Toxic levels of ammonia in human brain abscess.
OBJECTIVE
Brain abscesses could lead to cerebral symptoms through tissue destruction, edema, changes in brain architecture, and increased intracranial pressure. However, the possibility that the pus itself could contribute to symptoms has received little attention. Brain abscesses are areas of tissue destruction, proteolysis, and formation of free amino acids, which are energy substrates for bacteria and possible sources of ammonia. Ammonia is neurotoxic, may cause brain edema, and could contribute to the symptoms of brain abscesses.


METHODS
The authors analyzed the extracellular phase of pus from 14 patients with brain abscesses with respect to ammonia and amino acids. For comparison, CSF from 10 patients undergoing external ventricular drainage was included. The ammonia-forming ability of Streptococcus intermedius and Staphylococcus aureus, two common microbial isolates in brain abscesses, was studied in vitro.


RESULTS
In brain abscesses ammonia was 15.5 mmol/L (median value; range 1.7-69.2 mmol/L). In CSF ammonia was 29 μmol/L (range 17-55 μmol/L; difference from value in pus: p < 0.001). The total concentration of amino acids in brain abscesses was 1.12-16 times higher than the ammonia concentration (p = 0.011). The median glucose value in pus was 0 mmol/L (range 0-2.1 mmol/L), lactate was 21 mmol/L (range 3.3-26.5 mmol/L), and pH was 6.8 (range 6.2-7.3). In vitro, S. intermedius and S. aureus formed ammonia at 6-7 mmol/L in 24 hours when incubated with 20 proteinogenic amino acids plus g-aminobutyric acid (GABA), taurine, and glutathione at 1 mmol/L.


CONCLUSIONS
Intracerebral abscesses contain toxic levels of ammonia. At the concentrations found in pus, ammonia could contribute to the brain edema and the symptoms of brain abscesses.
Departments of 1 Neurosurgery and.
Daniel
D
Dahlberg
Departments of 1 Neurosurgery and.
Jugoslav
J
Ivanovic
Complex Neurology and Neurohabilitation, Oslo University Hospital, Oslo; and.|Norwegian Defence Research Establishment (FFI), Kjeller, Norway.
Bjørnar
B
Hassel
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism*; D001922:Brain Abscess / Q000175:diagnosis / Q000378:metabolism* / Q000382:microbiology*; D001929:Brain Edema / Q000209:etiology* / Q000378:metabolism; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013211:Staphylococcus aureus; D034367:Streptococcus intermedius; D055815:Young Adult
D000596:Amino Acids; D000641:Ammonia
GABA = g-aminobutyric acid; GSH = glutathione, reduced form; HPLC = high-performance liquid chromatography; OD600 = optical density at 600 nm; amino acids; ammonia; brain abscess; cerebrospinal fluid; infection; lactate