PROTON MAGNETIC-RESONANCE SPECTROSCOPY STUDIES ON HUMAN BRAIN MYO-INOSITOL IN HYPO-OSMOLARITY AND HEPATIC-ENCEPHALOPATHY

Background/Aims: Recent in vivo studies using proton magnetic resonance (H-1-MR) spectroscopy showed low levels of myo-inositol in the brain in hepatic encephalopathy; the pathogenetic relevance of this observation is unclear. Methods: Myo-inositol and glutamine levels in the brain were studied in vivo by H-1-MR spectroscopy in patients with hypo-osmolarity and hepatic encephalopathy. Results: A patient with severe plasma hypoosmolarity (222 mOsm/L) had almost undetectable signals for myo-inositol and glutamine/glutamate in the brain. Both signals reappeared after normalization of plasma osmolarity, suggesting that both myo-inositol and glutamine were released as organic osmolytes from the brain. A decreased cerebral myo-inositol signal is also found in low-grade hepatic encephalopathy but is accompanied by an increased glutamine signal. Cirrhotics without hepatic encephalopathy have near-normal inositol signals, and patients with acquired immunodeficiency syndrome encephalopathy have increased inositol signals. Conclusions: The H-1-MR spectroscopic myo-inositol signal in the human brain predominantly reflects an osmosensitive inositol pool. It is hypothesized that its depletion in latent hepatic encephalopathy points to a disturbance of cell volume homeostasis in the brain as an early pathogenetic event. This may partly be caused by a hyperammonemia-induced glutamine accumulation in the brain.