The EEG response to pyridoxine-IV neither identifies nor excludes pyridoxine-dependent epilepsy.
OBJECTIVE
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.


CONCLUSIONS
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.
Bok
Levinus A
LA
Department of Pediatrics, Máxima Medical Center, Veldhoven, The Netherlands.
Maurits
Natasha M
NM
Willemsen
Michèl A
MA
Jakobs
Cornelis
C
Teune
Laura K
LK
Poll-The
Bwee Tien
BT
de Coo
Irenaeus F
IF
Toet
Mona C
MC
Hagebeuk
Eveline E
EE
Brouwer
Oebele F
OF
van der Hoeven
Johannes H
JH
Sival
Deborah A
DA
D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D003937:Diagnosis, Differential; D004569:Electroencephalography / Q000187:drug effects* / Q000706:statistics & numerical data; D004827:Epilepsy / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051938:Munc18 Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D011736:Pyridoxine / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D013036:Spasms, Infantile / Q000175:diagnosis / Q000235:genetics
D051938:Munc18 Proteins; C497937:STXBP1 protein, human; C089507:ALDH7A1 protein, human; D000444:Aldehyde Dehydrogenase; D011736:Pyridoxine