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Impaired cognition is recognized in IIH and can be exacerbated by medications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This human experimental medicine study was a secondary analysis that focused on an unblinded randomized, sequential, cross\u2010over extension of a previously completed randomized controlled trial. This study evaluated females with active IIH, recruited from University Hospital Birmingham, UK. Participants were treated, in randomized order, for 2\u2009weeks with acetazolamide, amiloride, furosemide, spironolactone, and topiramate; assessment was at baseline and 2\u2009weeks with a minimum 1\u2010week drug washout between drugs. The primary outcome was change in ICP at 2\u2009weeks post\u2010drug administration. The cognitive evaluation was an exploratory study of the trial. ICP was recorded with telemetric, intraparenchymal ICP monitors (Raumedic, Hembrechts, Germany). Adverse events were recorded, and cognition was assessed utilizing the National Institutes of Health Toolbox Cognitive Battery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fourteen participants were recruited and evaluated by intention\u2010to\u2010treat analysis. Mean (standard deviation) body mass index was 37.3 (7.0) kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      and ICP was 33.2 (7.1) cm cerebrospinal fluid (CSF) at baseline. ICP fell with four drugs (mean [standard error (SE)]), acetazolamide \u22123.3 (1.0) mmHg,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001, furosemide \u22123.0 (0.9) mmHg,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001, spironolactone \u22122.7 (0.9) mmHg,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003, and topiramate \u22122.3 (0.9) mmHg,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.010. There was no significant difference between drugs. Side effects were common with acetazolamide (100%, 11\/11) and topiramate (93%, 13\/14). Baseline cognitive performance was impaired,\n                      <jats:italic>T<\/jats:italic>\n                      \u2010score (mean [SE]) 37.2 (2.6). After treatment, there was a further significant reduction in the fluid cognition domain (ability to process and integrate) with acetazolamide (mean\n                      <jats:italic>T<\/jats:italic>\n                      \u2010score [SE]), \u22125.0 (2.6),\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.057 and topiramate \u22124.1 (2.0),\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.061.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Acetazolamide, furosemide, spironolactone, and topiramate marginally reduced ICP. While their effects were not significant, this study was not powered to detect a difference between drugs. Participants reported significant side effects with acetazolamide and topiramate including cognitive decline. Cognitive measures were impaired by acetazolamide and topiramate. Therapeutics with greater efficacy and a favorable side effect profile are an unmet need in the treatment of IIH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.14897","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T06:51:26Z","timestamp":1737701486000},"page":"258-268","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["A randomized sequential cross\u2010over trial evaluating five purportedly\n                    <scp>ICP<\/scp>\n                    \u2010lowering drugs in idiopathic intracranial hypertension"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6785-9352","authenticated-orcid":false,"given":"James L.","family":"Mitchell","sequence":"first","affiliation":[{"name":"Translational Brain Science, Department of Metabolism and Systems Science, College of Medicine and Health University of Birmingham  Birmingham 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