{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T17:53:31Z","timestamp":1785779611658,"version":"3.56.0"},"reference-count":113,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":153,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-NS89757"],"award-info":[{"award-number":["R01-NS89757"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-DC12519"],"award-info":[{"award-number":["R01-DC12519"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-DC14942"],"award-info":[{"award-number":["R01-DC14942"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011892","name":"Kaohsiung Chang Gung Memorial Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011892","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Normal pressure hydrocephalus is typically defined by the triad of gait disturbance, cognitive impairment, and urinary incontinence, and is characterized on MRI by disproportionately enlarged subarachnoid-space. Gait disturbance is also a commonly reported symptom in Parkinsonian disorders, especially progressive supranuclear palsy, although the frequency, clinical significance and mechanisms of hydrocephalus in these disorders are unclear. We aimed to assess the prevalence of hydrocephalic MRI parameters in a large cohort of Parkinsonian disorders and evaluate associations with clinical features and abnormalities on MRI and PET. Two hundred and thirty-eight participants with a Parkinsonian disorder, including 181 progressive supranuclear palsy, 36 corticobasal syndrome and 21 Parkinson\u2019s disease, were enrolled from Mayo Clinic by the Neurodegenerative Research Group between September 2009 to October 2023. Automated detection of disproportionately enlarged subarachnoid-space hydrocephalus (D) was applied and using Evans\u2019 index (E) cut-off point &amp;gt;0.3, participants were classified based on both measures as imaging-suggestive of hydrocephalus (D+E+), enlarged subarachnoid-space only (D+E\u2212), large Evans\u2019 index only (D\u2212E+) and no imaging evidence of hydrocephalus (D\u2212E\u2212). Demographic, clinical and imaging features, including magnetic resonance parkinsonism index, cortical and subcortical volumes, white matter hyperintensities, diffusion tractography metrics, and metabolism on PET, were compared across groups. Among the 238 participants, 24 had borderline subarachnoid space scores and were excluded. The remaining 214 participants were classified as: D+E+ (n = 20, 9%); D+E\u2212 (n = 8, 4%); D\u2212E+ (n = 71, 33%) and D\u2212E\u2212 (n = 115, 54%). Among the progressive supranuclear palsy participants, 11% were D+E+, 4% D+E\u2212, 34% D\u2212E+ and 51% D\u2212E\u2212. Most cases (n = 18) in the imaging-suggestive of hydrocephalus D+E+ group had progressive supranuclear palsy. The D+E+ participants were older, had more disorientation, more downgaze palsy, greater midbrain and cortical atrophy, lower striatal metabolism, greater degeneration of long-range white matter tracts, larger cistern areas and more periventricular and deep white matter hyperintensities compared to the D\u2212E\u2212 participants without imaging evidence of hydrocephalus. The D+E\u2212 participants had the highest metabolism in the paracentral lobule and superior parietal gyrus. The D\u2212E+ participants showed worse disease severity and greater midbrain and cortical atrophy compared to the D\u2212E\u2212 participants. These findings demonstrate that disproportionately enlarged subarachnoid-space hydrocephalus occurs in \u223c15% of progressive supranuclear palsy participants, and is associated with worse clinical and imaging outcomes, as well as white matter hyperintensities. We hypothesize that disproportionately enlarged subarachnoid-space may be a mechanistic byproduct of degeneration and subsequent cerebrospinal fluid flow re-distribution in progressive supranuclear palsy.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf206","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T07:24:09Z","timestamp":1748849049000},"source":"Crossref","is-referenced-by-count":4,"title":["Evaluation of disproportionately enlarged subarachnoid-space hydrocephalus in progressive supranuclear palsy"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2895-794X","authenticated-orcid":false,"given":"Mu-Hui","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]},{"name":"Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine , Kaohsiung 83301 ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L","family":"Gunter","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryota","family":"Satoh","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodolfo G","family":"Gatto","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farwa","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather M","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A","family":"Stierwalt","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M","family":"Machulda","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yehkyoung C","family":"Stephens","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossam","family":"Youssef","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nha Trang","family":"Thu Pham","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7916-622X","authenticated-orcid":false,"suffix":"Jr","given":"Clifford R","family":"Jack","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val J","family":"Lowe","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2930-8634","authenticated-orcid":false,"given":"Keith 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