title: Induced hyperammonemia alters neuropsychology, brain MR spectroscopy and magnetization transfer in cirrhosis.
abstract: Hyperammonemia is a universal finding after gastrointestinal hemorrhage in cirrhosis. We administered an oral amino acid solution mimicking the hemoglobin molecule to examine neuropsychological changes, brain glutamine levels, and brain magnetization transfer ratio (MTR). Forty-eight metabolically stable patients with cirrhosis and no evidence of "overt" hepatic encephalopathy (HE) were randomized to receive 75 g of amino acid solution or placebo; measurements were performed before and 4 hours after administration. Neuropsychological tests included the Trails B Test, Digit Symbol Substitution Test, memory subtest of the Randt battery, and reaction time. Plasma was collected for ammonia and amino acid measurements, and brain metabolism was studied using proton magnetic resonance (MR) spectroscopy in the first 16 randomized patients. In 7 other patients, MTR was measured. A significant increase in ammonia levels was observed in the amino acid group (amino acid group, 76 +/- 7.3 to 121 +/- 6.4 micromol/L; placebo, 83 +/- 3.3 to 78 +/- 2.9 micromol/L; P <.001). Neuropsychological function improved significantly in the placebo group, but no significant change in neuropsychological function was observed in the amino acid group. Brain glutamate/glutamine (Glx)/creatine (Cr) ratio increased significantly in the amino acid group. MTR decreased significantly from 30 +/-2.9 to 23 +/- 4 (P <.01) after administration of the amino acid solution. In conclusion, an improvement in neuropsychological test results followed placebo, which was not observed in patients administered the amino acid solution. Induced hyperammonemia resulted in an increase in brain Glx/Cr ratio and a decrease in MTR, which may indicate an increase in brain water as the operative mechanism.
authors.affiliation: Liver Unit, Royal Infirmary of Edinburgh, Edinburgh, Scotland.
authors.forename: Sherzad
authors.initials: S
authors.lastname: Balata
authors.forename: Steven W M
authors.initials: SW
authors.lastname: Olde Damink
authors.forename: Karen
authors.initials: K
authors.lastname: Ferguson
authors.forename: Ian
authors.initials: I
authors.lastname: Marshall
authors.forename: Peter C
authors.initials: PC
authors.lastname: Hayes
authors.forename: Nicolaas E p
authors.initials: NE
authors.lastname: Deutz
authors.forename: Roger
authors.initials: R
authors.lastname: Williams
authors.forename: Joanna
authors.initials: J
authors.lastname: Wardlaw
authors.forename: Rajiv
authors.initials: R
authors.lastname: Jalan
mesh_terms: D000596:Amino Acids / Q000097:blood; D000641:Ammonia / Q000097:blood; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D005260:Female; D005973:Glutamine / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry; D006801:Humans; D022124:Hyperammonemia / Q000139:chemically induced / Q000175:diagnosis* / Q000523:psychology*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011522:Protons; D012996:Solutions
chemical_list: D000596:Amino Acids; D006454:Hemoglobins; D011522:Protons; D012996:Solutions; D005973:Glutamine; D000641:Ammonia