Pyridoxine dependent epilepsy: a suggestive electroclinical pattern

Editor—There are several problems with describing the electroclinical pattern in pyridoxine dependent seizures.1 One is defining the electrical features. Until now all published reports (including four of the five cases of Nabbout and colleagues) have described the electroencephalogram (EEG) in neonates who have received other anticonvulsants beforehand. It seems likely that anticonvulsants could affect the EEG, as suggested by the infant with the most pronounced burst suppression pattern in the paper of Nabbout and colleagues. The only other method of assessing the electrical pattern is on withdrawal, when we, like others, found that a continuous or intermittent high volt slow wave pattern with or without spikes was typical.2 It would be very useful to know the EEG features of the patient who did not receive any other drugs before pyridoxine, as this would be the first description of the true electrical pattern in pyridoxine dependent seizures.

This study raises issues on the use of EEGs in neonatal units. Very few of the neonates reported in the literature or in the UK study3 had EEGs before receiving pyridoxine. Presumably this reflects difficulties in obtaining EEGs out of hours or when there is no facility attached to the neonatal unit, as well as the desire to treat without delay. As a result, for some neonatal units it may be difficult to detect a specific electroclinical pattern.

A second difficulty is that the clinical features are not very specific. The neonatal presentation can be: as an acute encephalopathy, followed by later seizures; as seizures accompanied by encephalopathy (both of which introduce a wide differential diagnosis); as seizures alone; or, more unusually, as apparent acute abdominal obstruction or respiratory distress, usually accompanied by irritable behaviour, again followed by seizures. In some reports, seizures have been precipitated by sudden sounds or movements, although some of these could be an exaggerated startle response. Although we too found that a variety of seizures, especially generalised tonic and generalised clonic, occurred in most of our cases,2 some only had one or two seizure types. In the UK study, five of the 20 definite and probable cases with an early onset were reported to have a single seizure type (unpublished data).

The third concern is that Nabbout and colleagues did not include later presenting cases (older than 28 days) in their report. These also appear to be pyridoxine dependent as judged by trials of withdrawal and occurrence in siblings. They accounted for three of the 23 definite and probable cases in the UK population study, although a further five had early seizures that responded to routine anticonvulsants and then remained seizure free for several weeks or months. In all these, both the clinical and electrical features can differ from neonates. For example, the inter-ictal EEG can be normal, or show focal or generalised spikes or sharp waves with or without high voltage slow activity. The clinical features include recurrent episodes of status and less varied seizure types. Concentrating on a possible neonatal pattern risks overlooking such cases.

As Nabbout and colleagues emphasise, there needs to be a high index of suspicion. Clinically it is important that pyridoxine dependency should be considered in all early childhood seizures, because (a) other features may be misleading and (b) early treatment does appear to be beneficial.