1. 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

2. 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

3. 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

4. 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:
FONDE : A major new international research initiative (Marseille)

5. FONDE : A major new international research initiative (Marseille)
NEWLY DIAGNOSED EPILEPSY Outcomes from July 1982 to May (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)

6. 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:

7. 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:

8. 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

9. FONDE : A major new international research initiative (Marseille)
OUTCOMES BY NUMBER OF PRE-TREATMENT SEIZURES
– >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% % % % % % 11 4 7 3 5 %
p = 0.024
FONDE : A major new international research initiative (Marseille)

10. 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% % % % % 5 8 %

11. 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 – – – >20
(n=3) (n=164) (n=335) (n=64) (n=53) (n=64)
Number of pre-treatment seizures
0% % % % % % 7 6 4 3
p < 0.001

12. FONDE : A major new international research initiative (Marseille)
NEWLY DIAGNOSED EPILEPSY Predictors of refractoriness (multivariate analysis)
Odds ratio % CI p value
Family history
Febrile seizures
Traumatic brain injury <0.001
Psychiatric comorbidity
Recreational drug use <0.001
10 or more seizures <0.001
Hitiris N et al. Epilepsy Research 2007; 75: 192-6

13. FONDE : A major new international research initiative (Marseille)
NEWLY DIAGNOSED EPILEPSY Predictors of refractoriness (multivariate analysis)
Odds ratio 95% CI p value
Family history
Febrile seizures
Traumatic brain injury <0.001
Psychiatric comorbidity
Recreational drug use <0.001
10 or more seizures <0.001
Hitiris N et al. Epilepsy Research 2007; 75: 192-6

14. 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

15. FONDE : A major new international research initiative (Marseille)
EPILEPSY MORTALITY
N SMR % CI p value
Newly diagnosed p= Chronic epilepsy 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. 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% % % 7 5
(N=222) (N=314) (N=244) % * +
* p = 0.041
+ p = 0.035
Mohanraj R, Brodie MJ. Eur J Neurol 2006;13:277-82

17. 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

18. 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