Predictors of epilepsy surgery outcome: a meta-analysis

Epilepsy Research 62 (2004) 75–87

Predictors of epilepsy surgery outcome: a meta-analysis C. Toninia,b , E. Beghia,c,∗ , A.T. Bergd , G. Bogliuna,c , L. Giordanoa , R.W. Newtone , A. Tettoa,f , E. Vitellia,g , D. Vitezich , S. Wiebei a

Laboratory of Neurological Disorders, Institute for Pharmacological Research “Mario Negri”, Via Eritrea, 62, 20157 Milan, Italy b Department of Neurology, Hospital “G. Salvini”, Garbagnate M, Italy c Department of Neurology, University of Milano-Bicocca, Hospital “San Gerardo”, Monza, Italy d Department of Biological Sciences, Northern Illinois University, DeKalb, IL, USA e Department of Neurology, Manchester’s Children’s Hospital, Manchester, UK f Department of Neurology, Hospital “L. Mandic”, Merate, Italy g Department of Neurology, Hospital “Maggiore”, Lodi, Italy h Department of Pharmacology, School of Medicine, University of Rijeka, Rijeka, Croatia i Department of Clinical Neurological Sciences, University of Western Ontario, London, Canada Received 10 February 2004; received in revised form 29 August 2004; accepted 31 August 2004

Abstract The potential efficacy of temporal and extratemporal resection in patients with partial epilepsy uncontrolled by anti-epileptic drugs is undisputed. However, there are still uncertainties about which patients will benefit most. A systematic review of the available literature has been undertaken by four pairs of reviewers to assess the overall outcome of epilepsy surgery and to identify factors better correlated to seizure outcome. A Medline search for studies on epilepsy surgery published since 1984 was performed. Studies were included if they had a well-defined population and design, a sample size of at least 30 patients, an MRI performed in least 90% of cases, an expected duration of follow-up of at least one year, and a post-operative outcome measured as seizure remission. A good outcome was considered as seizure control or seizure-free status for at least one year or Engel class I. Based on the review of 47 articles meeting all the eligibility criteria, febrile seizures (odds ratio, OR, 0.48; 95% confidence interval, CI, 0.27–0.83), mesial temporal sclerosis (OR 0.47; 95% CI 0.35–0.64), tumors (OR 0.58; 95% CI 0.42–0.80), abnormal MRI (OR 0.44; 95% CI 0.29–0.65), EEG/MRI concordance (OR 0.52; 95% CI 0.32–0.83), and extensive surgical resection (OR 0.24; 95% CI 0.16–0.36) were the strongest prognostic indicators of seizure remission (positive predictors); by contrast, postoperative discharges (OR 2.41; 95% CI 1.37–4.27) and intracranial monitoring (OR 2.72; 95% CI 1.60–4.60) predicted an unfavorable prognosis (negative predictors). Firm conclusions cannot be drawn for extent of resection, EEG/MRI concordance and post-operative discharges for the heterogeneity of study results. Neuromigrational defects, CNS infections, vascular lesions, interictal spikes, and side of resection did not affect the chance of seizure remission after surgery.

∗

Corresponding author. Tel.: +39 02 3901 4542; fax: +39 02 3320 0231. E-mail address: [email protected] (E. Beghi).

0920-1211/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.eplepsyres.2004.08.006

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Despite a number of limitations, the results of the review provide some insight into the selection of the best surgical candidates in clinical practice but raise concerns on the quality of published reports, and may serve as the basis for the identification of better standards to assess surgical outcome in observational studies. © 2004 Elsevier B.V. All rights reserved. Keywords: Epilepsy; Extratemporal; Post-operative

1. Introduction Despite optimal pharmacotherapy about 20–30% of patients do not become seizure-free (Annegers et al., 1979; Collaborative Group, 1992; Cockerell et al., 1995; Kwan and Brodie, 2000). For some of these patients, surgery is a therapeutic option. Success of resective epilepsy surgery has been estimated to increase from 43 to 85% during the period 1986–1999 (NIH Consensus Conference, 1990; Engel et al., 1993, 2003). Data from multiple sources suggest that 55–70% of patients undergoing temporal resection and 30–50% of patient undergoing extratemporal resection become completely seizure-free. A recent prospective randomized controlled trial of surgery for temporal lobe epilepsy showed that 58% of patients randomized to surgery was seizure-free compared to 8% of medical group (Wiebe et al., 2001). However, in that study 64% of patients who had surgery were seizure-free. Surgery is considered a valuable option for medically intractable epilepsy even in the absence of a proven drug resistance (Engel and Shewmon, 1993); in addition, surgical outcome may be greatly influenced by the presence of selected prognostic indicators (Tonini et al., 1997; Berg et al., 1998). However, there are still uncertainties on who are the best surgical candidates, i.e., those who are most likely to present good surgical outcome. In a recent narrative literature review of temporal resections, good surgical outcome appeared associated with a number of factors (hippocampal sclerosis, anterior temporal localization of interictal epileptiform activity, absence of preoperative generalized seizures, and absence of seizures in the first post-operative week) (McIntosh et al., 2001). However, the published results were frequently confusing and contradictory, thus preventing inferences for clinical practice. Methodological issues (e.g., sample size, selection criteria, and methods of analysis) were indicated by the authors as the most likely explanation of the conflicting literature reports. For this reason, a

quantitative review of the available literature has been undertaken to assess the overall outcome of epilepsy surgery and to identify the factors better correlating to seizure outcome. The aim of the study was to perform a meta-analysis of the results of published observational studies and assess the prognostic significance of selected variables outlining the characteristics of the clinical condition, the correlations between the epileptogenic and functional lesion, and the type of surgical procedure.

2. Material and methods 2.1. Identification of studies and eligibility criteria A Medline search addressed to studies on epilepsy surgery published since 1984 (the advent of Magnetic Resonance Imaging) was performed. The keywords used in the search were (randomized) trials and epilepsy surgery, neurosurgery, surgical treatment and partial epilepsy, partial seizures and outcome, predictors and predictive factors, and prognosis. The target population was represented by children, adolescents, and adults considered surgical candidates, as having drug resistant partial seizures and secondarily generalized seizures of temporal or extratemporal origin. Studies were included if they satisfied a methodological standard: (1) well-defined study design (prospective and/or retrospective); (2) sample size of at least 30 patients; (3) well-defined population (age, sex, seizure type and frequency, duration of epilepsy, etiology, MRI diagnosis, surgical findings); (4) MRI performed in at least 90% of cases; (5) expected duration of follow-up for at least one year; (6) post-operative outcome measured as seizure remission. Reports were excluded if they were in abstract form, in book chapters, or if they were not sufficiently clear about their methods, they were written in languages other than English, Italian, French,German, or Spanish,

C. Tonini et al. / Epilepsy Research 62 (2004) 75–87

or they did not meet all the above inclusion criteria. Excluded were also repeated publications from the same institution (among which only the most recent was retained for review) unless they were dealing with different prognostic factors. 2.2. Strategy of the systematic review and data collection Eight investigators participated in the study (A.T., A.T.B., C.T., D.V., E.V., G.B., R.W.N., S.W.); the eligible articles were examined by four pairs of reviewers and were reviewed independently; each pair reviewed about one-fourth of the articles and had to reach a consensus on the eligibility of all articles. Consensus was also required on each variable reported in the data collection form; any disagreement led to a new revision of the critical issue by the two reviewers and any persisting disagreement was solved in conference; in selected cases, conflicting data recordings were solved by an independent evaluator (EB). A database was implemented for the identification and inclusion of the suitable articles, i.e., fulfilling the inclusion criteria and with complete information about the outcome of epilepsy and prognostic factors. The data were collected using a semi-structured form for each study. All the following variables were considered: (1) methods of assessment of eligible studies; (2) demographic and clinical characteristics (number of patients selected for surgery, age [with special attention to patients younger and older than 12 years],

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sex, disease duration, history of febrile seizures or relevant CNS disorder); (3) MRI pre-operative diagnosis (mesial temporal sclerosis, tumors, other CNS abnormalities, normal); (4) surgical findings (age at surgery, side of resection, surgical procedure [temporal or extratemporal], extent of resection); (5) histopathological diagnosis (same categories as MRI); duration of follow-up; post-surgery findings (drop-outs, adverse events); (6) prognostic indicators: different indicators were described as factors affecting the outcome of epilepsy surgery in terms of seizure remission (neuromigration defects, febrile seizures, tumors, vascular disorders, CNS infections, mesial temporal sclerosis, abnormal MRI, EEG/MRI concordance, interictal spikes, intracranial monitoring, extent of resection, post-operative discharges). Mesial temporal sclerosis and tumors required pathological confirmation. The review was limited to factors, which were clinically relevant and/or reported by at least two studies. The outcome of seizures after epilepsy surgery was classified according to the Engel’s four categories (1987) (Table 1) or it was reported as such when different definitions were used. We considered good outcome as seizure control or seizure-free status for at least one year or Engel class I; improved outcome as near complete control or moderate improvement or Engel classes II and III; worse outcome as slightly reduced or unchanged or worsened seizure frequency or Engel class IV. For the purposes of this review, improved and worse outcome were then combined into a single category (poor outcome).

Table 1 Classification of the outcome of epilepsy surgery Class 1

Free of disabling seizures Completely seizure-free since surgery, non-disabling simple partial seizures only since surgery, some disabling seizures after surgery but completely seizure-free for at least two years, and convulsions only when medications are withdrawn

Class 2

Almost seizure-free Initially seizure-free but has disabling seizures now, rare disabling seizures since surgery, more than rare seizures after surgery but now rare seizures for at least two years, nocturnal seizures only

Class 3

Worthwhile improvement Worthwhile seizure reduction or prolonged seizure-free intervals amounting to half the follow-up period, but not less than two years

Class 4

No worthwhile improvement No significant seizure reduction, no appreciable change, or seizures getting worse

Source: Engel (1987).

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2.3. Data analysis Each study’s results were assessed for heterogeneity using the chi-square test. For each prognostic factor the raw numbers were pooled into a 2 × 2 contingency table correlating that variable, whether present or absent, to the outcome of surgery (good versus poor). For each variable the chance of seizure remission (good outcome) was calculated as odds ratio with 95% confidence interval. Data analysis was performed in the entire sample (all surgical sites) and, separately, in patients undergoing temporal resection.

3. Results 3.1. Description of studies and clinical characteristics The Medline search (1984–2001) selected 1051 studies on epilepsy surgery of which 619 were excluded because the prognosis of seizures after surgery was not assessed, and 383 were excluded because they met one or more exclusion criteria. Two additional studies were excluded because the same patient population and the same prognostic indicators were considered in a subsequent (more recent) publication. Only 47 articles met all the pre-requisites for eligibility. Ten studies were prospective, 35 were retrospective, and 2 both prospective and retrospective (see Appendix A). Temporal lobe resection was reported in 29 studies, extratemporal resection in 2 studies, and both temporal and extratemporal resection in 16 studies. The sample included 3336 adults and 175 children. There were 1247 women (35%) and 1469 men (42%) whose age at surgery ranged from less than 1–86 years. Sex was not specified in 795 cases (23%). Disease duration ranged from less than 1–81 years. Side of resection was left in 1089 cases (31%), right in 1014 cases (29%), and unspecified in 1408 cases (40%). MRI findings were available for 3475 patients (99%); of these, 2073 (60%) were abnormal, 536 (15%) were normal, and 866 (25%) were not specified. The commonest abnormalities included mesial temporal sclerosis (1116 cases), tumors (457 cases), and cortical dysplasia (74 cases). Surgical specimens were available for 1813 patients and were normal in 157 cases (9%) and abnormal in

1656 cases (91%); the commonest abnormal findings included mesial temporal sclerosis (694 cases), tumors (468 cases), and cortical dysplasia (168 cases). The variables considered were not defined in all studies; Appendix A shows the general characteristics of the sample. The duration of follow-up varied from 4 to 216 months. Adverse events of epilepsy surgery were reported in 17 studies (36%) and were characterized by wound infections (0.9%), hemiparesis (0.5%), hemianopsia (0.4%), and language disturbances (0.2%); in 18 studies (38%) adverse events were not described and in 12 studies (26%) they were not assessed. 3.2. Surgical seizure outcome A total of 3511 patients were assessed. Seizure outcome was assessed using the Engel’s classification in 22 studies and other definitions in 25. A good outcome was achieved in 2223 cases (63%); 732 patients (21%) had an improved outcome, while 418 cases (12%) had a poor outcome. Outcome was not specified in 138 patients (4%). Seizure-free patients were 35–80% (median 67%). 3.3. Factors predicting prognosis Figs. 1 and 2 show the OR with 95% CI for poor outcome for each prognostic factor, and the heterogeneity of the eligible studies. Febrile seizures (OR 0.48; 95% CI 0.27–0.83), abnormal MRI (OR 0.44; 95% CI 0.29–0.65), mesial temporal sclerosis (OR 0.47; 95% CI 0.35–0.64), tumors (OR 0.58; 95% CI 0.42–0.80), EEG/MRI concordance (OR 0.52; 95% CI 0.32–0.83), and extensive surgical resection (OR 0.24; 95% CI 0.16–0.36) were the strongest prognostic indicators of seizure remission after epilepsy surgery (positive predictors); by contrast, post-operative discharges (OR 2.41; 95% CI 1.37–4.27) and intracranial monitoring (OR 2.72; 95% CI 1.60–4.60) predicted an unfavorable prognosis (negative predictors); neuromigrational defects (OR 1.51; 95% CI 0.96–2.37), CNS infections (OR 1.37; 95% CI 0.54–3.46), vascular lesions (OR 1.51; 95% CI 0.68–3.34), interictal spikes (OR 0.55; 95% CI 0.25–1.16), and side of resection (OR 1.7; 95% CI 0.74–1.84) did not affect the chance of seizure remission after surgery.

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Fig. 1. Patient-related predictors of surgical outcome. For each variable, the data are expressed as odds ratios (OR). Squares represent each independent study and diamonds show pooled data with 95% confidence intervals (CI).

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The predictive value of prognostic factors was higher where heterogeneity of study results was lower, except for extent of resection (p = 0.001), EEG/MRI concordance (p = 0.044), and post-operative discharges (p = 0.035), where conflicting data emerged with only some studies reporting a favorable outcome. The results were virtually unchanged when the analysis was limited to temporal lobe surgery.

4. Discussion The potential efficacy of temporal and extratemporal resection in patients with partial epilepsy uncontrolled

by conventional treatment is undisputed (Engel et al., 2003) and has been confirmed by our review, which showed that about two-third of patients had a good surgical outcome. The safety of the surgical procedures has been also confirmed here and is in line with other reports showing that less than 5% of patients have permanent post-operative neurological deficits secondary to accidental damage of CNS tissue (Engel, 1996; Engel et al., 2003). Although the criteria adopted to identify the indications and the applications of epilepsy surgery have evolved in the last decades (Engel and Shewmon, 1993; Spencer, 1994), no attempt was made to define patient and procedure-related prognostic indicators. This systematic review showed that the

Fig. 2. Procedure-related predictors of surgical outcome. For each variable, the data are expressed as odds ratios (OR). Squares represent each independent study and diamonds show pooled data with 95% confidence intervals (CI).

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Fig. 2. (Continued ).

strongest predictors of success of surgery include, in decreasing order, the extent of resection, an abnormal (any type) MRI finding, mesial temporal sclerosis, history of febrile seizures, EEG/MRI concordance, and tumor. By contrast, adverse prognostic factors include the need of intracranial monitoring and the presence of post-operative discharges. A better surgical outcome after extensive compared to limited resection has been confirmed by the consistency of the examined reports (all but two showing a higher rate of seizure remission in patients undergoing extensive resection). This finding is confirmed by the results of a randomized clinical trial (included in the review) comparing extensive (total hippocampectomy) and restrictive resection (partial hippocampectomy) in patients with temporal lobe epilepsy (Wyler et al., 1995). In that study, at one year post-operatively, the total hippocampectomy group had a significantly

better seizure outcome compared with the partial hippocampectomy group (69% versus 38% seizure-free), and examination of time to first seizure (survival analysis) revealed significantly superior outcomes associated with total hippocampectomy. Anteromesial temporal lobe resections (most commonly indicated for surgical removal of mesial temporal sclerosis) have been repeatedly followed by seizure remission, as shown by the results of a recent review (Engel et al., 2003). In this report, 1150 out of 1769 patients were free of disabling seizures. In addition, in a multivariable analysis model, mesial temporal sclerosis coupled with documented etiology and partial seizures was found to identify patients with nearly 100% chance of being seizure-free (Berg et al., 1998). Mesial temporal sclerosis is the specific pathophysiologic basis of mesial temporal lobe epilepsy, which is the prototype of a surgically remediable syndrome (Engel, 1996).

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Compared to other CNS lesions, tumors are followed by a higher chance of seizure remission. Outcome is best for patients with neoplastic lesions and temporal lobe (Schramm et al., 2001) or frontal lobe epilepsy (Zaatreh et al., 2002) and is independent of the duration of their seizures. This finding is biologically plausible, as the epileptogenic area is more easily detectable and represents a focal pathology whereas non-tumoral lesions represent a heterogeneous group of clinical conditions, often with more diffuse pathology, many of which are less easily resectable resulting in a poor surgical outcome. The good outcome associated with the presence of any abnormal MRI findings can be interpreted in the light of the positive outcome with the commonest abnormalities detected by MRI (mesial temporal sclerosis and tumors). Consistency of findings across studies and homogeneity of results are against a chance finding. Although there are occasional reports showing that the prognosis of epilepsy surgery is better or uneventful in patients with normal neuroimaging (Sotero de Menezes et al., 2001; Roberts et al., 2001), it must be noted that an abnormal MRI may reflect a variety of CNS conditions, which we know are associated with a good prognosis. Mesial temporal sclerosis, glial tumors, and congenital malformations are all intended as discrete structural lesions, which are surgically remediable syndromes (Engel, 1996). The good outcome associated with a history of febrile seizures can be interpreted in the light of their association with mesial temporal sclerosis. Although, based on experimental and clinical evidence, it is still unknown whether prolonged febrile seizures and febrile status epilepticus are a risk factor for mesial temporal sclerosis (Maher and McLachlan, 1995; Davies et al., 1996; Sarkisian et al., 1999; Szabo et al., 1999; Scott et al., 2002), the strong association between the two conditions seems undisputed. EEG/MRI concordance is correlated with positive surgical outcome. Hippocampal atrophy documented by volumetric analysis shows lateralization of an epileptic focus in up to 93% of cases, consistent with the results of lateralized EEG findings. These non-invasive methods decrease the need for invasive investigations in patients with temporal lobe epilepsy (Cascino et al., 1991; Cendes et al., 1993). The poor prognostic sig-

nificance of intracranial recording may be interpreted on this basis, as invasive monitoring is now limited to patients with medically refractory seizures who do not fulfill the criteria for a surgically remediable syndrome. In these cases, less than 50% of cases may become seizure-free post-operatively (Engel, 1996). Invasive EEG recording may be required when scalp EEG does not localize the epileptogenic area documented by MRI, an EEG epileptogenic focus is not confirmed by neuroimaging, MRI shows a large atrophic area or cortical dysplasia, or functional mapping is necessary because the epileptogenic lesion lies close to cortical areas where essential functions are represented. Patients requiring intracranial recording may thus have less easily identifiable epileptogenic areas, which per se prevent successful surgical approach. Persistence of post-operative discharges may be subjected to similar interpretations. However, this latter finding still requires investigation as our data may be biased by the significant heterogeneity of the study results. The prognostic significance of other clinical conditions (CNS infections, vascular disorders, neuromigrational defects) is ill-defined. The heterogeneity and the variable severity of CNS infectious or vascular disorders may explain why the prognosis of epilepsy surgery cannot be anticipated for the entire disease category and should be assessed on an individual basis. Seizure freedom in patients with neuromigrational defects is uncertain owing to difficulties in defining and fully excising the epileptogenic cortex (Duchowny et al., 2000). In addition, cerebral malformations may be part of a multifocal process in which another lesion, which cannot be visualized (and is not removed) is actually responsible for the epileptic condition. Large brain malformations (confined to one hemisphere) may be also included. In these cases, the surgical success may be less likely (Engel, 1996). The small number of studies subjected to review is another possible explanation of our negative findings. This review has several limitations. Some are intrinsic in the procedure of any systematic review and others pertain to lack of standard criteria for the implementation and conduct of observational studies of surgical outcome. The first major limitation is intrinsic to all studies based on data pooling and meta-analysis. Although an oversimplification was used here to define surgical outcome (i.e., seizure remission), data

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were extracted from studies using different criteria for seizure outcome or a coding system – the Engel’s classification (Engel, 1987) – whose class I includes individuals completely seizure-free, non-disabling simple partial seizures, some disabling seizures after surgery but no seizures for at least two years, or convulsions only after medication withdrawal. A second limitation is the variable length of the follow-up across studies. We limited our review to studies with an expected follow-up of at least one year (actually, duration of follow-up was less than 12 months in few patients). Although this interval can be considered crucial for the prediction of surgical outcome, the chance of seizure remission after surgery can be significantly affected by the differing duration of follow-up. A third limitation is inherent to the forced dichotomization of each putative prognostic predictor, which means that each factor is contrasted to a variety of other factors (e.g., tumor or mesial temporal sclerosis) or it may include a number of different conditions (e.g., abnormal MRI) each of which may be associated with differing clinical outcomes. A fourth limitation is that any variable was examined without considering the role of other (known or unknown) confounders, which may be the true prognostic predictors. This limitation refers to factors like the use of intracranial recording and febrile seizures. In addition, we cannot know the prognostic significance of factors other than those examined in this review. Last (but not least) is the presumed heterogeneity of the examined studies, which mostly depends on the differing design and the changing techniques and operative procedures. Engel et al. (2003) identified major methodological deficiencies in the published studies on epilepsy surgery, which included the retrospective design, the scarcity of data on pre-operative seizures, and the absence of masking in seizure outcome assessment. In their extensive review of seizure outcome after temporal resection, McIntosh et al. (2001) identified several characteristics which are likely to have contributed to the high percentage of inconclusive findings: different procedures for the selection of surgical candidates, small sample numbers, differing technological and procedural approaches, and varied outcome measurements. The use of a retrospective design may also bias the study results for the lack of standardization in data collection and the differing duration of follow-up. We attempted to control these sources of bias in part by using

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restrictive criteria for study acceptance and measuring the heterogeneity of the study results. With few exceptions, the predictive value of prognostic factors was higher where heterogeneity of study results was lower. These findings reinforce the concept that at least some patient-related predictors (history of febrile seizures, mesial temporal sclerosis, tumors) and a procedure-related predictor (intracranial monitoring) cannot be explained by other variables or unknown factors. By contrast, the significant heterogeneity of the results of studies assessing the extent of surgical resection, the EEG/MRI concordance, and the presence of post-operative discharges prevents us from drawing firm conclusions based on this meta-analysis. The extent of resection may be mostly affected by the underlying pathology, the site of surgery and the changing surgical procedures. In our review, there were two studies showing equal effectiveness of extensive and limited resection. The first study (Morris et al., 1998) assessed surgical outcome in patients with temporal or extratemporal ganglioglioma. In these cases, the extent of surgical resection might be affected by tumor size, which may in turn affect epilepsy outcome after surgery. In the second study (Arruda et al., 1996), two different surgical techniques (amygdalohippocampectomy and temporal lobe resection) were compared in patients with mesial temporal sclerosis. However, the two surgical procedures were performed by two neurosurgeons independently and comparative findings were not available for some disease characteristics, like pre-operative seizure frequency and drug treatments. The potential of confounding is even stronger for EEG/MRI concordance and presence of post-operative discharges. Focal MRI lesions do not necessarily indicate the site of seizure onset (Holmes et al., 1999). There are reports on post-operative discharges showing non-significant findings (Ficker et al., 1999) or variable results depending on follow-up duration (Tuunainen et al., 1994). Poor inter-rater agreement may also be expected in the interpretation of the EEG records, as shown by a recent review of clinical practice (Gilbert et al., 2003). The general consensus in the literature is in fact that post-resection interictal spiking is not a reliable prognostic factor. Even with these limitations, the results of our review provide some insight for the selection of

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the best surgical candidates in clinical practice and raise some concerns on the quality of the published reports, which may serve as the basis for the identification of better standards for the assessment of surgical outcome in future observational studies.

Acknowledgements The authors are indebted to Ms. Vanna Pistotti and Mr. Walter Vigoni for their valuable help in article search, and Ms. Susanna Franceschi for typing the manuscript.

Appendix A Table A1 General characteristics of the studies included in the review Author, year

Study design

Participants (children)

Males

Age at surgery Duration (min–max/y) of epilepsy (min–max/y)

Prognostic indicators studied

Intervention Outcome Good measures outcome (N)

Follow-up (min–max/mos)

Adam et al. (1996) Adelson et al. (1992) Arruda et al. (1996) Awad et al. (1991) Berkovic et al. (1995) Brainer-Lima et al. (1996) Britton et al. (1994) Cascino et al. (1996) Cascino et al. (1995) Chee et al. (1993) Prevedello et al. (2000) Delbeke et al. (1996) Duchowny et al. (1998) Erba et al. (1992) Garcia et al. (1991) Garcia et al. (1994) Gilliam et al. (1997a,b) Gilliam et al. (1997a,b) Goldstein et al. (1996) Holmes et al. (1997) Holmes et al. (2000) Jack et al. (1992) Jennum et al. (1993) Jeong et al. (1999) Kilpatrick et al. (1997) Kuzniecky et al. (1993) Kuzniecky et al. (1996) Li et al. (1997) Li et al. (1999) Lorenzo et al. (1995) Malla et al. (1998) Mathern et al. (1999) Morris et al. (1998) O’Brien et al. (1996) O’Brien et al. (2000) Paolicchi et al. (2000) Radhakrishnan et al. (1998) Rossi et al. (1994) Salanova et al. (1994) Sperling et al. (1992) Swartz et al. (1992) Weinand et al. (1992)

PR RE RE RE PR RE RE RE RE RE RE RE RE PR RE PR RE RE RE RE RE CO RE RE PR PR RE RE RE RE RE RE RE RE RE RE CO RE RE PR PR RE

30 33 74 47 135 32 (7) 51 159 165 40 84 38 31 (31) 46 55 51 33 78 33 44 126 50 64 93 50 34 47 64 38 48 160 198 38 46 36 83 (75) 175 138 98 51 34 89

11 19 34 38 NS 24 NS NS NS 25 48 15 16 28 NS NS 18 40 17 17 71 27 45 54 28 14 20 23 23 NS 77 111 22 24 23 40 77 100 46 31 NS NS

18–44 0–17 32.1 (10.5)** 2–45 11–58 6–57 6–60 11–57 32.1 (10.5)** 18–53 19–43 15–59 0–3 4–34 9–47 NS 1–12 9–50 0–15 14–55 6–69 14–51 8–52 9–51 16–57 7–38 7–42 8–73 14–63 NS 8–57 0–37 2–56 16–58 1–56 0–12 7–86 1–46 8–53 17–59 29 (NS)** 6–52

h, j c * , g* , h* , f* i i c, g k i x j l j c g c, e, f m c, g, h, k d, f g, k c, f, l a, h b, k x c, i, m a, c c, d, f a, c, g c * , g* e, f, i c g c * , g* , h* b, c, d, e, f h, i c d, f, g, h, k d, f, g, i a, c, g, m f, i, k a, c, j, l f x a * , c* , f* , k*

T T–EXT T T–EXT T T–EXT T–EXT T T T T T T–EXT T T T T–EXT T T T T–EXT T T–EXT T T T T T–EXT T–EXT EXT T T–EXT T–EXT T T–EXT T–EXT T T–EXT T T T T

12–44 18–72 33.4 (13.1)** 20–114 18–81 4–68 24–96 12–70 12 12 15–44 18–58 12 38–216 12–48 12–48 7–72 12 24–120 62–48 24–72 12–34 12 18–33 12–38 12–30 12 12–157 12–180 12 12–94 6–120 6–41 12–33 12–40 12–120 24–68 36 12–96 21–64 20–71 12–54

NS NS NS 0–29 NS 2–30 NS –2 NS 3–36 10–33 NS NS 1–31 NS NS 1–11 NS 0–12 3–46 1–46 2–37 1–38 NS NS 2– NS NS NS NS 2–55 0–31 1–29 2–43 NS NS 0–81 3– 1–43 NS NS 2–42

E A E O E E E E E A E E O O E O O A O A O O O O E O E E E E E O A E O O O O E E E A

26 23 53 27 74 29 34 111 113 28 53 23 16 37 35 36 22 53 15 22 54 40 42 78 39 23 32 44 16 17 116 78 26 36 14 44 134 86 53 41 27 57

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Table A1 (Continued) Author, year

Study design

Participants (children)

Males

Age at surgery (min–max/y)

Duration of epilepsy (min–max/y)

Prognostic indicators studied

Intervention

Outcome measures

Good outcome (N)

Follow-up (min–max/mos)

Weinand et al. (2001) Wyler et al. (1995) Wyllie et al. (1998) Zentner et al. (1995) Zentner et al. (1996)

RE PR RE RE PR

48 70 136 (62) 178 60

31 33 78 82 39

12–54 NS 13–20 3–64 1–49

NS NS NS 2–52 2–35

x i d, f, h c, f f, i

T T T–EXT T EXT

O O E E O

33 37 93 103 30

12–47 12 12–88 12–72 20–85

Ref: reference; RE: retrospective; PR: prospective; CO: retrospective and prospective combined; NS: not specified; T: temporal; EXT: extratemporal; A: seizure-free > one year; E: Engel classification; O: other definitions (see text for explanation); a: febrile seizures; b: CNS infections; c: mesial temporal sclerosis; d: neuromigration defects; e: vascular diseases; f: tumor; g: abnormal MRI; h: intracranial monitoring; i: extent of resection; j: side of resection; k: EEG/MRI concordance; l: interictal seizures; m: post-operative discharges; x: other variables not studied (mental retardation; unilateral ictal ECoG; subdural ictal EEG; underlying pathology by PET, quantitative MRI, MRI hippocampal volumetry); yr: year; mos: months. ∗ Rough data unavailable to calculate the ORs. ∗∗ Mean and S.D.

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