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Fluids and Barriers of the CNS
Published in: Fluids and Barriers of the CNS 1/2015

Open Access 01-12-2015 | Research

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

Authors: Milos Ivkovic, Martin Reiss-Zimmermann, Heather Katzen, Matthias Preuss, Ilhami Kovanlikaya, Linda Heier, Noam Alperin, Karl T Hoffmann, Norman Relkin

Published in: Fluids and Barriers of the CNS | Issue 1/2015

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Abstract

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.
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Metadata
Title
MRI assessment of the effects of acetazolamide and external lumbar drainage in idiopathic Normal Pressure Hydrocephalus
Authors
Milos Ivkovic
Martin Reiss-Zimmermann
Heather Katzen
Matthias Preuss
Ilhami Kovanlikaya
Linda Heier
Noam Alperin
Karl T Hoffmann
Norman Relkin
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Fluids and Barriers of the CNS / Issue 1/2015
Electronic ISSN: 2045-8118
DOI
https://doi.org/10.1186/s12987-015-0004-z

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