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Modulation of neural activation following treatment of hepatic encephalopathy

Lookup NU author(s): Dr Brian Saxby


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Objective: To measure changes in psychometric state, neural activation, brain volume (BV), and cerebral metabolite concentrations during treatment of minimal hepatic encephalopathy. Methods: As proof of principle, 22 patients with well-compensated, biopsy-proven cirrhosis of differing etiology and previous minimal hepatic encephalopathy were treated with oral L-ornithine L-aspartate for 4 weeks. Baseline and 4-week clinical review, blood chemistry, and psychometric evaluation (Psychometric Hepatic Encephalopathy Score and Cognitive Drug Research Score) were performed. Whole-brain volumetric and functional MRI was conducted using a highly simplistic visuomotor task, together with proton magnetic resonance spectroscopy of the basal ganglia. Treatment-related changes in regional BV and neural activation change (blood oxygenation level dependent) were assessed. Results: Although there was no change in clinical, biochemical state, basal ganglia magnetic resonance spectroscopy, or in regional BV, there were significant improvements in Cognitive Drug Research Score (+1.2, p = 0.003) and Psychometric Hepatic Encephalopathy Score (+1.5, p = 0.003) with treatment. This cognitive amelioration was accompanied by changes in blood oxygenation level-dependent activation in the posterior cingulate and ventral medial prefrontal cortex, 2 regions that form part of the brain's structural and metabolic core. In addition, there was evidence of greater visual cortex activation. Conclusions: These structurally interconnected regions all showed increased function after successful encephalopathy treatment. Because no regional change in BV was observed, this implies that mechanisms unrelated to astrocyte volume regulation were involved in the significant improvement in cognitive performance. Neurology (R) 2013; 80: 1041-1047

Publication metadata

Author(s): McPhail MJW, Leech R, Grover VPB, Fitzpatrick JA, Dhanjal NS, Crossey MME, Pflugrad H, Saxby BK, Wesnes K, Dresner MA, Waldman AD, Thomas HC, Taylor-Robinson SD

Publication type: Article

Publication status: Published

Journal: Neurology

Year: 2013

Volume: 80

Issue: 11

Pages: 1041-1047

Print publication date: 01/03/2013

ISSN (print): 0028-3878

ISSN (electronic): 1526-632X

Publisher: Lippincott Williams & Wilkins


DOI: 10.1212/WNL.0b013e31828726e1


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