeronautics and Space Administration Lean Test (NLT). Participants' history of typical OI symptoms (e.g., dizziness, palpitations) before and during the NLT were recorded. Two hundred seventy-seven long covid patients and 50 frequency-matched healthy volunteers were tested. Healthy volunteers had no history of OI symptoms or symptoms during NLT or PoTS, 10% had asymptomatic OH. One hundred thirty (47%) long covid patients had previous history of OI symptoms and 144 (52%) developed symptoms during the NLT. Forty-one (15%) had an abnormal NLT, 20 (7%) met criteria for PoTS, and 21 (8%) had OH. Of patients with an abnormal NLT, 45% had no prior symptoms of OI. Relaxing the diagnostic thresholds for PoTS from two consecutive abnormal readings to one abnormal reading during the NLT, resulted in 11% of long covid participants (an additional 4%) meeting criteria for PoTS, but not in healthy volunteers. More than half of long covid patients experienced OI symptoms during NLT and more than one in 10 patients met the criteria for either PoTS or OH, half of whom did not report previous typical OI symptoms. We therefore recommend all patients attending long covid clinics are offered an NLT and appropriate management commenced.

Impact of COVID-19 infection on baseline autonomic symptoms in patients with preexisting postural tachycardia syndrome and orthostatic intolerance: A retrospective study.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) and dysautonomia following a SARS-CoV-2 infection have been recently reported. The underlying mechanism of dysautonomia is not well understood. The impact of this viral illness on the underlying autonomic symptoms has not been studied in patients with a pre-existing POTS diagnosis. Our study aims to report the impact of a COVID-19 infection on patients with preexisting POTS, both during the acute phase of the disease and post-recovery. METHODS: Institutional Review Board (IRB) approval was obtained to access charts of the study subjects. All patients with known POTS disease who acquired COVID-19 infection between April 2020 and May 2021 were included. The end point of the study was worsening POTS related symptoms including orthostatic dizziness, palpitation, fatigue and syncope/ presyncope post COVID-19 infection that required escalation of therapy. Basic demographics, details of POTS diagnosis, medications, Additional information regarding COVID 19 infection, duration of illness, need for hospitalization, worsening of POTS symptoms, need for ED visits, the type of persisting symptoms and vaccination status were obtained from the retrospective chart review. RESULTS: A total of 41 patients were studied. The alpha-variant was the most common causing SARS-CoV-2 infection. 27% (11 patients) of them had tested positive for COVID- 19 infection more than once. About 38 (92.7%) of them reported having worsening of their baseline POTS symptoms during the active infection phase. About 28 patients (68%) experienced worsening of their dysautonomia symptoms for at least 1-6 months post infection. Nearly 30 patients (73.2%) required additional therapy for their symptom control and improvement. CONCLUSIONS: Patients with pre-existing POTS, most experienced a worsening of their baseline autonomic symptoms after suffering the COVID-19 infection which required additional pharmacotherapy for their symptom improvement.

Study protocol for the Heads-Up trial: a phase II randomized controlled trial investigating head-up tilt sleeping to alleviate orthostatic intolerance in Parkinson's Disease and parkinsonism.

BACKGROUND: In persons with Parkinson's Disease (PD) or certain forms of atypical parkinsonism, orthostatic hypotension is common and disabling, yet often underrecognized and undertreated. About half of affected individuals also exhibit supine hypertension. This common co-occurrence of both orthostatic hypotension and supine hypertension complicates pharmacological treatments as the treatment of the one can aggravate the other. Whole-body head-up tilt sleeping (HUTS) is the only known intervention that may improve both. Evidence on its effectiveness and tolerability is, however, lacking, and little is known about the implementability. METHODS: In this double-blind multicenter randomized controlled trial (phase II) we will test the efficacy and tolerability of HUTS at different angles in 50 people with PD or parkinsonism who have both symptomatic orthostatic hypotension and supine hypertension. All participants start with one week of horizontal sleeping and subsequently sleep at three different angles, each maintained for two weeks. The exact intervention will vary between the randomly allocated groups. Specifically, the intervention group will consecutively sleep at 6°, 12° and 18°, while the delayed treatment group starts with a placebo angle (1°), followed by 6° and 12°. We will evaluate tolerability using questionnaires and compliance to the study protocol. The primary endpoint is the change in average overnight blood pressure measured by a 24-hour ambulatory blood pressure recording. Secondary outcomes include orthostatic blood pressure, orthostatic tolerance, supine blood pressure, nocturia and various other motor and non-motor tests and questionnaires. DISCUSSION: We hypothesize that HUTS can simultaneously alleviate orthostatic hypotension and supine hypertension, and that higher angles of HUTS are more effective but less tolerable. The Heads-Up trial will help to clarify the effectiveness, tolerability, and feasibility of this intervention at home and can guide at-home implementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT05551377; Date of registration: September 22, 2022.

Improvement in chronic pelvic pain, orthostatic intolerance and interstitial cystitis symptoms after treatment of pelvic vein insufficiency.

OBJECTIVES: Comorbidities associated with venous origin chronic pelvic pain (VO-CPP) were evaluated pre and post venous treatment to assess change. MATERIALS AND METHODS: 45 women with VO-CPP were treated with venous stenting and/or embolization. Four surveys assessed symptoms pre- and post-treatment: IPPS (chronic pelvic pain), PUF (interstitial cystitis), OHQ (dysautonomia), and modified ROME III (IBS). Prevalence of joint hypermobility was investigated. RESULTS: Ages were 18-65. Pretreatment, 64% and 49% of women were in the severe range for PUF and OHQ, respectively. 40% and 56% met criteria for IBS and Ehlers-Danlos syndrome/Hypermobility Spectrum Disorder (EDS/HSD), respectively. 17eceived an iliac stent, 5 pelvic embolization, and 23 both. Post-treatment, average scores improved: IPPS (by 55%), PUF (34%), and OHQ (49%). Rome III improved only slightly. CONCLUSION: Pelvic pain, interstitial cystitis, and dysautonomia were frequently found with VO-CPP and improved after venous treatment. EDS/HSD and IBS were common in these women.

Detection of Elevated Level of Tetrahydrobiopterin in Serum Samples of ME/CFS Patients with Orthostatic Intolerance: A Pilot Study.

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a multisystem chronic illness characterized by severe muscle fatigue, pain, dizziness, and brain fog. Many patients with ME/CFS experience orthostatic intolerance (OI), which is characterized by frequent dizziness, light-headedness, and feeling faint while maintaining an upright posture. Despite intense investigation, the molecular mechanism of this debilitating condition is still unknown. OI is often manifested by cardiovascular alterations, such as reduced cerebral blood flow, reduced blood pressure, and diminished heart rate. The bioavailability of tetrahydrobiopterin (BH4), an essential cofactor of endothelial nitric oxide synthase (eNOS) enzyme, is tightly coupled with cardiovascular health and circulation. To explore the role of BH4 in ME/CFS, serum samples of CFS patients (n = 32), CFS patients with OI only (n = 10; CFS + OI), and CFS patients with both OI and small fiber polyneuropathy (n = 12; CFS + OI + SFN) were subjected to BH4 ELISA. Interestingly, our results revealed that the BH4 expression is significantly high in CFS, CFS + OI, and CFS + OI + SFN patients compared to age-/gender-matched controls. Finally, a ROS production assay in cultured microglial cells followed by Pearson correlation statistics indicated that the elevated BH4 in serum samples of CFS + OI patients might be associated with the oxidative stress response. These findings suggest that the regulation of BH4 metabolism could be a promising target for understanding the molecular mechanism of CFS and CFS with OI.

The Principal Components of Autonomic Dysfunction in Fibromyalgia Assessed by the Refined and Abbreviated Composite Autonomic Symptom Score.

BACKGROUND: We have recently confirmed that non-pain autonomic dysfunction symptoms occur in fibromyalgia and can be assessed with the 31-item Composite Autonomic Symptom Score (COMPASS 31) instrument. Fibromyalgia patients have been found to have higher scores than matched controls across all six domains of this instrument. OBJECTIVES: To analyse the principal components of the autonomic COMPASS 31 domain scores in fibromyalgia patients to understand better the fundamental dimensions of dysautonomia in this disorder. METHODS: A principal component analysis of fibromyalgia autonomic domain scores was carried out using a varimax orthogonal rotation with decomposition being based on the correlation matrix and setting a threshold of greater than one for the eigenvalues. RESULTS: Three mutually orthogonal principal components, accounting for over 80% of the total variance, were identified. The first was a function of the secretomotor, orthostatic intolerance and pupillomotor domains; the second was a function of the vasomotor and urinary bladder domains; and the third was a function of the gastrointestinal and orthostatic intolerance domains. There was a positive correlation between symptom domain scores of the Revised Fibromyalgia Impact Questionnaire and the first principal component scores (rs = 0.536, p = 0.006). CONCLUSION: This analysis has reduced the dimensionality of autonomic dysfunction in fibromyalgia patients from six to three. The internal structure of the fibromyalgia dysautonomia data reflected by these results may help in the elucidation of the aetiology of this complex and difficult-to-treat disorder.

Orthostatic Intolerance and Chiari I Malformation.

Individuals with Chiari malformation can present with symptoms of fatigue, lightheadedness, and syncope-the cardinal features of orthostatic intolerance. Similar orthostatic symptoms can complicate the clinical course following Chiari decompression. The presence of orthostatic intolerance in patients with Chiari malformation is not surprising given the location of the major circulatory control centers and their pathways in the brainstem. This article reviews the normal physiologic response to upright posture and the common forms of orthostatic intolerance encountered in clinical practice. The authors describe the relationship between orthostatic intolerance and Chiari malformation and provide suggestions regarding the evaluation and management of these disorders.

Gluten-free diet in postural orthostatic tachycardia syndrome (POTS).

OBJECTIVES: Postural orthostatic tachycardia syndrome (POTS) is a chronic disorder of the autonomic nervous system that is associated with orthostatic intolerance (OI) and gastrointestinal (GI) symptoms. We aimed to determine if a gluten-free diet (GFD) may be an effective treatment in patients with POTS. METHODS: Patients with confirmed POTS and without celiac disease who followed GFD for 4 weeks retrospectively completed pre- and post- GFD COMPASS-31 questionnaires. Paired-samples t-tests were conducted to compare COMPASS-31 scores before and after adopting GFD. RESULTS: All 20 patients (all females, age 16-62 years (mean age 33)), had POTS symptoms for 1-30 years (mean 10.8, SD = 10.23 years). Eleven patients had co-morbid mast cell activation syndrome, and 8 had hypermobile Ehlers-Danlos syndrome. Pre-GFD COMPASS-31 scores (mean 57.8) were significantly higher than post-GFD scores (mean 38.2, t(19) = -8.92, p < 0.00001), with the largest improvement noted in the OI (p < 0.00001), vasomotor, (p = 0.0034), and GI (p = 0.0004) domains and with a mean reduction in total COMPASS-31 score by 33.9% after implementing GFD. All patients reported improved symptoms on GFD with mean self-assessed improvement of 50.5% (range 10-99%). DISCUSSION: GFD may be effective in reducing the symptom burden in patients with POTS, particularly in the OI, vasomotor, and GI symptom domains. Large prospective studies are necessary to confirm whether GFD is an effective long-term treatment option for patients.

Cardiac arrhythmias in postural tachycardia syndrome and orthostatic intolerance.

BACKGROUND AND OBJECTIVES: There is sparse literature on cardiac arrhythmias and the utility of ambulatory rhythm monitoring in patients with postural tachycardia syndrome and orthostatic intolerance. This study's primary aim was to investigate the prevalence of arrhythmias in this population. Knowing the prevalence and types of arrhythmias in dysautonomia patients could influence the decision to pursue ambulatory rhythm monitoring and ultimately guide therapy. METHODS: This retrospective descriptive study examined the frequency of cardiac arrhythmias, as detected by ambulatory rhythm monitoring, in children with postural tachycardia syndrome/orthostatic intolerance or syncope who were seen at the Children's National Hospital Electrophysiology Clinic between January 2001 and December 2020. RESULTS: In postural tachycardia syndrome/orthostatic intolerance patients, arrhythmia was detected on 15% of 332 ambulatory rhythm monitors. In syncope patients, arrhythmia was detected on 16% of 157 ambulatory rhythm monitors, not significantly different from the postural tachycardia syndrome/orthostatic intolerance group. The difference in rate of arrhythmia detection between 24-hour Holter and 2-week Zio® monitoring was not statistically significant. CONCLUSION: This study suggests that a substantial proportion of postural tachycardia syndrome/orthostatic intolerance patients may have concomitant underlying cardiac arrhythmias, at a frequency similar to what is seen in patients undergoing primary evaluation for cardiac symptoms such as chest pain, palpitations, and syncope. In the appropriate clinical context, physicians caring for postural tachycardia syndrome/orthostatic intolerance patients should consider additional evaluation for arrhythmias beyond sinus tachycardia.

Temporomandibular disorders and autonomic dysfunction: Exploring the possible link between the two using a questionnaire survey.

OBJECTIVE: To assess autonomic function and investigate factors related to its dysfunction in patients with temporomandibular disorders (TMD) from a biopsychosocial perspective. METHODS: Seventy-six patients with TMD were investigated by clinical examination and questionnaires concerning biopsychosocial aspects (The Brief Pain Inventory, the Pain Catastrophizing Scale, and the Symptom Checklist-90-Revised) and autonomic dysfunction (The COMPASS 31). RESULTS: Seventy-one patients were included in the study. The result of multiple regression analysis showed that four variables (sex, depression, age, and pain interference) were significantly associated with autonomic dysfunction. Increased orthostatic intolerance and bladder dysfunction were observed in females and males, respectively. Younger age was associated with higher orthostatic intolerance, while higher pain interference was associated with higher secretomotor dysfunction and bladder dysfunction. Further, higher depression scores were linked to higher scores in the gastrointestinal subdomain. CONCLUSION: Autonomic dysfunction may affect TMD-related pain in the context of a biopsychosocial perspective.

Orthostatic Intolerance after COVID-19 Infection: Is Disturbed Microcirculation of the Vasa Vasorum of Capacitance Vessels the Primary Defect?

Following COVID-19 infection, a substantial proportion of patients suffer from persistent symptoms known as Long COVID. Among the main symptoms are fatigue, cognitive dysfunction, muscle weakness and orthostatic intolerance (OI). These symptoms also occur in myalgic encephalomyelitis/chronic fatigue (ME/CFS). OI is highly prevalent in ME/CFS and develops early during or after acute COVID-19 infection. The causes for OI are unknown and autonomic dysfunction is hypothetically assumed to be the primary cause, presumably as a consequence of neuroinflammation. Here, we propose an alternative, primary vascular mechanism as the underlying cause of OI in Long COVID. We assume that the capacitance vessel system, which plays a key role in physiologic orthostatic regulation, becomes dysfunctional due to a disturbance of the microvessels and the vasa vasorum, which supply large parts of the wall of those large vessels. We assume that the known microcirculatory disturbance found after COVID-19 infection, resulting from endothelial dysfunction, microthrombus formation and rheological disturbances of blood cells (altered deformability), also affects the vasa vasorum to impair the function of the capacitance vessels. In an attempt to compensate for the vascular deficit, sympathetic activity overshoots to further worsen OI, resulting in a vicious circle that maintains OI. The resulting orthostatic stress, in turn, plays a key role in autonomic dysfunction and the pathophysiology of ME/CFS.

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

BACKGROUND: The role of sympathetic nerve activity to maintain sinus rate acceleration remains unclear. OBJECTIVE: 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. METHODS: 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 ß-blockers. RESULTS: 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. CONCLUSION: 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.

Skin sympathetic nerve activity in patients with chronic orthostatic intolerance.

BACKGROUND: Chronic orthostatic intolerance (OI) is characterized by the development of tachycardia and other symptoms when assuming an upright body position. OBJECTIVE: The purpose of this study was to test the hypothesis that skin sympathetic nerve activity (SKNA) bursts are specific symptomatic biomarkers in patients with chronic OI. METHODS: We used an electrocardiogram monitor with a built-in triaxial accelerometer to simultaneously record SKNA and posture in ambulatory participants. Study 1 compared chronic OI (14 women and 2 men; mean age 35 ± 10 years) with reference control participants (14 women; mean age 31 ± 6 years). Study 2 included 17 participants with chronic OI (15 women and 2 men; mean age 39 ± 12 years) not yet treated with ivabradine, pyridostigmine, or ß-blockers. RESULTS: In study 1, there were 124 episodes (8 ± 4 per participant) of postural changes, with 11 episodes (8.9%) associated with symptoms. In comparison, 0 of 104 postural changes (7 ± 3 per participant) in controls were symptomatic (P = .0011). In participants with chronic OI, the SKNA bursts associated with symptoms had higher burst frequencies, longer burst durations, and larger mean burst areas than did bursts during asymptomatic periods. However, SKNA bursts and tachycardia were asymptomatic in controls. We analyzed 110 symptomatic episodes in study 2 (6 ± 5 per participant). Among them, 98 (89.1%) followed at least 1 SKNA burst. In comparison, only 41 (37.3%) had heart rate exceed 100 beats/min 1 minute before symptom onset (P < .0001). CONCLUSION: SKNA bursts are a highly specific, albeit insensitive, symptomatic biomarker for chronic OI.

Incidence and Risk Factors of Orthostasis After Primary Hip and Knee Arthroplasty.

BACKGROUND: Postoperative orthostatic intolerance can limit mobilization after hip and knee arthroplasty. The literature is lacking on the incidence and risk factors associated with orthostatic intolerance after elective arthroplasty. METHODS: A retrospective case-control study of primary total hip, total knee, and unicompartmental knee arthroplasty patients was conducted. Patients with orthostatic events were identified, and potential demographic and perioperative risk factors were recorded. Orthostatic intolerance was defined as postoperative syncope, lightheadedness, or dizziness, limiting ambulation and/or requiring medical treatment. Statistical analysis was completed using Pearson's chi-square test for categorical data and t-tests for continuous data. Binary logistic regression was performed. RESULTS: A total of 500 consecutive patients were included. The overall incidence of orthostatic intolerance was 18%; 25% in total hip arthroplasty (THA) and 11% in total knee arthroplasty. On univariate analysis, significant risk factors for developing postoperative orthostatic intolerance include older age, female gender, THA surgery, lower American Society of Anesthesiologists class, absence of recreational drug use, lower estimated blood volume, lower preoperative diastolic blood pressure, spinal with monitored anesthesia care (MAC), posterior approach for THA, bupivacaine use in spinal, percent of blood loss, postoperative oxycodone or tramadol use, higher postoperative intravenous fluid volume, and lower postoperative hemoglobin. Multivariate analysis demonstrated persistent significance of female gender, THA surgery, spinal with MAC, bupivacaine use in spinal, and more intravenous fluid administered postoperatively. CONCLUSION: Orthostatic intolerance affects a significant number of arthroplasty patients. Awareness of risk factors and modification of perioperative variables linked to orthostatic intolerance may assist the surgeon in choosing the appropriate surgical setting, educating patients, and improving early postoperative recovery.

Autonomic neuropathy as post-acute sequela of SARS-CoV-2 infection: a case report.

Symptoms of autonomic dysfunction, particularly those of orthostatic intolerance, continue to represent a major component of the currently recognized post-acute sequelae of SARS-CoV-2 infections. Different pathophysiologic mechanisms can be involved in the development of orthostatic intolerance including hypovolemia due to gastrointestinal dysfunction, fatigue-associated deconditioning, and hyperadrenergic state due to pandemic-related anxiety. Additionally, there has been a well-established association of a common primary autonomic disorder like postural orthostatic tachycardia syndrome, a subtype of orthostatic intolerance, with antecedent viral infections. Here we report a case of neuropathic type postural orthostatic tachycardia syndrome as a form of autonomic neuropathy that developed following COVID-19 infection.

Delayed symptoms and orthostatic intolerance following peanut challenge.

BACKGROUND: Clinical reactions to Oral Food Challenge (OFC) in peanut-allergic individuals have been well-characterised, but rates and phenotypes of symptom recurrence beyond the first hour after objective symptoms are less well-characterised. OBJECTIVE: To evaluate the rate of new-onset symptoms occurring at least 1 h after stopping OFC in peanut-allergic children and adults undergoing peanut-OFC. METHODS: We prospectively collected data relating to adverse events following positive reactions at double-blind, placebo-controlled food challenges (DBPCFC) to peanut in children and adults evaluated for eligibility to participate in two clinical trials (NCT02149719, NCT02665793). The trials included people aged 8 to 45 with primary, IgE-mediated peanut allergy at DBPCFC. The challenge protocol included consumption of a light meal 1 h after reaction. RESULTS: A total of 121 participants (64 children, 57 adults) had immediate, objective symptoms at DBPCFC, 25 (17 children, 8 adults) with anaphylaxis. Thirty-three (27%) had progression or recurrence of symptoms ≥ 1 h after objective clinical reaction, of whom 8 developed anaphylaxis. In 23 cases, the onset of new symptoms was associated with consumption of a light meal. In eight cases, symptoms were limited to a symptomatic postural fall in blood pressure noted in preparation for discharge, without any other new features of an allergic reaction. CONCLUSIONS & CLINICAL RELEVANCE: Progressive or new-onset symptoms ≥1 h following initial allergic reaction at OFC are common and can include orthostatic hypotension. Recurrent symptoms may be temporally associated with food consumption.

Median Arcuate Ligament Syndrome with Orthostatic Intolerance: Intermediate-Term Outcomes following Surgical Intervention.

OBJECTIVES: To report the intermediate-term outcome following surgical intervention for median arcuate ligament syndrome (MALS) in adolescents and young adults with orthostatic intolerance (OI) to assess clinical improvement in the gastrointestinal and 5 other functional domains and if relief of arterial obstruction is associated with resolution of clinical symptoms. STUDY DESIGN: Thirty-one patients were given 2 dysautonomia-designed questionnaires to assess changes in symptoms following operative intervention in 6 functional domains and underwent postoperative repeat abdominal ultrasound examinations. RESULTS: Average follow-up after surgery was 22.4 ± 14.8 months. Self-assessed quality of health on a Likert scale (1-10 with 10 being normal) improved from 4.5 ± 2.1 preoperatively to 5.3 ± 2.4 postoperatively (P = not significant). Gastrointestinal symptoms of abdominal pain, nausea, and vomiting improved in 63% (P = .007), 53% (P = .040), and 62% (P = .014) of patients, respectively. Cardiovascular symptoms of dizziness, syncope, chest pain, and palpitations improved in 45% (P = not significant), 50% (P = not significant), 54% (P = .043), and 54% (P = .037) of patients, respectively. Transabdominal ultrasound peak supine expiratory velocity decreased from 348 ± 105 cm/s preoperatively to 251 ± 109 cm/s at 6 months or more after a ligament release procedure. Decrease of the postoperative celiac artery Doppler velocity was not associated with an improvement in gastrointestinal symptoms (P = .075). CONCLUSIONS: Adolescent and young adult patients with median arcuate ligament syndrome and OI have a good response to surgical intervention. About two-thirds of patients report significant improvement in symptoms of abdominal pain, nausea, and vomiting. Despite these encouraging data, many patients with MALS and OI continue to have an impaired quality of health.

Association of transient orthostatic hypotension with falls and syncope in patients with Parkinson disease.

OBJECTIVES: To assess the frequency of transient orthostatic hypotension (tOH) and its clinical impact in Parkinson disease (PD), we retrospectively studied 173 patients with PD and 173 age- and sex-matched controls with orthostatic intolerance, who underwent cardiovascular autonomic function testing under continuous noninvasive blood pressure (BP) monitoring. METHODS: We screened for tOH (systolic BP fall ≥20 mm Hg or diastolic ≥10 mm Hg resolving within the first minute upon standing) and classic OH (cOH, sustained systolic BP fall ≥20 mm Hg or diastolic ≥10 mm Hg within 3 minutes upon standing). In patients with PD, we reviewed the medical records of the 6 months preceding and following autonomic testing for history of falls, syncope, and orthostatic intolerance. RESULTS: tOH occurred in 24% of patients with PD and 21% of controls, cOH in 19% of patients with PD and in none of the controls, independently of any clinical-demographic or PD-specific characteristic. Forty percent of patients with PD had a history of falls, in 29% of cases due to syncope. Patients with PD with history of orthostatic intolerance and syncope had a more severe systolic BP fall and lower diastolic BP rise upon standing, most pronounced in the first 30-60 seconds. CONCLUSIONS: tOH is an age-dependent phenomenon, which is at least as common as cOH in PD. Transient BP falls when changing to the upright position may be overlooked with bedside BP measurements, but contribute to orthostatic intolerance and syncope in PD. Continuous noninvasive BP monitoring upon standing may help identify a modifiable risk factor for syncope-related falls in parkinsonian patients.

Gastrointestinal motility evaluation in children with orthostatic intolerance: Mayo Clinic experience.

OBJECTIVE: Orthostatic intolerance (OI) and autonomic dysfunction (AD) are common in adolescents and young adults. Patients experience multisystem symptoms including gastrointestinal (GI), postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), or only symptoms of OI (SOI) without significant findings on 70-degree head-up tilt testing (HUT). We hypothesize that patients with POTS, OH, and SOI show differences in GI symptoms and motility test and that heart rate (HR) changes on HUT predict severity of GI dysmotility. STUDY DESIGN: From medical records of patients (<18 years) with OI, we collected demographics, presenting symptoms, GI manifestations, and GI motility testing. Data were compared between the 3 groups (POTS, OH, and SOI). We assessed changes in HR on HUT with changes on GI motility evaluation. RESULTS: Two hundred twenty-nine patients were included (73% females). Abdominal pain (65%), nausea (49%), vomiting (18%), and constipation (24%) were the most common GI symptoms. In patients who had motility evaluation, there were 27% (53/193) with delayed gastric emptying (GE) at 4 hours, 35% (32/92) with delayed colonic transit (CT), 55% (17/31) with reduced gastric accommodation (GA), and 75% (21/28) with dyssynergic defecation (DD). Among 100 POTS, 34 OH, and 95 SOI patients, no significant differences in GI symptoms or motility tests were identified and HR changes on HUT were not associated with changes on motility tests. CONCLUSION: GI symptoms are frequent in adolescents with OI and are associated with delayed GE, reduced GA, delayed CT, and presence of DD.