Surgery for epilepsy

Siobhan West; Sarah J Nevitt; Jennifer Cotton; Sacha Gandhi; Jennifer Weston; Ajay Sudan; Roberto Ramirez; Richard Newton

doi:10.1002/14651858.CD010541.pub3

. 2019 Jun 25;2019(6):CD010541. doi: 10.1002/14651858.CD010541.pub3

Surgery for epilepsy

Siobhan West ^1,^✉, Sarah J Nevitt ², Jennifer Cotton ³, Sacha Gandhi ⁴, Jennifer Weston ⁵, Ajay Sudan ¹, Roberto Ramirez ⁶, Richard Newton ¹

Editor: Cochrane Epilepsy Group

PMCID: PMC6591702 PMID: 31237346

Abstract

Background

This is an updated version of the original Cochrane review, published in 2015.

Focal epilepsies are caused by a malfunction of nerve cells localised in one part of one cerebral hemisphere. In studies, estimates of the number of individuals with focal epilepsy who do not become seizure‐free despite optimal drug therapy vary between at least 20% and up to 70%. If the epileptogenic zone can be located, surgical resection offers the chance of a cure with a corresponding increase in quality of life.

Objectives

The primary objective is to assess the overall outcome of epilepsy surgery according to evidence from randomised controlled trials.

Secondary objectives are to assess the overall outcome of epilepsy surgery according to non‐randomised evidence, and to identify the factors that correlate with remission of seizures postoperatively.

Search methods

For the latest update, we searched the following databases on 11 March 2019: Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946 to March 08, 2019), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP).

Selection criteria

Eligible studies were randomised controlled trials (RCTs) that included at least 30 participants in a well‐defined population (age, sex, seizure type/frequency, duration of epilepsy, aetiology, magnetic resonance imaging (MRI) diagnosis, surgical findings), with an MRI performed in at least 90% of cases and an expected duration of follow‐up of at least one year, and reporting an outcome related to postoperative seizure control. Cohort studies or case series were included in the previous version of this review.

Data collection and analysis

Three groups of two review authors independently screened all references for eligibility, assessed study quality and risk of bias, and extracted data. Outcomes were proportions of participants achieving a good outcome according to the presence or absence of each prognostic factor of interest. We intended to combine data with risk ratios (RRs) and 95% confidence intervals (95% CIs).

Main results

We identified 182 studies with a total of 16,855 included participants investigating outcomes of surgery for epilepsy. Nine studies were RCTs (including two that randomised participants to surgery or medical treatment (99 participants included in the two trials received medical treatment)). Risk of bias in these RCTs was unclear or high. Most of the remaining 173 non‐randomised studies followed a retrospective design. We assessed study quality using the Effective Public Health Practice Project (EPHPP) tool and determined that most studies provided moderate or weak evidence. For 29 studies reporting multivariate analyses, we used the Quality in Prognostic Studies (QUIPS) tool and determined that very few studies were at low risk of bias across domains.

In terms of freedom from seizures, two RCTs found surgery (n = 97) to be superior to medical treatment (n = 99); four found no statistically significant differences between anterior temporal lobectomy (ATL) with or without corpus callosotomy (n = 60), between subtemporal or transsylvian approach to selective amygdalohippocampectomy (SAH) (n = 47); between ATL, SAH and parahippocampectomy (n = 43) or between 2.5 cm and 3.5 cm ATL resection (n = 207). One RCT found total hippocampectomy to be superior to partial hippocampectomy (n = 70) and one found ATL to be superior to stereotactic radiosurgery (n = 58); and another provided data to show that for Lennox‐Gastaut syndrome, no significant differences in seizure outcomes were evident between those treated with resection of the epileptogenic zone and those treated with resection of the epileptogenic zone plus corpus callosotomy (n = 43). We judged evidence from the nine RCTs to be of moderate to very low quality due to lack of information reported about the randomised trial design and the restricted study populations.

Of the 16,756 participants included in this review who underwent a surgical procedure, 10,696 (64%) achieved a good outcome from surgery; this ranged across studies from 13.5% to 92.5%. Overall, we found the quality of data in relation to recording of adverse events to be very poor.

In total, 120 studies examined between one and eight prognostic factors in univariate analysis. We found the following prognostic factors to be associated with a better post‐surgical seizure outcome: abnormal pre‐operative MRI, no use of intracranial monitoring, complete surgical resection, presence of mesial temporal sclerosis, concordance of pre‐operative MRI and electroencephalography, history of febrile seizures, absence of focal cortical dysplasia/malformation of cortical development, presence of tumour, right‐sided resection, and presence of unilateral interictal spikes. We found no evidence that history of head injury, presence of encephalomalacia, presence of vascular malformation, and presence of postoperative discharges were prognostic factors of outcome.Twenty‐nine studies reported multi‐variable models of prognostic factors, and showed that the direction of association of factors with outcomes was generally the same as that found in univariate analyses.

We observed variability in many of our analyses, likely due to small study sizes with unbalanced group sizes and variation in the definition of seizure outcome, the definition of prognostic factors, and the influence of the site of surgery

Authors' conclusions

Study design issues and limited information presented in the included studies mean that our results provide limited evidence to aid patient selection for surgery and prediction of likely surgical outcomes. Future research should be of high quality, follow a prospective design, be appropriately powered, and focus on specific issues related to diagnostic tools, the site‐specific surgical approach, and other issues such as extent of resection. Researchers should investigate prognostic factors related to the outcome of surgery via multi‐variable statistical regression modelling, where variables are selected for modelling according to clinical relevance, and all numerical results of the prognostic models are fully reported. Journal editors should not accept papers for which study authors did not record adverse events from a medical intervention. Researchers have achieved improvements in cancer care over the past three to four decades by answering well‐defined questions through the conduct of focused RCTs in a step‐wise fashion. The same approach to surgery for epilepsy is required.

Plain language summary

Surgery for epilepsy

Background

Focal epilepsies are caused by abnormal electrical discharges in specific (localised) parts of the brain. In up to 30% of people, these seizures are not controlled by medication. If the site of origin of these signals (the epileptogenic zone) can be located from the description of the seizures, or via findings of magnetic resonance imaging (MRI) (a medical imaging scan that uses strong magnetic fields and radio waves to produce detailed images of the inside of the body) and electroencephalography (EEG) (recording of electrical activity along the scalp), the person should be offered the chance of having the epileptogenic zone removed. We studied characteristics of people undergoing surgery and details of surgery type that might be linked to the best chance of surgical cure of epileptic seizures.

Study characteristics

We examined evidence from 182 included studies reporting the experience of 16,855 people of all ages. The evidence is current to March 2019.

Key results

In total, 10,696 people (64% of the total who had surgery in all studies) experienced a good outcome from surgery, defined as freedom from epileptic seizures.

Two randomised controlled trials (RCTs) established the superiority of surgery over use of different antiepileptic medications. Seven RCTs compared different types of surgery. Three trials found no difference in seizure outcomes; one removed 2.5cm or 3.5cm of the anterior temporal lobe (ATL ‐ the part of the brain in which the epileptogenic zone is often located) or surgically removed the ATL with or without an additional procedure to sever the nerves that connect the two halves of the brain. The third trial found that completely removing the hippocampus (the part of the brain in which the epileptogenic zone is often located) was superior to removing only part of the hippocampus. A fourth trial showed that removing the ATL was superior to a surgical procedure using radiation therapy, Two trials showed no difference between different types of surgical procedures to remove the ATL or hippocampus and the final trial showed that for Lennox‐Gastaut syndrome, results show no significant differences in seizure outcomes between those undergoing resection of the epileptogenic zone and those with resection plus corpus callosotomy.

We identified some factors associated with a better outcome from surgery, including a well‐defined abnormality on the MRI scan corresponding with what was expected from the description of seizures and EEG findings, complete surgical removal of the lesion, and a history of febrile seizures (seizures associated with fever in a young child) often associated with mesial temporal sclerosis (scarring in the inner portions of the temporal lobe of the brain).

More spread out brain abnormalities that might be associated with brain injury or an abnormality of brain development were not associated with a good outcome. The presence of such abnormalities is often associated with a need to embark on more detailed pre‐operative investigations including intracranial (inside the skull) EEG monitoring. We would have liked to examine the collective effect of these factors (i.e. the effect on outcome if a person has a history of febrile seizures, brain injury, and an MRI abnormality altogether); however, studies did not report enough information to allow this.

Quality of the evidence

Most studies included in this review were of poor quality and had a retrospective design (whereby individuals are recruited after the result of surgery has been recorded, which looks back for the existence of factors related to the results of surgery). Researchers used variable surgical approaches for different sites of the brain, different processes to select candidates for surgery, and different definitions of freedom from seizures after surgery, and they measured these outcomes at varying points. Fewer than half the studies gave details of complications and deaths associated with surgery.

Conclusions

We encourage researchers that future studies should have a prospective design (a design whereby individuals are recruited before surgery has taken place, which identifies factors of interest before surgery and follows up with individuals after surgery to record outcomes). Studies should use appropriate statistical methods to examine the collective effect of factors that may predict the outcome of surgery. Study authors should clearly record death during or after surgery, as well as complications and side effects from surgery.

Summary of findings

Background

This review is an update of a review that was previously published in the Cochrane Database of Systematic Reviews (Issue 7, 2015) on "Surgery for epilepsy" (West 2015).

Description of the condition

Epilepsy has been redefined very recently by the International League Against Epilepsy (ILAE) as "a disease of the brain defined by any of the following conditions: (1) at least two unprovoked (or reflex) seizures occurring > 24 h apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years; (3) diagnosis of an epilepsy syndrome" (Fisher 2014). Epilepsy is a common condition with a prevalence of around 1 in 200 people. Despite optimal pharmacotherapy, about 20% to 30% of individuals do not become seizure‐free (Annegers 1979; Collaborative 1992; Cockerell 1995; Kwan 2000). For some of these people, surgery is a therapeutic option.

Description of the intervention

The intervention involves localisation of the epileptogenic focus and then, if the potential benefit is assessed to outweigh the risk, surgical resection. Feindel 2009 has thoroughly reviewed the history of the development of surgery for epilepsy. This work was pioneered by Victor Horsley when, in 1886, he operated on a 22‐year‐old man who had developed a focal epilepsy following a head injury. A highly vascular scar associated with an old depressed comminuted skull fracture was excised along with a border of cortex. The presence of a discrete cortical vascular scar and the arrest of focal motor seizures following its excision provided direct support for Hughlings Jackson's concept of the aetiology of focal epilepsy. It subsequently became evident that a variety of pathologies could give rise to the focal epilepsies. Techniques of cortical stimulation along with the advent of electroencephalography in the 1930s aided localisation. Until the 1940s, surgery was directed mainly to the convexity of the cerebral hemispheres, most often for removal of traumatic scars or tumours. The work of Frederic Gibbs and William Lennox from 1936 promoted electroencephalography (EEG) into a strategic position for diagnosis and early classification of the epilepsies. Herbert Jasper, working with Wilder Penfield, used EEG to develop new approaches for surgery for epilepsy, particularly in the temporal lobe and mesial temporal structures. A major obstacle to removal of these structures was lack of knowledge about their function (Feindel 2009).

Penfield considered EEG and emerging techniques for electrocorticography (ECoG) useful if they could disclose pathological areas in the brain. If a visible lesion was not found at the place indicated by the recording of epileptic activity, Penfield usually would decline to perform a resection. A success rate of just over 50% indicated that resection limited to the anterolateral temporal cortex did not eliminate all epileptogenic tissue in many people. Researchers then provided greater focus on mesial temporal structures. Jasper noted that a cure could be effected even when no abnormality was visible in the excised material, and added, "it seems clear, therefore, that the pathophysiological state of spike foci may not always be associated with structural alterations which can be seen by present methods of microscopic examination" (Feindel 2009). This led to more detailed pathological study of excised material ‐ an approach led by Murray Falconer with Alfred Meyer. More sophisticated EEG study, cortical stimulation, and detailed descriptions of seizure semiology revealed the importance of the human claustroamygdaloid complex in short‐term memory, consciousness, and emotions. As resection of anteromesial structures became the accepted treatment for temporal lobe epilepsy, the hippocampus was elucidated as important for short‐term recent memory function. This observation led to the inclusion of a neuropsychologist in most surgery selection teams. Temporary and partial suppression of one cerebral hemisphere by injection of intracarotid sodium amytal, a technique introduced by Wada, became a useful test for determining the laterality of speech function and for evaluating memory responses in people with bitemporal seizure activity. Functional magnetic resonance imaging (fMRI), along with neuropsychometry, is now superseding this initial approach.

Other sophisticated technological developments followed: the advent of computerised tomography in the 1970s; magnetic resonance imaging (MRI) in the 1990s; computerised analysis of ictal and inter‐ictal EEG activity; fMRI with psychometric analysis and ever more sophisticated stereotaxis guiding the placement of deep electrodes for long‐term EEG analysis; and surgical intervention. These techniques have been complemented by the co‐registration of single‐photon emission computed tomography (SPECT) and positron emission tomography (PET) findings (Feindel 2009), and, most recently, by improved co‐registration and simultaneous review of both structural and functional data from PET/MRI (Shin 2015). These developments are now leading to more precise localisation of epileptogenic foci and a reduction in the risk of removing eloquent cortex. This approach has led to greater opportunity for accurate assessment for a surgical cure for any person with drug‐resistant focal epilepsy. However, sophisticated technology has a place only in the setting of a good interdisciplinary team working in harmony and incorporating the skills of a neurologist, a neurophysiologist, a psychiatrist, a neuropsychologist, and a neurosurgeon with postoperative help from remedial therapists who have good scope for liaison with educational, vocational, and social services for good postoperative rehabilitation.

Success rates for resective epilepsy surgery are estimated to have increased from 43% to 85% during the period from 1986 to 1999 (Engel 1993a; Engel 2003; National 1990a). Data from multiple sources suggest that 55% to 70% of individuals undergoing temporal resection and 30% to 50% of those undergoing extratemporal resection become completely seizure‐free. A prospective randomised controlled trial of surgery for temporal lobe epilepsy showed that 58% of individuals randomised to surgery were seizure‐free compared to 8% of those in the medical group (Wiebe 2001). Surgery is considered a valuable option for medically intractable epilepsy, even in the absence of proven drug resistance (Engel 1993b).

How the intervention might work

The rationale for the intervention is initial localisation of the epileptogenic focus followed by its surgical resection. The mainstay for investigation is MRI. Concordance between an MRI scan and EEG findings along with seizure semiology is sought. Key is accurate localisation of the epileptogenic focus to an area of the brain that might safely be removed without inducing neurological impairment. If the lesion is not well defined, further imaging via PET, SPECT, or PET/MRI may supplement accurate placement of indwelling EEG electrodes to achieve this aim (see Description of the intervention). When the epileptogenic focus can be removed safely, epilepsy may be cured with a corresponding improvement in quality of life.

Why it is important to do this review

Surgical outcomes may be greatly influenced by the presence of selected prognostic indicators (Berg 1998; Tonini 1997). However, uncertainties remain about which patients are most likely to achieve good surgical outcomes. Good surgical outcomes appear to be associated with various factors (i.e. hippocampal sclerosis, anterior temporal localisation of interictal epileptiform activity, absence of pre‐operative generalised seizures, and absence of seizures in the first postoperative week) (McIntosh 2001). However, published trial results are frequently confusing and contradictory, thus preventing inferences for clinical practice. The initial version of this Cochrane review (West 2015) was the first to investigate the association between specific prognostic factors and surgical outcomes. It complemented and updated the only systematic review to date to examine factors predictive of the outcome of epilepsy surgery (Tonini 2004). This review informs the surgical selection process and allows refinement of the risk/benefit analysis for surgical intervention.

Objectives

The primary objective is to assess the overall outcome of epilepsy surgery according to evidence from randomised controlled trials.

Methods

Criteria for considering studies for this review

Types of studies

In the original review (West 2015), we included studies if they satisfied the following criteria.

Randomised controlled trial (RCT), cohort study, or case series, prospective and/or retrospective.
A sample size of at least 30 participants undergoing surgery.
A well‐defined population (age, sex, seizure type and frequency, duration of epilepsy, aetiology, MRI diagnosis, surgical findings).
MRI performed in at least 90% of cases.
Expected duration of follow‐up of at least one year.
A reported outcome related to postoperative seizure control.

We excluded reports if they were provided in abstract form or in book chapters, or if they did not present sufficiently clear details about their methods; if they were written in languages other than English, Italian, French, German, or Spanish (due to the availability of translators for detailed data extraction); or if they did not meet all of the above inclusion criteria. We also excluded repeated publications from the same institution (among which we retained only the most recent for review) unless they dealt with different prognostic factors.

For this update, to provide the most clinically relevant and high‐quality updated evidence, we included only new RCTs meeting the other inclusion criteria. We did not include in this updated review new studies using a non‐randomised design.

Types of participants

We included children, adolescents, and adults who were considered surgical candidates and had drug‐resistant focal seizures and secondarily generalised seizures of temporal or extratemporal origin (i.e. seizures that continue despite treatment with anticonvulsant medication).

Types of interventions

We included studies that provided surgical treatment for drug‐resistant focal seizures and secondarily generalised seizures of temporal or extratemporal origin. For RCTs, we considered all control groups for comparison, including those given medical treatment or no treatment and those undergoing different surgical techniques. In the original version of this review (West 2015), we considered non‐randomised studies with or without control groups (i.e. case series) for inclusion.

Types of outcome measures

Primary outcomes

Seizure outcome (proportion achieving a good outcome from surgery)

The outcome of seizures after epilepsy surgery is classified according to Engel's four categories with subcategories (Engel 1987; Engel 1993b), or it is reported as such when different definitions are used (see the Table below).

Engel class	Description (subclasses)
Class 1: free of disabling seizures	1A: completely seizure‐free since surgery  1B: non‐disabling simple focal seizures only since surgery  1C: some disabling seizures after surgery, but free of disabling seizures for at least 2 years  1D: generalised convulsion with antiepileptic drug withdrawal only Class 2 (rare disabling seizures; 'almost seizure‐free')
Class 2: almost seizure‐free (rare disabling seizures)	2A: initially free of disabling seizures, but rare seizures now  2B: rare disabling seizures since surgery  2C: more than rare disabling seizures after surgery, but rare seizures for at least 2 years  2D: nocturnal seizures only
Class 3: worthwhile improvement	3A: worthwhile seizure reduction  3B: prolonged seizure‐free intervals amounting to greater than half the follow‐up period, but not less than 2 years
Class 4: no worthwhile improvement	4A: no significant seizure reduction  4B: no appreciable change  4C: seizures worse

Surgery compared with medical treatment for epilepsy
Patient or population: adults and children with drug‐resistant epilepsy suitable for surgical intervention Settings: outpatients (following surgery in hospital) Intervention: surgery Comparison: medical treatment
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect  (95% CI)	No. of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Assumed risk	Corresponding risk
	Medical treatment	Surgery
Proportion free from seizures at 1 year	71 per 1000	692 per 1000  (334 to 1000 per 1000)^a	RR 9.78 (4.73 to 20.21)	196 (2 studies)	⊕⊕⊝⊝  low^b,c	RR > 1 indicates advantage for surgery One study measured freedom from seizures as 'all seizures impairing awareness', and another study measured freedom from seizures as ILAE Class 1
Proportion free from all seizures (including auras) at 1 year	25 per 1000	375 per 1000  (52 to 1000 per 1000)^a	RR 15.00 (2.08 to 108.23)	80 (1 study)	⊕⊝⊝⊝  very low^b,c,d	RR > 1 indicates advantage for surgery
The basis for the assumed risk* is the event rate in the control group (medical treatment). The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: confidence interval; ILAE: International League Against Epilepsy; RR: risk ratio.
GRADE Working Group grades of evidence.  High certainty (quality): further research is very unlikely to change our confidence in the estimate of effect.  Moderate certainty (quality): further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Low certainty (quality): further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.  Very low certainty (quality): we are very uncertain about the estimate.

Comparison of surgical interventions for epilepsy
Patient or population: adults and children with drug‐resistant epilepsy suitable for surgical intervention Settings: outpatients (following surgery in hospital) Intervention: experimental surgical intervention (see comments) Comparison: control surgical intervention (see comments)
Outcomes	*Illustrative comparative risks  (95% CI)**		Relative effect  (95% CI)	No. of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control  surgical intervention (see comments)	Experimental  surgical intervention (see comments)
Proportion free from seizures (Engel Class 1 or 1A) at 1 year and at 5 years	There were no clear differences between the ATL, SAH and PHC groups in terms of seizure freedom (by either Engel Class definition) at 1 year or at 5 years		NA	43 (1 study)	⊕⊕⊝⊝  low ^a,b	Interventions are anterior temporal lobectomy (ATL), selective amygdalohippocampectomy (SAH) or parahippocampectomy (PHC). All pairs of interventions were compared
P roportion with remission of seizures (at least Engel Class IB) between 25 and 36 months	778 per 1000	513 per 1000 (350 to 770 per 1000)	RR 0.66 (0.45 to 0.99)	58 (1 study)	⊕⊕⊝⊝  low^b,c	Experimental Intervention is Stereotactic radiosurgery (SRS) Control intervention is anterior temporal lobectomy (ATL) RR > 1 indicates advantage for SRS
Proportion free from seizures (Engel Class 1) at 1 year	650 per 1000	741 per 1000 (494 to 1000 per 1000)^d	RR 1.14 (0.76 to 1.70)	43 (1 study)	⊕⊕⊝⊝  low^e,f	Experimental Intervention is resection with corpus callosotomy (CCT) Control intervention is resection only RR > 1 indicates advantage for resection with CCT The RR of seizure freedom for the resection with CCT group compared to the resection only group at 3 years was 1.19 (95% CI 0.72 to 1.95; P = 0.50) and at 5 years was 1.09 (95% CI 0.53 to 2.21; P = 0.82)
Proportion free from seizures (Engel Class 1) at 2 years	600 per 1000	732 per 1000  (510 to 1000 per 1000)^d	RR 1.22 (0.85 to 1.76)	60 (1 study)	⊕⊕⊕⊝  moderate^e	Experimental Intervention is anterior temporal lobectomy with corpus callosotomy (aCCT) Control intervention is anterior temporal lobectomy without corpus callosotomy (ATL) RR > 1 indicates advantage for aCCT
Proportion free from all seizures (including auras, ILAE 1a) at 1 year	640 per 1000	589 per 1000 (378 to 934 per 1000)	RR 0.92 (0.59 to 1.46)	47 (1 study)	⊕⊕⊝⊝  low^b,g	Experimental intervention is Subtemporal selective amygdalohippocampectomy (SAH) Control intervention is Transsylvian SAH RR > 1 indicates advantage for Subtemporal SAH
Proportion free from all seizures (including auras) at 1 year	382 per 1000	695 per 1000  (428 to 1000 per 1000)^d	RR 1.82 (1.12 to 2.93)	70 (1 study)	⊕⊕⊝⊝  low^b,c	Experimental intervention is total resection Control intervention is partial resection RR > 1 indicates advantage for total resection
Proportion free from seizures (Engel Class 1) at 1 year	728 per 1000	743 per 1000  (626 to 874 per 1000)	RR 1.02 (0.86 to 1.2)	207 (1 study)	⊕⊕⊕⊝  moderate^b	Experimental Intervention is a 2.5‐cm resection Control intervention is 3.5‐cm resection RR > 1 indicates advantage for 2.5‐cm resection
The basis for the assumed risk* is the event rate in the control group (medical treatment). The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  aCCT: anterior temporal lobectomy with corpus callosotomy; ATL: anterior temporal lobectomy without corpus callosotomy; CCT: corpus callosotomy; CI: confidence interval; RR: risk ratio; parahippocampectomy (PHC); selective amygdalohippocampectomy (SAH).
GRADE Working Group grades of evidence.  High certainty (quality): further research is very unlikely to change our confidence in the estimate of effect.  Moderate certainty (quality): further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Low certainty (quality): further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.  Very low certainty (quality): we are very uncertain about the estimate.

Author (year)	Outcome scale used	Study design	Participants  having surgery	Good outcome	Males	Site of surgery	Age at surgery (min to max), years^a	Duration of epilepsy (min to max), years^a	Follow‐up (min to max), months^a
Aaberg 2012	Engel Class Scale	Retrospective	54	30	32	Temporal and extratemporal	0.5 to 16	NA	> 24
Adam 1996	Engel Class Scale	Prospective	30	26	11	Temporal only	18 to 44	NA	12 to 44
Adelson 1992	> 1 year seizure‐free	Retrospective	33	23	19	Temporal and extratemporal	0 to 17	NA	18 to 72
Alfstad 2011	Engel Class Scale	Retrospective	48	25	26	Temporal and extratemporal	24.6 (NA)	14.5 (NA)	> 24
Alonso‐Vanegas 2018	Engel Class Scale	Prospective	43	38	15	Temporal	18 to 56	NA	12 to 60
Althausen 2013	> 1 year seizure‐free	Retrospective	61	45	29	Extratemporal only	14.5 (12.0)	11.9 (10.8)	13 to 233
Arruda 1996	Engel Class Scale	Retrospective	74	53	34	Temporal only	32.1 (10.5)	NA	33.4 (13.1)
Awad 1991	> 1 year seizure‐free	Not stated	47	27	38	Temporal and extratemporal	2 to 45	0 to 29	20 to 114
Babini 2013	Engel Class Scale	Retrospective	30	26	20	Temporal and extratemporal	3 to 18	0 to 16	12 to 204
Barbaro 2018	'Other' scale	Prospective	58	37	28	Temporal	40.2 (13.4)	28.6 (14.5)	12 to 36
Battaglia 2006	Engel Class Scale	Not stated	45	32	29	Temporal only	0 to 7	0 to 5	24 to 179
Baumann 2007	Engel Class Scale	Retrospective	168	118	90	Temporal and extratemporal	1 to 71	0 to 41	12 to 39
Bautista 2003	> 1 year seizure‐free	Retrospective	43	28	29	Temporal and extratemporal	29.6 (10.9)	2 to 48	> 12
Bell 2009	Engel Class Scale	Retrospective	40	24	17	Temporal only	13 to 62	1 to 36	18 to 126
Benifla 2006	Engel Class Scale	Retrospective	106	78	65	Temporal only	13.5 (NA)	5.9 (NA)	24 to 162
Berkovic 1995	Engel Class Scale	Prospective	135	74	NA	Temporal only	11 to 58	NA	18 to 81
Blount 2004	Engel Class Scale	Retrospective	30	12	13	Temporal and extratemporal	11.7 (4.4)	NA	> 30
Blume 2004	Engel Class Scale	Retrospective	70	26	41	Temporal and extratemporal	6 to 65	1 to 41	24 to 144
Boesebeck 2007	'Other' scale	Retrospective	81	33	51	Extratemporal only	16 to 53	2 to 43	> 24
Boshuisen 2010	'Other' scale	Retrospective	43	33	18	Temporal and extratemporal	0 to 14	0 to 12	12 to 188
Brainer‐Lima 1996	Engel Class Scale	Retrospective	32	29	24	Temporal and extratemporal	6 to 57	2 to 30	4 to 68
Britton 1994	Engel Class Scale	Retrospective	51	34	NA	Temporal and extratemporal	6 to 60	NA	24 to 96
Caraballo 2011	Engel Class Scale	Retrospective	45	33	27	Not stated	0 to 18	NA	12 to 192
Cascino 1995	Engel Class Scale	Retrospective	165	113	NA	Temporal only	32.1 (10.5)	NA	> 12
Chabardes 2005	Engel Class Scale	Retrospective	54	47	24	Temporal only	NA	2.5 to 41	48 to 100
Chang 2009	Engel Class Scale	Retrospective	57	45	NA	Temporal and extratemporal	NA	NA	> 12
Chee 1993	> 1 year seizure‐free	Retrospective	38	28	25	Temporal only	18 to 53	3 to 36	> 12
Chkhenkeli 2007	Engel Class Scale	Retrospective	67	12	NA	Temporal only	NA	NA	>24
Choi 2004a	Engel Class Scale	Retrospective	35	27	19	Temporal only	16 to 61	4 to 22	16 to 105
Chung 2005	Engel Class Scale	Retrospective	128	58	85	Temporal and extratemporal	NA	NA	26.9 (12)
Cossu 2005	Engel Class Scale	Retrospective	165	93	NA	Temporal and extratemporal	NA	NA	> 12
Cossu 2008	Engel Class Scale	Retrospective	113	77	67	Temporal and extratemporal	1 to 15	0 to 14	24 to 115
Costello 2009	Engel Class Scale	Retrospective	42	32	21	Temporal and extratemporal	45 to 66	0.5 to 55.5	13 to 173
Cukiert 2002	Engel Class Scale	Prospective	100	89	43	Temporal only	28 (9)	NA	18 to 48
Dagar 2011	> 1 year seizure‐free	Retrospective	112	89	67	Temporal and extratemporal	0 to 18	0 to 15	> 12
Dalmagro 2005	Engel Class Scale	Retrospective	43	28	23	Not stated	22.4 (NA)	14.7 (11.5)	> 12
de Tisi 2011	'Other' scale	Retrospective	615	245	287	Temporal and extratemporal	16 to 63	20.7 (median)	12 to 228
Delbeke 1996	Engel Class Scale	Retrospective	38	23	15	Temporal only	15 to 59	NA	18 to 58
Dellabadia 2002	Engel Class Scale	Retrospective	35	20	NA	Temporal and extratemporal	NA	NA	22 to 48
Devlin 2003	Engel Class Scale	Retrospective	33	17	21	Temporal and extratemporal	0 to 17	7.4 (median)	12 to 96
Ding 2016	Engel Class Scale	Prospective	43	30	24	Temporal and Extratemporal	4 to 18	NA	12 to 60
Donadio 2011	Engel Class Scale	Retrospective	84	60	45	Temporal and extratemporal	2 to 59	1 to 50	12 to 126
Dorward 2011	Engel Class Scale	Retrospective	33	18	18	Extratemporal only	3 to 19	0.5 to 16	49.4 (NA)
Duchowny 1998	> 1 year seizure‐free	Retrospective	31	16	16	Temporal and extratemporal	0 to 3	NA	> 12
Dunkley 2011	Engel Class Scale	Retrospective	42	20	24	Temporal and extratemporal	0 to 3	0 to 3	27 to 158
Dunlea 2010	Engel Class Scale	Retrospective	199	119	95	Temporal and extratemporal	1 to 61	0.5 to 43	12 to 288
Dwivedi 2017	'Other' scale	Prospective	57	44	44	Temporal and Extratemporal	0.8 to 17.0	0.4–16.3	> 12
Elsharkawy 2008a	Engel Class Scale	Retrospective	218	121	129	Extratemporal only	16 to 69	1 to 65	12 to 60
Elsharkawy 2009a	Engel Class Scale	Retrospective	430	311	220	Temporal and extratemporal	16 to 61	1 to 57	> 24
Elsharkawy 2011a	Engel Class Scale	Retrospective	47	38	33	Temporal only	32 (12)	11.8 (8.8)	6 to 72
Engman 2004	'Other' scale	Retrospective	54	35	NA	Temporal only	34 (median)	NA	33.6 (median)
Erba 1992	> 1 year seizure‐free	Retrospective	46	37	28	Temporal only	4 to 34	1 to 31	38 to 216
Erickson 2005	Engel Class Scale	Retrospective	71	46	27	Temporal only	5 to 64	0 to 46	> 12
Fauser 2004	Engel Class Scale	Retrospective	59	35	34	Temporal only	2 to 66	NA	6 to 48
Fujiwara 2012	> 1 year seizure‐free	Retrospective	44	23	0	Temporal and extratemporal	NA	NA	12 to 26
Garcia 1991	> 1 year seizure‐free	Retrospective	55	35	NA	Temporal only	9 to 47	NA	12 to 48
Garcia 1994	> 1 year seizure‐free	Prospective	51	36	NA	Temporal only	NA	NA	12 to 48
Gelinas 2011	Engel Class Scale	Retrospective	67	52	39	Temporal and extratemporal	0 to 16	2.7 (NA)	75.6 (NA)
Georgakoulias 2008	Engel Class Scale	Retrospective	50	42	25	Temporal only	14 to 62	NA	60 to 120
Gilliam 1997a	> 1 year seizure‐free	Retrospective	78	53	18	Temporal and extratemporal	1 to 12	1 to 11	7 to 72
Gilliam 1997b	> 1 year seizure‐free	Retrospective	33	22	40	Temporal only	9 to 50	NA	> 12
Goldstein 1996	'Other' scale	Retrospective	33	15	17	Temporal only	0 to 15	0 to 12	24 to 120
Greiner 2011	> 1 year seizure‐free	Retrospective	54	42	NA	Temporal and extratemporal	0.5 to 40	7.6 (median)	> 12
Grivas 2006	Engel Class Scale	Retrospective	52	37	22	Temporal only	50 to 71	1 to 62	12 to 84
Gyimesi 2007	'Other' scale	Retrospective	100	74	NA	Temporal only	NA	NA	> 24
Hader 2004	Engel Class Scale	Retrospective	39	21	16	Temporal and extratemporal	0 to 18.5	0.19	> 18
Hajek 2009	Engel Class Scale	Retrospective	35	25	15	Temporal only	10 to 58	5 to 47	24 to 91
Hallbook 2010	> 1 year seizure‐free	Retrospective	110	88	71	Temporal and extratemporal	0 to 18	NA	12 to 84
Hamiwka 2005	Engel Class Scale	Retrospective	38	17	NA	Temporal and extratemporal	0.5 to 18	NA	> 24
Hartley 2002	Engel Class Scale	Retrospective	35	20	11	Temporal and extratemporal	1 to 18	1 to 17	36 to 72
Hartzfield 2008	Engel Class Scale	Retrospective	56	24	35	Temporal only	8 to 70	4.5 to 41	6 to 108
Hemb 2010	> 1 year seizure‐free	Retrospective	325	223	229	Temporal and extratemporal	7.7(6.3)	4.9 (4.6)	> 24
Holmes 1997	> 1 year seizure‐free	Retrospective	44	22	17	Temporal only	14 to 55	3 to 46	12 to 48
Holmes 2000	'Other' scale	Retrospective	126	54	71	Temporal and extratemporal	6 to 69	1 to 46	24 to 72
Jack 1992	> 1 year seizure‐free	Retrospective	50	34	27	Temporal only	14 to 51	2 to 37	12 to 34
Janszky 2003a	Engel Class Scale	Retrospective	84	60	NA	Temporal only	NA	NA	> 24
Janszky 2003b	Engel Class Scale	Retrospective	147	123	NA	Temporal only	NA	NA	> 6
Jaramillo‐Betancur 2009	Engel Class Scale	Retrospective	67	43	52	Temporal only	27 (11)	20 (10)	> 24
Jayakar 2008	Engel Class Scale	Retrospective	101	44	60	Temporal and extratemporal	1.5 to 21	NA	> 24
Jayalakshmi 2011	Engel Class Scale	Retrospective	78	50	44	Temporal and extratemporal	2 to 16	1 to 16	12 to 58
Jeha 2006	> 1 year seizure‐free	Retrospective	371	231	NA	Temporal only	NA	NA	> 12
Jehi 2012	> 1 year seizure‐free	Retrospective	312	165	149	Temporal only	2.5 to 74	1 to 64	42 (20.4)
Jennum 1993	> 1 year seizure‐free	Retrospective	64	42	45	Temporal and extratemporal	8 to 52	1 to 38	> 12
Jeong 1999	'Other' scale	Not stated	93	78	54	Temporal only	9 to 51	NA	18 to 33
Kan 2008	Engel Class Scale	Retrospective	58	43	34	Temporal and extratemporal	2 to 21	0.5 to 15	12 to 96
Kang 2009	Engel Class Scale	Retrospective	244	194	108	Temporal only	18 to 68	NA	12 to 204
Kanner 2009	Engel Class Scale	Retrospective	100	86	60	Temporal only	31.2 (10.7)	12.7 (NA)	24 to 168
Kilpatrick 1997	Engel Class Scale	Prospective	50	39	28	Temporal only	16 to 57	NA	12 to 38
Kim 2009	> 1 year seizure‐free	Retrospective	166	94	102	Temporal and extratemporal	3 to 51	0.5 to 37	95.3 (NA)
Kim 2010a	Engel Class Scale	Retrospective	177	75	121	Temporal and extratemporal	11 to 51	1 to 50	24 to 180
Kim 2010b	> 1 year seizure‐free	Retrospective	40	14	26	Temporal and extratemporal	4 to 51	1 to 48	> 24
Kloss 2002	Engel Class Scale	Combination	68	34	30	Temporal and extratemporal	0 to 16	NA	12 to 108
Knowlton 2008	Engel Class Scale	Prospective	62	37	33	Temporal and extratemporal	1 to 60	NA	> 12
Kral 2007	'Other' scale	Retrospective	40	27	23	Temporal and extratemporal	5 to 47	1 to 45	97 (54)
Krsek 2013	Engel Class Scale	Retrospective	106	64	49	Not stated	0 to 30	NA	> 24
Kuzniecky 1993	'Other' scale	Prospective	34	23	14	Temporal only	7 to 38	> 2	12 to 30
Kwan 2010	Engel Class Scale	Retrospective	41	27	22	Extratemporal only	0 to 17.5	0 to 16	72 (NA)
Lackmayer 2013	'Other' scale	Retrospective	45	32	21	Temporal only	40.8 (10.2)	13.0 (10.1)	> 12
Lee 2006	'Other' scale	Retrospective	51	37	29	Temporal only	16 to 50	4 to 38	> 24
Lee 2008	Engel Class Scale	Not stated	71	38	44	Extratemporal only	12 to 57	3 to 34	> 24
Lee 2010	Engel Class Scale	Retrospective	52	36	31	Temporal only	9 to 54	1 to 33	14 to 42
Lee 2011	Engel Class Scale	Retrospective	40	37	23	Temporal only	1 to 15	0 to 14	11 to 151
Lei 2008	> 1 year seizure‐free	Retrospective	196	180	210	Temporal and extratemporal	17 to 66	NA	> 48
Li 1997	Engel Class Scale	Retrospective	51	39	23	Temporal and extratemporal	8 to 73	NA	12 to 157
Li 1999	Engel Class Scale	Not stated	38	16	23	Temporal and extratemporal	14 to 63	NA	12 to 180
Liang 2010	Engel Class Scale	Prospective	60	40	34	Temporal and extratemporal	16.7 (NA)	NA	> 24
Liang 2012	Engel Class Scale	Retrospective	206	173	94	Temporal and extratemporal	6 to 14	2 to 14	> 12
Liava 2012	Engel Class Scale	Retrospective	52	39	NA	Extratemporal only	1 to 26	7.9 (NA)	18 to 162
Lopez‐Gonzalez 2012	> 1 year seizure‐free	Retrospective	86	65	63	Temporal only	1 to 18	1 to 17	> 12
Lorenzo 1995	Engel Class Scale	Retrospective	48	17	NA	Extratemporal only	NA	NA	> 12
Madhavan 2007	Engel Class Scale	Retrospective	70	37	39	Temporal and extratemporal	9.9 (10.2)	NA
Mani 2006	Engel Class Scale	Retrospective	122	86	72	Temporal and extratemporal	8.2 (5.5)	5.2 (4.6)	> 6
Mathern 1999	'Other' scale	Retrospective	198	78	111	Temporal and extratemporal	0 to 37	0 to 31	6 to 120
McIntosh 2012	'Other' scale	Retrospective	81	11	38	Extratemporal only	4 to 60	16 (median)	12 to 212
Mihara 2004	Engel Class Scale	Retrospective	357	269	NA	Temporal and extratemporal	2 to 55	1 to 40	24 to 196
Miserocchi 2013	Engel Class Scale	Retrospective	68	58	43	Temporal only	1 to 15	0.5 to 14	> 12
Morino 2009	> 1 year seizure‐free	Retrospective	62	55	24	Temporal only	34.4 (NA)	NA	> 12
Morris 1998	Engel Class Scale	Retrospective	36	26	22	Temporal and extratemporal	2 to 56	1 to 29	6 to 41
O'Brien 1996	> 1 year seizure‐free	Retrospective	46	36	24	Temporal only	16 to 58	2 to 43	12 to 33
O'Brien 2000	Engel Class Scale	Retrospective	36	14	23	Temporal and extratemporal	1 to 56	NA	12 to 40
Oertel 2005	> 1 year seizure‐free	Prospective	35	20	11	Temporal only	35.1 (NA)	NA	12 to 42
Paglioli 2006	Engel Class Scale	Prospective	160	143	88	Temporal only	8 to 62	3 to 60	24 to 132
Paolicchi 2000	> 1 year seizure‐free	Retrospective	75	44	40	Temporal and extratemporal	0 to 12	NA	12 to 120
Park 2002	Engel Class Scale	Retrospective	148	108	76	Temporal and extratemporal	0.5 to 18	0 to 19	0 to 166
Park 2006	Engel Class Scale	Retrospective	30	20	19	Temporal and extratemporal	0 to 13	1 to 18	12 to 64
Perego 2009	Engel Class Scale	Retrospective	37	29	19	Temporal only	33 (10)	19 (NA)	> 36
Perry 2010	Engel Class Scale	Retrospective	83	34	50	Temporal and extratemporal	NA	0 to 17	> 24
Phi 2009	Engel Class Scale	Retrospective	87	80	49	Temporal only	1 to 62	0 to 48	12 to 128
Phi 2010	'Other' scale	Retrospective	41	20	20	Temporal and extratemporal	1 to 17	1 to 11	24 to 153
Pinheiro‐Martins 2012	Engel Class Scale	Retrospective	70	33	27	Extratemporal only	1 to 52	1 to 36	59.1 (30.5)
Prevedello 2000	Engel Class Scale	Retrospective	84	53	48	Temporal only	19 to 43	10 to 33	15 to 44
Raabe 2012	Engel Class Scale	Retrospective	76	57	55	Not stated	6 to 67	0 to 53	24 to 200
Radhakrishnan 1998	Engel Class Scale	Combination	175	134	77	Temporal only	7 to 86	0 to 81	24 to 68
Rausch 2003	> 1 year seizure‐free	Not stated	42	21	21	Temporal only	NA	NA	109 to 228
Remi 2011	Engel Class Scale	Retrospective	154	138	NA	Temporal and extratemporal	NA	NA	22 to 228
Roberti 2007	Engel Class Scale	Retrospective	42	27	17	Temporal only	10 to 52	3 to 51	44 to 121
Rossi 1994	'Other' scale	Retrospective	138	86	100	Temporal and extratemporal	1 to 46	> 3	> 36
Russo 2003	Engel Class Scale	Retrospective	101	64	67	Temporal and extratemporal	0 to 53	0 to 46	> 12
Sagher 2012	Engel Class Scale	Retrospective	96	85	46	Temporal only	17 to 59	1 to 57	> 12
Sakamoto 2009	'Other' scale	Retrospective	36	19	16	Temporal only	12 to 58	4 to 49	24 to 63
Salanova 1994	Engel Class Scale	Retrospective	89	53	46	Temporal only	8 to 53	1 to 43	12 to 96
Sarkis 2012	Engel Class Scale	Retrospective	62	38	34	Temporal only	1 to 56	NA	6 to 170
Schramm 2011	Engel Class Scale	Prospective	207	152	100	Temporal only	39.7 (13.2)	22 (median)	> 12
Seymour 2012	Engel Class Scale	Retrospective	291	153	159	Temporal only	3 to 59	NA	28 to 144
Sinclair 2003	Engel Class Scale	Retrospective	77	57	39	Temporal and extratemporal	0 to 16	0 to 15	12 to 144
Sindou 2006	Engel Class Scale	Not stated	100	85	42	Temporal only	18 to 58	NA	12 to 120
Sola 2005	Engel Class Scale	Retrospective	137	74	63	Temporal only	12 to 69	1 to 44	24 to 138
Spencer 2005	> 1 year seizure‐free	Prospective	355	264	174	Temporal and extratemporal	NA	NA	> 12
Sperling 1992	Engel Class Scale	Prospective	51	41	31	Temporal only	17 to 59	NA	21 to 64
Stavrou 2008	Engel Class Scale	Retrospective	53	45	31	Temporal and extratemporal	NA	3.4 (0.8)	> 24
Suppiah 2009	Engel Class Scale	Retrospective	174	94	75	Temporal only	10 to 61	NA	57 (32)
Swartz 1992	> 1 year seizure‐free	Prospective	34	27	NA	Temporal only	29 (NA)	NA	20 to 71
Tanriverdi 2010	Engel Class Scale	Retrospective	256	160	123	Temporal only	30.3 (10.5)	20.6 (10.7)	> 12
Tatum 2008	> 1 year seizure‐free	Retrospective	39	22	15	Temporal only	33.8 (10.9)	14.5 (NA)	30.8
Terra‐Bustamante 2005a	Engel Class Scale	Prospective	107	62	55	Temporal and extratemporal	10.2 (5.4)	6.4 (4.8)	12 to 108
Terra‐Bustamante 2005b	Engel Class Scale	Prospective	35	27	11	Temporal only	1 to 18	0 to 15	12 to 84
Tezer 2008	Engel Class Scale	Retrospective	109	90	42	Temporal only	15 to 52	18.5 (7.8)	57.4 (30.6)
Theodore 2012	> 1 year seizure‐free	Prospective	41	26	19	Temporal only	34.2 (9.5)	25 (12)	12 to 132
Tigaran 2003	Engel Class Scale	Retrospective	65	32	41	Extratemporal only	4 to 50	1 to 40	12 to 144
Tripathi 2008	Engel Class Scale	Retrospective	55	29	33	Temporal and extratemporal	1 to 45	NA	60 to 120
Trottier 2008	Engel Class Scale	Retrospective	96	73	69	Extratemporal only	0.5 to 52	16 (NA)	> 12
Urbach 2007	Engel Class Scale	Retrospective	42	25	20	Extratemporal only	7 to 50	2 to 42	> 12
Ure 2009	Engel Class Scale	Retrospective	74	28	0	Not stated	14 to 53	NA	12 to 336
Velasco 2011	Engel Class Scale	Prospective	163	93	NA	Not stated	NA	NA	14 to 73
Vogt 2018	'Other' scale	Prospective	47	29	22	Temporal	19 to 77	4 to 71	>12
Walz 2003	> 1 year seizure‐free	Not stated	98	85	44	Temporal only	36.2 (10.7)	25.2 (10.5)	12 to 90
Weinand 1992	> 1 year seizure‐free	Retrospective	89	57	NA	Temporal only	6 to 52	2 to 42	12 to 54
Wellmer 2012	Engel Class Scale	Retrospective	165	106	NA	Not stated	NA	NA	24 to 103
Widdess‐Walsh 2007	> 1 year seizure‐free	Retrospective	48	22	26	Temporal and extratemporal	2 to 56	0 to 27	32.4 (median)
Wiebe 2001	> 1 year seizure‐free	Prospective	36	23	NA	Temporal only	NA	NA	> 12
Wieshmann 2008	Engel Class Scale	Retrospective	76	46	32	Not stated	NA	NA	> 12
Wray 2012	Engel Class Scale	Retrospective	52	36	24	Temporal and extratemporal	0 to 17	NA	> 12
Wyler 1995	> 1 year seizure‐free	Prospective	70	38	33	Temporal only	NA	NA	> 12
Wyllie 1998	Engel Class Scale	Not stated	136	92	78	Temporal and extratemporal	13 to 20	NA	12 to 88
Yang 2011	'Other' scale	Retrospective	99	27	63	Not stated	8 to 59	NA	12 to 72
Yeon 2009	Engel Class Scale	Retrospective	60	50	37	Temporal and extratemporal	NA	1 to 26	34.9 (22.5)
Yu 2009	Engel Class Scale	Retrospective	43	26	28	Extratemporal only	4 to 43	1 to 30	33.6 (16.8)
Yu 2012a	> 1 year seizure‐free	Retrospective	100	61	NA	Temporal and extratemporal	26.8 (7.6)	14.3 (8.3)	12 to 108
Yu 2012b	> 1 year seizure‐free	Retrospective	222	148	NA	Temporal and extratemporal	12.5 (8.1)	6.6 (4.3)	12 to 108
Zangaladze 2008	> 1 year seizure‐free	Combination	99	66	NA	Temporal and extratemporal	NA	NA	> 24
Zentner 1995	Engel Class Scale	Retrospective	167	103	82	Temporal only	3 to 64	2 to 52	12 to 72
Zentner 1996	Engel Class Scale	Prospective	56	30	39	Extratemporal only	1 to 49	2 to 35	20 to 85

Author	Design	Study design	Selection bias rating	Study design rating	Confounders rating	Blinding rating	Data collection rating	Withdrawals rating	Global rating
Aaberg 2012	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Adam 1996	Prospective	Cohort	Moderate	Moderate	Strong	Weak	Weak	Strong	Weak
Adelson 1992	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Weak	Not applicable	Weak
Alfstad 2011	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Alonso‐Vanegas 2018	Prospective	Randomised controlled trial	Strong	Strong	Strong	Weak	Strong	Strong	Moderate
Althausen 2013	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Weak	Not applicable	Weak
Arruda 1996	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Awad 1991	Not stated	Cohort	Moderate	Moderate	Strong	Weak	Strong	Weak	Weak
Babini 2013	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Barbaro 2018	Prospective	Randomised controlled trial	Moderate	Strong	Strong	Strong	Strong	Strong	Strong
Battaglia 2006	Not stated	Cohort	Moderate	Moderate	Strong	Weak	Weak	Weak	Weak
Baumann 2007	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Weak	Not applicable	Weak
Bautista 2003	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Bell 2009	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Benifla 2006	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Berkovic 1995	Prospective	Cohort	Moderate	Moderate	Strong	Weak	Weak	Strong	Weak
Blount 2004	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Blume 2004	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Boesebeck 2007	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Boshuisen 2010	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Brainer‐Lima 1996	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Weak	Not applicable	Weak
Britton 1994	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Caraballo 2011	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Cascino 1995	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Weak	Not applicable	Weak
Chabardes 2005	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Chang 2009	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Chee 1993	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Weak	Not applicable	Weak
Chkhenkeli 2007	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Choi 2004a	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Chung 2005	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Cossu 2005	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Cossu 2008	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Costello 2009	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Cukiert 2002	Prospective	Cohort	Moderate	Moderate	Strong	Weak	Weak	Strong	Weak
Dagar 2011	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Dalmagro 2005	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
de Tisi 2011	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Delbeke 1996	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Dellabadia 2002	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Devlin 2003	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Ding 2016	Prospective	Randomised controlled trial	Moderate	Strong	Strong	Weak	Strong	Strong	Moderate
Donadio 2011	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Dorward 2011	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Duchowny 1998	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Weak	Not applicable	Weak
Dunkley 2011	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Dunlea 2010	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Dwivedi 2017	Prospective	Randomised controlled trial	Strong	Strong	Strong	Strong	Strong	Strong	Strong
Elsharkawy 2008a	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Elsharkawy 2009a	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Elsharkawy 2011a	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Engman 2004	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Weak
Erba 1992	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Erickson 2005	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Fauser 2004	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Weak	Not applicable	Weak
Fujiwara 2012	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Garcia 1991	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Garcia 1994	Prospective	Cohort	Moderate	Moderate	Strong	Weak	Strong	Weak	Weak
Gelinas 2011	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Georgakoulias 2008	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Gilliam 1997a	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Gilliam 1997b	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Goldstein 1996	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Weak	Not applicable	Weak
Greiner 2011	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Grivas 2006	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Gyimesi 2007	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Hader 2004	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Hajek 2009	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Weak	Not applicable	Weak
Hallbook 2010	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Hamiwka 2005	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Hartley 2002	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Hartzfield 2008	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Hemb 2010	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Holmes 1997	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Weak	Not applicable	Weak
Holmes 2000	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Jack 1992	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Janszky 2003a	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Weak	Not applicable	Weak
Janszky 2003b	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Jaramillo‐Betancur 2009	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Jayakar 2008	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Jayalakshmi 2011	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Weak	Not applicable	Weak
Jeha 2006	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Jehi 2012	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Jennum 1993	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Jeong 1999	Not stated	Cohort	Moderate	Moderate	Strong	Weak	Strong	Weak	Weak
Kan 2008	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Kang 2009	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Kanner 2009	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Kilpatrick 1997	Prospective	Cohort	Moderate	Moderate	Strong	Weak	Weak	Weak	Weak
Kim 2009	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Kim 2010a	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Kim 2010b	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Kloss 2002	Combination	Cohort	Moderate	Moderate	Strong	Weak	Weak	Weak	Weak
Knowlton 2008	Prospective	Cohort	Moderate	Moderate	Strong	Weak	Strong	Weak	Weak
Kral 2007	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Krsek 2013	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Kuzniecky 1993	Prospective	Cohort	Moderate	Moderate	Strong	Weak	Weak	Strong	Weak
Kwan 2010	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Lackmayer 2013	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Weak
Lee 2006	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Lee 2008	Not stated	Cohort	Moderate	Moderate	Strong	Weak	Weak	Weak	Weak
Lee 2010	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Lee 2011	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Weak	Not applicable	Weak
Lei 2008	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Li 1997	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Li 1999	Not stated	Cohort	Moderate	Moderate	Strong	Weak	Weak	Weak	Weak
Liang 2010	Prospective	Randomised controlled trial	Moderate	Strong	Strong	Moderate	Strong	Strong	Strong
Liang 2012	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Liava 2012	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Lopez‐Gonzalez 2012	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Lorenzo 1995	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Madhavan 2007	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Mani 2006	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Mathern 1999	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Strong	Not applicable	Moderate
McIntosh 2012	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Mihara 2004	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Miserocchi 2013	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Morino 2009	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Weak	Not applicable	Weak
Morris 1998	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Strong	Not applicable	Moderate
O'Brien 1996	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Strong	Not applicable	Moderate
O'Brien 2000	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Oertel 2005	Prospective	Cohort analytic	Moderate	Strong	Moderate	Weak	Weak	Weak	Weak
Paglioli 2006	Prospective	Cohort	Moderate	Moderate	Strong	Weak	Strong	Strong	Moderate
Paolicchi 2000	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Park 2002	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Park 2006	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Perego 2009	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Perry 2010	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Phi 2009	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Phi 2010	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Pinheiro‐Martins 2012	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Prevedello 2000	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Weak	Not applicable	Weak
Raabe 2012	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Radhakrishnan 1998	Combination	Cohort	Moderate	Moderate	Strong	Weak	Strong	Weak	Weak
Rausch 2003	Not stated	Cohort	Moderate	Moderate	Strong	Weak	Strong	Weak	Weak
Remi 2011	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Roberti 2007	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Rossi 1994	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Russo 2003	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Sagher 2012	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Sakamoto 2009	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Salanova 1994	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Sarkis 2012	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Schramm 2011	Prospective	Randomised controlled trial	Moderate	Strong	Strong	Strong	Weak	Strong	Moderate
Seymour 2012	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Sinclair 2003	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Weak	Not applicable	Weak
Sindou 2006	Not stated	Cohort	Moderate	Moderate	Strong	Weak	Weak	Weak	Weak
Sola 2005	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Spencer 2005	Prospective	Cohort	Moderate	Moderate	Strong	Weak	Strong	Weak	Weak
Sperling 1992	Prospective	Cohort	Moderate	Moderate	Strong	Weak	Strong	Strong	Moderate
Stavrou 2008	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Suppiah 2009	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Swartz 1992	Prospective	Cohort	Moderate	Moderate	Strong	Weak	Weak	Weak	Weak
Tanriverdi 2010	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Tatum 2008	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Terra‐Bustamante 2005a	Prospective	Cohort	Moderate	Moderate	Strong	Weak	Strong	Weak	Weak
Terra‐Bustamante 2005b	Prospective	Cohort	Moderate	Moderate	Strong	Weak	Strong	Weak	Weak
Tezer 2008	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Theodore 2012	Prospective	Cohort	Moderate	Moderate	Strong	Weak	Weak	Weak	Weak
Tigaran 2003	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Tripathi 2008	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Trottier 2008	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Urbach 2007	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Ure 2009	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Velasco 2011	Prospective	Cohort analytic	Strong	Strong	Strong	Weak	Weak	Strong	Weak
Vogt 2018	Prospective	Randomised controlled trial	Strong	Strong	Strong	Moderate	Strong	Strong	Strong
Walz 2003	Not stated	Cohort	Moderate	Moderate	Strong	Weak	Weak	Weak	Weak
Weinand 1992	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Wellmer 2012	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Widdess‐Walsh 2007	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Wiebe 2001	Prospective	Randomised controlled trial	Strong	Strong	Strong	Weak	Strong	Strong	Moderate
Wieshmann 2008	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Weak	Not applicable	Weak
Wray 2012	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Wyler 1995	Prospective	Randomised controlled trial	Moderate	Strong	Strong	Strong	Strong	Strong	Strong
Wyllie 1998	Not stated	Cohort	Strong	Moderate	Strong	Weak	Strong	Weak	Weak
Yang 2011	Retrospective	Retrospective case series	Moderate	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Yeon 2009	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Strong	Not applicable	Moderate
Yu 2009	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Yu 2012a	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Yu 2012b	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Zangaladze 2008	Combination	Cohort	Moderate	Moderate	Strong	Weak	Weak	Weak	Weak
Zentner 1995	Retrospective	Retrospective case series	Strong	Moderate	Strong	Weak	Weak	Not applicable	Weak
Zentner 1996	Prospective	Cohort	Strong	Moderate	Strong	Weak	Weak	Strong	Weak

Quality assessment criteria	Number and proportion of studies
Method of identifying participants	Retrospective	144 (79%)
	Prospective	26 (14%)
	Combination	3 (2%)
	Not stated	9 (5%)
A. Selection bias
(Q1) Are the individuals selected to participate in the study likely to be representative of the target population?	Very likely	129 (71%)
	Somewhat likely	53 (29%)
(Q2) What percentage of selected individuals agreed to participate?	80% to 100%	9 (5%)
	less than 60%	1 (1%)
	Can't tell	28 (15%)
	Not applicable	144 (79%)
Selection bias rating	Moderate	64 (35%)
Selection bias rating	Strong	118 (65%)
B. Study design	Retrospective case series	144 (79%)
	Cohort	27 (15%)
	Cohort analytic	2 (1%)
	Randomised controlled trial	9 (5%)
Study design rating	Moderate	171 (94%)
Study design rating	Strong	11 (6%)
C. Confounders
(Q1) Were there important differences between groups before the intervention?	No	181 (99%)
	Unclear/Can't tell	1 (1%)
(Q2) If yes, indicate the percentage of relevant confounders that were controlled (either in the design (e.g. stratification, matching) or in the analysis)?	Unclear/Can't tell	1 (1%)
	Not applicable	181 (99%)
Confounders rating	Strong	181 (99%)
Confounders rating	Moderate	1 (1%)
D. Blinding
(Q1) Was (were) the outcome assessor(s) aware of the intervention or exposure status of participants?	Yes	176 (97%)
	No	4 (2%)
	Can't tell	2 (1%)
(Q2) Were the study participants aware of the research question?	Yes	176 (97%)
	No	4 (1%)
	Can't tell	2 (1%)
Blinding rating	Strong	4 (2%)
	Moderate	2 (1%)
	Weak	176 (97%)
E. Data collection methods
(Q1) Were data collection tools shown to be valid?	Yes	95 (52%)
(Q1) Were data collection tools shown to be valid?	Unclear/Can't tell	87 (48%)
(Q2) Were data collection tools shown to be reliable?	Yes	95 (52%)
(Q2) Were data collection tools shown to be reliable?	Unclear/Can't tell	87 (48%)
Data collection rating	Strong	95 (52%)
Data collection rating	Weak	87 (48%)
F. Withdrawals and dropouts
(Q1) Were withdrawals and dropouts reported in terms of numbers and/or reasons per group?	Yes	17 (9%)
	No	21 (12%)
	Not applicable	144 (79%)
(Q2) Indicate the percentage of participants completing the study.	80% to 100%	17 (9%)
	Can't tell	21 (12%)
	Not applicable	144 (79%)
Withdrawals rating	Strong	17 (9%)
	Weak	21 (12%)
	Not applicable	144 (79%)
G. Intervention integrity
(Q1) What percentage of participants received the allocated intervention or exposure of interest?	80% to 100%	182 (100%)
(Q2) Was the consistency of the intervention measured?	Yes	164 (90%)
(Q2) Was the consistency of the intervention measured?	No	18 (10%)
(Q3) Is it likely that participants received an unintended intervention (contamination or co‐intervention) that may have influenced the results?	No	182 (100%)
H. Analyses
(Q1) Unit of allocation	Individual	182 (100%)
(Q2) Unit of analysis	Individual	182 (100%)
(Q3) Are the statistical methods appropriate for the study design?	Yes	159 (87%)
	No stats	23 (13%)
(Q4) Is the analysis performed by intervention allocation status (i.e. intention‐to‐treat) rather than by the actual intervention received?	Yes	182 (100%)
Global rating	Strong	5 (3%)
	Moderate	79 (43%)
	Weak	98 (54%)

Study	Random sequence generation (selection bias)	Allocation concealment (selection bias)	Blinding of participants, personnel, and outcome assessors (performance and detection bias)	Incomplete outcome data (attrition bias)	Selective reporting (reporting bias)	Other bias
Alonso‐Vanegas 2018: judgement	Low	Unclear	High	Low	Low	Low
Support for judgement	Computer generated randomisation list	No information provided	Not blinded	No exclusions or withdrawals stated, all randomised patients seem to be included	Seizure outcome and safety outcomes described in the methods section well reported in the results. No protocol available to assess planned outcomes a priori	No other bias detected
Barbaro 2018: judgement	Unclear	Unclear	Low	Low	Low	Low
Support for judgement	Described as randomised but no further details provided	No information provided	Single‐blinded, outcome assessors were blinded	Attrition rates clearly stated, all participants included in seizure remission analysis up to 36 months	Seizure outcome, cognition and quality of life outcomes described in the methods section well reported in the results. No protocol available to assess planned outcomes a priori	No other bias detected
Ding 2016 : judgement	High	High	Unclear	Low	Low	Low
Support for judgement	Quasi‐randomisation based on odd or even patient ID number; not an adequate method of randomisation	Quasi‐randomisation meaning that allocation was not concealed	No information provided	All participants followed for 3 years and included in the outcome at 3 years; attrition at 5 years clearly reported	Seizure outcome, complications, and intelligence /quality of life changes described in the methods section well reported in the results. No protocol available for assessment of planned outcomes a priori	No other bias detected
Dwivedi 2017 : judgement	Low	Low	Low	Low	Low	Low
Support for judgement	Computer‐generated non‐stratified randomisation	Allocation concealed with sealed opaque envelopes	Primary outcome measure of freedom from seizures assessed in a blinded manner	All participants followed for 12 months and included in the outcome at 12 months	Protocol available as an online supplement to the publication. All pre‐specified outcomes reported	No other bias detected
Liang 2012: judgement	High	High	Unclear	Low	Low	Low
Support for judgement	Quasi‐randomisation based on odd or even patient ID number; not an adequate method of randomisation	Quasi‐randomisation meaning that allocation was not concealed	No information provided	All participants followed for 2 years and included in the outcome at 2 years	Seizure outcome, complications, and behavioural changes described in the methods section well reported in the results. No protocol available for assessment of planned outcomes a priori	No other bias detected
Schramm 2011: judgement	Low	Low	Low	Low	Low	Low
Support for judgement	Computer‐generated blocked randomisation list prepared	Each centre received the randomisation codes in numbered and sealed envelopes, with each envelope allocating the extent of resection for 1 particular participant at that centre. Envelopes were to be used in the given sequence for participants as they were included into the study. Envelopes had to be opened in the OR not before the morning of surgery. Thus, the type of surgery (selective amygdalohippocampectomy or lobectomy) was determined before the envelope was opened, but the content of the envelope determined the mesial extent of resection	Neither study participants nor epileptologists assessing outcomes were told of the result of the randomisation (i.e. they were not aware whether a short or a long resection had been done); the only person who knew this was the surgeon. OR notes did not mention the planned resection extent. In particular, persons performing MRI volumetry were blinded to group assignment	No losses to follow‐up; all participants included in analysis of outcome at 1 year	Seizure outcome, extent of resection, and complications described in the methods section well reported in the results. No protocol available for assessment of planned outcomes a priori	No other bias detected
Vogt 2018: judgement	Low	Low	Unclear	High	Low	Low
Support for judgement	Computer generated randomisation list	Allocation communicated to the surgeon after the patient was brought into the operating theatre	No information provided	Seven out of 54 (13%) randomised participants who did not complete neuropsychological assessments at 1 year were excluded from all analyses	Seizure outcome and neuropsychological outcomes described in the methods section well reported in the results. No protocol available to assess planned outcomes a priori	No other bias detected
Wiebe 2001: judgement	Unclear	Low	Unclear	Low	Low	Low
Support for judgement	Participants "randomly assigned…after stratification according to the presence or absence of generalized motor seizures"; no further information given	Random assignments prepared outside the study centre and delivered in sealed, opaque, sequentially numbered envelopes	Blinding not possible for anyone involved (surgical vs medical treatment); unclear whether outcome was influenced by this	Full details of attrition given: "No patients were lost to follow‐up. There were no crossovers from the medical group to the surgical group. One patient in the medical group died (a sudden, unexplained death) 7.5 months into the study. No deaths occurred in the surgical group." Intention‐to‐treat approach taken	Seizure outcome and quality of life described in the methods section well reported in the results. No protocol available for assessment of planned outcomes a priori	No other bias detected
Wyler 1995: judgement	Unclear	Unclear	Low	Low	Low	Low
Support for judgement	Study described as randomised; no further information given	No information provided	Participants and outcome assessors blinded; not possible to blind surgeons by design	All participants included in assessment of outcome at 1 year; intention‐to‐treat approach taken	Seizure outcome and neuropsychological outcomes described in the methods section well reported in the results. No protocol available for assessment of planned outcomes a priori	No other bias detected

Date	Event	Description
11 March 2019	New search has been performed	Searches were updated 11 March 2019 (RCTs only); 5 new RCTs have been included
11 March 2019	New citation required but conclusions have not changed	Conclusions remain unchanged

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Proportion free from seizures at 1 year	2	196	Risk Ratio (M‐H, Fixed, 95% CI)	9.78 [4.73, 20.21]
1.1 Free from seizures impairing awareness at 1 year	1	80	Risk Ratio (M‐H, Fixed, 95% CI)	7.67 [2.50, 23.51]
1.2 Free from seizures (ILAE Class 1) at 1 year	1	116	Risk Ratio (M‐H, Fixed, 95% CI)	11.39 [4.37, 29.64]
2 Proportion free from all seizures (including auras) at 1 year	1	80	Risk Ratio (M‐H, Fixed, 95% CI)	15.0 [2.08, 108.23]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Parahippocampectomy (PHC) or anterior temporal lobectomy (ATL): Proportion free from seizures (Engel Class Scale)	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.1 Engel Class 1 at 1 year	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Engel Class 1A at 1 year	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 Engel Class 1 at 5 years	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.4 Engel Class 1A at 5 years	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Parahippocampectomy (PHC) or Selective Amygdalohippocampectomy (SAH): Proportion free from seizures (Engel Class Scale)	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
2.1 Engel Class 1 at 1 year	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 Engel Class 1A at 1 year	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.3 Engel Class 1 at 5 years	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.4 Engel Class 1A at 5 years	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Selective Amygdalohippocampectomy (SAH) or Anterior Temporal Lobectomy (ATL): Proportion free from seizures (Engel Class Scale)	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
3.1 Engel Class 1 at 1 year	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 Engel Class 1A at 1 year	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.3 Engel Class 1 at 5 years	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.4 Engel Class 1A at 5 years	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Stereotactic radiosurgery (SRS) or anterior temporal lobectomy (ATL): proportion with remission of seizures (at least Engel Class IB) between 25 and 36 months	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
5 Resection with or without corpus callosotomy (CCT): Proportion free from seizures (Engel Class 1)	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
5.1 Engel Class 1 at 1 year	1	43	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.76, 1.70]
5.2 Engel Class 1 at 3 years	1	43	Risk Ratio (M‐H, Fixed, 95% CI)	1.19 [0.72, 1.95]
5.3 Engel Class 1 at 5 years	1	43	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [0.53, 2.21]
6 Anterior temporal lobectomy (ATL) with or without corpus callosotomy (CCT): Proportion free from seizures (Engel Class 1) at 2 years	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	1.22 [0.85, 1.76]
7 Subtemporal or transsylvian selective amygdalohippocampectomy (SAH): Proportion free from all seizures (including auras, ILAE 1a) at 1 year	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
8 Total or partial hippocampectomy: Proportion free from all seizures (including auras) at 1 year	1	70	Risk Ratio (M‐H, Fixed, 95% CI)	1.82 [1.12, 2.93]
9 Length of resection (2.5 or 3.5 cm): Proportion free from seizures (Engel Class 1) at 1 year	1	207	Risk Ratio (M‐H, Fixed, 95% CI)	1.02 [0.86, 1.20]

Outcome or subgroup title	No. of studies	Statistical method	Effect size
1 Proportion with a good outcome of surgery	178	Proportion (good outcome) (Fixed, 95% CI)	Totals not selected
1.1 > 1 year seizure‐free	42	Proportion (good outcome) (Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Engel Class Scale	116	Proportion (good outcome) (Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 'Other' scale	20	Proportion (good outcome) (Fixed, 95% CI)	0.0 [0.0, 0.0]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Good outcome by MRI results	43	3999	Risk Ratio (M‐H, Fixed, 95% CI)	0.78 [0.73, 0.83]
1.1 > 1 year seizure‐free	17	1691	Risk Ratio (M‐H, Fixed, 95% CI)	0.82 [0.74, 0.90]
1.2 Engel Class Scale	22	2097	Risk Ratio (M‐H, Fixed, 95% CI)	0.75 [0.69, 0.81]
1.3 'Other' scale	4	211	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.53, 1.32]
2 Good outcome by use of intracranial monitoring (IM)	21	1547	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.78, 0.93]
2.1 > 1 year seizure‐free	6	634	Risk Ratio (M‐H, Fixed, 95% CI)	0.88 [0.76, 1.02]
2.2 Engel Class Scale	14	863	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.77, 0.94]
2.3 'Other' scale	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.53 [0.28, 0.98]
3 Good outcome by presence of mesial temporal sclerosis (MTS)	46	4430	Risk Ratio (M‐H, Fixed, 95% CI)	1.17 [1.12, 1.23]
3.1 > 1 year seizure‐free	9	958	Risk Ratio (M‐H, Fixed, 95% CI)	1.25 [1.13, 1.39]
3.2 Engel Class Scale	31	2949	Risk Ratio (M‐H, Fixed, 95% CI)	1.13 [1.07, 1.20]
3.3 'Other' scale	6	523	Risk Ratio (M‐H, Fixed, 95% CI)	1.31 [1.14, 1.51]
4 Good outcome by concordance of pre‐op MRI and EEG	23	1778	Risk Ratio (M‐H, Fixed, 95% CI)	1.25 [1.15, 1.37]
4.1 > 1 year seizure‐free	8	744	Risk Ratio (M‐H, Fixed, 95% CI)	1.21 [1.07, 1.37]
4.2 Engel Class Scale	12	770	Risk Ratio (M‐H, Fixed, 95% CI)	1.27 [1.11, 1.46]
4.3 'Other' scale	3	264	Risk Ratio (M‐H, Fixed, 95% CI)	1.40 [1.02, 1.93]
5 Good outcome by history of febrile seizures (FS)	15	1368	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [1.01, 1.17]
5.1 > 1 year seizure‐free	5	644	Risk Ratio (M‐H, Fixed, 95% CI)	1.18 [1.05, 1.32]
5.2 Engel Class Scale	9	631	Risk Ratio (M‐H, Fixed, 95% CI)	1.01 [0.92, 1.11]
5.3 'Other' scale	1	93	Risk Ratio (M‐H, Fixed, 95% CI)	1.11 [0.90, 1.37]
6 Good outcome by history of head injury (HI)	7	551	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.86, 1.13]
6.1 > 1 year seizure‐free	2	152	Risk Ratio (M‐H, Fixed, 95% CI)	0.87 [0.72, 1.05]
6.2 Engel Class Scale	3	174	Risk Ratio (M‐H, Fixed, 95% CI)	1.17 [0.99, 1.37]
6.3 'Other' scale	2	225	Risk Ratio (M‐H, Fixed, 95% CI)	0.83 [0.51, 1.33]
7 Good outcome by presence of encephalomalacia	5	317	Risk Ratio (M‐H, Fixed, 95% CI)	0.78 [0.52, 1.17]
7.1 Engel Class Scale	4	218	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.60, 1.33]
7.2 'Other' scale	1	99	Risk Ratio (M‐H, Fixed, 95% CI)	0.28 [0.04, 1.87]
8 Good outcome by presence of focal cortical dysplasia (FCD)/malformation of cortical development (MCD)	46	3572	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.85, 0.95]
8.1 > 1 year seizure‐free	8	784	Risk Ratio (M‐H, Fixed, 95% CI)	0.92 [0.84, 1.02]
8.2 Engel Class Scale	33	2386	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.82, 0.96]
8.3 'Other' scale	5	402	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.73, 1.13]
9 Good outcome by presence of tumour	41	3357	Risk Ratio (M‐H, Random, 95% CI)	1.23 [1.14, 1.32]
9.1 > 1 year seizure‐free	7	656	Risk Ratio (M‐H, Random, 95% CI)	1.17 [0.97, 1.41]
9.2 Engel Class Scale	28	2199	Risk Ratio (M‐H, Random, 95% CI)	1.23 [1.13, 1.33]
9.3 'Other' scale	6	502	Risk Ratio (M‐H, Random, 95% CI)	1.35 [1.07, 1.70]
10 Good outcome by presence of vascular malformation	19	1488	Risk Ratio (M‐H, Fixed, 95% CI)	1.07 [0.94, 1.21]
10.1 > 1 year seizure‐free	1	46	Risk Ratio (M‐H, Fixed, 95% CI)	1.06 [0.62, 1.79]
10.2 Engel Class Scale	13	973	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.98, 1.34]
10.3 'Other' scale	5	469	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.74, 1.20]
11 Good outcome by unilateral or bilateral interictal spikes	18	1414	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [1.05, 1.24]
11.1 > 1 year seizure‐free	7	521	Risk Ratio (M‐H, Fixed, 95% CI)	1.08 [0.94, 1.24]
11.2 Engel Class Scale	6	502	Risk Ratio (M‐H, Fixed, 95% CI)	1.19 [1.04, 1.36]
11.3 'Other' scale	5	391	Risk Ratio (M‐H, Fixed, 95% CI)	1.16 [0.97, 1.39]
12 Good outcome by extent of resection	40	3013	Risk Ratio (M‐H, Fixed, 95% CI)	1.41 [1.32, 1.50]
12.1 > 1 year seizure free	9	640	Risk Ratio (M‐H, Fixed, 95% CI)	2.00 [1.66, 2.41]
12.2 Engel Class Scale	28	2189	Risk Ratio (M‐H, Fixed, 95% CI)	1.29 [1.21, 1.39]
12.3 'Other' scale	3	184	Risk Ratio (M‐H, Fixed, 95% CI)	1.59 [1.15, 2.20]
13 Good outcome by extent of resection	39	2930	Risk Ratio (M‐H, Fixed, 95% CI)	1.46 [1.37, 1.56]
13.1 Site of surgery: extratemporal only	1	30	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.76, 5.29]
13.2 Site of surgery: temporal only	13	1266	Risk Ratio (M‐H, Fixed, 95% CI)	1.11 [1.03, 1.20]
13.3 Site of surgery: temporal and extratemporal	25	1634	Risk Ratio (M‐H, Fixed, 95% CI)	1.92 [1.72, 2.15]
14 Good outcome by side of surgical resection	37	2976	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.91, 1.01]
14.1 > 1 year seizure‐free	5	290	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.91, 1.13]
14.2 Engel Class Scale	27	2407	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.89, 1.02]
14.3 'Other' scale	5	279	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.82, 1.07]
15 Good outcome by side of surgical resection	36	2933	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.90, 0.98]
15.1 Site of surgery: extratemporal only	2	123	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.76, 1.39]
15.2 Site of surgery: temporal only	30	2592	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.89, 0.98]
15.3 Site of surgery: temporal and extratemporal	4	218	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.84, 1.14]
16 Good outcome by presence of postoperative discharges	6	542	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.68, 1.22]
16.1 > 1 year seizure‐free	2	109	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.24, 3.93]
16.2 Engel Class Scale	4	433	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.70, 1.03]
17 Good outcome by presence of postoperative discharges	6	542	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.79, 1.04]
17.1 Site of surgery: temporal only	3	381	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.70, 0.94]
17.2 Site of surgery: temporal and extratemporal	3	161	Risk Ratio (M‐H, Fixed, 95% CI)	1.20 [0.89, 1.61]

Methods	Retrospective case series
Participants	54 children from a single Norwegian centre
Interventions	Lesionectomy or hemispherotomy; 44 had resective surgery, temporal and extratemporal
Outcomes	Assessed as Engel class at 12 and 24 months post surgery
Notes	—

Methods	Prospective case series
Participants	30 adults aged 18 to 44 from a single French centre
Interventions	Anteromedial temporal lobe resections
Outcomes	Seizure outcome assessed by Engel class at a mean of 24 months and at least 12 months after surgery
Notes	—

Methods	Pilot, unblinded randomised controlled trial conducted at a tertiary‐care neurological center located in Mexico City,
Participants	Adult participants, over the age of 18 years of age, with medically refractory mesial temporal lobe epilepsy and hippocampal sclerosis (typical clinical seizures, mesial temporal lobe focal MRI findings, and concordant epileptiform activity with ILAE pathologic confirmation of HS,failure to acceptably control seizures with 2 to 3 antiepileptic drugs over 2 years).
Interventions	Randomisation to anterior temporal lobectomy (ATL, n = 14), selective amygdalohippocampectomy (SAH, n = 15) or parahippocampectomy (PHC, n = 14)
Outcomes	Freedom from seizures according to the Engel Class Scale at 1 year and 5 years after surgery
Notes

Methods	Randomised controlled trial conducted at 14 treatment centers based in the USA, UK, and India
Participants	Participants over the age of 18 years who were eligible for anterior temporal lobectomy (ATL) to treat pharmaco‐resistant unilateral mesial temporal lobe epilepsy (MRI evidence of concordant unilateral hippocampal sclerosis without significant secondary cortical lesions and at least 3 focal‐onset seizures with impairment of consciousness occurred during stable anticonvulsant administration documented over three months),
Interventions	Randomisation to stereotactic radiosurgery (SRS, n = 31 analysed) or anterior temporal lobectomy (ATL, n = 27 analysed); a total of 63 participants were randomised and five withdrew before surgery.
Outcomes	Seizure remission outcome is defined by the seizure‐free (defined as at least Engel scale IB) rate between 25 and 36 months. Adverse events Verbal memory and quality of life (not relevant to this review).
Notes

Methods	Case series; unclear whether prospective or retrospective
Participants	45 children with refractory epilepsy operated on before 7 years from 1 Italian centre
Interventions	19 had hemispherectomy, 9 had multi‐lobar resection, 17 had focal resection ‐ 9 temporal, 4 frontal, 4 parieto‐occipital
Outcomes	Seizure outcome at least 2 years after the time of surgery
Notes	Focus on neurocognitive outcome

Methods	Multi‐centre retrospective case series
Participants	Participants were 168 consecutive children and adults with a single supratentorial cerebral cavernous malformation and symptomatic epilepsy. Centres in Switzerland, Italy, Germany, USA, and Canada
Interventions	Type of surgery: temporal and extratemporal
Outcomes	Seizure outcome by Engel class was determined in the first, second, and third postoperative years
Notes	—

Methods	Retrospective cohort study
Participants	615 people from a single UK centre, aged 16 to 63 years at surgery, who had undergone surgery for epilepsy
Interventions	Temporal and extratemporal surgery
Outcomes	Seizure freedom assessed using ILAE outcome score at follow‐up, at least 12 months from surgery
Notes	—

Methods	Prospective study with participants "randomly allocated" to either surgical treatment group
Participants	43 Chinese children aged 4 to 18 with Lennox‐Gastaut syndrome submitted to surgery with a localised epileptogenic
Interventions	Randomisation to exclusive resective surgery (n = 20) or to resective surgery combined with CCT (n = 23)
Outcomes	Seizure outcome by Engel class determined at 12 months after surgery
Notes	Study conducted to compare the outcome of the 2 surgical approaches. 25 children recruited without a localised epileptogenic zone were enrolled into a 'medical therapy' group; however as this group was not randomised within the study (2018 update), these 25 children are not included within the review

Methods	Single‐centre retrospective case series
Participants	67 children between 3 months and 16 years of age with recurrent seizures attributable to a discrete lesion on neuroimaging
Interventions	Site of surgery was temporal and extratemporal
Outcomes	Seizure outcome was examined 1 year post surgery and at subsequent follow‐ups using Engel's classification
Notes	—

PERMALINK

Surgery for epilepsy

Siobhan West

Sarah J Nevitt

Jennifer Cotton

Sacha Gandhi

Jennifer Weston

Ajay Sudan

Roberto Ramirez

Richard Newton

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Background

Description of the condition

Description of the intervention

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Types of outcome measures

Primary outcomes

Seizure outcome (proportion achieving a good outcome from surgery)

Secondary outcomes

Seizure outcome according to prognostic factors of interest

Pre‐operative factors

Operative factors

Postoperative factors

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Measures of treatment effect

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

'Summary of findings' and certainty of the evidence

for the main comparison.

2.

Results

Description of studies

Results of the search

1.

2.

Included studies

1. Study characteristics and participant demographics for 182 included studies.

Excluded studies

Risk of bias in included studies

2. Quality assessment of 182 included studies according to EPHPP tool.

3. Summary of EPHPP tool quality assessment component ratings.

A. Selection bias

B. Study design

4. Risk of bias assessment of six randomised controlled trials.

C. Confounders

D. Blinding

E. Data collection methods

F. Withdrawals and dropouts

G. Intervention integrity

H. Analyses

Overall rating

Adequacy of EPHPP quality assessment tool

Assessment of risk of bias in studies reporting multi‐variable prognostic models according to the Quality in Prognostic Studies (QUIPS) tool

Methods	Retrospective case series from 2 centres in the USA
Participants	54 participants, aged 6 months to 40 years at the time of surgery, who had had a hemispherectomy
Interventions	Extratemporal (i.e. all had hemispherectomy)
Outcomes	Seizure freedom assessed using Engel's classification at least 1 year post surgery
Notes	—

Methods	Retrospective case series; a German/Hungarian collaboration
Participants	130 adult patients (no age range provided) who had undergone epilepsy surgery for intractable medial temporal lobe epilepsy
Interventions	Temporal lobe surgery
Outcomes	Seizure freedom at 24 months after surgery compared with not seizure‐free
Notes	—

Methods	Retrospective case series from 1 centre in Canada
Participants	39 children, aged 2 months to 18.5 years, at surgery with a medically intractable epilepsy and focal cortical dysplasia on histology
Interventions	Temporal and extratemporal
Outcomes	Seizure outcome measured using Engel's classification at least 1.5 years after surgery
Notes	—

Methods	Retrospective case series from a single UK centre
Participants	35 children (24 females, 11 males; mean age 9.6 years; age range 11 months to 18 years) with a partial epilepsy, who had had a SPECT scan before surgery
Interventions	Temporal, extratemporal, and hemispherectomy
Outcomes	Seizure outcome measured using Engel's classification; range of follow‐up since surgery was 3 to 6 years (mean 4.8 years)
Notes	—

Methods	Retrospective case review from a single US centre
Participants	192 children operated on before 1997 vs 397 children operated on from 1998 to 2008, all with a refractory epilepsy
Interventions	Extratemporal and temporal and hemispherectomies
Outcomes	Seizure freedom at time of follow‐up, which was at least 12 months
Notes	—

Methods	Retrospective case series; nested case‐control study
Participants	89 teenagers and adults from Columbia
Interventions	Temporal lobectomies
Outcomes	Seizure outcome by Engel class determined at 12 and 24 months after surgery
Notes	—

Methods	Retrospective case review
Participants	87 children with refractory partial epilepsy
Interventions	Temporal, extratemporal, and hemispherectomy
Outcomes	Seizure outcome by Engel class determined at least 12 months after surgery
Notes	—

Methods	Retrospective and prospective case series
Participants	68 participants from 1 German centre younger than 18 years of age
Interventions	Types of resection included lesionectomy, lesion and corticectomy, lobectomy, and multi‐lobar resection
Outcomes	Seizure outcome was assessed using Engel's classification at 2 years postoperatively
Notes	—

Methods	Prospective case series from a single US centre
Participants	62 patients with mean age at surgery of 26 years (minimum age 1 year, maximum age 60 years), who required intracranial electroencephalography (ICEEG) because epileptic focus was not sufficiently localised with scalp EEG and MRI
Interventions	Temporal and extratemporal
Outcomes	Seizure outcome measured using Engel's classification at least 1 year post surgery; range of follow‐up was 1.5 to 10.5 years, with mean time of 4.2 years, and median of 3.5 years. Patients with < 1 year follow‐up were excluded
Notes	—

Methods	Retrospective cases series from a single German centre
Participants	49 patients with mean age at surgery of 18 years (range 5 to 47 years) with focal cortical dysplasia
Interventions	Temporal and extratemporal
Outcomes	Seizure outcome measured using the ILAE classification with mean follow‐up of 8.1 (SD 4.5) years
Notes	—