Serum and CSF glutamine levels in valproate-related hyperammonemic encephalopathy.
OBJECTIVE
To investigate ammonia and glutamine levels in valproate (VPA)-related hyperammonemic encephalopathy (VHE).


METHODS
We reviewed the medical records and EEG recordings of seven adults diagnosed with VHE.


RESULTS
Venous ammonia levels were elevated in five (71%) of the seven patients. Elevated serum or cerebrospinal fluid (CSF) glutamine levels were found in four (80%) of five cases tested, including two who had normal ammonia levels. Initial behavioral signs included violent outbursts in three patients, paranoid ideation severe enough to require restraint in two cases, and milder abnormalities in two instances. The severity of encephalopathy was not related to any particular serum VPA level. In four patients serum VPA levels did not exceed 100 microg/ml, and in one case, VHE developed after taking only one 250-mg dose. Symptoms eventually cleared after reducing the dose of, or discontinuing, VPA. Liver-function tests were normal. Each of six patients tested had EEG findings that supported the diagnosis of VHE and excluded nonconvulsive status epilepticus. The rate of normalization of one patient's serum glutamine level and the EEGs of two cases correlated better with the timing of their delayed clinical recovery than did the more rapid rate of decline of the serum ammonia levels.


CONCLUSIONS
Serum or CSF glutamine levels are initially elevated in a majority of patients with suspected VHE, sometimes in the absence of hyperammonemia. Glutamine levels may be useful adjunctive laboratory tests for the diagnosis of VHE.
Vossler
David G
DG
Swedish Epilepsy Center, Swedish Medical Center, Department of Neurology, University of Washington, Seattle 98122, USA. david.vossler@swedish.org
Wilensky
Alan J
AJ
Cawthon
David F
DF
Kraemer
Diana L Abson
DL
Ojemann
Linda M
LM
Caylor
Lisa M
LM
Morgan
John D
JD
D000293:Adolescent; D000328:Adult; D000641:Ammonia / Q000097:blood; D000927:Anticonvulsants / Q000009:adverse effects*; D001921:Brain / Q000503:physiopathology; D001927:Brain Diseases / Q000139:chemically induced* / Q000503:physiopathology*; D004569:Electroencephalography; D005260:Female; D005973:Glutamine / Q000097:blood* / Q000134:cerebrospinal fluid*; D006801:Humans; D022124:Hyperammonemia / Q000139:chemically induced* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D014635:Valproic Acid / Q000009:adverse effects*
D000927:Anticonvulsants; D005973:Glutamine; D014635:Valproic Acid; D000641:Ammonia