Welcome, pardner, to our new feature, Research Round-up! In each issue, we’ll bring you summaries of some of the latest EDS research to hit the medical journals. We’ll usually have five or so articles, but we’ve got a special edition this time—10 articles for your information and enjoyment! Yee-haw! Hitch up your horse, grab a sarsaparilla, and check out what’s new in EDS research.
Special shout-out this month to the latest on the search for a genetic cause of hEDS: Norris Lab Finds hEDS Gene: Kallikrein
“Management of childbearing with hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders: A scoping review and expert co-creation of evidence-based clinical guidelines”
Published in PLoS One on May 15, 2024 | Link to full-text article
Research by: Sally Pezaro, Isabelle Brock, Maggie Buckley, Sarahann Callaway, Serwet Demirdas, Alan Hakim, Cheryl Harris, Carole High Gross, Megan Karanfil, Isabelle Le Rey, Laura McGillis, Bonnie Nasar, Melissa Russo, Lorna Ryan, Natalie Blagowidow
Summary: Fifteen co-creators from the International Consortium on the Ehlers-Danlos Syndromes and Hypermobility Spectrum Disorders got together to create “expert guidelines for the management of pregnancy, birth, and postpartum recovery” for patients with hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorder (HSD). They reviewed scholarly articles and case reports about childbearing in hEDS/HSD in a number of languages. Using the results of this reading material, practical and clinical experience, and patient and public involvement, they created guidelines based on over a million participants. The guidelines stress a multi-disciplinary approach–meaning doctors from a variety of specialties should be involved in the full spectrum of pregnancy care–as well as individualized management, since what works for one person with hEDS/HSD doesn’t necessarily work for another. The guidelines are broken down by stage of pregnancy (including prior to pregnancy) and provide action points, such as what to do for patients with POTS or MCAS during pregnancy, what mode of birth might be most beneficial, and how to deal with wound healing after delivery. Read the full guidelines in table format.
“Diagnosis and treatment of the Ehlers-Danlos syndromes in China: synopsis of the first guidelines”
Published in Orphnet Journal of Rare Diseases on May 13, 2024 | Link to full-text article
Research by: Kexin Xu, Guozhuang Li, Zhihong Wu, Terry Jianguo Zhang, & Nan Wu on behalf of the Chinese Multi-Disciplinary Working Group on the Ehlers-Danlos Syndromes
Summary: In news that will surprise no one with EDS, patients with EDS in China are having a difficult time getting a correct diagnosis. They run into some of the same problems their US and European counterparts do: lack of knowledge from providers, dismissal of symptoms, misdiagnosis, and more. Even those who do get diagnosed can’t find a medical provider who can help them manage their EDS. To help, the Chinese Multi-Disciplinary Working Group on the Ehlers-Danlos Syndromes (the Group) was established, and Chinese Guidelines for Diagnosis and Treatment of the Ehlers-Danlos Syndromes were published in December 2023. As usual, the guidelines stress a multi-disciplinary approach to the treatment of EDS. The guidelines are broken down by the medical department and recommendations are given for EDS patients seen in that department. While the guidelines start off with diagnostic criteria similar to those in the US, the Chinese guidelines provide instructions to dermatologists, orthopedic surgeons, gastroenterologists, and other specialists while stressing the importance of including nursing care, rehabilitation, psychology, and nutrition experts in EDS care. Read the full guidelines. (You will need to have your browser or another service translate from Chinese.)
“C1-2 hypermobility and its impact on the spinal cord: a finite element analysis”
Published in the Journal of Neurosurgery on May 3, 2024 (online ahead of print) | Link to abstract of article
Research by: Arpan A Patel, Jacob K Greenberg, Michael P Steinmetz, Sarel Vorster, Edin Nevzati, Alexander Spiessberger
Summary: A final element analysis (FEA) was done on the C-1-2 joints of the upper spine/neck. An FEA uses computerized models to replicate structures that are difficult to experiment on in real life. The researchers wanted to know how mechanical impact to the C-1-2 joint would affect the spinal cord, they created two models of the vertebrae: one with 25° and 50° of C1-on-C2 rotation, and one with 2.5 and 5 mm of C1-on-C2 lateral translation (side-to-side movement.) There was “significant spinal cord stress” during 50 degrees of rotation and 5 mm of side-to-side movement, which were “consistent with values found during severe spinal cord compression and in patients with myelopathy.” Bottom line? This is “biomechanical evidence” that a hypermobile C-1-2 joint leads to spinal cord stress, which could be the cause of other conditions related to the neck and spine.
“Correlation between benign joint hypermobility syndrome and headache in children and adolescents”
Published in BMC Musculoskeletal Disorders on May 2, 2024 | Link to full-text article
Research by: Moshen Jari, Sogol Alesaeidi
Summary: This study took place in Isfahan, Iran, and evaluated 4,832 students between the ages of seven and sixteen–798 with benign hypermobility joint syndrome (BHJS) and 912 without. They were evaluated using a questionnaire for the International Classification of Headache Disorders. The probability of headaches in children with BJHS was 3.7 times higher than those without BJHS, with older children more likely to have headaches than younger children. The children reported migraines most frequently, and children with BJHS were 4.5 times more likely to have migraines than those without.
“Vascular Ehlers-Danlos Syndrome: A Comprehensive Natural History Study in a Dutch National Cohort of 142 Patients”
Published in Circulation: Genomic and Precision Medicine on April 16, 2024 (online ahead of print) | Link to full-text article
Research by: Serwet Demirdas, Lisa M van den Bersselaar, Rosan Lechner, Jessica Bos, Suzanne I M Alsters, Marieke J H Baars, Annette F Baas, Özlem Baysal, Saskia N van der Crabben, Eelco Dulfer, Noor A A Giesbertz, Apollonia T J M Helderman-van den Enden, Yvonne Hilhorst-Hofstee, Marlies J E Kempers, Fenne L Komdeur, Bart Loeys, Daniëlle Majoor-Krakauer, Charlotte W Ockeloen, Eline Overwater, Peter J van Tintelen, Marsha Voorendt, Vivian de Waard, Alessandra Maugeri, Hennie T Brüggenwirth, Ingrid M B H van de Laar, Arjan C Houweling
Summary: This Dutch study looked at 142 individuals, 50% of whom were female. Forty-six patients were index patients–those with vEDS. The rest of the patients were family members of the index patient. The researchers looked at molecular and clinical data and performed a one-time physical examination of all patients. They found that being male, where on the COL3A1 gene the mutation took place, and physical appearance highly suggestive of vEDS (thin, translucent skin; narrow nose; prominent eyes; a thin border around the lips [called the vermillion]; small lower jaw; and limbs, especially the hands, that look more aged) increase the risk for major events, like aortic aneurysm, pneumothorax, and aortic dissection. Being male, the type and location of the genetic mutation, and physical appearance can also be risk factors for adverse events occurring at an earlier age. Researchers suggest these findings be used, along with more research, to improve diagnostic criteria and treatment of vEDS.
“Impairment of lung volume perception and breathing control in hypermobile Ehlers-Danlos syndrome”
Published in Scientific Reports on Apr 6, 2024 | Link to full-text article
Research by: Adrien Hakimi, Cyrille Bergoin, Anna De Jesus, Eric Hermand, Claudine Fabre, Patrick Mucci
Summary: Proprioception is the sense of where the body is in space. It helps us with things like avoiding banging into doors and knowing whether our bodies will fit that chair. Many studies have shown patients with EDS have impaired proprioception (no, you’re not just clumsy!) This study asks if impaired proprioception applies to how much air is in the lungs at any given moment, and does doing a cognitive task affect how EDS patients breathe? A device was developed to “assess the accuracy of lung volume perception.” There were two groups of 19 subjects–one group with hEDS and one without. When the device measured that a subject had inhaled 30% of their lung capacity, the hEDS patients perceived their lung capacity as lower than those without hEDS. When subjects were given a task to focus on that mostly used their brain skills (opposed to physical skills), their breathing became erratic. These findings could help with future research into respiratory issues in hEDS, lung volume perception, ventilation, and exercise pathology.
“Web-based survey investigating cardiovascular complications in hypermobile Ehlers-Danlos syndrome after COVID-19 infection and vaccination”
Published in PLoS One on March 21, 2024 | Link to full-text article
Research by: Anthony L Guerrerio, Allyson Mateja, Gretchen MacCarrick, Jonathan Fintzi, Erica Brittain, Pamela A Frischmeyer-Guerrerio, Harry C Dietz
Summary: Information about how COVID affects the EDS body has been greatly important and often lacking when the community needed it the most. This study added a huge piece to the EDS/COVID puzzle by asking if there was an increase in adverse events in patients with hEDS after a COVID-19 illness and after a COVID-19 vaccination. Three hundred and sixty-eight people, mostly from the United States, responded to the web-based survey. The researchers found that there was an increase in new abnormal heart rhythms in hEDS patients who had COVID-19. No other cardiovascular issues were found after a COVID-19 illness or vaccine.
“Do people with ME/CFS and joint hypermobility represent a disease subgroup? An analysis using registry data”
Published in Frontiers in Neurology on March 13, 2024 | Link to full-text article
Research by: Kathleen Mudie, Allison Ramiller, Sadie Whittaker, Leslie E Phillips
Summary: Using self-reported data from 815 patients, 126 of them with joint hypermobility, researchers found that patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and joint hypermobility (particularly those with EDS) have distinct clinical characteristics. Their symptoms are more severe that patients with ME/CFS and no joint hypermobility, and they have a reduced health-related quality of life, especially related to physical functioning and pain. The authors recommend that this subgroup of people with ME/CFS and joint hypermobility highlights the need for more research, possibly leading to better distinction between the groups and better care.
“Mismatch between subjective and objective dysautonomia”
Published in Scientific Reports on Jan 30, 2024 | Link to full-text article
Research by: Peter Novak, David M Systrom, Sadie P Marciano, Alexandra Knief, Donna Felsenstein, Matthew P Giannetti, Matthew J Hamilton, Jennifer Nicoloro-SantaBarbara, Tara V Saco, Mariana Castells, Khosro Farhad, David M Pilgrim, William J Mullally
Summary: Often times, autonomic dysfunction is diagnosed based on a questionnaire that the patient fills out. The responses to these questionnaires–and almost any questionnaire–can be impaired by faulty memory, bias, and other subjective impulses. In this study, the researchers wanted to know if the responses that patients provided on their questionnaires matched the data that clinical tools were measuring. They found very little match between the questionnaire and the clinical data, both in patients overestimating and underestimating their symptoms. They recommend finding a better way to test for autonomic dysfunction than using a survey.
“Assessment of a novel Ehlers-Danlos syndromes disability index”
Published in Frontiers in Rehabilitation Sciences on April 19, 2024
Research by: Stephen Chai, Patricia Roney, John Fagan, Emily Rose Rosario
Summary: Have you ever had to fill out a survey at a physician’s office or with a physical therapist that has you rate how well you can do certain activities and how that affects your life? Those surveys are an easy way for providers to see how much the condition affects you and your quality of life. The researchers in this study looked at a disability index for Ehlers-Danlos syndrome created by Casa Colina Hospital and Centers for Healthcare. (You can see the index in the study link if you scroll down and click on Figure 1.) They had 222 patients fill out the index, and while they feel that the index did a good job measuring symptoms, quality of life, and tracking improvement, they urge researchers and doctors to continue to refine and rebuild a disability index for EDS patients that takes all domains of life into consideration and potentially address the differences between subtypes of EDS.
If you have an article you’d like to see in the Research Round-Up, email kate [at] ChronicPainPartners [dot] com.
Kate Schultz
July 2024
