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. 2019 Aug 23;14(8):e0221626.
doi: 10.1371/journal.pone.0221626. eCollection 2019.

Cerebral metabolite alterations in patients with posttransplant encephalopathy after liver transplantation

Henning Pflugrad  1   2 , Anita Blanka Tryc  1   2 , Annemarie Goldbecker  1   2 , Hannelore Barg-Hock  3 , Christian Strassburg  4 , Jürgen Klempnauer  2   3 , Heinrich Lanfermann  5 , Karin Weissenborn  1   2 , Peter Raab  5
Affiliations

Cerebral metabolite alterations in patients with posttransplant encephalopathy after liver transplantation

Henning Pflugrad et al. PLoS One. .

Abstract

Background: In the first weeks after liver transplantation about 30% of the patients develop a posttransplant encephalopathy. A posttransplant encephalopathy comprises metabolic-toxic caused symptoms such as disorientation, confusion, hallucinations, cognitive dysfunction and seizures. We hypothesize that alterations of cerebral metabolites before liver transplantation predispose posttransplant encephalopathy development after liver transplantation.

Methods: 31 patients with chronic liver disease underwent magnetic resonance spectroscopy (MRS) before liver transplantation to assess glutamine/glutamate (Glx), myo-Inositol (mI), choline (Cho), creatine/phosphocreatine- and N-acetyl-aspartate/N-acetyl-aspartate-glutamate concentrations in the thalamus, lentiform nucleus and white matter. Of these, 14 patients underwent MRS additionally after liver transplantation. Furthermore, 15 patients received MRS only after liver transplantation. Patients' data were compared to 20 healthy age adjusted controls.

Results: Patients showed significantly increased Glx and decreased mI and Cho concentrations compared to controls before liver transplantation (p≤0.01). The MRS values before liver transplantation of patients with posttransplant encephalopathy showed no significant difference compared to patients without posttransplant encephalopathy. Patients after liver transplantation showed increased Glx concentrations (p≤0.01) compared to controls, however, patients with and without posttransplant encephalopathy did not differ. Patients with posttransplant encephalopathy who underwent MRS before and after liver transplantation showed a significant mI increase in all three brain regions (p<0.04) and Glx decrease in the lentiform nucleus after liver transplantation (p = 0.04) while patients without posttransplant encephalopathy only showed a mI increase in the thalamus (p = 0.04).

Conclusion: Patients with and without posttransplant encephalopathy showed no significant difference in cerebral metabolites before liver transplantation. However, the paired sub-analysis indicates that the extent of cerebral metabolite alterations in patients with liver cirrhosis might be critical for the development of posttransplant encephalopathy after liver transplantation.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow chart.
This flow chart displays the application of the exclusion criteria. MRI, magnetic resonance imaging; OLT, liver transplantation; n, number.
Fig 2
Fig 2. Voxel positions.
Illustration of the positions of the 2D-CSI-Grid, indicating the voxel position within the putamen (solid white box) and the thalamus (dashed white box). Triplanar illustration of the position of the single voxel spectroscopy within the parietal white matter, avoiding cerebrospinal fluid.
Fig 3
Fig 3. Example of metabolite spectrums of a patient.
Example of the LCModel-analysis of a thalamic 2D-CSI voxel acquired with TE 30ms (TE = time of echo) in a patient. The grey line following the peaks represents the fit by the program, the thin line below the spectrum indicates the baseline calculated by the LCModel program. Ins = inositol peak, Cho = choline peak, Cr = creatine/phosphocreatine peak, Glx = glutamate/glutamine peaks, NAA = N-acetyl-aspartate peak.
Fig 4
Fig 4. Change of MRS values from before to after OLT in patients with PTE.
This figure illustrates the significant changes of cerebral metabolite concentrations from before to after OLT in the 7 patients that developed a PTE. * p<0.05; Th, Thalamus; Ln, Lentiform nucleus; pWM, parietal white matter; mI, myo-Inositol; Glx, glutamine/glutamate; OLT, liver transplantation; U, arbitrary unit.
Fig 5
Fig 5. Change of MRS values from before to after OLT in patients without PTE.
This figure illustrates the changes of cerebral metabolite concentrations from before to after OLT in the 7 patients without PTE. * p<0.05; Th, Thalamus; Ln, Lentiform nucleus; pWM, parietal white matter; mI, myo-Inositol; Glx, glutamine/glutamate; OLT, liver transplantation; U, arbitrary unit.
See this image and copyright information in PMC

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