MRI assessment of the effects of acetazolamide and external lumbar drainage in idiopathic Normal Pressure Hydrocephalus

Background: The objective was to identify changes in quantitative MRI measures in patients with idiopathic normal pressure hydrocephalus (iNPH) occurring in common after oral acetazolamide (ACZ) and external lumbar drainage (ELD) interventions. Methods: A total of 25 iNPH patients from two clinical sites underwent serial MRIs and clinical assessments. Eight received ACZ (125-375 mg/day) over 3 months and 12 underwent ELD for up to 72 hours. Five clinically-stable iNPH patients who were scanned serially without interventions served as controls for the MRI component of the study. Subjects were divided into responders and non-responders to the intervention based on gait and cognition assessments made by clinicians blinded to MRI results. The MRI modalities analyzed included T1-weighted images, diffusion tensor Imaging (DTI) and arterial spin labelling (ASL) perfusion studies. Automated threshold techniques were used to define regions of T1 hypo-intensities. Results: Decreased volume of T1-hypointensities and decreased mean diffusivity (MD) within remaining hypointensities was observed after ACZ and ELD but not in controls. Patients responding positively to these interventions had more extensive decreases in T1-hypointensites than non-responders: ACZ-responders (4,651 ± 2,909 mm³), ELD responders (2,338 ± 1,140 mm³), ELD non-responders (44 ± 1,188 mm³). Changes in DTI MD within T1-hypointensities were greater in ACZ-responders (7.9% ± 2%) and ELD-responders (8.2% ± 3.1%) compared to ELD non-responders (2.1% ± 3%). All the acetazolamide-responders showed increases in whole-brain-average cerebral blood flow (wbCBF) estimated by ASL (18.8% ± 8.7%). The only observed decrease in wbCBF (9.6%) occurred in an acetazolamide-non-responder. A possible association between cerebral atrophy and response was observed, with subjects having the least cortical atrophy (as indicated by a positive z-score on cortical thickness measurements) showing greater clinical improvement after ACZ and ELD. Conclusions: T1-hypointensity volume and DTI MD measures decreased in the brains of iNPH patients following oral ACZ and ELD. The magnitude of the decrease was greater in treatment responders than non-responders. Despite having different mechanisms of action, both ELD and ACZ may decrease interstitial brain water and increase cerebral blood flow in patients with iNPH. Quantitative MRI measurements appear useful for objectively monitoring response to acetazolamide, ELD and potentially other therapeutic interventions in patients with iNPH.