Refractory absence seizures: An Italian multicenter retrospective study

In a long term retrospective study on children with refractory Childhood Absence Epilepsy (CAE), published in EJPN, Franzoni and colleagues (Franzoni et al., 2015) report a higher incidence of cognitive impairment in children with longer duration of childhood absence epilepsy indicating the not so benign nature of this condition.

 The study included 92 children, one of the largest published cohorts with refractory absence seizure. Comparisons were made between 45 subjects with continuing absence seizures (49%) and the remaining 47 who had become seizure free (51%) after a period of drug-resistance. The authors defined refractory seizures as the failure of an adequate trial of two tolerated and appropriate antiepileptic drug schedules (firstly as monotherapy or secondly even in combinations) to achieve sustained seizure control (first-line choice Valproic Acid, Ethosuximide, Levetiracetam).

They included children with refractory childhood absence epilepsy with age of seizure onset 0–14 years, brief absence seizure with abrupt or severe impairment of consciousness with or without automatisms, bilateral synchronous and symmetrical discharge of rhythmic 3 Hz spikes and slow wave complexes during ictal EEG and a normal interictal background activity including transient focal epileptiform abnormalities and normal neurological examination.

Children with atypical absence seizures, ictal EEG with spike-wave complexes less than 2.7 Hz and more than 4 Hz , interictal EEG with persistent focal epileptiform abnormalities, sensory precipitation of absence seizures, abnormal pre-, peri- and post-natal history, metabolic abnormalities, abnormalities on neuroradiology and neurological examination were excluded from the study.
No significant correlation was seen between age of onset, presence of a myoclonic component, family history and abnormalities at interictal EEG between children with refractory CAE and those who had become seizure free.

The study thus did not identify any risk factors which would predict the prognosis in Childhood Absence Epilepsy (CAE). However it showed that a longer duration of CAE, higher frequency of seizures and the number of AEDs used correlated with increased cognitive impairment.

None of the 19 patients (21%) in the study who were investigated for Glucose Transporter (GLUT1) deficiency turned out to be positive. This is in keeping with findings from the 2013 multicenter study from Italy of 84 children with early onset absence epilepsy where SLC2A1 gene mutations were not detected in any of the study subjects (Agostinelli et al., 2013). However in a 2012 study of 504 probands with idiopathic generalized epilepsy from Melbourne, approximately 12% of patients with early onset absence epilepsy were potentially carriers of Glut1D, prompting the authors to recommend SLC2A1 mutational analysis in these children (Arsov et al., 2012).

References

• Agostinelli, S., Traverso, M., Accorsi, P., Beccaria, F., Belcastro, V., Capovilla, G., ... Verrotti, A. (2013). Early-onset absence epilepsy: SLC2A1 gene analysis and treatment evolution. European Journal of Neurology, 20(5), 856–859. doi:10.1111/j.1468-1331.2012.03871.x
• Arsov, T., Mullen, S. A., Rogers, S., Phillips, A. M., Lawrence, K. M., Damiano, J. A., ... Scheffer, I. E. (2012). Glucose transporter 1 deficiency in the idiopathic generalized epilepsies. Annals of Neurology, 72(5), 807–815. doi:10.1002/ana.23702
• Franzoni, E., Matricardi, S., Di Pisa, V., Capovilla, G., Romeo, A., Tozzi, E., ... Verrotti, A. (2015). Refractory absence seizures: An Italian multicenter retrospective study. European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society. doi:10.1016/j.ejpn.2015.07.008

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