Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH

Noam Alperin, Carlos J. Oliu, Ahmet M. Bagci, Sang H. Lee, Ilhami Kovanlikaya, David Adams, Heather Katzen, Milos Ivkovic, Linda Heier, Norman Relkin

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Abstract

Objective: To assess the effects of low-dose acetazolamide treatment on volumetric MRI markers and clinical outcome in idiopathic normal-pressure hydrocephalus (iNPH). Methods: 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 lowdose 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. Results: 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. Conclusions: These preliminary findings provide new evidence that low-dose acetazolamide can reduce PVH and may improve gait in 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. Classification of evidence: This study provides Class IV evidence that low-dose acetazolamide reverses PVH volume and, in some cases, improves gait in iNPH.

Original languageEnglish
Pages (from-to)1347-1351
Number of pages5
JournalNeurology
Volume82
Issue number15
DOIs
StatePublished - Apr 15 2014

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Normal Pressure Hydrocephalus
Acetazolamide
Gait
Therapeutics
White Matter
Dose
Hydrocephalus
Lateral Ventricles
Research Ethics Committees
Biomarkers

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Alperin, N., Oliu, C. J., Bagci, A. M., Lee, S. H., Kovanlikaya, I., Adams, D., ... Relkin, N. (2014). Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH. Neurology, 82(15), 1347-1351. https://doi.org/10.1212/WNL.0000000000000313

Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH. / Alperin, Noam; Oliu, Carlos J.; Bagci, Ahmet M.; Lee, Sang H.; Kovanlikaya, Ilhami; Adams, David; Katzen, Heather; Ivkovic, Milos; Heier, Linda; Relkin, Norman.

In: Neurology, Vol. 82, No. 15, 15.04.2014, p. 1347-1351.

Research output: Contribution to journalArticle

Alperin, N, Oliu, CJ, Bagci, AM, Lee, SH, Kovanlikaya, I, Adams, D, Katzen, H, Ivkovic, M, Heier, L & Relkin, N 2014, 'Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH', Neurology, vol. 82, no. 15, pp. 1347-1351. https://doi.org/10.1212/WNL.0000000000000313
Alperin, Noam ; Oliu, Carlos J. ; Bagci, Ahmet M. ; Lee, Sang H. ; Kovanlikaya, Ilhami ; Adams, David ; Katzen, Heather ; Ivkovic, Milos ; Heier, Linda ; Relkin, Norman. / Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH. In: Neurology. 2014 ; Vol. 82, No. 15. pp. 1347-1351.
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