Epileptic Disorders - Editor's Choice
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Giuseppe Gobbi, Giulia Loiacono, Antonella Boni, Lucia Marangio, Alberto Verrotti
Commentary by Aristea S. Galanopoulou MD PhD, Epileptic Disorders Associate Editor
Adrenocorticotropic hormone (ACTH) has been extensively used in the treatment of West syndrome (WS) but also for other early life epileptic encephalopathies, such as Landau Kleffner syndrome (LKS), and continuous spike wave in slow wave sleep syndrome (CSWS). These are epileptic syndromes that manifest in infancy or early childhood, do not necessarily have the same types of epileptic seizures, but have prominent interictal epileptic abnormalities with neurodevelopmental sequelae. Gobbi et al (Epileptic Disorders, June issue) report here beneficial effects of ACTH treatment in 5/6 young patients with drug-resistant frontal lobe epilepsy. Unlike patients with the classical ACTH-responsive epileptic encephalopathies (WS, LKS, CSWS), this small cohort included teenagers as well as children (range 4 to 17 years old). Their seizures were atypical absences, tonic or tonic versive or drop attacks, and all had secondary bilateral synchrony with focal abnormalities on their EEGs. Seizures stopped within 6 weeks in 83% of them. Among the responders, 60% maintained seizure freedom at 6 months of follow up while eventually all initial responders achieved seizure freedom at 12 months of follow up. No serious adverse effects were reported in this cohort.
The findings of Gobbi et al (Gobbi et al. 2014) indicate that ACTH may not be strictly the medical treatment for WS or LKS and CSWS but could potentially be considered in other drug resistant epileptic syndromes, as in frontal lobe epilepsy. Precedents do exist to support this concept. Snead et al (Snead et al. 1983) reported that 12/18 (66.7%) of children with drug-resistant epilepsies without infantile spasms responded to high dose ACTH, although the relapse rate was 40%. Okumura et al (Okumura et al. 2006) reported seizure freedom in 13/15 patients (86.7%) with generalized seizures (atypical absences, tonic, drop attacks or myoclonic but not infantile spasms) although again 46% relapsed. Kalra et al (Kalra et al. 2009) also reported therapeutic effects of ACTH in two patients (3 and 7 year old) with drug resistant epilepsies. In a Cochrane type review performed by Gayatri et al (Gayatri et al. 2007) only one double blind randomized prospective study was found that intended to evaluate the efficacy of steroids or ACTH4-9 analogue in children with intractable epilepsy without infantile spasms (Pentella et al. 1982). The study showed mild to moderate reduction in seizures in 3 / 4 children.
The existing small cohort studies are certainly valuable and maintain our interest in further exploring the possibilities of ACTH therapy in the pediatric epilepsy population, raising important questions. Which epilepsy syndromes might benefit from ACTH beyond WS / LKS / CSWS? Is ACTH beneficial only for very young patients or also for older age groups as the Gobbi study suggests? What are the long-term outcomes of ACTH treatment? The need for randomized, blinded, controlled, well powered studies to address these questions is evident, although such studies are not easy to be done.