Low concentrations of cerebrospinal fluid GABA correlate to a reduced response to phenobarbital therapy in primary canine epilepsy

In this study, we investigated whether pretreatment cerebrospinal fluid (CS F) neurotransmitter concentrations of gamma-aminobutyric acid (GABA) and gl utamate (GLU) were correlated with response to phenobarbital treatment in d ogs with primary epilepsy. Eleven untreated dogs, 6 males and 5 females, wi th a median age of onset of seizures of 3 years (range: 0.5-5 pears) were s elected for therapy based on progressive or serious seizure patterns. The m edian interval between the first observed seizure and start of phenobarbita l therapy was 485 days (range: 101-1,765 days), All dogs were purebred, wit h the exception of 1 male dog. Oral phenobarbital was started at 2.5 mg/kg every 12 hours. Trough serum phenobarbital concentrations were measured at 15, 45, 90, 180, 360, 540, and 720 days after the start of treatment. There was no difference in the mean trough serum concentration or in the mean nu mber of seizures recorded between each time period of phenobarbital measure ment over the 2-year evaluation. No correlation was found between CSF GLU, GABA, or GLU:GABA ratio and the total number of seizures recorded before or after initiation of phenobarbital therapy. Lower CSF GABA concentration, h owever, was correlated with a lower seizure frequency difference (the total number of seizures before phenobarbital therapy minus the total number of seizures after phenobarbital therapy for an identical lime period of evalua tion) and lower percentage reduction in seizures: ([total number of seizure s before phenobarbital therapy minus the total number of seizures after phe nobarbital therapy] divided by the total number of seizures before phenobar bital therapy) x 100. There was no correlation between CSF GLU and the seiz ure frequency difference and percentage reduction in seizures. A negative c orrelation between the CSF GLU:GABA ratio and seizure frequency difference was found. Thus, dogs with an initial lower CSF GABA concentration before p henobarbital therapy did not respond as well as did dogs with a higher CSF GABA concentration.