Clinical observation of Methazolamide in the treatment of idiopathic normal pressure hydrocephalus patients

Abstract

Background: Cerebrospinal fluid (CSF) shunt intervention is currently the standard and most effective treatment for idiopathic normal-pressure hydrocephalus (iNPH). However, many patients do not undergo surgery due to various reasons. The study aimed to assess the efficacy and safety of methazolamide (MTZ) in the treatment of iNPH. Methods: A 12-week randomized, double-blind, drug-placebo clinical studywas conducted at the Aviation General Hospital. Participants with a diagnosis of possible or probable iNPH according to Japanese second iNPH guidelines were consecutively recruited from September 2019 to May 2021. All patients were inoperable or had refused surgical treatment due to various reasons. The patients were assigned (2:1) to the MTZ or placebo group via a computer-generated randomization list. The gait and cognition function were assessed, and brain MRI scans were taken before and 12 weeks after drug administration. The primary endpoint was the difference change in the Boon gait sum score relative to baseline between the drug and placebo groups. Secondary endpoints were differences in MMSE and MOCA scores. In addition, the adverse reactions were also monitored. Results: Twenty participants were randomly included in the MTZ group and 12 in the placebo group. A total of 26 patients, 17 in the MTZ and 9 in the placebo group, were included in the final efficacy analysis. The difference in Boon sum score relative to baseline between the groups was -6.06 points (95% CI, -9.37 to -2.75; p =0.001) after 12 weeks of treatment. However, there was no significant difference in the MMSE and MoCA scores between the drug and placebo groups (MMSE 0.36, 95% CI, -2.36 to 3.09; p = 0.78; MoCA 0.001, 95% CI, -1.98 to 1.98; p = 1.00). No serious adverse reactions such as hypokalemia or acidosis occurred in any of the patients. Conclusions: MTZ significantly improved the gait of iNPH patients without any adverse effects. Large sample studies are needed for further confirmation of our results.