Predicting antiepileptic drug response in children with epilepsy

Figures & data

Figure 1. Potential predictive factors involved in seizure outcome of children with epilepsy.

AED: Antiepileptic drug.

Table 1. Reported factors predicting drug response in multivariate analyses of individual population-based studies in Western countries that reported a follow-up of 10 years or more.

Variable	Number in remission	Risk estimation (95%CI)	p-value	Study authors (total number of cases; average follow-up in years)	Ref.
Predictors of seizure remission on or off AEDs
Pre-seizure factors
Remote symptomatic etiology	37/83 (45%) vs 46/83 (55%)	RR: 0.8 (0.6–1.1)	ns overall cohort	Sillanpää et al. (1998) (n = 176; 31 years)	[2]
	35/74 (47%) vs 39/74 (53%)	RR: 0.9 (0.7–1.2)	ns overall incident cohort^†	Sillanpää et al. (1998) (n = 176; 31 years)	[2]
Normal vs abnormal intelligence	100/130 (77%) vs 24/64(38%)	RR: 2.1 (1.5–2.9)	p < 0.001	Brorson and Wranne (1987) (n = 194; 12 years)	[3]
Normal vs abnormal neurological examination	108/151 (72%) vs 16/43(35%)	RR: 1.9 (1.3–2.9)	p < 0.001	Brorson and Wranne (1987) (n = 194; 12 years)	[3]
Seizure frequency 2 per 6 months vs >2 per 6 months	85/109 (78%) vs 39/46(46%)	RR: 1.7 (1.3–2.2)	p < 0.001	Brorson and Wranne (1987) (n = 194; 12 years)	[3]
One seizure type vs several seizure types	89/123 (72%) vs 35/71(49%)	RR: 1.5 (1.1–1.9)	p = 0.001	Brorson and Wranne (1987) (n = 194; 12 years)	[3]
Localization-related idiopathic vs others	13/14 (93%) vs 84/130 (65%)	RR: 1.4 (1.2–1.7)	p = 0.0361	Sillanpää and Schmidt (2006) (n = 144; 37 years)	[8]
Localization-related symptomatic vs others	39/65 (0%) vs 58/79 (73%)	RR: 0.8 (0.6–1.0)	p = 0.00875	Sillanpää and Schmidt (2006) (n = 144; 37 years)	[8]
Temporal lobe vs others	23/43 (53%) vs 74/101(73%)	RR: 0.7 (0.5–1.0)	p = 0.0205	Sillanpää and Schmidt (2006) (n = 144; 37 years)	[8]
Generalized vs others	29/45 (64%) vs 68/99 (69%)	RR: 0.9 (0.7–1.2)	p = 0.6148	Sillanpää and Schmidt (2006) (n = 144; 37yrs)	[8]
Generalized idiopathic vs others	27/31 (87%) vs 70/113 (62%)	RR: 1.4 (1.2–1.7)	p = 0.0082	Sillanpää and Schmidt (2006) (n = 144; 37 years)	[8]
Generalized cryptogenic/symptomatic vs others	2/14 (14%) vs 95/130 (73%)	RR: 0.2 (0.1–0.7)	p < 0.0001	Sillanpää and Schmidt (2006) (n = 144; 37 years)	[8]
Seizure-related factors
Complex partial seizures	35/74 (47%) vs 39/74 (53%)	RR: 0.3 (0.2–0.5)	p < 0.001 overall cohort	Sillanpää et al. (1998) (n = 176; 31 years)	[2]
Complex partial seizures	15/43 (35%) vs 39/74 (53%)	RR: 03 (0.1–0.6)	p 0.001 overall incident cohort^†	Sillanpää et al. (1998) (n = 176; 31 years)	[2]
Atonic seizures	3/14 (21%) vs 11/14 (79%)	RR: 0.2 (0.1–0.7)	p < 0.002 overall cohort	Sillanpää et al. (1998) (n = 176; 31 years)	[2]
Atonic seizures	35/74 (47%) vs 39/74 (53%)	RR: 0.3 (0.2–0.5)	p < 0.001 overall incident cohort^†	Sillanpää et al. (1998) (n = 176; 31 years)	[2]
Treatment-related factors
Early response to therapy	80/102 (78%) vs 40/102(39%)	RR: 3.7 (2.0–6.7)	p < 0.001 overall cohort	Sillanpää et al. (1998) (n = 176; 31 years)	[2]
Early response to therapy	50/73 (68%) vs 23/73(32%)	RR: 2.2 (1.2–4.0)	p < 0.001 incident cohort	Sillanpää et al. (1998) (n = 176; 31 years)	[2]
Entering 1 year remission within first 5 years of treatment	93/97 (96%) vs 27/47 (57%)	RR: 4.7 (1.9–11.4)	p < 0.001	Sillanpää and Schmidt (2006) (n = 144; 37 years)	[8]
Likelihood for 5YTR off AEDs	45/120(45%) vs 1/8(8%)	OR: 9.0 (1.1–71.9)	p = 0.0383	Sillanpää and Schmidt (2009)	[44]
Predictors of not entering seizure remission
Pre-seizure factors
Symptomatic etiology	37/83 (33%) vs 75/93 (81%)	RR: 0.6 (0.4–0.7)	p < 0.001	Sillanpää et al. (1998) (n = 176; 31 years)	[2]
Normal vs abnormal intelligence	23/74(31%) vs 39/74(53%)	RR: 0.6 (0.4–0.9)	p < 0.05	Brorson and Wranne (1987) (n = 194; 12 years)	[3]
Seizure-related factors
Weekly vs less than weekly seizures prior to treatment	23/37 (62%) vs 55/65 (85%)	HR: 1.7 (1.04–2.9)	p = 0.00350 for never entering 1-year remission	Sillanpää and Schmidt (2009) (n = 102; 37 years)	[15]
Frequent seizures (undefined)	46/85 (54%) vs 24/109 (22%)	RR: 2.4 (1.6–3.7)	p < 0.01	Brorson and Wranne (1987) (n = 194; 12 years)	[3]
Several types of seizures	36/71(51%) vs 34/123 (28%)	RR: 1.8 (1.3–2.6)	p = 0.001	Brorson and Wranne, (1987) (n = 194; 12 years)	[3]
Seizure-cluster vs no seizure cluster prior to drug treatment	5/12(42%) vs 12/94 (13%)	RR: 3.3 (1.4–7.7)	p = 0.012	Sillanpää and Schmidt (2008) (120; 37 years)	[14]
Treatment-related factors
Weekly vs less than weekly seizures during first year of treatment	2/8 (25%) vs 18/19 (95%)	HR: 8.2 (1.6–43.0)	p = 0.0125 for drug-resistant epilepsy	Sillanpää and Schmidt (2009) (n = 102; 37 years)	[15]
Weekly vs less than weekly seizures during first year of treatment	During first year of treatment 19/38 (50%) vs 59/64 (92%)	HR: 2.7 (1.5–5.0)	p = 0.001 never entering terminal 1-year remission	Sillanpää and Schmidt (2009) (n = 102; 37 years)	[15]

^†Remission off medication.

Predictors of entering 5-year remission and predictors of not entering remission, each as defined by the study authors, are given separately.

5YTR: 5-year terminal remission; AED: Antiepileptic drug; HR: Hazard ratio; ns: Not significant; OR: Odds ratio; RR: Rate ratio.

Activity Evaluation: Where 1 is strongly disagree and 5 is strongly agree

	1	2	3	4	5
1. The activity supported the learning objectives.
2. The material was organized clearly for learning to occur.
3. The content learned from this activity will impact my practice.
4. The activity was presented objectively and free of commercial bias.

Sillanpää M, Jalava M, Kaleva O, Shinnar S. Long-term prognosis of seizures with onset in childhood. N. Engl. J. Med.338, 1715–1722 (1998).

 PubMed Web of Science ®Google Scholar

Brorson LO, Wranne L. Long-term prognosis in childhood epilepsy: survival and seizure prognosis. Epilepsia28, 324–330 (1987).

 Google Scholar

Sillanpää M, Schmidt D. Natural history of treated childhood-onset epilepsy: prospective, long-term population-based study. Brain129, 617–624 (2006).

 PubMed Web of Science ®Google Scholar

Sillanpää M, Schmidt D. Delayed time to first remission identifies poor long-term drug response of childhood-onset epilepsy: a prospective population-based study. Epil. Behav.16, 507–511 (2009).

 PubMed Web of Science ®Google Scholar

Sillanpää M, Schmidt D. Early seizure frequency and aetiology predict long-term medical outcome in childhood-onset epilepsy. Brain132, 989–998 (2009).

 PubMed Web of Science ®Google Scholar

Sillanpää M, Schmidt D. Seizure clustering during drug treatment affects seizure outcome and mortality of childhood-onset epilepsy. Brain131, 938–944 (2008).

 PubMed Web of Science ®Google Scholar