title: Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH.
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 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.
  
  
  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.
  
  
  METHODS
  This study provides Class IV evidence that low-dose acetazolamide reverses PVH volume and, in some cases, improves gait in iNPH.
authors.affiliation: From the Departments of Radiology (N.A., C.J.O., A.M.B., S.H.L.) and Neurology (D.A., H.K.), University of Miami, FL; and the Departments of Radiology (I.K., M.I.) and Neurology (L.H., N.R.), Weill Cornell Medical College, New York, NY.
authors.forename: Noam
authors.initials: N
authors.lastname: Alperin
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Oliu
authors.forename: Ahmet M
authors.initials: AM
authors.lastname: Bagci
authors.forename: Sang H
authors.initials: SH
authors.lastname: Lee
authors.forename: Ilhami
authors.initials: I
authors.lastname: Kovanlikaya
authors.forename: David
authors.initials: D
authors.lastname: Adams
authors.forename: Heather
authors.initials: H
authors.lastname: Katzen
authors.forename: Milos
authors.initials: M
authors.lastname: Ivkovic
authors.forename: Linda
authors.initials: L
authors.lastname: Heier
authors.forename: Norman
authors.initials: N
authors.lastname: Relkin
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005684:Gait / Q000187:drug effects; D006801:Humans; D006850:Hydrocephalus, Normal Pressure / Q000188:drug therapy* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000086:Acetazolamide