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.

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.

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.

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.

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.

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.

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.

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.