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Metab Brain Dis. 2011 Sep;26(3):203-12. doi: 10.1007/s11011-011-9251-0. Epub 2011 Jul 20.

Absence of neuropsychological impairment in hyperammonaemia in healthy young adults; possible synergism in development of hepatic encephalopathy (HE) symptoms?

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  • 1Department of Sport and Exercise Science, Chelsea School, University of Brighton, 30 Carlisle Road, Eastbourne BN20 7SN, UK.


The aetiology of minimal hepatic encephalopathy (mHE) remains unclear. It is generally accepted that hyperammonaemia plays a major role, however there are a multitude of metabolic perturbations present. To determine the contribution of hyperammonaemia to mHE symptom development, ten healthy males (Age:25 ± 5 yrs, BM:76.3 ± 7.1 kg, Height:178.6 ± 4.5 cm, mean ± SD) received two 4 h intravenous infusions of either a 2% ammonium chloride solution (AMM) or a placebo (PLA;0.9% sodium chloride) using a double blind cross-over design. Sensations of fatigue were measured at baseline, 2 and 4 h using the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) questionnaire. Learning & memory, motor control and cognition were assessed using Rey's Auditory Verbal Learning Test (AVL), Continuous Compensatory Tracking (COMPTRACK) Task and Inhibitory Control Test (ICT) respectively. Arterialised venous blood samples were collected every hour, and analysed for ammonia concentration. There was a significantly higher plasma ammonia concentration in the AMM trial than the PLA trial at every time point during the infusion, peaking at 2 h (57 ± 4 μmol/L PLA, 225 ± 14 μmol/L AMM; p < 0.05). At 2 h there were significantly higher sensations of general fatigue (Z = -2.527, p = 0.008, 2 tailed) and physical fatigue (Z = -2.156, p = 0.027, 2 tailed), and lower sensations of vigour (Z = -2.456, p = 0.012, 2 tailed) for the AMM trial. There were no significant effects on the performance of the psychological tasks. These results demonstrate that hyperammonaemia in the absence of other complications induces significant sensations of fatigue but does not cause the typically observed performance impairment in individuals with mHE. Supporting the hypothesis for synergism between ammonia and other co-factors in mHE.

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