Pyridoxine‐dependent Seizures: Demographic, Clinical, Mri and Psychometric Features, and Effect of Dose on Intelligence Quotient

Abstract

SUMMARY A regional population‐based survey identified six patients with pyridoxine dependency. Four presented on the first day of life and the other two at 1 and 8 months of age. Apart from multiple seizure types, other presenting features included jitteriness; encephalopathy, at first thought to be hypoxic‐ischaemic; hepatomegaly, and abdominal distension with bilious vomiting. Later problems included break‐through fits with fever; transient visual agnosia; squint; severe articulatory apraxia; motor delay with later dyspraxia; macrocephaly. and post‐haemorrhagic hydrocephalus. Magnetic resonance imaging showed variable structural abnormalities in all the early onset cases. Psychometric assessment revealed a stereotyped pattern of intelligence scale subtest scores, with a specific impairment of expressive verbal ability. In a prospective open study over one year, an.‐ increased dose of pyridoxine was associated with an improvement in IQ, particularly in performance subtests. Pyridoxine dependency is more common than has been thought. It has a wider range of clinical features than the classical neonatal seizures and causes specific impairments of higher function, some of which may be reversible. The dosage of pyridoxine should be optimal for IQ as well as seizure control. RÉSUMÉ Comitialité pyridoxine‐dépendaiite Caractéristiques déinograpliiques, cliniques. IRM et psychométriques. Effet de dose sur le Ql Une étude de population régionale identifia six patients pyridoxine‐dépendants. Quatre cas se révélèrent le jour de la naissance, et les deux autres à I et 8 mois d'âge. En dehors d'une comitialité d'aspect variable, les autres caractéristiques présentes incluaicnt le sautillement permanent; une encéphalopathie rattachée initialement a une origine hypoxique‐ischémique; une hépatomégalie, et une distension abdominalc et vomisserrients biljaires. Les problèmes ultérieurs incluaienl des crises hyperthermiques soudaines; une agnosie visuelle transitoire; un strabisme; une apraxic articulatoire sévère; un retard motcur avec dyspraxic ultérieure; unc macrocéphalie, et une hydrocéphalic post‐hémorragique. L'imageric de résonance magnétique révélait des anomalies structurales variables dans tous les cas à début précoce. L'évaluation psychométrique révélait un groupement stéréotypé des scores aux subtests d'échellc d'intelligence, avec un trouble spécifique de l'aptitudc a l'expression verbale. Lors d'une etude prospective ouvertc sur un an. une dose accrue de pyridoxine se traduisit par un progrès du Ql, particulièrement dans les subtests de performance. La dépéndance à la pyridoxine est plus fréquente qu'il n'a été pense. La variété des manifestations cliniqucs déborde les classiques crises néonatales et cause des altérations spécifiques des fonctions supérieurcs, certaines étant réversibles. Le dosage de la pyridoxine doit etre maintenu optimal pour le Ql aussi bien que pour le contrôle des crises. ZUSAMMENFASSUNG Pyridoxin abháuingige Anfälle: denwgntphische, klinische. MRl bezogene ttnd psychomeirische Merkmale. Einf...

Antenatal treatment in two Dutch families with pyridoxine-dependent seizures

“…Not only is PDS characterised by seizures but also by encephalopathic symptoms such as agitation, jitteriness, irritability, startle reactions and feeding problems [16]. Reports on cerebral imaging have shown cerebral haemorrhage, non-specific white matter abnormalities, hydrocephalus, hypoplasia of the posterior part of the corpus callosum, cerebellar hypoplasia and a megacisterna magna [5,15,19,33]. At older age, cortical atrophy with ventricular dilation is sometimes observed in affected patients [5,15,34].…”

‘Pyridoxine treatment in a subgroup of children with pervasive developmental disorders’

“…3,4 Interestingly, autistic behaviour and all these clinical features are also seen in children with pyridoxine-dependent epilepsy, whose seizures ceased with high doses of pyridoxine. [5][6][7] The observed similarity in these clinical features has led us to speculate that this subtype of PDDs might have a similar pathophysiological mechanism to pyridoxine-dependent epilepsy. Baxter and colleagues 6 reported that, after receiving high-dose pyridoxine, seizures ceased and intelligence quotient (IQ) scores improved among children with pyridoxine-dependent epilepsy.…”

“…It has been reported that a long-term administration of pyridoxine may induce adverse effects such as a sensory peripheral neuropathy. 11 Third, we were unsure of the optimal dosage of pyridoxine to administer in this trial, but our use of 100 mg to 200 mg pyridoxine per day has been recommended by Baxter and colleagues 6,12 for the treatment of pyridoxine-dependent epilepsy. Fourth, we did not have an objective way to measure hypersensitivity to sound.…”

“…We expected an effect size of each IQ score change of 10 with 5SDs in the pyridoxine group, based on the findings of Baxter and coworkers. 6 Based on this expectation, a sample size of 4 pairs would allow a significance level of 0.05 and a power of 0.65. This power calculation was based on an unpaired t-test.…”

Long-Term Follow-up of a Successfully Treated Case of Congenital Pyridoxine-Dependent Epilepsy

“…Our adult subject demonstrates psychometric function slightly above previously averaged IQ values of children with PDS, in keeping with her early and continued therapy. It seems likely that preservation of intellect is dependent upon adequate pyridoxine replacement (Baxter et al 1996), but may vary with differing genotypes (Striano et al 2009;Scharer et al 2010) or unknown environmental influences (Alfadhel et al 2012). Further restoration of higher functions may prove possible with additional dietary modification such as lysine restriction (van Karnebeek et al 2012), emphasizing the complex pathogenesis of antiquitin defects beyond that of central pyridoxine deficiency.…”