Autonomic dysfunction, characterized by orthostatic intolerance and presyncope, is understudied in youth. Mental health comorbidities are commonly reported and sometimes blamed for the onset of autonomic dysfunction; however, no studies have yet examined this relationship. This study aimed to establish the prevalence rate of mental health diagnoses in a pediatric sample of patients with autonomic dysfunction, characterize the temporal relationship between autonomic and mental health symptom onset, and understand patients' perspectives on this relationship. Pediatric patients completed surveys at autonomic dysfunction clinic follow-up appointments. Surveys obtained patient self-reported metal health conditions, autonomic symptoms, and patient-perceived timelines. Patients then described their understanding of the relationship between their mental and physical health. Authors analyzed qualitative data using content analysis. Of 142 patients approached, 127 completed surveys (response rate 88.8%; Mean age = 16.1); 70.1% reported a mental health diagnosis, and 4.7% suspected a mental health condition. Anxiety was the most reported concern (72.4%). Patients reported mental health concerns preceding (37.6%), co-occurring (12.2%), or succeeding (38.1%) their autonomic dysfunction symptoms. Qualitative responses revealed patients perceived bidirectional or unidirectional relationships between mental health and autonomic dysfunction, although some patients were uncertain. Patients described varied relationships between mental health symptoms and autonomic dysfunction, emphasizing the individualized nature of these experiences. Although the rate of mental health diagnoses was pointedly high, temporal associations appeared patient-specific rather than consistent across the sample. Providers should consider routine screening and treatment of mental health concerns as part of comprehensive care for youth with autonomic dysfunction.

Autonomic dysfunction, or dysautonomia, is increasingly being recognized as a complication of concussion. While the symptoms can overlap with other postconcussion sequelae, it is important to distinguish the patient suffering from postconcussion dysautonomia in order to provide proper symptomatic management and aid in recovery. This narrative review will summarize the available, high-quality literature regarding autonomic testing abnormalities in patients with a history of concussion, interpret these findings in the context of the sympathetic and parasympathetic divisions of the autonomic nervous system, and discuss an approach to managing postconcussion dysautonomia.

Orthostatic intolerance and postural orthostatic tachycardia syndrome (POTS) are increasingly recognized conditions in pediatrics, often requiring intensive counseling and trials of medications as part of the eventually successful management. Telemedicine offers potential benefits for follow up care in this population. To evaluate clinical outcomes and quality of life (QOL) in pediatric patients with orthostatic intolerance managed through telemedicine follow up, a retrospective chart review was conducted on 220 pediatric patients with significant orthostatic intolerance symptoms who received telemedicine follow up between January 2024 and May 2025. Patients were triaged following initial clinic assessment and managed with lifestyle modifications, iron and vitamin D supplementation when indicated, and potentially medications. QOL was assessed on a 1-10 scale. Baseline and follow up QOL scores were compared over time. The cohort was 94.5% female with a mean age of 15.3 ± 2.0 years; 36.3% of the patients met criteria for a diagnosis of POTS. Over an average follow up of 17.8 months, QOL scores improved significantly from 5.6 at baseline to 7.7 at the last visit (p < 0.005) and 8.2 at best reported visit (p < 0.005). Symptom prevalence decreased notably, particularly lightheadedness, palpitations, and fatigue. Telemedicine follow up for pediatric orthostatic intolerance is associated with significant improvements in symptom burden and quality of life. Frequently scheduled visits can improve follow up rate and compliance as well as support effective use of clinical resources.

Chiari malformation type 1 (CM-I) is frequently associated with connective tissue disorders (CTDs), particularly Ehlers-Danlos syndrome (EDS), which may increase surgical risk and complicate management. Familial clustering of CM-I and CTDs has been reported, but their prevalence within families remains underexplored. This study aimed to determine the prevalence of CTDs and comorbidities among family members of CM-I patients, comparing familial and sporadic cases. We conducted a retrospective survey-based study of patients who underwent posterior fossa decompression for CM-I between 2008 and 2023 by the senior author. Eligible patients (n = 890) were invited to complete a 10-item questionnaire regarding family history of CM-I, CTDs, and related comorbidities. Responses were stratified into familial (≥1 relative with CM-I) and sporadic groups. Group comparisons were performed using χ2 or Fisher exact tests. Of 354 complete responses, 308 (87.0%) reported a family history of CM-I. Compared with sporadic cases, familial CM-I patients more often reported a family history of joint replacement or surgery (59.1% vs 39.5%, P = .0162), joint dislocation/injury (58.5% vs 16.7%, P < .0001), easy bruising (80.0% vs 57.1%, P = .0010), and CTDs (53.4% vs 18.9%, P < .0001), with EDS being the most common. Familial CM-I respondents were also more likely to report hyperflexibility (69.4% vs 47.7%, P = .0045) and systemic comorbidities, including postural orthostatic tachycardia syndrome (24.0% vs 13.0%) and mast cell activation disorder (9.4% vs 0%). Familial CM-I is strongly associated with CTDs, particularly EDS, and systemic comorbidities such as hypermobility, postural orthostatic tachycardia syndrome, and mast cell activation disorder. These findings support a heritable link between CM-I and CTDs and highlight the importance of detailed family history and connective tissue evaluation in CM-I patients. Comprehensive assessment and counseling of at-risk relatives may improve diagnosis, surgical planning, and long-term outcomes.

Dysautonomia, including postural orthostatic tachycardia syndrome (POTS) and related orthostatic disorders, is frequently associated with debilitating gastrointestinal (GI) symptoms in adolescents, including chronic nausea, early satiety, postprandial fullness, and functional dysmotility. Despite the significant disease burden, pharmacological options for GI dysmotility in this population remain poorly studied. To our knowledge, no prior case series has described metoclopramide as a targeted prokinetic bridge therapy specifically in adolescents with dysautonomia-associated GI dysmotility symptoms. We describe three adolescent females (ages 13, 16, and 16 years) with specialist-confirmed dysautonomia and refractory GI symptoms who were treated with a standardized short-course, low-dose metoclopramide bridge protocol (5 mg three times daily, tapered over approximately 12 weeks). All patients received concurrent multidisciplinary management including dietary modification, neuromodulators, integrative therapies, and behavioral support. All three demonstrated subjective improvement in nausea and GI symptoms, enabling engagement with broader rehabilitative and nutritional interventions. No extrapyramidal symptoms or serious adverse effects were observed. Cumulative metoclopramide doses across all three cases ranged from approximately 770 to 1050 mg-well below the threshold associated with tardive dyskinesia risk in contemporary real-world data. Short-course, low-dose metoclopramide, administered as part of a structured multidisciplinary protocol with explicit safety counseling and planned taper, may serve as a feasible bridge therapy for adolescents with dysautonomia-associated GI dysmotility symptoms. These observations are hypothesis-generating and should be interpreted with caution given the small sample size, concurrent multidisciplinary interventions, and absence of standardized outcome instruments. They support the need for prospective investigation of short-course, weight-dosed metoclopramide use in this specific population.

Prior to the COVID-19 pandemic, the etiology of postural orthostatic tachycardia syndrome (POTS) remained elusive. Since the pandemic, a newly recognized disorder, termed Long COVID, has emerged with a significant subset of patients developing dysautonomia and a multitude of comorbidities consistent with POTS. The aim of this study was to determine if pre-pandemic POTS and Long COVID POTS share a common inflammatory-associated biomarker profile. Volunteers were recruited for four study groups; patients diagnosed with POTS prior to the pandemic, Long COVID-associated POTS, SARS-CoV-2-recovered controls, and naïve controls. All participants completed a COMPASS-31 survey and a medical history questionnaire. Plasma biomarkers of the innate and adaptive immune system were quantified using a custom multiplex bead assay and ELISAs. Both POTS cohorts demonstrated indistinguishable and significant elevations in 14 of the 15 measured biomarkers including markers of the NLRP3 axis (Caspase-1p20, interleukins IL-1β, IL-18), regulatory cytokine IL-10, and immune activation markers (sCD40L, sCD40, sCD30) compared to controls. Multivariate PERMANOVA analysis revealed no significant difference in global cytokine profiles between the two POTS cohorts. Random Forest classification accurately distinguished POTS from controls, with IL-18 emerging as the most important feature. These associative findings suggest that pre-pandemic POTS and Long COVID-associated POTS share a distinct inflammatory profile among measured cytokines. The identification of IL-18 as a key biomarker, alongside Caspase-1p20 and other inflammatory cytokines, are compatible with inflammasome-related signaling. Further investigation is necessary to characterize the role of the inflammasome, platelet activation, and immune dysregulation in POTS and Long COVID.

We aimed to evaluate multi-domain autonomic function in patients with spontaneous intracranial hypotension (SIH) and investigate its association with clinical and radiological features. SIH often presents with orthostatic symptoms that overlap with autonomic disorders; however, the prevalence and distribution of autonomic dysfunction in SIH remain poorly characterized. In this cross-sectional study conducted at a tertiary care center in Seoul, Republic of Korea, 34 patients with imaging-confirmed SIH underwent a comprehensive autonomic function testing between October 2024 and February 2025. The autonomic function testing battery included heart rate response to deep breathing, Valsalva maneuver, head-up tilt test, and quantitative sudomotor axon reflex test. Hemodynamic responses during head-up tilt were monitored using both intermittent brachial and continuous beat-to-beat blood pressure measurements. Autonomic abnormalities were determined using age- and sex-matched Korean normative data. All enrolled patients presented with extradural fluid collection on spinal magnetic resonance imaging, indicating SIH due to dural tears. Autonomic dysfunction was identified in 18 of 34 (52.9%) of patients in the orthostatic domain, nine of 34 (26.5%) in the cardiovagal domain, and 10 of 34 (29.4%) in the sudomotor domain. Postural orthostatic tachycardia syndrome was the most frequent orthostatic abnormality, observed in 12 of 34 (35.3%) patients, followed by classical orthostatic hypotension in four of 34 (11.8%), syncope in one of 34 (2.9%), and delayed orthostatic hypotension in one of 34 (2.9%). No significant associations were identified between domains of autonomic dysfunction and the clinical or imaging features of SIH in false discovery rate-corrected analyses. In patients with SIH due to dural tears, orthostatic hemodynamic abnormalities were common, with postural orthostatic tachycardia syndrome being the most frequent phenotype.

Patients with Ehlers-Danlos syndrome (EDS)/hypermobility spectrum disorders (HSD) report higher rates of chronic gastrointestinal (GI) symptoms, disorders of gut-brain interaction (DGBI), and extraintestinal comorbidities. We conducted a systematic review and meta-analysis to assess the prevalence of chronic GI symptoms and comorbid conditions in hEDS/HSD. Electronic databases were searched until December 2025 for studies reporting on chronic GI symptoms in hEDS/HSD patients. Pooled prevalence rates, odds ratios (ORs), and 95% confidence intervals (CIs) were calculated using the random effects model. The final dataset of 19 studies included 17,455 hEDS/HSD patients and 1,677,465 controls. The odds of chronic GI symptoms were higher in patients with hEDS/HSD compared to controls (OR 4.29, 95% CI 3.1-6.0). 65.3% (95% CI 51.4-77.0) of hEDS/HSD patients reported at least one chronic GI symptom, with heartburn being the most common (34.7%, 95% CI 28.3-41.7). The prevalence of DGBI in hEDS/HSD patients was 44.2% (95% CI 23.9-66.6), with functional dysphagia the most common DGBI at 34.2% (95% CI 25.7-43.8). Gastroesophageal reflux disease was reported in 41.3% (95% CI 27.2-57.0). In hEDS/HSD patients, the most common extraintestinal comorbidity was chronic fatigue (49%, 95% CI 34.6-63.6), followed by migraine (38.2%, 95% CI 19.9-60.5), orthostatic intolerance (OI) (35.9%, 95% CI 26.6-46.4), fibromyalgia (27.9%, 95% CI 16.0-44.0) and postural orthostatic tachycardia syndrome (POTS) (21.9%, 95% CI 5.2-59.1). Overall, > 60% of hEDS/HSD patients report chronic GI symptoms. DGBI, co-morbidities, including POTS, were highly prevalent in hEDS/HSD patients. However, the quality of the evidence is low due to significant clinical heterogeneity observed in the analyses. While the associations may suggest a causal relationship, the results should be interpreted with caution.

Ehlers-Danlos syndromes (EDSs) are heritable connective tissue disorders caused by defects in collagen and related extracellular matrix proteins. Because the vocal fold (VF) lamina propria is a collagen-dependent structure, the voice might be expected to be affected, yet voice and laryngeal involvement has received comparatively little attention. This scoping review, conducted according to the Joanna Briggs Institute framework and reported following the PRISMA extension for Scoping Reviews (PRISMA-ScR), mapped the available evidence on voice and laryngeal manifestations in adults with EDS. PubMed, Scopus, and Web of Science were searched to 11 March 2026, and thirteen studies were included: four questionnaire-based and nine clinical or instrumental. Self-reported voice complaints were common across EDS and hypermobility spectrum disorder populations, ranging from mild-to-moderate handicap in large cohorts to frequent, fluctuating difficulties in professional singers, although their prevalence varied with population and assessment method. Direct laryngeal examination revealed a recurring substrate of cricoarytenoid joint subluxation or fixation, arytenoid prolapse, and hyolaryngeal instability, together with microvascular and mucosal fragility, characteristically accompanied by preserved VF mobility. Muscle tension dysphonia was the most frequent diagnosis in high-vocal-demand cohorts. Reflux, vocal load, and autonomic comorbidities such as postural orthostatic tachycardia syndrome were frequently reported and may modulate the clinical picture. The evidence indicates that voice and laryngeal involvement is a plausible, multi-level manifestation of EDS that remains under-recognised. The current literature is limited by small, heterogeneous, and largely uncontrolled studies; prospective research using standardised multimodal assessment is needed to clarify its prevalence, mechanisms, and management.

Postural orthostatic tachycardia syndrome (POTS) is a debilitating autonomic disorder characterized by excessive orthostatic tachycardia and significant functional impairment. Conventional therapies, including beta-blockers, often provide incomplete relief or are poorly tolerated. Ivabradine, a selective If channel inhibitor, reduces heart rate without affecting blood pressure or myocardial contractility, making it a promising option, particularly in post-COVID POTS. This systematic review and meta-analysis evaluated the efficacy and safety of ivabradine in patients with POTS. PubMed, Embase, and the Cochrane Library were searched through August 2025 in accordance with PRISMA guidelines (PROSPERO CRD420251073600). Eligible studies included randomized controlled trials, observational studies, and case series reporting ivabradine outcomes in POTS. Primary outcomes were changes in standing and supine heart rate; secondary outcomes included symptom burden, quality of life, and adverse events. A random-effects model was used, heterogeneity was assessed through sensitivity analyses, and certainty of evidence was evaluated using GRADE. Nine studies involving 245 patients were included. Ivabradine significantly reduced standing heart rate (-18.5 bpm; 95% CI -23.3 to -13.8) and supine heart rate (-9.7 bpm; 95% CI -13.4 to -6.1). Symptom improvement particularly palpitations, lightheadedness, and exercise intolerance was consistently reported across classic, pediatric, hyperadrenergic, and post-COVID subgroups. Adverse events were infrequent and mild, most commonly transient visual disturbances, with no reports of severe bradycardia or hypotension. Heterogeneity was high, largely driven by pediatric and post-COVID cohorts. In conclusion, ivabradine appears to provide meaningful heart rate reduction and symptomatic improvement in POTS with a favorable safety profile. However, evidence is limited by small, heterogeneous, predominantly observational studies, underscoring the need for large, multicenter randomized controlled trials.

Paediatric dysautonomia has become increasingly recognised in children and adolescents, particularly in the post-COVID era. Affected patients commonly present with dizziness, palpitations, exercise intolerance, fatigue, and syncope, although reported prevalence varies widely because of evolving definitions and heterogeneous referral patterns. Contemporary evidence suggests that post-COVID dysautonomia arises from complex interactions among central autonomic network dysfunction, neurovascular dysregulation, impaired venous return, endothelial injury, hypovolemia, and altered cerebral perfusion, with tachycardia often representing a compensatory physiological response rather than a primary cardiac abnormality. Clinical phenotypes include postural orthostatic tachycardia syndrome, neurocardiogenic syncope, orthostatic hypotension, inappropriate sinus tachycardia, and undifferentiated orthostatic intolerance, frequently accompanied by fatigue, cognitive dysfunction, gastrointestinal symptoms, sleep disturbances, and post-exertional symptom exacerbation. Paediatric dysautonomia is best conceptualised as a distributed brain-heart-vascular network disorder that requires mechanistic understanding, standardised orthostatic assessment, and careful exclusion of structural heart disease and arrhythmia. The rapid expansion of specialised dysautonomia programmes and direct-to-consumer diagnostic pathways has also contributed to broader, and occasionally premature, application of autonomic diagnoses. Management should follow a stepwise, mechanism-guided approach emphasising patient education, trigger avoidance, hydration and salt optimisation, lower-body compression, individualised exercise rehabilitation, pacing strategies when post-exertional symptom exacerbation is present, school accommodations, and phenotype-directed pharmacotherapy for persistent functional impairment. Although post-COVID dysautonomia shares features with established paediatric autonomic disorders, important gaps remain in disease definitions, mechanistic understanding, and evidence-based treatment, underscoring the need for multidisciplinary care, standardised diagnostic frameworks, and prospective paediatric research.

Hypermobile Ehlers-Danlos syndrome (hEDS), frequently presents with pain and autonomic symptoms suggestive of small fiber neuropathy (SFN). However, systematic comparisons between hEDS and idiopathic SFN (iSFN) using combined clinical, functional, and morphological approaches are lacking. We prospectively studied a population of SFN patients who also fulfilled the 2017 criteria for hEDS (hEDS/SFN) and compared them with a group of iSFN patients of similar age. All underwent SFN-Symptoms Inventory Questionnaire (SFN-SIQ), Douleur Neuropathique 4 (DN4), and the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaires, quantitative sensory testing (QST), autonomic testing (cardiovascular reflexes, sympathetic skin response, dynamic sweat test), and skin biopsy from leg, thigh, and fingertip. Clinical, morphological and functional data were compared with our normative dataset and between the two patient groups. 35 hEDS/SFN and 38 iSFN patients were included in the study. hEDS/SFN patients had earlier symptom onset (19.5 ± 5.9 years vs. 35.2 ± 8.7 years, p < 0.001), more generalized distribution, and higher COMPASS-31 scores (54.3 ± 16.9 vs. 33.9 ± 19.4 p < 0.01), particularly in orthostatic intolerance, gastrointestinal, and urinary domains. Postural Orthostatic Tachycardia Syndrome (POTS) was present in half of hEDS/SFN patients while it was not found in iSFN (51.5% vs. 0.0%). Skin biopsy revealed similar intraepidermal nerve fiber loss in both groups, but hEDS had greater autonomic fiber loss (p < 0.05). Small fiber involvement in hEDS is characterized by earlier onset, more generalized pain and severe autonomic symptoms, and higher autonomic morpho-functional impairment compared with iSFN. Systematic autonomic assessment and targeted management should be considered in this population.

Postural orthostatic tachycardia syndrome (POTS) is associated with autonomic dysregulation, but ambulatory markers that capture autonomic phenotype remain incompletely defined. To compare Holter-derived heart rate variability (HRV) metrics between adolescents with POTS and healthy controls and to derive candidate discriminatory thresholds. Retrospective case-control analysis of an existing Holter dataset (POTS n = 19, controls n = 44). Heart rate variability was processed in Kubios HRV Premium. Between-group comparisons used Welch's t-test with Benjamini-Hochberg false discovery rate adjustment. Nonparametric sensitivity analyses yielded similar results. Discrimination was assessed using receiver operating characteristic analysis; optimal thresholds were defined by the Youden index. An exploratory penalized logistic regression model (L1 regularization) was fit with standardized candidate HRV predictors and internal cross-validation. Among 19 POTS patients and 44 control subjects, POTS demonstrated lower time- and frequency-based HRV, higher rate-related and sympathetic composite indices, and lower parasympathetic composite measures. The strongest univariate discriminator was PNSi (Parasympathetic Nervous System index; AUROC 0.874; threshold ≤ -1.10; sensitivity 77.8%; specificity 88.6%). Other high-performing discriminators included SNSi, mean RR, mean heart rate, and SDNNi. Holter-derived HRV metrics demonstrate a reproducible pattern consistent with reduced parasympathetic modulation and relative sympathetic predominance in POTS. Several variables yield candidate discriminatory thresholds that may support physiologic phenotyping and warrant validation in independent cohorts.

Postural orthostatic tachycardia syndrome (POTS) is a disorder characterized by a sudden onset of orthostatic intolerance upon standing, which may be relieved when lying down. The most common complications associated with POTS are trauma or injury from falling or fainting. Pediatric patients with POTS may have comorbidities that interfere with their quality of life. Careful management of the disorder is essential to prevent injury. POTS management is often misunderstood, which may lead to misdiagnosis and invalidation by health care professionals. This article discusses how POTS affects pediatric patients and the implications for nursing practice.

There is a growing body of literature evaluating both postural orthostatic tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (EDS). We conducted a systematic review to evaluate what is currently known about the co-existence of both conditions. A search of MEDLINE and EMBASE was performed in December 2025 and data were collected in tables and pooled to determine the prevalence of POTS in EDS and EDS in POTS. A total of 30 studies were included with 8421 patients with EDS and 12,983 patients with POTS. The average age across 16 studies that reported mean age was 33.3 years. POTS in patients with EDS ranges from 17.5% to 92.7% depending on the population. EDS in patients with POTS ranges from 17.9% to 50.0% depending on the population. One study suggested that patients with EDS and POTS had greater medication use, pain medications and greater number of clinic visits compared to POTS alone while another suggests that these patients have greater gastrointestinal symptoms and the odds were greatest for postprandial distress syndrome, chronic nausea and vomiting syndrome, vomiting and post-prandial fullness. We conclude that EDS and POTS frequently co-occur, and proportions of patients with POTS and EDS depends on the population evaluated. Overall, more research is needed to better understand how to effectively manage patients living with both EDS and POTS.

Functional disorders affecting the cardiorespiratory system are common. Non-cardiac chest pain affects more than 10% of the population. It can result from gastro-oesophageal reflux or chest wall disorders but is also very often associated with anxiodepressive disorders, particularly panic disorder. Postural orthostatic tachycardia syndrome (POTS), a rarer entity, is characterized by a sharp increase in heart rate without orthostatic hypotension when standing. The pathophysiological mechanisms of POTS include 'partial' autonomic neuropathy, hypovolaemia and noradrenergic dysregulation, but it is also closely linked to anxiety disorders and deconditioning to exertion. Functional respiratory disorders, particularly hyperventilation syndrome, are accompanied by various manifestations ranging from tetany to gastrointestinal symptoms. They are highly prevalent, especially among women and people suffering from anxiety, and particularly in the case of associated respiratory disease such as asthma. The diagnosis of hyperventilation syndrome is based on the Nijmegen questionnaire. The pathophysiology does not necessarily involve hypocapnia but is related to cerebral conditioning phenomena and vicious circles linked to anticipatory anxiety. Cardiorespiratory functional disorders are often linked to each other and to other functional somatic disorders and have in common a dysregulation of the autonomic nervous system. Psychological, cognitive and behavioural factors play a central role in their persistence. While each has its specificities, all have a complex circular causality. Their management currently relies primarily on physical rehabilitation, often associated with symptomatic treatments such as beta-blockers. The place of cognitive and behavioral therapies would be well worth exploring in these disorders.

Long COVID-19 is recognized as a condition associated with autonomic nervous system (ANS) dysfunction. However, quantitative evidence of its impact on heart rate variability (HRV) and blood pressure (BP) regulation during postural changes remains limited. This study assessed autonomic imbalance in post-COVID-19 patients by evaluating HRV and BP responses during tilt table testing, comparing long COVID-19 patients with healthy controls. A total of 61 participants were enrolled, 39 long COVID-19 patients (Study Group, SG) and 22 healthy controls (Control Group, CG). HRV was analyzed using time- and frequency-domain parameters. BP monitoring evaluated systolic, and diastolic blood pressure (SBP, and DBP respectively), and Pulse pressure (PP = SBP-DBP) was calculated for each phase. SG participants exhibited marked autonomic dysfunction during tilt. In the upright phase, they showed a significant increase in mean RR intervals (p = 0.0136), reduced normalized low-frequency (LF) with p = 0.0316, increased normalized high-frequency (HF) with p = 0.0315, and a decreased low-frequency/high-frequency (LF/HF) ratio (p = 0.0316), indicating a blunted sympathetic response and impaired autonomic adaptation to orthostatic stress. BP responses were also impaired: SG demonstrated attenuated changes in PP (ΔPP) when transitioning from the upright position to the recovery phase (p < 0.037). Within-group analysis confirmed persistent RR interval instability (p < 0.0001), incomplete normalization of LF and HF components (both p < 0.0001), and delayed recovery of PP after return to supine position. BP responses were also diminished: SG showed smaller ΔPP when moving from standing upright to the recovery phase (p < 0.037). Baroreflex sensitivity values did not differ between groups. Long COVID-19 patients display significant autonomic dysregulation, characterized by reduced HRV, abnormal BP responses. These findings highlight the value of tilt testing in uncovering hidden dysautonomia and support the need for targeted interventions, including pharmacologic modulation and long-term HRV/BP monitoring, to improve cardiovascular stability in long COVID-19.

Postural orthostatic tachycardia syndrome (POTS) is a multifactorial disorder of the autonomic nervous system characterised by an excessive increase in heart rate (HR) on standing and a wide range of debilitating symptoms, including fatigue, exercise intolerance, cognitive impairment and a high prevalence of depression, anxiety and sleep disturbances. Conventional pharmacological strategies often offer limited relief and do not sufficiently address non-cardiac symptoms. Auricular vagal neuromodulation therapy (AVNT) and slow-paced diaphragmatic breathing (SDB) have each demonstrated promise in modulating autonomic function and alleviating symptom burden but their combined effects in POTS have yet to be investigated. This single-centre, partially blinded, 12-week randomised controlled trial will be conducted at the Medical University of Vienna. A total of 100 participants with confirmed POTS will be recruited, with 25 per group. This sample size is already accounting for an anticipated 30% dropout rate. Participants will be randomised using stratified block randomisation with a 1:1:1:1 allocation ratio, stratified based on the presence or absence of post-exertional malaise (yes/no) to one of four groups: (1) AVNT+SDB, (2) AVNT+normal breathing, (3) sham AVNT+SDB and (4) sham AVNT+normal breathing. The primary endpoint is the change in orthostatic HR (ΔHR) during a 70° head-up tilt test. Secondary outcomes include beat-to-beat blood pressure responses, respiratory sinus arrhythmia, end-tidal CO₂, handgrip strength, activity monitoring and validated patient-reported measures, including Chalder Fatigue Scale, Malmö POTS Symptom Score, Nijmegen Questionnaire, Short Form Health Survey, Hospital Anxiety and Depression Scale and Vanderbilt Orthostatic Symptom Score. Interventions consist of daily 60-minute AVNT (or sham) sessions combined with standardised breathing training (10-15 min/day). This study has been approved by the Ethics Committee of the Medical University of Vienna (EK number 1270/2024) and will be conducted in accordance with the Declaration of Helsinki and International Conference on Harmonisation-Good Clinical Practice guidelines. Results will be disseminated through peer-reviewed publications, conference presentations and reporting in the trial registry. Participants will receive study results in an accessible format. NCT06996314.

Pelvic venous disorders (PeVD) are recognised causes of chronic pelvic pain; emerging evidence suggests that venous outflow obstruction or reflux can also provoke orthostatic intolerance (OI) by infra-diaphragmatic pooling and reduced preload. Diagnostic and therapeutic frameworks for this overlap remain poorly defined. We systematically searched PubMed, Ovid MEDLINE, Scopus, and Cochrane to 20 May 2025. Two reviewers extracted data; risk of bias used design-specific validated tools. Sixteen studies met criteria (4 case reports, 7 case series, 2 single-arm cohorts, 2 case-control, 1 cross-sectional), comprising 964 participants (93% female; age 7-67 years). Case-control data suggested left common iliac or left renal-vein compression is more prevalent in patients with postural tachycardia syndrome than in controls. Paediatric series linked left renal-vein entrapment with orthostatic symptoms and proteinuria. Imaging confirmation used duplex ultrasound, CT, CT-venography, intravascular ultrasound, and dynamic MRA with 4D-flow. Eleven studies reported interventions (iliac stenting, ovarian/internal-iliac embolization, superficial venous ablation, renal-vein transposition or robotic auto-transplantation). Orthostatic symptoms generally improved; cohorts using the Orthostatic Hypotension Questionnaire showed ∼50% mean reduction, and several stented patients no longer met POTS criteria. Follow-up was typically ≤12 months. Overall risk of bias was high for single-arm cohorts and moderate for case-control studies. Available evidence supports a biologically plausible link between pelvic venous obstruction and OI suggests PeVD-directed procedures can ameliorate OI in selected patients. Prospective, multicentre studies with standardized imaging thresholds, objective autonomic endpoints, and longer follow-up are needed to define patient selection and comparative effectiveness.

Superior mesenteric artery (SMA) syndrome is a rare cause of proximal intestinal obstruction resulting from compression of the third portion of the duodenum between the aorta and the SMA. It most commonly occurs in slender individuals or those experiencing rapid weight loss, but presentations can be atypical and diagnostically challenging. We report the case of a 28-year-old female with history of postural orthostatic tachycardia syndrome and gastroparesis who presented with recurrent nausea and intractable vomiting following a 110-lb weight loss after prior obesity. Upper gastrointestinal endoscopy and gallbladder ultrasonography were unremarkable. Computed tomography of the abdomen demonstrated findings consistent with SMA syndrome, including severe narrowing of the aortomesenteric angle and reduced aortomesenteric distance. The patient subsequently underwent robotic-assisted duodenojejunostomy with resolution of symptoms. This case highlights an atypical presentation of SMA syndrome following massive weight loss and demonstrates the feasibility of robotic duodenojejunostomy as an effective treatment option.

The diagnosis and management of hypermobility spectrum disorders and hypermobile Ehlers-Danlos syndrome (HSD/hEDS) are a healthcare challenge because of the wide array of symptoms, lack of diagnostic biomarkers, and evolving management guidelines. This study aimed to describe patient experiences, disability, and self-perceived success managing HSD/hEDS, with or without comorbid postural orthostatic tachycardia syndrome, mast cell activation syndrome, or hip dysplasia. This anonymous online survey explored symptoms, impact on life/function, healthcare experiences, and symptom management status of individuals in the US aged greater than or equal to 13 years with HSD/hEDS. Frequencies and central tendencies were calculated for multiple-choice items. Free-response items were categorized using WHO domains of disability. Seventy-two survey responses were analyzed. The most frequent symptoms were joint hypermobility, joint pain, and subluxations. Disabilities were reported in all six WHO life domains, with life activities being the most common. Most participants (58%) reported symptoms were not well-managed and were more likely to report financial barriers to care and more health conditions compared with other participants. This sample of individuals with HSD/hEDS experiences complex, multifactorial challenges with disability and symptom management. These challenges may be related to comorbidities and financial barriers. Interdisciplinary care models and targeted rehabilitation approaches may improve participation and outcomes, particularly when combined with strategies to reduce logistical and economic barriers.

Establishing evidence of vaccine safety is critical for optimizing vaccine coverage. This study aimed to assess the risk of developing neurological disorders following human papillomavirus (HPV) vaccination. This retrospective cohort study compared the risk of developing neurological disorders between HPV-vaccinated and unvaccinated cohorts using the TriNetX platform. Outcomes included complex regional pain syndrome (CRPS), postural orthostatic tachycardia syndrome (POTS), polyneuropathies, dysautonomia, Guillain-Barré syndrome (GBS), encephalitis, myelitis or optic neuritis, Bell's palsy, epilepsy, narcolepsy, and intracranial injury (negative control outcome). The hazard ratios (HRs) were estimated by propensity score matching. In the US, following propensity score matching, 715,540 participants from each cohort were matched. The HRs were 0.58 [0.47-0.73] for CRPS; 0.78 [0.69-0.87] for POTS; 0.60 [0.53-0.69] for polyneuropathies; 0.67 [0.62-0.73] for dysautonomia; 0.69 [0.38-1.26] for GBS; 0.62 [0.50-0.77] for encephalitis, myelitis or optic neuritis; 1.00 [0.87-1.15] for Bell's palsy; 0.67 [0.63-0.71] for epilepsy; 0.67 [0.63-0.71] for narcolepsy; and1.02 [0.99-1.04] for intracranial injury. No increased risk of the selected neurological adverse events was observed in the vaccinated group. The data should be interpreted with caution given potential residual confounders. This study contributes to the establishment of evidence for the safety of HPV vaccines.

Postural orthostatic tachycardia syndrome (POTS) is a chronic autonomic disorder characterized by an excessive increase in heart rate upon standing, accompanied by symptoms such as dizziness, fatigue, palpitations, cognitive impairment, and sleep disturbances. Sleep dysfunction is increasingly recognized as a significant contributor to symptom burden and reduced quality of life among individuals with POTS. Emerging evidence suggests that patients with POTS may experience heightened sympathetic activity during sleep, leading to disrupted autonomic regulation and fragmented sleep patterns. While the pathophysiological mechanisms underlying sleep disturbances in POTS are multifactorial, modifiable lifestyle factors - including dietary habits and environmental exposures - may play an underexplored role. Dietary factors such as high-fat meals or specific dietary patterns may influence sleep architecture and nocturnal awakenings, whereas interventions such as gluten-free diets have shown potential benefits in alleviating certain gastrointestinal and vasomotor symptoms associated with POTS. Environmental determinants, including chronic noise exposure and light pollution, can further disrupt circadian rhythms by impairing melatonin secretion and altering sleep quality. These disruptions may exacerbate autonomic imbalance, perpetuating daytime symptoms such as tachycardia and fatigue. Despite plausible mechanistic links, targeted research examining the influence of diet and environmental factors on sleep quality in POTS remains limited. Addressing these modifiable factors may provide novel lifestyle-based strategies to complement pharmacological management and improve patient outcomes.