Pyridoxine‐dependent epilepsy: An under‐recognised cause of intractable seizures

Abstract

Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder causing intractable seizures in neonates and infants. PDE patients are typically resistant to anti-epileptic treatment but respond to the administration of pyridoxine. Different seizure types have been reported in PDE, and episodes of status epilepticus are common. Electroencephalographic or neuroimaging abnormalities are not pathognomonic for this disorder. Intellectual disability is frequent at the follow-up. Recently, elevated urinary α-aminoadipic semialdehyde has been shown to be a reliable biomarker of this disorder, and mutations in the ALDH7A1 gene, encoding α-aminoadipic semialdehyde dehydrogenase, have been demonstrated in the large majority of PDE patients. However, early consideration of a pyridoxine trial remains the most important issue in a neonate or in an infant with intractable early onset seizures.

Levetiracetam in neonatal seizures as first-line treatment: A prospective study

“…In regards, several studies have suggested a neuroprotective effect of LEV in both epileptic and nonepileptic disorders. [161718192021] LEV has been demonstrated to increase the expression of gamma glutamate transporters (GLTs) excitatory amino acid transporter 1/glutamate–aspartate transporter (EAAT1/GLAST) and EAAT2/GLT1, which mechanism has been proposed one of the most important effects of LEV in neuroprotection. [1516] This hypothesis fits well with those changes described in brains after traumatic insults, consisting in increased concentration of glutamate in the extracellular areas, with secondary enhanced activation of N-methyl-D-aspartate receptors and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors on neurons and culminating in neurodegeneration.…”

“…[1516] This hypothesis fits well with those changes described in brains after traumatic insults, consisting in increased concentration of glutamate in the extracellular areas, with secondary enhanced activation of N-methyl-D-aspartate receptors and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors on neurons and culminating in neurodegeneration. [161718192021] In this context, LEV has also been demonstrated to decrease the expression of pro-oxidant protein-inducible nitric oxide synthase and increase the expression of the antioxidant protein cysteine/glutamate exchanger in the hippocampus,[20] diminishing those damages caused by seizure-induced oxidative stress. [22]…”

The patient with infantile seizures

“…Often times, neurologists will administer pyridoxal-5 0 -phosphate to intractably seizing neonates if they fail the pyridoxine challenge so as to not miss this rare disorder. The best diagnostic test, however, is measuring pyridoxal-5 0 -phosphate in the CSF [9].…”

Status Epilepticus and Refractory Status Epilepticus Management

“…For patients who have responded to therapy testing can be performed for mutations in known genes. 117 Other vitamin response epilepsies will typically present during infancy, but late onset PNPO deficiency responding only to PLP as well as late onset biotinidase deficiency responding to biotin have both been described. 118,119 Thus, a trial of PLP or biotin could be considered in refractory SE.…”