{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:46:24Z","timestamp":1785818784223,"version":"3.56.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS) is a debilitating disease that affects millions worldwide. Its cause remains unknown, although many physiological mechanisms are impaired. Structural abnormalities in the craniocervical region seem to be more prevalent in patients with ME\/CFS, with a possible impact on intracranial pressure (ICP) and lumbar puncture (LP) measurements. This study aimed to quantify the occurrence of elevated cerebrospinal fluid (CSF) opening pressure and a possible association with clinical symptoms and radiological variables in craniocervical segments in a cohort of patients with ME\/CFS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study included 34 patients previously diagnosed with ME\/CFS as part of a larger case\u2013control study, for whom LP was performed only in the case group. Key measurements included age, sex, opening pressure from LP, symptomatic relief post-LP, and radiological variables with potential influence on CSF dynamics. Individuals were stratified into two groups according to opening pressure (OP) measurements using 20 cmH\n                      <jats:sub>2<\/jats:sub>\n                      O as the cutoff value, with subsequent statistical comparisons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall, the majority of participants reported moderate disease severity (65%) and concomitant self-reported low quality of life. The median CSF opening pressure was 18 (IQR 8) cmH\n                      <jats:sub>2<\/jats:sub>\n                      O, ranging from 11 to 29.5. Opening pressure stratification showed that 21 of the 34 cases (62%) had an OP measurement of &amp;lt;20 cmH\n                      <jats:sub>2<\/jats:sub>\n                      O (low-OP group) and 13 cases (38%) had an OP measurement of \u226520 cmH\n                      <jats:sub>2<\/jats:sub>\n                      O (high-OP group). The two OP groups did not differ significantly in baseline characteristics, including disease severity and quality of life. However, for certain radiological measurements, the high-OP group presented with measures reflecting a wider spinal canal, including a significantly larger foramen magnum diameter (33.9\u202fmm), which was higher than the measures in the low-OP group (31.7\u202fmm). Estimates of symptom relief 1\u20134\u202fdays post-LP were significantly higher among patients in the high-OP group (80%) than among those in the low-OP group (19%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study suggests that a proportion of patients with ME\/CFS have elevated CSF opening pressures and may experience symptom relief following CSF subtraction. Our data indicate that some anatomical structures in the craniocervical area may be related to CSF pressure, although interpretation is challenging and merits further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1869714","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:27:35Z","timestamp":1785817655000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cerebrospinal fluid opening pressure in relation to symptomatology and craniocervical anatomy in patients with myalgic encephalomyelitis\/chronic fatigue syndrome"],"prefix":"10.3389","volume":"13","author":[{"given":"C.","family":"Jolley","sequence":"first","affiliation":[{"name":"Kirk Kerkorian School of Medicine at the University of Nevada, Las Vegas (UNLV)","place":["Las Vegas, NV, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Brag\u00e9e","sequence":"additional","affiliation":[{"name":"Brag\u00e9e Clinics","place":["Stockholm, Sweden"]},{"name":"Department of Neurobiology, Care Sciences and Society, Karolinska Institutet","place":["Huddinge, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Soinne","sequence":"additional","affiliation":[{"name":"Brag\u00e9e Clinics","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Huhmar","sequence":"additional","affiliation":[{"name":"Brag\u00e9e Clinics","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Billing","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Bertilson","sequence":"additional","affiliation":[{"name":"Brag\u00e9e Clinics","place":["Stockholm, Sweden"]},{"name":"Department of Neurobiology, Care Sciences and Society, Karolinska Institutet","place":["Huddinge, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Sjogren","sequence":"additional","affiliation":[{"name":"Brag\u00e9e Clinics","place":["Stockholm, Sweden"]},{"name":"Department of Neurobiology, Care Sciences and Society, Karolinska Institutet","place":["Huddinge, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3389\/FIMMU.2024.1386607","article-title":"Myalgic encephalomyelitis\/chronic fatigue syndrome: the biology of a neglected disease","volume":"15","author":"Arron","year":"2024","journal-title":"Front Immunol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1001\/JAMA.2015.1346","article-title":"Beyond Myalgic encephalomyelitis\/chronic fatigue syndrome: an IOM report on redefining an illness","volume":"313","author":"Clayton","year":"2015","journal-title":"JAMA"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"412","DOI":"10.3389\/FPED.2018.00412","article-title":"Estimating prevalence, demographics, and costs of ME\/CFS using large scale medical claims data and machine learning","volume":"6","author":"Valdez","year":"2019","journal-title":"Front Pediatr"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"953","DOI":"10.7326\/0003-4819-121-12-199412150-00009","article-title":"The chronic fatigue syndrome: a comprehensive approach to its definition and study","volume":"121","author":"Fukuda","year":"1994","journal-title":"Ann Intern Med"},{"key":"ref5","volume-title":"Myalgic Encephalomyelitis (or Encephalopathy)\/Chronic Fatigue Syndrome: Diagnosis and Management","year":"2021"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/S12967-020-02269-0","article-title":"Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome\/myalgic encephalomyelitis (CFS\/ME)","volume":"18","author":"Lim","year":"2020","journal-title":"J Transl Med"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/21641846.2014.978109","article-title":"Chronic fatigue syndrome and co-morbid and consequent conditions: evidence from a multi-site clinical epidemiology study","volume":"3","author":"Bateman","year":"2015","journal-title":"Fatigue."},{"key":"ref8","year":"2019"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"91","DOI":"10.3390\/DIAGNOSTICS9030091","article-title":"Myalgic encephalomyelitis\/chronic fatigue syndrome: a comprehensive review","volume":"9","author":"Rivera","year":"2019","journal-title":"Diagnostics (Basel)"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e113629","DOI":"10.5812\/AAPM.113629","article-title":"A comprehensive update of the current understanding of chronic fatigue syndrome","volume":"11","author":"Noor","year":"2021","journal-title":"Anesth Pain Med"},{"key":"ref11","first-page":"741","article-title":"Chronic fatigue syndrome: diagnosis and treatment","volume":"86","author":"Yancey","year":"2012","journal-title":"Am Fam Physician"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1093\/clinids\/21.6.1386","article-title":"Seroepidemiology of chronic fatigue syndrome: a case-control study","volume":"21","author":"Mawle","year":"1995","journal-title":"Clin Infect Dis"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"828","DOI":"10.3389\/FNEUR.2020.00828","article-title":"Signs of intracranial hypertension, hypermobility, and Craniocervical obstructions in patients with Myalgic encephalomyelitis\/chronic fatigue syndrome","volume":"11","author":"Brag\u00e9e","year":"2020","journal-title":"Front Neurol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/S12967-018-1397-7","article-title":"Improvement of severe myalgic encephalomyelitis\/chronic fatigue syndrome symptoms following surgical treatment of cervical spinal stenosis","volume":"16","author":"Rowe","year":"2018","journal-title":"J Transl Med"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.mehy.2018.07.007","article-title":"The putative glymphatic signature of chronic fatigue syndrome: a new view on the disease pathogenesis and therapy","volume":"118","author":"Wostyn","year":"2018","journal-title":"Med Hypotheses"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1007\/S00381-017-3480-4","article-title":"A comprehensive review of the foramina of Luschka: history, anatomy, embryology, and surgery","volume":"33","author":"Johal","year":"2017","journal-title":"Childs Nerv Syst"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1227\/00006123-199408000-00006","article-title":"Quantitative cine-mode magnetic resonance imaging of Chiari I malformations: an analysis of cerebrospinal fluid dynamics","volume":"35","author":"Armonda","year":"1994","journal-title":"Neurosurgery"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e22","DOI":"10.1136\/JNNP-2019-ABN.69","article-title":"FM1-7 Cranio-cervical instability in ehlers-danlos syndrome employing upright, dynamic MR imaging; a comparative study","volume":"90","author":"Prezerakos","year":"2019","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/S0022-3476(99)70173-3","article-title":"Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome","volume":"135","author":"Rowe","year":"1999","journal-title":"J Pediatr"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/S10143-017-0830-3","article-title":"Utility of the clivo-axial angle in assessing brainstem deformity: pilot study and literature review","volume":"41","author":"Henderson","year":"2017","journal-title":"Neurosurg Rev"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1016\/j.amjmed.2017.02.013","article-title":"Joint hypermobility syndrome: recognizing a commonly overlooked cause of chronic pain","volume":"130","author":"Kumar","year":"2017","journal-title":"Am J Med"},{"key":"ref22","volume-title":"Chronic Fatigue Syndrome Myalgic Encephalomyelitis Primer for Clinical Practitioners 2014 Edition International Association for Chronic Fatigue Syndrome\/Myalgic Encephalomyelitis IACFS\/ME","year":"2014"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"2321","DOI":"10.1007\/S00586-015-3925-Y","article-title":"CT morphometry of adult thoracic intervertebral discs","volume":"24","author":"Fletcher","year":"2015","journal-title":"Eur Spine J"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"230","DOI":"10.3171\/2014.10.SPINE14346","article-title":"The diagnostic value of magnetic resonance imaging measurements for assessing cervical spinal canal stenosis","volume":"22","author":"R\u00fcegg","year":"2015","journal-title":"J Neurosurg Spine"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/J.WNEU.2017.08.018","article-title":"Cervical Cord-Canal mismatch: a new method for identifying predisposition to spinal cord injury","volume":"108","author":"Nouri","year":"2017","journal-title":"World Neurosurg"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"2336","DOI":"10.1016\/j.ajem.2016.08.045","article-title":"The quantitative evaluation of intracranial pressure by optic nerve sheath diameter\/eye diameter CT measurement","volume":"34","author":"Bekerman","year":"2016","journal-title":"Am J Emerg Med"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"3129","DOI":"10.2147\/JPR.S186878","article-title":"The link between idiopathic intracranial hypertension, fibromyalgia, and chronic fatigue syndrome: exploration of a shared pathophysiology","volume":"11","author":"Hulens","year":"2018","journal-title":"J Pain Res"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1177\/2042533313507920","article-title":"Lumbar puncture, chronic fatigue syndrome and idiopathic intracranial hypertension: a cross-sectional study","volume":"4","author":"Higgins","year":"2013","journal-title":"JRSM Short Rep"},{"key":"ref29","first-page":"1443000223","article-title":"What do lumbar puncture and jugular venoplasty say about a connection between chronic fatigue syndrome and idiopathic intracranial hypertension?","volume":"2014","author":"Higgins","year":"2014","journal-title":"EJMINT"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1080\/21641846.2021.1956223","article-title":"A paradigm for chronic fatigue syndrome: caught between idiopathic intracranial hypertension and spontaneous intracranial hypotension; caused by cranial venous outflow obstruction","volume":"9","author":"JN","year":"2021","journal-title":"Fatigue"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/J.MEHY.2017.06.014","article-title":"Chronic fatigue syndrome and idiopathic intracranial hypertension: different manifestations of the same disorder of intracranial pressure?","volume":"105","author":"Higgins","year":"2017","journal-title":"Med Hypotheses"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"3464","DOI":"10.16965\/IJAR.2016.367","article-title":"Morphometry and surgical importance of foramen magnum","volume":"5","author":"Sandeep","year":"2017","journal-title":"Int J Approx Reason"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/978-3-7091-0956-4_39","article-title":"Evidence for altered spinal canal compliance and cerebral venous drainage in untreated idiopathic intracranial hypertension","volume":"114","author":"Alperin","year":"2012","journal-title":"Acta Neurochir Suppl"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.wneu.2020.01.231","article-title":"The Retroverted dens: a review of its anatomy, terminology, and clinical significance","volume":"137","author":"Ishak","year":"2020","journal-title":"World Neurosurg"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1007\/S00264-010-1203-5","article-title":"Degenerative cervical spondylolisthesis: a systematic review","volume":"35","author":"Jiang","year":"2011","journal-title":"Int Orthop"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"E1115","DOI":"10.1097\/BRS.0B013E31829B1487","article-title":"Prevalence and motion characteristics of degenerative cervical spondylolisthesis in the symptomatic adult","volume":"38","author":"Suzuki","year":"1976","journal-title":"Spine (Phila Pa 1976)"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1016\/j.eprac.2025.12.020","article-title":"Low vasopressin in Myalgic Encephalomyelitise\/chronic fatigue syndrome","volume":"32","author":"Huhmar","year":"2025","journal-title":"Endocr Pract"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1097\/WNO.0000000000000834","article-title":"Variability of consecutive lumbar puncture opening pressures","volume":"40","author":"Kilgore","year":"2020","journal-title":"J Neuroophthalmol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1227\/01.NEU.0000209915.16235.6D","article-title":"Posture-induced changes in intracranial pressure: a comparative study in patients with and without a cerebrospinal fluid block at the craniovertebral junction","volume":"58","author":"Poca","year":"2006","journal-title":"Neurosurgery"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"257","DOI":"10.3171\/2021.1.JNS204218","article-title":"Comparison of transorbital ultrasound measurements to predict intracranial pressure in brain-injured patients requiring external ventricular drainage","volume":"136","author":"Youm","year":"2021","journal-title":"J Neurosurg"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1007\/S12028-019-00762-Z","article-title":"Ratio of optic nerve sheath diameter to eyeball transverse diameter by ultrasound can predict intracranial hypertension in traumatic brain injury patients: a prospective study","volume":"32","author":"Du","year":"2019","journal-title":"Neurocrit Care"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1001\/JAMAOPHTHALMOL.2017.6560","article-title":"Ultrasonography assessments of optic nerve sheath diameter as a noninvasive and dynamic method of detecting changes in intracranial pressure","volume":"136","author":"Wang","year":"2018","journal-title":"JAMA Ophthalmol"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1869714\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:27:37Z","timestamp":1785817657000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1869714\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":42,"alternative-id":["10.3389\/fmed.2026.1869714"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1869714","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,4]]},"article-number":"1869714"}}