A major new international research initiative
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 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
NEWLY DIAGNOSED EPILEPSYEpilepsy wheel of fortune
Vagal nerve stimulation
Surgery
Seizure-free
Intolerable side-effects
Refractory
EARLY IDENTIFICATION OF EARLY IDENTIFICATION OF REFRACTORY EPILEPSYREFRACTORY EPILEPSY
Patrick Kwan and Martin J Brodie
Epilepsy Unit, University Department of Medicine & Therapeutics
Western Infirmary, Glasgow, Scotland
February 3, 2000; 342: 314-319
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)
NEWLY DIAGNOSED EPILEPSY
Categories of response to treatment (N=780)
Non-responders(35.4%)
Remission (59.2%)
Immediate responders
(31.4%)
Relapse (5.4%)
Responders (64.6%)
Mohanraj R, Brodie MJ. Eur J Neurol 2006; 13: 277-82
NEWLY DIAGNOSED EPILEPSY Remission rates according to age
0
20
40
60
80
100
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
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+
Percentage
Brodie MJ, Kwan P. Br Med J 2005;331:1317-22
Months on treatmentNumber relapsedNumber at risk
80
85
90
95
100
0 12 24 36 48 60 72 84 96 108 12042 54
36 313
40 217
42 96
14 479
0 504
10.4% 10.4% 8.0% 4.2%Risk of relapse (%) 12 8 4 2Years of follow up
% seizure free
KAPLAN-MEIR PLOT OF TIME TO RELAPSE
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
0
20
40
60
80
100
UncontrolledRelapseRemission
25% 24% 39% 34% 48% 55%
14 20 32 30 45 50
11 4
7 4
35
75 76 61 66 52 45
%
p = 0.024
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)
0
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
55 5 58
%
OUTCOMES BY NUMBER OF PRE-TREATMENT SEIZURES Three months before starting treatment
Relapse
Remission
0
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
3p < 0.001
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
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
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
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
Mohanraj R et al Lancet Neurology 2006; 5: 481-7
No increase in risk was observed in patients who were seizure-free
0
20
40
60
80
100
Idiopathic Cryptogenic Symptomatic
Uncontrolled
Relapse
Remission
34% 43% 44%
66 57 56
7 5
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
NEWLY DIAGNOSED EPILEPSY Outcomes by syndromic classification
NEWLY DIAGNOSED EPILEPSY
Interictal EEG of a patient with juvenile myoclonic epilepsy showing generalised multiple spike-and-wave complexes