REVIEW ARTICLE Refractory Epilepsy in Children Satinder Aneja & Puneet Jain Received: 3 March 2014 /Accepted: 2 July 2014 /Published online: 9 August 2014 # Dr. K C Chaudhuri Foundation 2014 Abstract Refractory epilepsy, estimated to affect 10–20 % children with epilepsy, can have profound effect on the edu- cation, social and cognitive functioning and recreational ac- tivities of the child. The definitions are still evolving. A detailed clinical evaluation may reveal an accurate syndromic and etiological diagnosis. The recent advances in neuroimag- ing and electrophysiology have revolutionized the manage- ment of children with refractory epilepsy and supplement the clinical evaluation. Genetic and metabolic evaluation may be indicated in selected cases. The rational use of anti-epileptic drugs, epilepsy surgery and dietary therapies are the mainstay in the management. Various experimental treatment options and pharmacogenetics offer hope for future. Keywords Refractory epilepsy . Intractable epilepsy . Polytherapy . Epilepsy surgery . Dietary therapy Introduction Approximately 10–20 % children with epilepsy develop drug- refractory epilepsy. The identification of refractory epilepsy can have broad implications regarding education, social func- tioning and recreational activities of the child. This review briefly discusses the definition, mechanisms, investigations and treatment modalities available for a child with refractory epilepsy. Definition Terms ‘refractory’, ‘intractable’, ‘drug-resistant’, ‘pharmaco- resistant’ have been used interchangeably in literature. Broad- ly, refractory epilepsy may be defined as failure of complete or acceptable control of seizures in response to the anti-epileptic drugs. Although many studies have used various definitions of refractory epilepsy [1–6], the definition is still evolving [7]. The consensus regarding the number of drug failures appeared to be 2–3 but the reported criteria for the seizure frequency were variable. Recently, International League against Epilepsy (ILAE) proposed a consensus definition for drug-resistant epilepsy [8]. However, for routine use, failure of seizure-control despite trial of three appropriate anti-epileptic drugs (AED) regimens at maximum tolerated doses should be considered as drug- refractoriness and is highly likely to indicate failure with subsequent AED trials. Another important concern is ‘pseudo’ or ‘apparent’ re- fractoriness. It should be excluded before a diagnosis of refractory epilepsy. The factors to be considered includes appropriateness of the drug for the epilepsy syndrome, com- pliance, ‘seizure mimickers’, adequate dosing and trial and drug interactions [9, 10]. Epidemiology The refractory epilepsy is seen in 9–23 % of children with epilepsy [3, 11, 12]. Few studies have also explored the factors which may predict intractability [3, 11, 13]. Younger age at onset, [13–15] neonatal status epilepticus, [11, 13, 16] high initial seizure frequency, [11, 13, 16] failure of response to first anti-epileptic drug, [17] specific epilepsy syndromes (infantile spasms, [13, 16] Lennox-Gastaut syndrome [13]), mixed seizure types, [13, 16] symptomatic/cryptogenic S. Aneja (*) : P. Jain Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children’ s Hospital, New Delhi 110001, India e-mail: drsaneja@gmail.com P. Jain Division of Pediatric Neurology, Department of Pediatrics, BLK Super Speciality Hospital, Pusa Road, New Delhi, India Indian J Pediatr (October 2014) 81(10):1063–1072 DOI 10.1007/s12098-014-1533-1