{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:02:14Z","timestamp":1790715734789,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T00:00:00Z","timestamp":1691366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000887","name":"Huntington's Disease Society of America","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000887","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Investigations of cerebrospinal fluid (CSF) flow aberrations in Huntington's disease (HD) are of growing interest, as impaired CSF flow may contribute to mutant Huntington retention and observed heterogeneous responsiveness to intrathecally administered therapies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We assessed net cerebral aqueduct CSF flow and velocity in 29 HD participants (17 premanifest and 12 manifest) and 51 age\u2010 and sex matched non\u2010HD control participants using 3\u2010Tesla magnetic resonance imaging methods. Regression models were applied to test hypotheses regarding: (i) net CSF flow and cohort, (ii) net CSF flow and disease severity (CAP\u2010score), and (iii) CSF volume after correcting for age and sex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Group\u2010wise analyses support a decrease in net CSF flow in HD (mean 0.14\u2009\u00b1\u20090.27\u2009mL\/min) relative to control (mean 0.32\u2009\u00b1\u20090.20\u2009mL\/min) participants (<jats:italic>p<\/jats:italic>\u2009=\u20090.02), with lowest flow in the manifest HD cohort (mean 0.04\u2009\u00b1\u20090.25\u2009mL\/min). This finding was explained by hyperdynamic CSF movement, manifesting as higher caudal systolic CSF flow velocity and higher diastolic cranial CSF flow velocity across the cardiac cycle, in HD (caudal flow: 0.17\u2009\u00b1\u20090.07\u2009mL\/s, cranial flow: 0.14\u2009\u00b1\u20090.08\u2009mL\/s) compared to control (caudal flow: 0.13\u2009\u00b1\u20090.06\u2009mL\/s, cranial flow: 0.11\u2009\u00b1\u20090.04\u2009mL\/s) participants. A positive correlation between cranial diastolic flow and disease severity was observed (<jats:italic>p<\/jats:italic>\u2009=\u20090.02).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretations<\/jats:title><jats:p>Findings support aqueductal CSF flow dynamics changing with disease severity in HD. These accelerated changes are consistent with changes observed over the typical adult lifespan, and may have relevance to mutant Huntington retention and intrathecally administered therapeutics responsiveness. 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