PURPOSE: Pyridoxine-dependent epilepsy (PDE) is characterized by 
therapy-resistant seizures (TRS) responding to intravenous (IV) pyridoxine. PDE 
can be identified by increased urinary alpha-aminoadipic semialdehyde (α-AASA) 
concentrations and mutations in the ALDH7A1 (antiquitin) gene. Prompt 
recognition of PDE is important for treatment and prognosis of seizures. We 
aimed to determine whether immediate electroencephalography (EEG) alterations by 
pyridoxine-IV can identify PDE in neonates with TRS.
METHODS: In 10 neonates with TRS, we compared online EEG alterations by 
pyridoxine-IV between PDE (n = 6) and non-PDE (n = 4). EEG segments were 
visually and digitally analyzed for average background amplitude and total power 
and relative power (background activity magnitude per frequency band and 
contribution of the frequency band to the spectrum).
RESULTS: In 3 of 10 neonates with TRS (2 of 6 PDE and 1 of 4 non-PDE neonates), 
pyridoxine-IV caused flattening of the EEG amplitude and attenuation of 
epileptic activity. Quantitative EEG alterations by pyridoxine-IV consisted of 
(1) decreased central amplitude, p < 0.05 [PDE: median -30% (range -78% to -3%); 
non-PDE: -20% (range -45% to -12%)]; (2) unaltered relative power; (3) decreased 
total power, p < 0.05 [PDE: -31% (-77% to -1%); -27% (-73% to -13%); -35% (-56% 
to -8%) and non-PDE: -16% (-43% to -5%); -28% (-29% to -17%); -26% (-54% to 
-8%), in delta-, theta- and beta-frequency bands, respectively]; and (4) similar 
EEG responses in PDE and non-PDE.
DISCUSSION: In neonates with TRS, pyridoxine-IV induces nonspecific EEG 
responses that neither identify nor exclude PDE. These data suggest that 
neonates with TRS should receive pyridoxine until PDE is fully excluded by 
metabolic and/or DNA analysis.