MRI assessment of the effects of acetazolamide and external lumbar drainage in idiopathic normal pressure hydrocephalus

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

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 mm(3)), ELD responders (2,338 ± 1,140 mm(3)), ELD non-responders (44 ± 1,188 mm(3)). 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.

Figures

Figure 1
Figure 1
Observed changes in T1-hypointensities and mean diffusivity after treatment. Left: Decrease in volume of T1-hypointensities (y axis) was higher among patients that experienced clinical improvement (red bar, ELD-improvement (N = 7) vs. ELD-no-improvement (purple bar set to zero N = 5): p = 0.008, and between ACZ-improvement (pink bar, N = 7) relative to no-intervention (blue bar, N = 5): p = 0.002). Patients that were not subject to intervention showed an increase in T1-hypointensities (blue bar). Right: Percentage decrease in DW-MRI mean diffusivity (MD) within remaining T1-hypointensites was higher in patients that experienced clinical improvement (ELD-improvement vs. ELD-No-Improvement: p = 0.007, ACZ vs. No-Intervention: p = 0.0002). Data are means +/− SEM.
Figure 2
Figure 2
Illustration of DW-MRI changes location. Left: Regional changes in mean diffusivity within T1-hypointensities, before versus after the acetazolamide treatment for patient ACZ_3. Right: Changes in isotropic water fraction, within white matter, on the same brain slice. Red indicates decrease in the isotropic water fraction, blue indicates increase.
Figure 3
Figure 3
Plot of symmetrized percent change in mean diffusivity (MD) within the remaining T1-hypointensities against volume of CSF drained in patients treated with external lumbar drainage. The outlier among the non-responding patients (by having high volume of drained CSF and high decrease in MD) is ELD_9. Her gait problems were attributed to Parkinson’s disease.
Figure 4
Figure 4
Symmetrized percent change in cerebral blood flow (CBF) after acetazolamide treatment. Left: a patient with normal blood pressure (ACZ_1). Right: the patient with acute hypertension (ACZ_6) did not experience increase in CBF.
Figure 5
Figure 5
A subject with remarkable long-term correlation between cognitive scores and T1-hypointensities volume. Left: Correlation between Alzheimer’s Disease Assessment Scale (ADAS) cognitive scores and the volume of the white matter T1-hypointensities, over a 5 year period, for the Alzheimer’s Disease Neuroimaging Initiative (ADNI) subject 0644 (an MCI case). All the data points were independently calculated and available at the ADNI portal [39]. Right: Hallmarks of CSF dysfunction on the same subject: ventriculomegaly and DESH pattern. Note lacunae in the deep gray matter, consistent with the radiologic presentation of dilated veins observed in untreated NPH patients [40].

References

    1. Kiefer M, Unterberg A. The differential diagnosis and treatment of normal-pressure hydrocephalus. Dtsch Arztebl Int. 2012;109:15–25.
    1. Malm J, Graff-Radford N, Ishikawa M, Kristensen B, Leinonen V, Mori E, et al. Influence of comorbidities in idiopathic normal pressure hydrocephalus research and clinical care. A report of the ISHCSF task force on comorbidities in INPH. Fluids Barriers CNS. 2013;10(1):22. doi: 10.1186/2045-8118-10-22.
    1. Jones D, Cercignani M. Twenty-five pitfalls in the analysis of diffusion MRI data. NMR Biomed. 2010;23:803–20. doi: 10.1002/nbm.1543.
    1. Kim M, Seo S, Lee K, Kim S, Leed J, Nam D, Na D. Differential diagnosis of idiopathic normal pressure hydrocephalus from other dementias using diffusion tensor imaging. AJNR Am J Neuroradiol. 2011;32:1496–503. doi: 10.3174/ajnr.A2531.
    1. Nicot B, Bouzerar R, Gondry-Jouet C, Capel C, Peltier J, Fichten A, et al. Effect of surgery on periventricular white matter in normal pressure hydrocephalus patients: comparison of two methods of DTI analysis. Acta Radiol. 2014;55(5):614–621. doi: 10.1177/0284185113504570.
    1. Panagiotopoulos V, Konstantinou D, Kalogeropoulos A, Maraziotis T. The predictive value of external continuous lumbar drainage, with cerebrospinal fluid outflow controlled by medium pressure valve, in normal pressure hydrocephalus. Acta Neurochir (Wien) 2005;147(9):953–958. doi: 10.1007/s00701-005-0580-9.
    1. Lim T, Yong S, Moon S. Repetitive lumbar punctures as treatment for normal pressure hydrocephalus. Eur Neurol. 2009;62(5):293–297. doi: 10.1159/000235808.
    1. Aimard G, Vighetto A, Gabet J, Bret P, Henry E. Acetazolamide: an alternative to shunting in normal pressure hydrocephalus? Preliminary results. Rev Neurol. 1990;146(6–7):437–439.
    1. Alperin N, Oliu C, Bagci A, Lee SH, Kovanlikaya I, Adams D, et al. Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH. Neurology. 2014;82(15):1347–1351. doi: 10.1212/WNL.0000000000000313.
    1. Relkin N, Marmarou A, Klinge P, Bergsneider M, Black P. Diagnosing idiopathic normal-pressure hydrocephalus. Neurosurgery. 2005;57(S3):4–16.
    1. Boon A, Tans J, Delwel E, Egeler-Peerdeman SM, Hanlo PW, Wurzer JA, et al. Dutch normal pressure hydrocephalus study: baseline characteristics with emphasis on clinical findings. Eur J Neurol. 1997;4:39–47. doi: 10.1111/j.1468-1331.1997.tb00297.x.
    1. Dai W, Garcia D, de Bazelaire C, Alsop D. Continuous flow-driven inversion for arterial spin labeling using pulsed radio frequency and gradient fields. Magn Reson Med. 2008;60:1488–1497. doi: 10.1002/mrm.21790.
    1. Folstein M, Folstein S, McHugh P. “Mini-mental state” A practical method for grading the cognitive state of patients for the clinician. J Psychiat Res. 1975;12(3):189–198. doi: 10.1016/0022-3956(75)90026-6.
    1. Tsakanikas D, Relkin N. Normal pressure hydrocephalus. Semin Neurol. 2007;27:58–65. doi: 10.1055/s-2006-956756.
    1. Fischl B. FreeSurfer. Neuroimage. 2012;62(2):774–781. doi: 10.1016/j.neuroimage.2012.01.021.
    1. Reuter M, Schmansky N, Rosas H, Fischl B. Within-Subject Template Estimation for Unbiased Longitudinal Image Analysis. Neuroimage. 2012;61(4):1402–1418. doi: 10.1016/j.neuroimage.2012.02.084.
    1. Jenkinson M, Smith S. A global optimization method for robust affine registration of brain images. Med Image Anal. 2001;5:143–156. doi: 10.1016/S1361-8415(01)00036-6.
    1. Leemans A, Jones D. The B-matrix must be rotated when correcting for subject motion in DTI data. Magn Reson Med. 2009;61(6):1336–49. doi: 10.1002/mrm.21890.
    1. Avants B, Epstein C, Grossman M, Gee J. Symmetric diffeomorphic image registration with cross-correlation: Evaluating automated labeling of elderly and neurodegenerative brain. Med Image Anal. 2008;12:26–41. doi: 10.1016/j.media.2007.06.004.
    1. Behrens T, Berg H, Jbabdi S, Rushworth M, Woolrich M. Probabilistic diffusion tractography with multiple fibre orientations: What can we gain? Neuroimage. 2007;34(1):144–155. doi: 10.1016/j.neuroimage.2006.09.018.
    1. Alsop D, Detre J. Reduced transit-time sensitivity in noninvasive magnetic resonance imaging of human cerebral blood flow. J Cereb Blood Flow Metab. 1996;16:1236–1249. doi: 10.1097/00004647-199611000-00019.
    1. Alsop D, Casement M, de Bazelaire C, Fong T, Press D. Hippocampal hyperperfusion in Alzheimer’s disease. Neuroimage. 2008;42(4):1267–1274. doi: 10.1016/j.neuroimage.2008.06.006.
    1. Meier U, Mutze S. Does the ventricle change size after shunt operation of normal pressure hydrocephalus? Acta Neurochir. 2005;95:257–259. doi: 10.1007/3-211-32318-X_52.
    1. Lenfeldt N, Hansson W, Larsson A, Birgander R, Eklund A, Malm J. Three-day CSF drainage barely reduces ventricular size in normal pressure hydrocephalus. Neurology. 2012;79(3):237–242. doi: 10.1212/WNL.0b013e31825fdf8a.
    1. Singer O, Melber J, Hattingen E, Jurcoane A, Keil F, Neumann-Haefelin T, et al. MR volumetric changes after diagnostic CSF removal in NPH. J Neurol. 2012;259(11):2440–2446. doi: 10.1007/s00415-012-6525-3.
    1. Bateman G, Siddique S. Cerebrospinal fluid absorption block at the vertex in chronic hydrocephalus: obstructed arachnoid granulations or elevated venous pressure? Fluids Barriers CNS. 2014;11:11. doi: 10.1186/2045-8118-11-11.
    1. Reiss-Zimmermann M, Scheel M, Dengl M, Preuß M, Fritzsch D, Hoffmann KT. The influence of lumbar spinal drainage on diffusion parameters in patients with suspected normal pressure hydrocephalus using 3 T MRI. Acta Radiol. 2013;55(5):622–630. doi: 10.1177/0284185113502334.
    1. Pena A, Bolton M, Whitehouse H, Pickard JD. Effects of brain ventricular shape on periventricular biomechanics: a finite-element analysis. Neurosurgery. 1999;45:107–116. doi: 10.1097/00006123-199907000-00026.
    1. Ziegelitz D, Starck G, Kristiansen D, Jakobsson M, Hultenmo M, Mikkelsen IK, et al. Cerebral perfusion measured by dynamic susceptibility contrast MRI is reduced in patients with idiopathic normal pressure hydrocephalus. J Magn Reson Imaging. 2014;39:1533–1542. doi: 10.1002/jmri.24292.
    1. Klinge P, Brooks D, Samii A, Weckesser E, van den Hoff J, Fricke H, et al. Correlates of local cerebral blood flow (CBF) in normal pressure hydrocephalus patients before and after shunting—a retrospective analysis of [(15)O]H(2)O PET-CBF studies in 65 patients. Clin Neurol Neurosurg. 2008;110:369–375. doi: 10.1016/j.clineuro.2007.12.019.
    1. Alsop D, Detre J, Golay X, Günther M, Hendrikse J, Hernandez-Garcia L, et al. Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: a consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia. Magn Reson Med. (in press 2014), doi:10.1002/mrm.25197.
    1. Liu Y, Zhu X, Feinberg D, Guenther M, Gregori J, Weiner MW, et al. Arterial spin labeling MRI study of age and gender effects on brain perfusion hemodynamics. Magn Reson Med. 2012;68(3):912–922. doi: 10.1002/mrm.23286.
    1. Hashimoto M, Ishikawa M, Mori E, Kuwana N. Study of INPH on neurological improvement (SINPHONI) Diagnosis of idiopathic normal pressure hydrocephalus is supported by MRI-based scheme: a prospective cohort study. Cerebrospinal Fluid Res. 2010;7:18. doi: 10.1186/1743-8454-7-S1-S18.
    1. Jovicich J, Marizzoni M, Sala-Llonch R, Bosch B, Bartrés-Faz D, Arnold J, et al. Brain morphometry reproducibility in multi-center 3 T MRI studies: a comparison of cross-sectional and longitudinal segmentations. Neuroimage. 2013;83:472–84. doi: 10.1016/j.neuroimage.2013.05.007.
    1. Rosen W, Mohs R, Davis K. A new rating scale for Alzheimer’s disease. Am J Psychiat. 1984;141:1356–64. doi: 10.1176/ajp.141.11.1356.
    1. Song X, Mitnitski A, Zhang N, Chen W, Rockwood K, for the Alzheimer’s Disease Neuroimaging Initiative Dynamics of brain structure and cognitive function in the Alzheimer’s disease neuroimaging initiative. J Neurol Neurosurg Psychiat. 2013;84(1):71–8. doi: 10.1136/jnnp-2012-303579.
    1. Tullberg M, Hellstrom P, Piechnik SK, Starmark JE, Wikkelso C. Impaired wakefulness is associated with reduced anterior cingulate CBF in patients with normal pressure hydrocephalus. Acta Neurol Scand. 2004;110:322–330. doi: 10.1111/j.1600-0404.2004.00325.x.
    1. Virhammar J, Laurell K, Ahlgren A, Cesarini K, Larsson E. Idiopathic normal pressure hydrocephalus: cerebral perfusion measured with pCASL before and repeatedly after CSF removal. J Cereb Blood Flow Metab. 2014 Aug 20. doi: 10.1038/jcbfm.2014.138 [Epub ahead of print]
    1. Alzheimer’s Disease Neuroimaging Initiative. []. Retrieved 2014-8-19.
    1. Espay A, Narayan R, Duker A, Barrett E, Jr, de Courten-Myers G. Lower-body parkinsonism: reconsidering the threshold for external lumbar drainage. Nat Clin Pract Neurol. 2008;4:50–55. doi: 10.1038/ncpneuro0688.

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