FONDE : A major new international research initiative (Marseille) Martin J Brodie on behalf of the EUCARE Management Group Presented by EUCARE is a joint initiative of the ILAE and IBE supported by an unrestricted educational grant from UCB Pharma

FONDE : A major new international research initiative (Marseille) FONDE STUDY Health burden of epilepsy FONDE : A major new international research initiative (Marseille) Around 5-10% of people will have a seizure at some time in their lives, 30% of whom will go on to develop epilepsy Thus 1% of the world’s population will have epilepsy at any given point in time, amounting to a total of 40 million 30-40% of people with epilepsy will have uncontrolled seizures accounting for over 80% of the overall cost This represents 1% of the Global Burden of Disease (WHO) and is equivalent to - breast cancer in women - lung cancer in men

FONDE : A major new international research initiative (Marseille) NEWLY DIAGNOSED EPILEPSY Epilepsy wheel of fortune Intolerable side-effects Vagal nerve stimulation Seizure-free Refractory Surgery

FONDE : A major new international research initiative (Marseille) EARLY IDENTIFICATION OF REFRACTORY EPILEPSY Patrick Kwan and Martin J Brodie Epilepsy Unit, University Department of Medicine & Therapeutics Western Infirmary, Glasgow, Scotland February 3, 2000; 342: 314-319 FONDE : A major new international research initiative (Marseille)

FONDE : A major new international research initiative (Marseille) NEWLY DIAGNOSED EPILEPSY Outcomes from July 1982 to May 2003 (N=780) Responder – seizure-free for a minimum of 12 months Immediate responder – no seizures after starting treatment Remission – no relapse after becoming seizure-free Relapse – controlled for at least one year then refractory Non-responder – never seizure-free for any 12 months MEDIAN AGE 29 YEARS (RANGE 9-93) MEDIAN FOLLOW-UP 6.6 YEARS (RANGE 2-21)

FONDE : A major new international research initiative (Marseille) NEWLY DIAGNOSED EPILEPSY Categories of response to treatment (N=780) Responders (64.6%) Non-responders (35.4%) Remission (59.2%) Immediate responders (31.4%) Relapse (5.4%) Mohanraj R, Brodie MJ. Eur J Neurol 2006; 13: 277-82

FONDE : A major new international research initiative (Marseille) NEWLY DIAGNOSED EPILEPSY Remission rates according to age Percentage 20 40 60 80 100 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+ n=59 n=131 n=99 n=87 n=71 n=56 n=51 n=36 n=34 n=35 n=31 n=19 n=29 n=23 n=11 n=8 Brodie MJ, Kwan P. Br Med J 2005;331:1317-22

FONDE : A major new international research initiative (Marseille) Months on treatment Number relapsed Number at risk 8 5 9 1 2 4 3 6 7 42 54 36 313 40 217 42 96 14 479 0 504 10.4% 8.0% 4.2% Risk of relapse (%) 12 Years of follow up % seizure free KAPLAN-MEIR PLOT OF TIME TO RELAPSE

FONDE : A major new international research initiative (Marseille) OUTCOMES BY NUMBER OF PRE-TREATMENT SEIZURES 1 2 3 - 5 6 - 10 11 – 20 >20 (n=28) (n=149) (n=212) (n=89) (n=69) (n=233) Number of pre-treatment seizures 20 40 60 80 100 Uncontrolled Relapse Remission 25% 24% 39% 34% 48% 55% 14 20 32 30 45 50 11 4 7 3 5 75 76 61 66 52 45 % p = 0.024 FONDE : A major new international research initiative (Marseille)

FONDE : A major new international research initiative (Marseille) OUTCOMES BY DURATION OF EPILEPSY PRIOR TO STARTING TREATMENT Uncontrolled Relapse Remission Time from first seizure until starting treatment (years) (n=440) (n=124) (n=105) (n=60) (n=51) 20 40 60 80 100 < 1 1 - 2 3 - 5 6 - 10 > 10 38% 43% 45% 47% 45% 33 38 40 39 40 62 57 55 53 55 5 8 %

FONDE : A major new international research initiative (Marseille) OUTCOMES BY NUMBER OF PRE-TREATMENT SEIZURES Three months before starting treatment Relapse Remission 20 40 60 80 100 % Uncontrolled none 1 2 – 5 6 – 10 11 – 20 >20 (n=3) (n=164) (n=335) (n=64) (n=53) (n=64) Number of pre-treatment seizures 0% 28% 38% 48% 49% 64% 21 32 48 45 61 100 72 62 52 51 36 7 6 4 3 p < 0.001

FONDE : A major new international research initiative (Marseille) NEWLY DIAGNOSED EPILEPSY Predictors of refractoriness (multivariate analysis) Odds ratio 95% CI p value Family history 1.89 1.15-3.00 0.011 Febrile seizures 3.36 1.58-7.18 0.002 Traumatic brain injury 3.26 1.59-4.69 <0.001 Psychiatric comorbidity 2.17 1.33-3.55 0.002 Recreational drug use 4.26 2.03-8.94 <0.001 10 or more seizures 2.77 1.98-3.89 <0.001 Hitiris N et al. Epilepsy Research 2007; 75: 192-6

FONDE : A major new international research initiative (Marseille) NEWLY DIAGNOSED EPILEPSY Predictors of refractoriness (multivariate analysis) Odds ratio 95% CI p value Family history 1.89 1.15-3.00 0.011 Febrile seizures 3.36 1.58-7.18 0.002 Traumatic brain injury 3.26 1.59-4.69 <0.001 Psychiatric comorbidity 2.17 1.33-3.55 0.002 Recreational drug use 4.26 2.03-8.94 <0.001 10 or more seizures 2.77 1.98-3.89 <0.001 Hitiris N et al. Epilepsy Research 2007; 75: 192-6

FONDE : A major new international research initiative (Marseille) NEWLY DIAGNOSED EPILEPSY Follow up of 97 consecutive patients undergoing antero-temporal lobectomy A lifetime history of depression was the sole predictor of post-surgical auras (p<0.0001) in seizure-free patients A lifetime history of depression was also a predictor of disabling seizures with or without auras (p=0.001). Kanner AM et al, Neurology, submitted

FONDE : A major new international research initiative (Marseille) EPILEPSY MORTALITY N SMR 95% CI p value Newly diagnosed 890 1.42 1.16-1.72 p=0.0007 Chronic epilepsy 2689 2.05 1.83-2.26 p<0.0001 No increase in risk was observed in patients who were seizure-free Mohanraj R et al Lancet Neurology 2006; 5: 481-7

FONDE : A major new international research initiative (Marseille) NEWLY DIAGNOSED EPILEPSY Outcomes by syndromic classification 20 40 60 80 100 Idiopathic Cryptogenic Symptomatic Uncontrolled Relapse Remission 34% 43% 44% 66 57 56 7 5 (N=222) (N=314) (N=244) % 27 38 39 * + * p = 0.041 + p = 0.035 Mohanraj R, Brodie MJ. Eur J Neurol 2006;13:277-82

FONDE : A major new international research initiative (Marseille) NEWLY DIAGNOSED EPILEPSY Interictal EEG of a patient with juvenile myoclonic epilepsy showing generalised multiple spike-and-wave complexes

FONDE : A major new international research initiative (Marseille) NEWLY DIAGNOSED EPILEPSY Treatment response in juvenile myoclonic epilepsies (N=55; 25% population) Non-responders (20%) Remission (73%) Immediate responders (36%) Relapse (7%) Responders (70%) Mohanraj R, Brodie MJ. Acta Neurol Scand 2007; 115: 204-8