Combined Diffusion Tensor Imaging and Magnetic Resonance Spectroscopy to Predict Neurological Outcome Before Transjugular Intrahepatic Portosystemic Shunt

Marika Rudler; Nicolas Weiss; Vincent Perlbarg; Maxime Mallet; Simona Tripon; Romain Valabregue; Małgorzata Marjańska; Philippe Cluzel; Damien Galanaud; Dominique Thabut

Disclosures

Aliment Pharmacol Ther. 2018;48(8):863-874. 

In This Article

Abstract and Introduction

Abstract

Background: Hepatic encephalopathy (HE) may occur after transjugular intrahepatic portosystemic shunt (TIPSS) placement. Multimodal magnetic resonance imaging (MRI), combining anatomical sequences, diffusion tensor imaging (DTI) and[1]H magnetic resonance spectroscopy, is modified in cirrhotic patients.

Aims: To describe multimodal MRI images before TIPSS, to assess if TIPSS induces changes in multimodal MRI, and to find predictors of HE after TIPSS in patients with cirrhosis.

Methods: Consecutive cirrhotic patients with an indication for TIPSS were prospectively screened. Diagnosis of minimal HE was performed using psychometric HE test score. Multimodal MRI was performed before and 3 months after TIPSS placement.

Results: Twenty–five consecutive patients were analysed (median age = 59, male gender 76%, median Child–Pugh score = 8,[5–8] MELD score = 12,[9–17] indication for TIPSS placement: ascites/secondary prophylaxis of variceal bleeding/other 20/3/2), no HE/minimal HE/overt HE: 21/4/0. 8/25 patients developed HE after TIPSS. Before TIPSS placement, metabolite concentrations were different in patients with or without minimal HE (lower myo–inositol, mI, higher glutamate/glutamine), but there were no differences in DTI data. TIPSS placement induced changes in metabolite concentrations even in asymptomatic patients, but not in DTI metrics. Baseline fractional anisotropy was significantly lower in patients who developed HE after TIPSS in five regions of interest.

Conclusions: TIPSS placement induced significant changes in cerebral metabolites, even in asymptomatic patients. Patients who developed HE after TIPSS displayed lower fractional anisotropy before TIPSS. Brain MRI with DTI acquisition may help selecting patients at risk of HE.

Introduction

Prevalence of overt hepatic encephalopathy (OHE) after TIPSS varies among series, reaching up to 50% in older studies where bare TIPSS were placed.[1] With the almost exclusive use of covered stents, this prevalence has decreased but still ranges between 20% and 30% at 1 year, in both controlled[2–7] and observational studies.[8,9] A meta–analysis showed that this prevalence was higher after TIPSS than in control group, that is, patients who did not undergo TIPSS placement.[9] Nevertheless, solid data are lacking on predictive factors of HE after TIPSS placement. Model for end–stage liver disease (MELD) score, low mean arterial pressure, age and post–TIPSS portosystemic pressure gradient (the latest being here of no use for predicting HE before TIPSS placement) are associated with higher risk of HE occurrence after bare TIPSS placement.[10] For covered TIPSS, there is only one study available,[5] and the same variables were pointed out, as well as sodium levels before TIPSS placement. This issue is even more complex when considering the prevalence of minimal hepatic encephalopathy (MHE) after TIPSS. MHE is a worrisome complication, which impairs largely the quality of life of patients, their productivity and the societal costs,[11–13] as well as prognosis.[14] There is no gold standard for the diagnosis of MHE, usually detected with using cumbersome neuropsychological tests or critical flicker frequency (CFF). Therefore, MHE is frequently under diagnosed in cirrhotic patients. Hence, the proportion of patients developing MHE after TIPSS is unknown and, more importantly, MHE is generally not sought for before TIPSS placement. In an elegant study, values of CFF before TIPSS placement were associated with a more frequent occurrence of OHE after TIPSS,[3] suggesting that MHE before TIPSS favours the occurrence of OHE after the procedure. Overall, predictive factors of post–TIPSS HE are warranted to perform a better selection of patients, with the aim to balance indication of TIPSS over liver transplantation for instance, or to start a prophylaxis of HE before TIPSS. The solid data are lacking regarding the development of MHE after TIPSS.

Cerebral magnetic resonance imaging (MRI) is the imaging method of reference in neurology. Multimodal MRI strategies, combining 1H–magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI), have been shown to be able to dissect pathophysiological background in different neurological diseases.[15–18] For example, DTI is a major parameter considered to assess prognosis of patients after cardiac arrest or traumatic brain injury.[16–18] This technique is able to distinguish cytotoxic oedema from interstitial brain oedema, and to determinate the microstructural integrity of the brain white matter. Several studies using MRS have been published in the setting of OHE.[19–21] They all reported characteristic spectra for HE, that is, a higher level of glutamate (GLu)/glutamine (GLn), and a lower level of myo–inositol (mI) and total choline (tCho). Outside MRS, data on multimodal MRI in HE are scarce and heterogeneous.

To date, only one pilot study has been performed on cerebral multimodal MRI in patients undergoing TIPSS placement.[22] Data were available in 10 patients who underwent MRI within 1 month after TIPSS placement. The authors found an increase in GLu/GLn and a decrease in mI after TIPSS. However, they could not identify any factor associated with further development of OHE or MHE after TIPSS. No data on DTI were described, when this sequence, used largely in prognostication of diffuse brain suffering, could be of major interest to predict HE after TIPSS.

We hypothesise that some patients, even asymptomatic, are prone to develop HE after TIPSS placement, and that cerebral multimodal MRI could be helpful in identifying these patients. Moreover, we suggest that cerebral multimodal MRI parameters could be modified after TIPSS placement. Hence, the aims of this prospective monocentric study were: (a) to describe anatomical and multimodal MRI images, that is, MR spectroscopy and DTI, in patients before TIPSS, according to the presence of MHE or not; (b) to assess if TIPSS by itself induces changes in anatomical and multimodal MRI; (c) to evaluate if some cerebral multimodal MRI parameters before TIPSS placement were associated with a higher occurrence of HE after TIPSS.

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