Abstract

Cerebral edema, a well-known feature of acute liver disease, can occur in cirrhotic patients regardless of hepatic encephalopathy (HE) and adversely affect prognosis. This study characterized and correlated functional HE abnormalities in the brain to cerebral edema using resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI). Forty-one cirrhotic patients (16 without HE, 14 minimal HE, 11 overt HE) and 32 healthy controls were assessed. The HE grade in cirrhotic patients was evaluated by the West Haven criteria and neuro-psychological examinations. Functional connectivity correlation coefficient (fc-CC) of the default mode network (DMN) was determined by rs-fMRI, while the corresponding mean diffusivity (MD) was obtained from DTI. Correlations among inter-cortical fc-CC, DTI indices, Cognitive Ability Screening Instrument scores, and laboratory tests were also analyzed. Results showed that gradual reductions of HE-related consciousness levels, from “without HE” or “minimal HE” to “overt HE”, correlated with decreased anterior-posterior fc-CC in DMN [F(4.415), p = 0.000)]. The MD values from regions with anterior-posterior fc-CC differences in DMN revealed significant differences between the overt HE group and other groups. Increased MD in this network was inversely associated with decreased fc-CC in DMN and linearly correlated with poor cognitive performance. In conclusion, cerebral edema can be linked to altered cerebral temporal architecture that modifies both within- and between-network connectivity in HE. Reduced fc-CC in DMN is associated with behavior and consciousness deterioration. Through appropriate targets, rs-fMRI technology may provide relevant supplemental information for monitoring HE and serve as a new biomarker for clinical diagnosis.

Highlights

  • Cerebral edema is a well-known feature of acute liver disease that can occur in cirrhotic patients regardless of hepatic encephalopathy (HE) and adversely affect prognosis [1]

  • In the posterior cingulate cortex (PCC) map, decreased function connectivity (fc-CC) in the left precuneus and right anterior cingulate cortex. doi (ACC) was associated with increased HE severity

  • In the mHE groups, PCC exhibited decreased connectivity with the right ACC compared to the normal groups

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Summary

Introduction

Cerebral edema is a well-known feature of acute liver disease that can occur in cirrhotic patients regardless of hepatic encephalopathy (HE) and adversely affect prognosis [1]. Given the very limited therapeutic efficacy in the overt stage of cerebral edema, awareness of early signs is critical for timely intervention in cirrhotic patients [2]. Diffusion-weighted images can shed light in HE diagnosis by showing that brain water content (mean diffusivity value) increases significantly, progressively affecting more regions as the HE grade increases [3]. Ammonia can contribute to chronic low-grade glial edema [4] and alter the glutamate-glutamine metabolism during detoxification. Ammonia can further potentiate the effects of neuro-inhibitors on the central nervous system [6,7].

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