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A major new international research initiative

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

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A major new international research initiative

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  1. Presented by Martin J Brodieon behalf of theEUCARE Management Group A major new international research initiative EUCARE is a joint initiative of the ILAE and IBE supported by an unrestricted educational grant from UCB Pharma

  2. FONDE STUDY Health burden of epilepsy • 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

  3. NEWLY DIAGNOSED EPILEPSY Epilepsy wheel of fortune Intolerable side-effects Vagal nerve stimulation Seizure-free Refractory Surgery

  4. 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

  5. MEDIAN AGE 29 YEARS (RANGE 9-93) MEDIAN FOLLOW-UP 6.6 YEARS (RANGE 2-21) NEWLY DIAGNOSED EPILEPSYOutcomes 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

  6. Remission (59.2%) Non-responders (35.4%) Relapse (5.4%) Immediate responders (31.4%) NEWLY DIAGNOSED EPILEPSYCategories of response to treatment(N=780) Responders (64.6%) Mohanraj R, Brodie MJ. Eur J Neurol 2006; 13: 277-82

  7. 100 80 60 40 20 0 NEWLY DIAGNOSED EPILEPSYRemission rates according to age Percentage 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

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

  9. OUTCOMES BY NUMBER OF PRE-TREATMENT SEIZURES % 25% 24% 39% 34% 48% 55% 100 14 20 32 30 45 50 11 Uncontrolled 4 80 Relapse 4 7 Remission 60 3 5 40 p = 0.024 75 76 61 66 52 45 20 0 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

  10. 38% 43% 45% 47% 45% % 100 80 33 38 40 39 40 Uncontrolled 5 Relapse 5 5 8 5 60 Remission 40 62 57 5553 55 20 0 < 1 1 - 2 3 - 5 6 - 10 > 10 (n=440) (n=124) (n=105) (n=60) (n=51) Time from first seizure until starting treatment (years) OUTCOMES BY DURATION OF EPILEPSY PRIOR TO STARTING TREATMENT

  11. OUTCOMES BY NUMBER OF PRE-TREATMENT SEIZURESThree months before starting treatment % 0% 28% 38% 48% 49% 64% 100 21 32 48 45 61 80 7 Uncontrolled 6 Relapse 60 Remission 4 3 40 p < 0.001 20 100 72 62 52 51 36 0 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

  12. NEWLY DIAGNOSED EPILEPSYPredictors 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

  13. NEWLY DIAGNOSED EPILEPSYPredictors 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

  14. 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

  15. 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

  16. NEWLY DIAGNOSED EPILEPSY Outcomes by syndromic classification * + * + 34% 43% 44% % Uncontrolled 100 Relapse 27 38 39 Remission 7 80 5 5 60 * p = 0.041 + p = 0.035 40 66 57 56 20 0 Idiopathic Cryptogenic Symptomatic (N=222) (N=314) (N=244) Mohanraj R, Brodie MJ. Eur J Neurol 2006;13:277-82

  17. NEWLY DIAGNOSED EPILEPSY Interictal EEG of a patient with juvenile myoclonic epilepsy showing generalised multiple spike-and-wave complexes

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

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