Paroxysmal events in glucose transporter type 1 deficiency syndrome: Early identification of their true nature is important

Abstract

In their study, Ito et al. collected clinical data of 14 individuals with glucose transporter type 1 deficiency syndrome (Glut1DS) to help identify the underlying nature of their paroxysmal episodes.¹ The retrospective analysis of epileptic and non-epileptic events showed that, contrarily to epileptic seizures: (1) non-epileptic events are situation-related, and can be provoked or ameliorated; (2) non-epileptic events are not accompanied by complete loss of consciousness; and (3) non-epileptic events can last for days and are followed by rapid recovery.¹

Infants may present with a great diversity of acute episodes of variable nature and pathological significance. One of the most frequent questions asked of neuropediatricians is to clarify if such events are epileptic or not. This difficult task requires specific expertise, as illustrated recently in the largest cohort published on the topic so far.² In that study, the clinical and work-up data of 1213 children referred to the First-Seizure Clinic of a tertiary children's hospital were analysed. A correct diagnosis was reached at initial evaluation in close to 70% of the total. Less than 3% of all children were later found to have been initially misdiagnosed. The authors essentially attribute these results to the expert evaluation proposed at their center, which includes a detailed patient history taking and neurological examination by a neuropediatrician, a standard electroencephalogram, and the involvement of neurophysiologists, neurologists, and specialized nurses to establish a diagnosis and propose treatment options.²

Determining the nature of paroxysmal events is a challenge of particular relevance in conditions where epileptic seizures and recurrent events of other origins coexist in the same child, like in those diagnosed with Glut1DS.³ In addition to epileptic seizures, recurrent non-epileptic episodes have been reported in up to 75% of them. These include distinctive paroxysmal eye–head movements, as well as paroxysmal (exercise-induced, kinesigenic, or non-kinesigenic) dyskinesias, and acute behavioural disturbances, all of which may mimic different forms of epileptic seizures with potential therapeutic consequences. It is therefore essential to identify suggestive elements to better guide investigations and treatment options in these children.

The results presented by Ito et al. need confirmation in larger scale, prospective studies, using a standardized work-up and multidisciplinary therapeutic process for all patients, as proposed by Slinger et al.² These results are nevertheless of definite interest. First, the coexistence of paroxysmal events of epileptic and non-epileptic nature in a single child is considered per se as suggestive of GLUT1-DS. It is thus important to recognize such a situation to launch appropriate diagnostic investigations in a timely manner. Second, recognizing the non-epileptic nature of certain acute episodes will help prevent the appearance of side effects due to unnecessary repeated increases of anti seizure medication doses.

This study also opens interesting research avenues. One of the questions that remains to be answered is whether early initiation of a ketogenic diet therapy (KDT) would allow control of paroxysmal non-epileptic events in the short- and longer-term. Early initiation of KDT has been demonstrated to considerably improve epileptic seizure control, as well as cognitive abilities in a significant proportion of children.³ Specific data regarding the efficacy of KDT on acute motor- and non-motor episodes are scarce and controversial, however. Pons et al. showed that the proportion of children with non-epileptic paroxysmal events was higher in the group of those treated with a KDT than in that of children treated differently.⁴ Alternative approaches have been proposed to treat paroxysmal non-epileptic events in patients with Glut1DS who do not tolerate KDT. For example, intermittent carbohydrate intake before planned activities has been recently reported to be efficient in two children with infrequent exercise-induced abnormal movements.⁵ These observations may represent another convincing argument in favour of early identification of the true nature of paroxysmal events in children with Glut1DS.