Epilepsy surgery in children: Evaluation of seizure outcome and predictive elements




To analyze the clinical outcome of epilepsy surgery in children, and to identify the factors related with a favorable seizure control among several presurgical, surgical and postsurgical variables.


One-hundred twenty children, younger than 16 years (69 male and 51 female), operated on for medically refractory focal epilepsy at the “C.Munari” Epilepsy Surgery Center of the Niguarda Hospital in Milan from 1998 to 2009, were identified. Seizure outcome was assessed according to the Engel's classification.

Statistical analysis was performed to identify predictive elements of seizure outcome among several presurgical, surgical, and postsurgical variables.

Key findings

There were 84 (70%) seizure-free patients (Engel's classes Ia and Ic), 93 (77.5%) in class I, 8 (6.7%) in class II, 9 in class III (7.5%), and 10 (8.3%) in class IV.


Our study confirms that epilepsy surgery is an established and effective treatment for partial epilepsy in children and suggest criteria to help identify early potential surgical candidates.

In recent years, increasing consensus has grown on the efficacy of surgery to treat drug-resistant focal epilepsy in children. Epilepsy surgery is now widely accepted as an effective therapeutic option in a select subset of these patients. In children, epilepsy surgery is not simply an extension of adult procedures; additional complicating factors must be considered, including different causes of epilepsy, the detrimental effects of seizures and antiepileptic drugs on the developing brain, and the capacity for functional plasticity in younger patients.

Previous studies report controversial results concerning the factors that predict postoperative outcome of seizures (Wyllie et al., 1998; Gashlan et al., 1999; Paolicchi et al., 2000; Cossu et al., 2008).

The aim of the present study was to analyze the clinical outcome after surgery according to the Engel classification (1993), and to identify factors related to a favorable seizure control among several presurgical, surgical, and postsurgical variables.

Material and Methods

After a retrospective review of the records of all patients operated on for medically refractory focal epilepsy at the “C.Munari” Epilepsy Surgery Center of the Niguarda Hospital in Milan from 1998 to 2009 (910 patients), we identified 120 children (age at surgery younger than 16 years).

Presurgical investigations and surgery were performed only after the patients’ parents (or tutors) had given their informed consent. A comprehensive presurgical workup included the following: (1) anamnestic data to establish family history of epilepsy, age of seizure onset, type and frequency of seizures; (2) neurologic examination and, when feasible, neuropsychological profile; (3) interictal scalp electroencephalography (EEG) and, when needed, long-lasting video-EEG (VEEG) monitoring with at least one ictal recording; (4) brain magnetic resonance imaging (MRI) using appropriate sequences, with particular attention to the region(s) of presumed ictal onset.

When appropriate, invasive monitoring with stereotactically implanted multilead intracerebral electrodes (stereoelectroencephalography, SEEG) was performed. SEEG is indicated when noninvasive investigations fail to satisfactorily localize the epileptogenic zone (EZ), according to one (or more) of the following patterns: (1) normal MRI and ictal/interictal scalp EEG findings were incongruous with ictal clinical semiology; (2) focal MRI abnormality and electroclinical findings suggested a wide involvement of extralesional areas; (3) ictal clinical semiology discordant with an apparently localizing ictal scalp EEG pattern (irrespective of MRI evidence); (4) large/diffuse/hemispheric/multifocal/bilateral MRI abnormalities and electroclinical findings suggested a localized/lateralized ictal onset; and (5) anatomic and/or electroclinical involvement of highly eloquent areas. In the latter instance, functional mapping conducted by intracerebral electrical stimulations (IES) allowed identification of both eloquent cortex and subcortical critical bundles. Depending on the child's cooperation, IES were employed to identify primary motor, somatosensory, visual, and speech areas.

All patients received tailored microsurgical resections aimed at removal of the EZ, as defined by anatomoelectroclinical data. Surgical specimens were routinely processed for histologic and immunohistochemical investigations. For histopathologic categorization, the revised World Health Organization (WHO) classification for tumors of the central nervous system (Kleihues & Cavenee, 2000) and a recent classification of focal cortical dysplasias (FCDs) (Tassi et al., 2002) were adopted.

With regard to seizure outcome evaluation, postsurgical follow-up was performed after 6–12 months (T1), 24 months (T2), and 60 months (T3). Postsurgical clinical and EEG data were reviewed: presence and frequency of seizures, EEG abnormalities (in the site of surgery or elsewhere), and number of antiepileptic drugs. Seizure outcome was assessed according to the Engel's classification (Engel, 1996). For reoperated patients, the outcome referred to the last procedure. Clinical variables included in the statistical analysis were the following:

  1. Demographic and clinical data: sex, family history of epilepsy and/or febrile seizures, personal history (prenatal and perinatal antecedents), neuropsychomotor development, neurologic status at time of surgery, age at seizure onset, history of infantile spasms (IS), and age of onset (<6 months, 6–24 months, or >24 months).
  2. Duration of epilepsy.
  3. Semiology of seizures according to Lüders et al. (1998) ictal clinical classification. If present, aura was classified as somatosensory, visual, auditory, olfactory, gustatory, autonomic, abdominal, and psychic.
  4. Specific clinical ictal characteristics: secondary generalization, fall, circadian rhythm (if seizures were present during wakefulness or sleep or both), duration (very brief: <30 s; brief: 30–60 s; long: 60> s; in series), recurrence of epileptic status, postictal deficit (motor or aphasic), seizure frequency: sporadic (<1/month), monthly (1–4/month), weekly (5–30/month), daily (more than 30/month); total number of antiepileptic drugs (AEDs) (0–3; >3).
  5. Electrophysiologic data: background activity: absent, symmetrical, or asymmetrical; interictal EEG abnormalities: type (slow wave or spikes) and site (focal, lobar, multilobar, hemispheric, or bilateral and diffuse); ictal EEG abnormalities: type (fast activity, rhythmic activity, flattening of electrical activity, flattening associated with a rhythmic activity or spasms), use and site of SEEG exploration: frontal unilobar, frontotemporal, central (frontoparietal), multilobar (frontal-parietotemporal), posterior, or hemispheric.
  6. Neuroimaging (MRI) data: presence of anatomic abnormalities, site and extension of the lesion (unilateral or bilateral; lobar or multilobar), other (aspecific) abnormal findings.
  7. Surgical data: age at surgery; site of surgical resection: temporal unilobar, frontal unilobar, temporal “plus,” posterior, including central area or multilobar; number of surgical resections, extent of lesion resection.
  8. Postsurgical data: histology of resected tissue, duration of follow-up, electroclinical data at T1 (first follow-up).

Included were 69 boys and 51 girls. The mean age at seizure onset was 47 months (range 1–168, standard deviation [SD] 42).

The mean age at surgery was 10 years (range 1–15, SD 3). The mean duration of epilepsy was 7 years (range 1–14, SD 4).

There were 84 seizure-free patients (70%) (Engel's classes Ia and Ic), 93 (77.5%) in class I, 8 (6.7%) in class II, 9 (7.5%) in class III, and 10 (8.3%) in class IV.

The mean duration of follow-up was of 57 months (range 12–142, SD 34); 98 patients had a postoperative follow-up of at least 24 months.

Statistical analysis

Seizure outcome was categorized as a dichotomous variable: absence (Engel's class I) versus recurrence (Engel's classes II–IV) of disabling seizures. Means (±SD) and percentages were used as descriptive statistics for clinical and demographic features. Univariate comparisons were made between groups using the chi-square test or the Fisher's exact test for categorical data, and the Student's t-test for independent variables for continuous data.

Crude odds ratios (ORs) and corresponding 95% confidence interval (CI) were also computed. Statistical significance was set at the <0.05 level.

A multivariate logistic regression analysis was performed to evaluate the effect of presurgical clinical variables on seizure outcome after surgery. All analyses were performed using STATA/SE for Windows, version 12 (StataCorp, College Station, TX, U.S.A.).


Tables 1-3 shows the results of univariate comparison analysis between the two groups class I and class II–IV.

Table 1. Presurgical clinical variables related to seizure outcome (n = 120)
VariableCategoriesEngel class, no. cases (%)p-Value
  1. a

    Pearson's chi-square test.

  2. b

    Fisher's exact test.

Personal historyNegative82 (84)16 (16)0.001a
Positive11 (50)11 (50)
Neuropsychomotor development/cognitive statusNormal75 (85)13 (15)0.001a
Retarded18 (56)14 (44)
Infantile spasmsPresent10 (50)10 (50)0.003b
Absent83 (83)17 (17)
Secondarily generalized seizuresAbsent80 (82)18 (18)0.022a
Present13 (59)9 (41)
Duration of seizuresVery brief31 (91)3 (9)0.002b
Brief52 (80)13 (20)
Long6 (50)6 (50)
In cluster4 (44)5 (56)
No. of total AEDs0–346 (94)3 (6)<0.0001a
>347 (66)24 (34)
MRI: focal lesionAbsent13 (54)11 (46)0.002a
Present80 (83)16 (17)
MRI: extension of lesionLobar72 (85)13 (15)0.026b
Multilobar12 (60)8 (40)
Epileptogenic zoneFrontal29 (78)8 (22)0.045b
Central6 (67)3 (33)
Frontotemporal0 (0)3 (100)
Temporal47 (81)11 (19)
Posterior9 (90)1 (10)
Hemispheric2 (67)1 (33)
Stereo EEGNone68 (86)11 (14)0.002a
Present25 (61)16 (39)
HistologyCryptogenic4 (50)4 (50)0.031b
Flogistic6 (75)2 (25)
Malformative56 (75)19 (25)
Tumoral27 (93)2 (7)
Table 2. Presurgical clinical variables related to seizure outcome (n = 120)
VariableTotalEngel classp-Value
  1. a

    Data are expressed as mean ± standard deviation (M ± SD).

  2. b

    Student's t-test.

aAge of onset (months) (M ± SD)47 ± 41.7751.59 ± 43.5331.11 ± 30.700.024b
aDuration of epilepsy (years) (M ± SD)7 ± 3.966.63 ± 4.078.29 ± 3.340.055b
Table 3. Multivariate logistic regression for presurgical clinical variables on the seizure outcome
 Univariate associationsModelsa
Crude OR(95% CI)Adjusted OR(95% CI)
  1. a

    Adjusted for sex.

Personal history
Negative1 12.41–37.5
Neuropsychomotor development/cognitive status
Infantile spasms
Absent1 11.73–23.9
Secondarily generalized seizures
Duration of seizures
Very brief0.380.10–1.49 
In cluster5.001.09–22.7 
No. of total AEDs
0–31 11.64–36.1
Age of onset (months)0.990.99–1.00 
Duration of epilepsy (years)1.110.99–1.23 
MRI: focal lesion
Stereo EEG
None1 11.20–12.5

A negative personal history for prenatal and perinatal antecedents, normal psychomotor development/cognitive status, absence of infantile spasms and secondarily generalized seizures, total number of AEDs (<3), and the demonstration of a recognizable focal lesion on MRI correlated with a positive seizure outcome.

Moreover, an older age of seizure onset was significantly associated with a better clinical outcome and a positive trend was found for a short duration of epilepsy.

The use of SEEG when noninvasive investigations fail to localize the epileptogenic zone (EZ) was correlated with a higher probability to result in class II–IV after surgery.

The histology of the epileptogenic lesion was also associated with a positive outcome: tumoral lesions were related to a more favorable outcome than others (cryptogenic, flogisitic, or malformative).

The major of the variables were confirmed to be related to good prognosis after epilepsy surgery by calculation of crude OR as shown in Table 3.

The logistic regression analysis, adjusted for sex, indicates that the risk of seizures after surgery increases for patients with positive personal history (OR 9.52, 95 CI% 2.41–37.5), presence of infantile spasms (OR 6.44, 95 CI% 1.73–23.9), total number of antiepileptic drugs AEDs >3 (OR 7.70, 95 CI% 1.64–36.1), and use of SEEG (OR 3.86, 95 CI% 1.20–12.5) (Table 3).

Accordingly the coexistence of negative personal history, absence of infantile spasms and secondarily generalized seizures, total number of antiepileptic drugs (AEDs) <3, and successful use of noninvasive investigations thus not requiring the SEEG results a significant predictor of a favorable seizure outcome.

Among postsurgical variables, normal electroclinical findings at the first follow-up (T1: 6–12 months) also correlated with a more favorable seizure outcome (Table 4). Other, more specific findings were significantly associated with seizure outcome: age of onset of IS (>24 months), hypomotor seizures, phasic postictal deficit, and focal cortical dysplasia type II (Table 5). Notably, among patients with IS, those with a late onset (>24 months of age) were more frequently seizure-free than those who presented early onset spasms.

Table 4. Postsurgical clinical variables related to seizure outcome (n = 120)
VariableCategoriesEngel class, no. cases (%)p-Value
  1. T1: 6–12 months after surgery.

  2. a

    Pearson's chi-square test.

Seizures at I follow-up (T1)Absent85 (96)4 (4)<0.0001a
Present8 (26)23 (74)
EEG at I follow-up (T1)Normal74 (94)5 (6)<0.0001°
Abnormal19 (46)22 (54)
Table 5. Clinical variables and seizure outcome in selected patient groups
VariableCategoriesTotalEngel class, no. cases (%)p-Value
  1. IS, infantile spasms; FCD, focal cortical dysplasia; MCDs, malformations of cortical development.

  2. a

    Fisher's exact test.

Age of onset of IS<6 month200 (0)7 (100)<0.0001a
6–24 month1 (33)2 (67)
>24 month9 (90)1 (10)
Motor seizuresClonic7721 (70)9 (30)0.019a
Hypomotor39 (89)5 (11)
Hypermotor1 (33)2 (67)
Postictal deficitMotor259 (64)5 (36)0.046a
Phasic11 (100)0 (0)
FCDType I343 (30)7 (70)0.001a
Type II17 (94)1 (6)
Mild MCDs5 (84)1 (16)


The goal of epilepsy surgery is to remove the epileptogenic zone or to interrupt its connections with the surrounding brain without creating new deficits or worsening an existing one.

In addition to the control of disabling seizures, surgery may result in improvement of developmental, psychosocial, and behavioral impairment experienced by children with early onset epilepsy (Duchowny et al., 1998) and submitted to long-lasting antiepileptic therapy (Loring & Meador, 2004). Early surgery in childhood may also take advantage of the child's brain plasticity and enhance recovery from seizure-related damage and from possible postsurgical neurologic deficits. Nevertheless, the prognosis for seizure control is often a puzzling issue, and it may be determined by several variables. Several studies in the literature report controversial results concerning the factors that predict postoperative seizure outcome (Wyllie et al., 1998; Gashlan et al., 1999; Kim et al., 2000, 2001; Paolicchi et al., 2000; Leiphart et al., 2001; Sotero de Menezes et al., 2001; Kloss et al., 2002; Park et al., 2002; Kral et al., 2003; Porter et al., 2003; Hamiwka et al., 2005; Lee et al., 2005; Terra-Bustamante et al., 2005).

Because it has been reported that 2-year postoperative outcome predicts long-term results on seizures (Salanova et al., 1999; Hamiwka et al., 2005), it is reasonable to assume that the results of surgery in our series are sufficiently stable.

Seventy-seven percent of patients resulted in class I according to data reported by literature (Depositario-Cabacar et al., 2008).

The recording of ictal events by long-lasting scalp video-EEG monitoring has been demonstrated as the most important diagnostic tool for localizing the epileptogenic zone as reported by others (Holmes et al., 1996). In our study, invasive explorations with SEEG were required in 41 of patients (34%). The different reported proportions of invasive recordings, ranging from 24% to 73% (Wyllie et al., 1998; Kim et al., 2000; Paolicchi et al., 2000; Sotero de Menezes et al., 2001; Kloss et al., 2002; Kral et al., 2003; Porter et al., 2003; Hamiwka et al., 2005; Terra-Bustamante et al., 2005) probably results from differences in the employed technique (subdural or intracerebral electrodes), in the team's experience, and in the complexity of selected patients.

These data confirm that a negative correlation with seizure outcome was found in relation to the more difficult localization of the epileptogenic zone and to the need to spare eloquent areas.

It might suggest that extratemporal epileptogenic zone, more often requiring the use of SEEG, is associated with a negative prognosis as reported on large pediatric series (Wyllie et al., 1998; Kim et al., 2000; Leiphart et al., 2001).

In the present series, age at onset of epilepsy and duration of epilepsy influenced surgical outcome, with higher chance of recurrences associated with earlier seizure onset.

Recent studies on the effects of seizures in the immature brain may be useful to interpret this finding (Aamodt & Constantine-Paton, 1999; Stafstrom et al., 2000; Ben-Ari & Holmes, 2006).

The establishment of an epileptogenic network at an early stage of brain maturation may result in a more widespread susceptibility to seizures, compared with brains experiencing the first seizure when the main physiologic networks have already developed. In such instances, focal resections could provide less satisfactory results because they interfere with only a part of more diffuse epileptogenic networks, possibly involving a larger amount of abnormally functioning cortex.

The presence of infantile spasms as predictors of intractable epilepsy and a worse postsurgical seizure outcome is worth noting. Nevertheless, a later (>24 months) onset of spasms seems to be associated with a better postoperative seizure outcome. The demonstration of a higher proportion of tumors as the underlying etiology and unilobar epileptogenic lesions in this group of patients in our series might explain this finding.

Most pathologies were represented by malformations of cortical development (MCDs) (62%) and tumors (24%), a figure consistent with other major pediatric surgical series (Wyllie et al., 1998; Kim et al., 2000; Paolicchi et al., 2000; Leiphart et al., 2001; Terra-Bustamante et al., 2005).

In keeping with others (Gashlan et al., 1999), our study found a correlation between good outcome and having a tumor as etiology. MCDs are common causes of epilepsy and developmental delay in children and young adults.

In a review of the literature (Sisodiya, 2000), only 38–40% of patients operated on for FCD achieved Engel Class I one or more years after surgery. Outcome in our patients with FCD was better than the average suggested by literature (73% of FCD patients in class I). This result could be explained by the fact that Taylor-type CD (type II) was more represented in our sample compared to type I CD (53% vs. 30%).

Hippocampal sclerosis (HS) represents the most common pathologic substrate of temporal lobe epilepsy in adults. However, the incidence in children has been reported to be lower: between 13% and 36% (Duchowny et al., 1998). In our study, HS was detected in 20 patients (16%) and it was associated with other lesions in most instances, indicating a prevalence of the so-called “dual pathology” in this population.

Seizure caused by hippocampal sclerosis (HS) is the most common indication for epilepsy surgery in adults, but not in children or adolescents. Similar to our results, Duchowny et al. (1998) and colleagues reported HS in only two (13%) of their preadolescent children who had temporal resection. These data suggest a gradual increase in HS among surgical candidates through adolescence, with a sharp increase during adulthood. However, because temporal lobe epilepsy due to HS often begins in childhood, this late increase might reflect referral bias. Compared with patients who have HS, patients with tumors or severe extratemporal epilepsy caused by cortical malformation may tend to be referred earlier to surgery.

The results of our study also indicate that postoperative seizures and abnormal EEG at the first follow-up (6–12 months) correlated with a less favorable outcome. This finding is in agreement with prior research that indicates that acute postoperative seizures are a predictor of a worse surgical outcome in pediatric postsurgical patients (Park et al., 2002).

In conclusion, our findings demonstrate that some clinical elements are useful to predict postoperative seizure outcome. They also suggest that other more specific clinical criteria could help identify early potential surgical candidates that need to be confirmed by future studies.

Such criteria, if validated, would avoid long surgical delays and prevent the detrimental effect of intractable epilepsy on psychomotor and cognitive development.


The authors have no conflicts of interest. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.