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DTI-MRI biomarkers in the search for normal pressure hydrocephalus aetiology: a review

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Abstract

Normal pressure hydrocephalus (NPH) is a clinical syndrome characterized by gait disturbances, urinary incontinence and dementia. Clinical presentation overlaps with Alzheimer disease (AD). Early recognition thus early intervention (shunting) is important for successful treatment, but lack of a diagnostic test with sufficient sensitivity and specificity complicates the diagnosis. We performed literature search and composed a structured review of imaging biomarkers of NPH. Morphometric studies are not sufficient to diagnose NPH. Hydrocephalus is a common finding in elderly people due to the symmetric brain atrophy and is even more pronounced in patients with AD. The key MRI biomarker seems to be diffusion tensor imaging (DTI). According to recent studies, the DTI analysis of the splenium corporis callosi, posterior limb of internal capsule, hippocampus and fornix combined with measurement of Evans index is a promising MRI biomarker of NPH and could be used for NPH diagnostics and in the differential diagnosis from AD and other dementias.

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Author information

Authors and Affiliations

  1. Department of Neurosurgery, Hospital Dessau, Auenweg 38, 06847, Dessau-Roßlau, Germany

    David Hoza

  2. Department of Neurosurgery, University Hospital Motol, V Úvalu 84, 150 06, Prague, Czech Republic

    Aleš Vlasák

  3. Department of Neurosurgery, Hospital Ústí nad Labem, Sociální péče 3316/12A, 401 13, Ústí nad Labem, Czech Republic

    Daniel Hořínek & Martin Sameš

  4. Department of Neurosurgery, Ruppiner Kliniken GmbH, Fehrbelliner Straße 38, 16816, Neuruppin, Germany

    Alex Alfieri

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  1. David Hoza
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Correspondence to David Hoza.

Additional information

Comments

Petra M Klinge, Providence, USA

Hozda et al. promote an important topic: non-invasive assessment of idiopathic normal pressure hydrocephalus (iNPH) using the potential of MRI biomarkers. The authors focussed on the pertinent literature of DTI-MRI findings in iNPH and suggest a clinically relevant “iNPH pattern” in vulnerable areas of the brain that allows to distinguish iNPH from other forms of dementia and to select best candidates for shunting. This is not a novel idea but the jury is still out there. Only limited studies are available; however, it should be acknowledged that Ivkovic M and Relkin N at Weill Cornell Medical College, NY, collected 3 T DTI data from 15 patients with probable iNPH and 25 controls and compared those to AD, PD or dementia with Lewy bodies. They developed a parametric model for the shape of intracranial mean diffusivity (MD) histograms that separates brain and ventricular components from a third component composed mostly of partial volume voxels. Using parameters for the MD histogram shape, they distinguished clinically probable NPH from the three other disorders with 86 % sensitivity and 96 % specificity. The technique yielded 86 % sensitivity and 88 % specificity when differentiating NPH from AD only (1).

Hozda et al. point out that conventional routine MRI studies, such as MRI volumetric studies of CSF spaces and brain volume and MRI flow studies, have not shown sufficient accuracy to support the diagnosis of iNPH and/or select ideal candidates for shunting. There are more promising contemporary studies that consider total cortical thickness (a correlate of cerebral atrophy). It was shown that mean ventricular volume was significantly greater in the NPH group and that individuals with NPH could be better distinguished from AD, PD and healthy controls when ventricular volume and total cortical thickness were considered in combination. This pilot study suggests that volumetric MRI measurements hold promise for improving NPH differential diagnosis (2).

It can be agreed with the authors that invasive tests, i.e. ICP measurement and spinal fluid drainage, are outlived and lack sufficient predictive accuracy and clinical relevance in the assessment of iNPH. This was supported by the prospective European multicentre study on the predictive value of the high-volume tap test. CSF drainage protocols are subject to short-term placebo effects, investigator biases and the lack of standard operating procedure criteria.

The merit of the paper proposed by Hozda et al. is the meticulous extraction of the different FA and MD patterns reported in the periventricular white matter, fornix, corpus callosum and hippocampus that show contrary trends in iNPH vs. AD. The table summarizes those findings. The authors conclude that MRI is a sensitive biomarker and recommend using DTI evaluation to be used routinely as a non-invasive test.

One still has to be very cautious about promoting MRI-DTI as a biomarker as routine measure or test in the assessment of iNPH over the traditional tests. As it stands now, there are clusters and pattern that suggest that DTI-MRI in the respective areas might differentiate iNPH from other dementias. This has to undergo further robust prospective trial. A test in iNPH is still seen as a test to select candidates for shunting, and that needs to be separated from establishing the diagnosis of iNPH against other dementias. On that note, there is no evidence how to translate FA and MD in MRI-DTI into actual anatomical and physiological and metabolic changes. As such, pathophysiology of FA and MD in MRI-DTI and how this might explain the iNPH syndrome is mere speculation. It is very educational though to read the authors suggestions and interpretations, and the discussion points are well taken, but the conclusion that DTI-MRI helps understand pathophysiology of NPH cannot be supported.

The authors are to be commended for the educational review and for promoting to perform MRI-DTI in relevant areas of the brain in iNPH and AD, and therefore, this review definitely helps changing gears in the clinical assessment of iNPH and encourages further research.

(1) AJNR Am J Neuroradiol. 2013 Jun-Jul;34(6):1168-74. Differential diagnosis of normal pressure hydrocephalus by MRI mean diffusivity histogram analysis. Ivkovic M1, Liu B, Ahmed F, Moore D, Huang C, Raj A, Kovanlikaya I, Heier L, Relkin N.

(2) Neurol Res Int. 2012;2012:718150. A pilot study of quantitative MRI measurements of ventricular volume and cortical atrophy for the differential diagnosis of normal pressure hydrocephalus. Moore DW, Kovanlikaya I, Heier LA, Raj A, Huang C, Chu KW, Relkin NR.

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Hoza, D., Vlasák, A., Hořínek, D. et al. DTI-MRI biomarkers in the search for normal pressure hydrocephalus aetiology: a review. Neurosurg Rev 38, 239–244 (2015). https://doi.org/10.1007/s10143-014-0584-0

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