Epilepsy is the tendency to have recurrent epileptic seizures and affects approximately one in 20 children at some point during childhood. The research program in epilepsy involves several researchers and includes the investigation of new treatments of intractable epilepsy including the ketogenic diet, vagal nerve stimulation and surgery. The major areas of my research have been the clinical and EEG features of epileptic seizures and the side-effects of antiepileptic drugs in children. More recently, the problem of preserving mental development in children with epilepsy has become a focus.

Protecting The Developing Brain Against Epileptic Discharges
Carmant L, Weiss S, Whiting S, Wirrell E, Dooley J. A randomized double blind trial of add-on flunarizine to prevent the cognitive deterioration associated with infantile spasms. CIHR funded April 2002 - Mar 2006, $476,480. This multicentre clinical trial examines the influence of a calcium channel blocker on the markedly delayed cognitive development that occurs in 90% of children with infantile spasm. The delayed development in these children is believed to be a consequence of the frequent epileptic discharges, and flunarazine has been demonstrated to have a protective effect in animal models.

Understanding Why Valproic Acid Is Hepatotoxic In Children
Abbott FS, Chang T, Farrell K. Valproic acid analogues: glutathione dependent metabolism and mechanisms of toxicity. CIHR funded October 2005 - September 2010, $578,890. Valproic acid is a very effective broad-spectrum antiepileptic drug whose use in children is complicated by the risk of liver failure, particularly in the very young child. We have demonstrated in animal and human studies that reactive oxygen species play a role in the toxicity of valproic acid and that glutathione has a protective effect. We are exploring further the mechanisms of valproate toxicity in children and looking at the effect of drug interactions in children on reactive oxygen species.

Understanding Why Children Develop an Epileptic Encephalopathy
Approximately 5% of children with epilepsy develop a state characterized by frequent epileptic discharges and a halt in mental development. These children rarely respond to conventional antiepileptic drugs, eventually become mentally retarded and are unable to live independently as adults or achieve competitive employment. Epileptic encephalopathy has been identified by the Canadian Pediatric Epilepsy Network as a major research focus and we have partnered with researchers in Ottawa and Calgary in the development of a study of non-convulsive status epilepticus in children with epileptic encephalopathy.

Sadleir LG, Connolly MB, Applegarth D, Hendson G, Clarke L, Rakshi C, Farrell K. Spasms in children with definite and probable mitochondrial disease. Eur J Neurol. 2004 Feb;11(2):103-110.

Gopaul VS, Farrell K, Abbott FS. The effects of age and polytherapy, risk factors of valproic acid (VPA) hepatotoxicity, on the excretion of thiol conjugates of (E)-2,4-diene VPA in epileptic patients on VPA. Epilepsia 2003 Mar;44(3):322-8.

Gopaul VS, Tang W, Farrell K, Abbott FS. Amino Acid Conjugates: Metabolites of 2-Propylpentanoic Acid (Valproic Acid) in Epileptic Patients. Drug Metab Dispos 2003 Jan 1;31(1):114-121.

Sherman EM, Slick DJ, Connolly MB, Steinbok P, Camfield C, Eyrl KL, Massey C, Farrell K. Validity of Three Measures of Health-related Quality of Life in Children with Intractable Epilepsy. Epilepsia. 2002;43(10):1230-8.

Gopaul SV, Farrell K, Abbott FS. Identification and characterization of N-acetylcysteine conjugates of valproic acid in humans and animals. Drug Metab Dispos. 2000 Jul;28(7):823-32.

Gopaul SV, Farrell K, Abbott FS. Gas chromatography/negative ion chemical ionization mass spectrometry and liquid chromatography/electrospray ionization tandem mass spectrometry quantitative profiling of N-acetylcysteine conjugates of valproic acid in urine: application in drug metabolism studies in humans. J Mass Spectrom. 2000 Jun;35(6):698-704.

Webb DW, Jones RR, Manzur AY, Farrell K. Retrospective study of late febrile seizures. Pediatr Neurol. 1999 Apr;20(4):270-3.

Hukin J, Farrell K, MacWilliam LM, Colbourne M, Waida E, Tan R, Mroz L, Thomas. Case-control study of primary human herpesvirus 6 infection in children with febrile seizures. Pediatrics. 1998 Feb;101(2):E3. URL: http://www.pediatrics.org/cgi/content/full/101/2/e3 .

Tabatabaei AR , Thies RL, Farrell K, Abbott FS. A rapid in vitro assay for evaluation of metabolism-dependent cytotoxicity of antiepileptic drugs on isolated human lymphocytes. Fundam Appl Toxicol. 1997 Jun;37(2):181-9.

Connolly MB , Langill L, Wong PK , Farrell K. Seizures involving the supplementary sensorimotor area in children: a video-EEG analysis. Epilepsia. 1995 Oct;36(10):1025-32.

Vesna Popovska - Research manager

Sheila Kent - Research nurse

Danijela Gasevic - Research assistant