Rozen, Todd D.

Background/Objective: It remains unknown whether patients with the more common forms of hypermobility carry an elevated risk for the development of intracranial/cervical artery abnormalities. The objective of this study was to determine the prevalence of unruptured intracranial aneurysms, spontaneous cervical artery dissections, and fibromuscular dysplasia in patients with hypermobile Ehlers–Danlos Syndrome (hEDS) and hypermobility spectrum disorders (HSD) who presented to an academic headache clinic. Methods: This is a retrospective cohort study. We used an electronic medical record to look for all patients seen at the Mayo Clinic Florida Headache Center and EDS Clinic between 2019 and 2025 with a diagnosis of hEDS or HSD and neuroimaging of both the intracranial and cervical arteries. Results: There were 103 patients who met the inclusion criteria. There was no statistically significant difference between hEDS and HSD patients in developing cerebral/cervical arterial anomalies. Of the sample, 95% of the hypermobile patients with abnormal neuroimaging also had migraine. A total of eleven (10.7%) patients (hEDS + HSD) were diagnosed with unruptured intracranial aneurysms. Trends included age less than 50 years, small aneurysms in the anterior circulation, and having migraine with aura. Five (4.8%) patients were diagnosed with spontaneous cervical artery dissection with trends for HSD, over the age of 50 years, vertebral artery involvement and a history of migraine without aura. Six (5.8%) patients were diagnosed with fibromuscular dysplasia with trends for HSD, over the age of 50 years, carotid artery involvement and a history of migraine with aura. Conclusions: This is the first study to identify that patients with the more common type of EDS, HSD and hEDS, and a possible concomitant history of migraine have a heightened risk for the development of unruptured intracranial aneurysms, spontaneous cervical artery dissections, and fibromuscular dysplasia. Our findings suggest the need for targeted screening with intracranial and extracranial arterial imaging for this unique patient population.

Objectives Heritable connective tissue disorders (HCTDs), including hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobile spectrum disorder (HSD), have complex clinical manifestations, but the prevalence of left common iliac vein (LCIV) compression in these groups is not well known. This study aimed to compare the prevalence of significant LCIV compression in patients with hEDS, HSD, and healthy controls. Methods This retrospective, IRB-approved, single-center study analyzed 109 patients (25 hEDS, 64 HSD, 20 controls) who underwent contrast-enhanced abdominal and pelvic CT imaging from 2020 to 2023. LCIV compression was measured on axial CT, with >50% luminal narrowing defined as significant. Statistical analyses included chi-square tests, odds ratios, and t -tests. Interrater reliability was evaluated using intraclass correlation coefficients. Results Significant LCIV compression occurred in 68.0% of hEDS, 65.6% of HSD, and 35.0% of controls ( p = 0.034). Both hEDS ( p = 0.027) and HSD ( p = 0.015) groups had significantly higher compression rates than controls, with no statistically significant difference between the two clinical groups ( p = 0.831). Odds of compression were nearly fourfold greater in hEDS (OR 3.95) and HSD (OR 3.54) compared to controls. Conclusion LCIV compression is significantly more prevalent in patients with hEDS and HSD than in healthy controls, warranting further investigation of its clinical significance.

Abstract May-Thurner physiology (MTP) can lead to various congestion syndromes due to compression of the left common iliac vein (LCIV) by the right common iliac artery (RCIA). This compression may result in venous reflux through the lumbar vein, leading to congestion of the spinal epidural venous plexus (EVP), which could contribute to refractory headaches. This case report details the clinical course of a patient with severe refractory new daily persistent headache associated with MTP who underwent ascending lumbar vein (ALV) embolization. The patient is a 59-year-old female with a 3-year history of daily persistent headache which failed multiple migraine prevention therapies and minimally invasive procedures. Imaging studies revealed significant LCIV compression by the RCIA, retrograde ALV flow, and EVP congestion. The patient underwent ALV embolization, resulting in significant symptomatic relief. At the 22-month follow-up, headache severity reduced by 80%, with the patient no longer requiring routine headache medications. Additionally, treatment of associated pelvic congestion syndrome through gonadal vein embolization resolved longstanding associated pelvic pain and pressure. This case highlights the role of venous congestion in refractory headache syndromes and underscores the potential of targeted venous interventions, such as embolization, in their management. The findings expand on emerging evidence linking venous compression syndromes to headache pathophysiology and support exploring interventional strategies as viable treatment options for selected patients. Further research is needed to validate these findings and establish evidence-based guidelines for clinical practice.

Abstract Objectives Patients with hypermobile Ehlers–Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) experience a wide array of symptoms and system disorders. This study aimed to identify whether differences occurred in 115 self-reported symptoms and comorbidities in patients diagnosed with hEDS or HSD. Methods In this study we analysed self-reported data from an EDS Clinic intake questionnaire in patients diagnosed with hEDS, HSD or no hypermobile conditions. Results From 1 November 2019 to 7 March 2024, the EDS Clinic saw 2088 patients. Using the 2017 diagnostic criteria, 66.5% were diagnosed with HSD (n = 1389), 20.3% with hEDS (n = 423), 10.6% with historic HSD (H-HSD) or localized HSD (L-HSD) (n = 256) (hypermobile controls) and 2.6% were not diagnosed with hEDS, HSD, H-HSD or L-HSD (n = 55) (controls). Symptoms/comorbidities that occurred with high prevalence in both hEDS and HSD included joint pain (hEDS 82.0%, HSD 88.9%), allergy (hEDS 77.0%, HSD 77.0%), subluxations (hEDS 71.2%, HSD 72.6%), brain fog (hEDS 70.0%, HSD 74.7%), headache (hEDS 68.1%, HSD 69.1%), anxiety (hEDS 60.3%, HSD 69.3%), depression (hEDS 52.2%, HSD 58.0%), migraine (hEDS 53.7%, HSD 52.5%), nausea (hEDS 54.6%, HSD 59.5%) and constipation (hEDS 53.0%, HSD 57.2%). In contrast, 9/115 (8%) symptoms/comorbidities were self-reported significantly more often in hEDS but 42/115 (37%) in HSD. hEDS patients reported more symptoms that suggest a defect in collagen, such as dislocation, hernias and rectal prolapse, while HSD patients reported more joint, muscle, allergy, neurological, gastrointestinal, sleep and psychological symptoms/comorbidities. Conclusion Although we found an overlap in some symptoms and comorbidities self-reported by hEDS/HSD patients, such as allergy/atopy, headache/migraine and gastrointestinal symptoms, our findings suggest key differences exist between the two diagnoses, suggesting that hEDS and HSD may be distinct conditions.

Background There is no defined preventive treatment protocol for persistent post-craniotomy headache. In several small case series and individual case reports onabotulinumtoxinA injected into the craniotomy scar has shown possible efficacy. What is lacking is long term follow-up and if focusing on the cranial suture lines along with the craniotomy scar can enhance improvement and provide more sustained benefit. Methods Retrospective chart review with case series. Results Four patients (three women, one man) with ICHD-3 defined persistent post craniotomy headache were treated using a novel onabotulinumtoxinA injection protocol. All the patients presented with continuous head pain of moderate to severe intensity. All had severe allodynia on the side of their craniotomy. All had significant reduction in quality of life. Our application of onabotulinumtoxinA involved injection into both the surgical scar and the transected/irritated cranial suture lines noted on neuroimaging and physical examination. With treatment all patients demonstrated significant benefit including a reduction in daily pain intensity (75%-100%), developing periods of pain freedom (2–7 days per week) and having a dramatic improvement in quality of life (close to 100% in all). The benefit was sustained for at least five years of follow-up. Conclusion From our case series it appears that injection not only along the painful craniotomy scar but into the involved cranial suture lines provides positive efficacy and sustained improvement in patients with persistent post craniotomy headache.

The authors have published on a unique subset of patients whose headaches worsened in the Trendelenburg position and who on time-resolved MR angiography demonstrated left renal vein compression (nutcracker physiology) with retrograde left second lumbar vein (L2LV) flow and regional spinal epidural venous plexus (EVP) congestion. We hypothesized that the spinal EVP congestion subsequently causes a secondary congestion of the cerebral venous system, which then leads to an elevation of CSF pressure above that individuals CSF pressure set point. This results in a daily headache from onset. Thus, eliminating the spinal EVP could conceivably improve or eliminate the manifested headache syndrome. We now present a case series of four patients with long-term follow-up utilizing lumbar vein coil embolization as a new therapeutic approach. In each patient, the MR angiography findings were verified by catheter-based venography. Treatment consisted of endovascular embolization of the second lumbar vein. Four patients have had coil embolization of which three are 1 year or longer from their procedure while one is 10 months posttreatment. All patients were women. Duration of daily headache prior to embolization ranged from 4 to 8 years. Post-embolization: Three patients are either headache free or 90–95% improved with substantial pain free time. There were no procedure-related complications. Our results suggest that embolization of L2LV in a specific patient population with nutcracker physiology may substantially improve head pain issues. This is a minimally invasive outpatient technique with no apparent side effects.

Objective To look at cigarette smoking history (personal and secondary exposure as a child) in non-cluster headache trigeminal autonomic cephalalgias seen at a headache clinic and to determine smoking exposure prevalence utilizing previously published data. Methods Retrospective chart review and PubMed/Google Scholar search Results Forty-eight clinic patients met ICHD-3 criteria for non-cluster headache trigeminal autonomic cephalalgias. Four had paroxysmal hemicrania, 75% were smokers and secondary exposure was noted in all. 16 patients had short lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) or short lasting unilateral neuralgiform headache attacks with autonomic symptoms (SUNA), 12.5% were smokers and secondary exposure was noted in 91%. Twenty-eight patients had hemicrania continua, 21% were smokers and secondary exposure was found in 62.5%. Since 1974 there have been 88 paroxysmal hemicrania, 50 SUNCT or SUNA and 89 hemicrania continua patients with a documented smoking exposure history. From current data and previous studies, a smoking history was noted in 60% paroxysmal hemicrania, 18% SUNCT and SUNA and 21% hemicrania continua patients. Conclusion A cigarette smoking history appears to be connected to paroxysmal hemicrania (personal and secondary exposure) and possibly to SUNCT/SUNA (secondary) and hemicrania continua (secondary).