Does acetazolamide improve normal pressure hydrocephalus?

Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH.

Alperin N, Oliu CJ, Bagci AM, et al.

Neurology 2014; 82:1347-1351.



To assess the effects of low-dose acetazolamide treatment on volumetric MRI markers and clinical outcome in idiopathic normal-pressure hydrocephalus (iNPH).


We analyzed MRI and gait measures from 8 patients with iNPH with serial MRIs from an institutional review board-approved imaging protocol who had been treated off-label with low-dose acetazolamide (125-375 mg/day). MRI studies included fluid-attenuated inversion recovery and 3D T1-weighted high-resolution imaging. Automated analyses were employed to quantify each patient’s ventricular, global white matter hyperintensities (WMH), and periventricular WMH (PVH) volumes prior to and throughout treatment. Clinical outcome was based on gait changes assessed quantitatively using the Boon scale.


Five of 8 patients responded positively to treatment, with median gait improvement of 4 points on the Boon scale. A significant decrease in PVH volume (-6.1 ± 1.9 mL, p = 0.002) was seen in these patients following treatment. One patient’s gait was unchanged and 2 patients demonstrated worsened gait and were referred for shunt surgery. No reduction in PVH volume was detected in the latter 2 patients. Nonperiventricular WMH and lateral ventricle volumes remained largely unchanged in all patients.


These preliminary findings provide new evidence that low-dose acetazolamide can reduce periventricular hyperintensities and may improve gait in idiopathic normal pressure hydrocephalus (iNPH). PVH volume, reflecting transependymal CSF, is shown to be a potential MRI indicator of pharmacologic intervention effectiveness. Further studies of pharmacologic treatment of iNPH are needed and may be enhanced by incorporating quantitative MRI outcomes.

This reference is cited in the neurochecklist:

Normal pressure hydrocephalus (NPH): treatment

Abstract link

By Lucien MonfilsOwn work, CC BY-SA 3.0, Link

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