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- Patients and Methods
Purpose: To retrospectively analyze the results on seizures of surgery in children with drug-resistant focal epilepsy. To identify the factors predicting seizure control among several presurgical, surgical, and postsurgical variables.
Methods: One hundred thirteen patients (67 male, 46 female), younger than 16 years, operated on from 1996 to 2004 and followed-up for at least 2 years were identified. Individualized microsurgical resections, aimed at removal of the epileptogenic zone, were performed according to the results of tailored presurgical evaluations, which included stereo-electroencephalographic recording with intracerebral electrodes when needed. Risk of seizure recurrence was assessed for the considered variables by bivariate and multivariate analysis.
Results: Mean age at surgery was 8.8 years, mean duration of epilepsy was 5.7 years, and mean age at seizure onset was 3.1 years. One hundred eight patients (96%) had an abnormal magnetic resonance imaging. At postoperative follow-up (mean duration 55.1 month), 77 patients (68%) were in Engel's class I, with 68 patients (60%) being seizure free (Engel's classes Ia and Ic). At multivariate analysis, variables associated with a significantly lower risk of seizure recurrence were unifocal lesion at MRI and older age at seizure onset (presurgical variables), temporal unilobar resection and complete lesionectomy (surgical variables), diagnosis of glial-neuronal tumors (postsurgical variables).
Conclusions: Surgery is a valuable option for children with drug-resistant focal epilepsies which may provide excellent results in a considerable amount of cases. Since results of surgery for epilepsy strongly depend on the presurgical identification of the Epileptogenic Zone, future work should be focused on refinement and implementation of diagnostic strategies.
In the last years, increasing consensus has grown on the efficacy of surgery to treat drug-resistant focal epilepsy in children (Wyllie et al., 1998; Leiphart et al., 2001; Bittar et al., 2002). In addition to control of disabling seizures, surgery may result in improvement of developmental, psychosocial and behavioural impairment experienced by children with early-onset epilepsy (Duchowny et al., 1998) and submitted to long-lasting antiepileptic therapy (Loring and Meador, 2004). Moreover, early surgery in childhood may take advantage of the child's brain plasticity and enhance the chances of 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. Furthermore, previous studies report controversial results concerning the factors which predict the postoperative outcome on seizures (Wyllie et al., 1998; Gashlan et al., 1999; Kim et al., 2000; Paolicchi et al., 2000; Kim et al., 2001; Kral et al., 2001; Leiphart et al., 2001; Sotero de Menezes et al., 2001; Kloss et al., 2002; Park et al., 2002; Porter et al., 2003; Hader et al., 2004; Hamiwka et al., 2005; Lee et al., 2005; Terra-Bustamante et al., 2005).
The aim of the present retrospective study was to analyze our experience in the surgical treatment of pediatric patients with drug resistant focal epilepsy, and to identify the factors predicting seizure control among several presurgical, surgical, and postsurgical variables.
- Top of page
- Patients and Methods
There were 67 male and 46 female patients. The mean age at surgery was 8.8 years (range 1–15, SD 4.3), the mean duration of epilepsy was 5.7 years (range, 0–14; SD, 3.8) and the mean age at seizure onset was 3.1 years (range, 0–15, SD, 3.4). Twenty-one patients had a focal neurologic deficit at physical examination: 17 presented a lateralized motor impairment of variable severity, 2 a visual field defect, and 2 had both a motor impairment and a visual field defect. Epileptologic antecedents were reported in 11 cases, and consisted of threatened abortion in 4 cases, placenta detachment in 2 cases, fetal suffering combined with febrile convulsions in 2 cases, gestosis in 1 case, mother's abdominal trauma during pregnancy in 1 case. All patients experienced seizures despite adequate trials of at least 2 antiepileptic drugs appropriate for the seizure type without success. Seizure frequency was daily (more than 30/month) in 65 patients, weekly (five-30/month) in 29 patients, monthly (one-four/month) in seven patients, sporadic (less than one/month) in 12 patients. Eight patients underwent surgery in other Institutions before referral to our Center; in these cases, previous resection had aimed at removal of an identified lesion, with unsatisfactory results on seizure control.
Magnetic resonance imaging
In 108 cases (96%) brain MRI revealed anatomical abnormalities (89 unifocal, 10 multifocal and nine hemispheric). In five patients MRI was normal. Mesial temporal sclerosis (MTS) was suspected at MRI in seven cases (six with a focal lesion and one with a hemispheric abnormality).
Seventeen patients underwent only interictal scalp EEG evaluation. In these cases, full convergence, as to localization of the EZ, of interictal EEG abnormalities, ictal clinical semiology and MRI findings enabled surgery without further investigations. In 55 cases, scalp video-EEG recording of habitual seizures was required, along with MRI, to define the surgical strategy. The remaining 41 patients received a SEEG investigation. Electrodes were stereotactically implanted monolaterally in 37 patients; four other patients had a prevailing monolateral implant, with some electrodes sampling also contralateral structures. The average monitoring period was eight days (range 1–21), and the whole procedure, including the sessions of IES for seizure induction and functional mapping, was generally well tolerated. The only complication was the breakage of an electrode under the cranial vault during an agitated seizure in a 13-year-old boy, which required surgical removal with no further sequelae.
Five patients (all with a negative MRI) underwent a cortical resection (corticectomy), based only on the electroclinical findings (1 scalp video-EEG and 4 SEEGs). In 90 cases a cortical resection was associated to lesionectomy, and the remaining 18 patients received a pure lesionectomy.
Table 1 details the sites of surgery. Twenty-one unilobar (18 extratemporal, three temporal), and 20 multilobar resections were performed after a SEEG investigation.
Table 1. Sites of surgical resections
|Site of resection||No. cases||%|
|Temporal unilobar||43||38 |
|Frontal unilobar||32||28 |
|Temporal +|| 4||4|
| Parietal|| 2|| |
| Occipital|| 1|| |
| Frontal|| 1|| |
| Occipital|| 1|| |
| Parietal|| 3|| |
| Occipital-parietal|| 5|| |
| Occipital and/or parietal + posterior temporal||11 || |
|Including central area|| 9||8|
| Central alone|| 1|| |
| Frontocentral|| 6|| |
| Parietocentral|| 2|| |
|Wide multilobar|| 5||4|
Ten patients (2 temporal, 2 frontal, and 6 multilobar resections) underwent a second operation, owing to poor seizure control following the first resection.
Surgical complications were observed in 4 cases (1 epidural empyema, one depressed skull fracture caused by the Mayfield clamp, 2 transient supratentorial hydrocephali).
New permanent postoperative deficits occurred in 11 cases (10%). One of these (a 1-year-old female patient with catastrophic epilepsy) presented an expected left hemiparesis after resection of a right parietocentral Taylor's FCD; the other 10 patients had new visual field defects. New transient morbidity was observed in 15 cases (13 limb motor impairments, 1 central facial palsy, 1 diplopia).
None of the 21 patients with preoperative focal deficits showed normalization of their neurologic status. In 3 cases, the preexisting deficits (2 hemiparesis, 1 visual field defect) were permanently worsened.
Results of histopathologic evaluations of surgical specimens are detailed in Table 2. Multiple pathologies were found in 27 cases. The most frequent association was among different forms of malformations of cortical development (MCD) (10 cases), followed by that of tumors with MCD (7 cases) and of MTS with other lesions (“dual pathology,” 9 cases). In 1 case both postinfarction and postencephalitic changes were found. In 2 cases MTS was the sole finding. Three patients had no histologic changes, but in 1 of these a previous diagnosis of low-grade glioma after earlier surgery was reported from another Institution.
Table 2. Pathologic findings disclosed at histologic examination of resected specimens
| Focal cortical dysplasias|| |
| Taylor's type||25|
| Tuberous sclerosis||11|
| Other MCD||27|
| Neuronal/glial-neuronal tumors|| |
| Gangliocytoma||2 (+1*)|
| Other tumors||7 (+1*)|
| Chronic/Rasmussen encephalitis|| 5|
| Cavernous angioma||2 (+1*)|
| Infarction gliosis|| 3|
| Postoperative gliosis|| 2|
|Mesial temporal sclerosis||11|
|No histological abnormalities|| 2|
Outcome on seizures
All the patients had a postoperative follow-up of at least 24 months (mean, 55.1 months; SD, 24.8; range, 24–115). According to the Engel's classification, there were 68 (60%) seizure-free patients (Engel's classes Ia and Ic), 77 (68%) in class I, 10 (9%) in class II, 11 (10%) in class III and 15 (13%) in class IV. For one child deceased for malignant progression of a grade II ganglioglioma, the last available outpatient control (6 years postoperatively) was considered. The outcome did not significantly differ between patients younger or older than 12 years.
At bivariate analysis, the variables significantly associated with seizure outcome were (Tables 3 and 4): preoperative MRI (p = 0.0009), age at seizure onset (p = 0.008), complete lesion removal (p = 0.0015), site of surgical resection (p = 0.00002), histologic diagnosis of neuronal/glial-neuronal tumor (p = 0.002) and of encephalitis (p = 0.035).
Table 3. Categorical variables and outcome on seizures: results of the bivariate statistical analysis (two-tailed Fischer's exact test)
|Variable||Type||Categories||Frequencies (no. cases)||Engel's Class (%)||p-value|
| Sex||Binomial||male|| 67|| 72||28||0.412|
|female|| 46|| 63||37|| |
| Seizure frequency||Multinomial||sporadic||12|| 92|| 8||0.310|
|monthly|| 7|| 71||29|| |
|weekly|| 29|| 66||34|| |
|daily|| 65|| 65||35|| |
| VEEG||Binomial||performed|| 96|| 65||35||0.087|
|not performed|| 17|| 88||12|| |
| SEEG||Binomial||performed|| 41|| 59||41||0.141|
|not performed|| 72|| 74||26|| |
| Lesion at MRI||Binomial||unifocal|| 89|| 76||24|| |
|not unifocal (multifocal/hemispheric/absent)|| 24|| 38||62||0.0009*|
| Complete lesionectomy||Binomial||performed|| 72|| 79||21||0.0015*|
|not performed|| 41|| 49||51|| |
| Resection side||Binomial||right|| 57|| 70||30||0.689|
|left|| 56|| 66||34|| |
| Resection site||Multinomial||Temporal|| 43|| 91||9|| |
|Frontal|| 32|| 63||37||0.00002*|
|Posterior|| 20|| 60||40|| |
|Incl. Central|| 9|| 56||44|| |
|Temporal-plus|| 4|| 25||75|| |
|Wide multilobar|| 5|| 0||100 || |
| FCD||Binomial||present|| 54|| 61||39||0.158|
|absent|| 59|| 75||25|| |
| Other MCD||Binomial||present|| 34|| 62||38||0.382|
|absent|| 79|| 71||29|| |
| Neuronal/glial-nuronal tumors||Binomial||present|| 35|| 89||11||0.002*|
|absent|| 78|| 59||41|| |
| Other tumors||Binomial||present|| 8|| 75||25||1|
|absent||105|| 68||32|| |
| Cavernous angiomas||Binomial||present|| 3||100||0||0.550|
|absent||110|| 67||33|| |
| Encephalitis||Binomial||present|| 5|| 20||80||0.035*|
|absent||108|| 70||30|| |
| Gliosis||Binomial||present|| 5|| 60||40||0.653|
|absent||108|| 69||31|| |
| Mesial temporal sclerosis||Binomial||present|| 11|| 64||36||0.742|
|absent||102|| 69||31|| |
| Histologic abnormalities||Binomial||present||111|| 68||32||1|
|absent|| 2||100||0|| |
Table 4. Numerical variables and outcome on seizure: results of the bivariate statistical analysis (Kruskal-Wallis rank sum test)
|Variable||All patients median (IQ range)||Engel's Class||p-value|
|I median (IQ range)||II-IV median (IQ range)|
|Age at seizure onset (yr)||2 (1–4)||2 (1–5) ||1 (0–3) ||0.008*|
|Duration of epilepsy (yr)||5 (3–8) ||5 (2–8) ||6 (3–9) ||0.352 |
|Age at surgery (yr)||9 (6–12)||9 (6–12)||7 (6–12) ||0.187 |
|Follow-up duration (mo)||57 (32–72)||52 (32–63)||60.5 (34.3–79.5)||0.327 |
The fitted regression models (Table 5) indicated a lower probability of seizure recurrence in patients with an unifocal lesion at MRI and in those with an older age at seizure onset (presurgical variables), in cases who received a temporal unilobar resection and in those submitted to complete lesionectomy (surgical variables) and in subjects with a diagnosis of neuronal/glial-neuronal tumors (postsurgical variables).
Table 5. Output of the fitted logistic regression models for, respectively, presurgical, surgical, and postsurgical variables, with recurrence of seizures (Engels classes II-IV) being the dependent variable
|Variables||Reference category||Compared category||p-value||OR||CIOR||RR||CIRR|
|Presurgical (pseudo-R2= 0.13)|
| Preoperative MRI||Unifocal lesion||Not unifocal (multifocal/hemispheric/absent)||0.002||0.20||0.07|| 0.54||0.25||0.09||0.60|
| Age at seizure onset||–||–||0.03 ||0.83||0.69|| 0.97||NA||NA||NA|
|Surgical (pseudo-R2= 0.23)|
| Resection site||Unilobar temporal||Frontal||0.008||5.53||1.66||22.20||2.07||1.33||2.51|
|Temporal-plus||0.012||25.78 ||2.51||615.72 ||1.18||1.18||1.33|
| Complete lesionectomy||No||Yes||0.05 ||0.40||0.23|| 1.01||0.45||0.18||1.01|
|Postsurgical (pseudo-R2= 0.08)|
| Neuronal/glial-neuronal tumor||Absent||Present||0.004||0.19||0.05|| 0.53||0.20||0.06||0.56|