{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:13:15Z","timestamp":1792793595694,"version":"4.5.0"},"reference-count":51,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: During tilt testing, myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS) patients experience an abnormal reduction in cerebral blood flow (CBF). The relationship between this CBF reduction and symptom severity has not been examined in detail. Our hypothesis was that ME\/CFS severity is related to the degree of the CBF reduction during tilt testing. Materials and Methods: First, from our database, we selected ME\/CFS patients who had undergone assessments of ME\/CFS symptomatology and tilt tests on the same day, one at the first visit and the second during a follow-up. The change in symptomatology was related to the change in CBF during the tilt test. Second, we combined the data of two previously published studies (n = 219), where disease severity as defined by the 2011 international consensus criteria (ICC) was available but not published. Results: 71 patients were retested because of worsening symptoms. The ICC disease severity distribution (mild-moderate-severe) changed from 51\/45\/4% at visit-1 to 1\/72\/27% at follow-up (p &lt; 0.0001). The %CBF reduction changed from initially 19% to 31% at follow-up (p &lt; 0.0001). Of 39 patients with stable disease, the severity distribution was similar at visit-1 (36\/51\/13%) and at follow-up (33\/49\/18%), p = ns. The %CBF reduction remained unchanged: both 24%, p = ns. The combined data of the two previously published studies showed that patients with mild, moderate, and severe disease had %CBF reductions of 25, 29, and 33%, respectively (p &lt; 0.0001). Conclusions: Disease severity and %CBF reduction during tilt testing are highly associated in ME\/CFS: a more severe disease is related to a larger %CBF reduction. The data suggest a causal relationship where a larger CBF reduction leads to worsening symptoms.<\/jats:p>","DOI":"10.3390\/medicina59122153","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T11:09:30Z","timestamp":1702379370000},"page":"2153","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Worsening Symptoms Is Associated with Larger Cerebral Blood Flow Abnormalities during Tilt-Testing in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS)"],"prefix":"10.3390","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2570-0914","authenticated-orcid":false,"given":"C. (Linda) M. C.","family":"van Campen","sequence":"first","affiliation":[{"name":"Stichting CardioZorg, Planetenweg 5, 2132 HN Hoofddorp, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3586-2677","authenticated-orcid":false,"given":"Peter C.","family":"Rowe","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans C.","family":"Visser","sequence":"additional","affiliation":[{"name":"Stichting CardioZorg, Planetenweg 5, 2132 HN Hoofddorp, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1111\/j.1365-2796.2011.02428.x","article-title":"Myalgic encephalomyelitis: International consensus criteria","volume":"270","author":"Carruthers","year":"2011","journal-title":"J. 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