Chapter 9
Surgical Treatment for Epilepsy
CQ 9-1

Which kinds of epilepsies (syndromes) are indications for
surgical treatment?
Summary
The following five epilepsies (syndromes) can be treated with surgery: (1) mesial temporal lobe epilepsy, (2) partial
epilepsy with responsible organic lesions detected, (3) partial epilepsy without detectable organic lesions, (4) partial
epilepsy due to extensive lesions within one hemisphere, and (5) intractable epilepsy with atonic seizures.

Comment
We consider that patients with epilepsy are candidates for surgical treatment when the epileptogenic zone can be
determined by examinations, and resection of the epileptogenic zone is expected to result in no or acceptable sequelae. The
above five epilepsy syndromes are treatable by surgery (surgically remediable syndromes)1). (1) Mesial temporal lobe epilepsy(MTLE), especially MTLE with hippocampal sclerosis (HS) (MTLE-HS), is considered to be the best indication for surgicaltreatment as an independent syndrome, and significant seizure control is predicted 2-4). (2) For partial epilepsy, when a lesion
is detected by diagnostic imaging and is resectable, we consider surgical treatment. Thermocoagulation surgery is effective
for gelastic seizures induced by hypothalamic hamartoma5). (3) Even when no lesion is depicted on MRI, surgical treatment
may be indicated if the epileptogenic zone can be detected by EEG and functional neuroimaging. (4) Partial epilepsy causedby extensive lesions in unilateral hemisphere is included as a candidate for surgical treatment. Since the arrest or regressionof psychomotor development is often induced in patients who have intractable epilepsy with infancy or early childhood
onset, early surgical treatment is recommended6). (5) Corpus callosotomy is effective for atonic seizures.

▪ References
1) Engel J Jr, Cascino GD, Shields WD. Surgically remediable syndromes. In: Engel J Jr, Pedley TA, eds. Epilepsy: A Comprehensive Textbook, 2nd
ed. Philadelphia; Wolters Kluwer/Lippincott Williams & Wilkins; 2007. p.1761-1769.
2) Wieser HG; ILAE Commission on Neurosurgery of Epilepsy. ILAE Commission Report. Mesial temporal lobe epilepsy with hippocampal sclerosis.
Epilepsia. 2004; 45(6): 695-714.
3) Wiebe S, Blume WT, Girvin JP, et al; Effectiveness and Efficiency of Surgery for Temporal Lobe Epilepsy Study Group. A randomized, controlled
trial of surgery for temporal-lobe epilepsy. N Engl J Med. 2001; 345(5): 311-318.
4) Téllez-Zenteno JF, Dhar R, Wiebe S. Long-term seizure outcomes following epilepsy surgery: a systematic review and meta-analysis. Brain. 2005;
128(Pt 5): 1188-1198.
5) Kameyama S, Shirozu H, Masuda H, et al. MRI-guided stereotactic radiofrequency thermocoagulation for 100 hypothalamic hamartomas. J
Neurosurg. 2016; 124(5): 1503-1512.
6) González-Martánez JA, Gupta A, Kotagal P, et al. Hemispherectomy for catastrophic epilepsy in infants. Epilepsia. 2005; 46(9): 1518-1525.

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CQ 9-2

Is temporal lobe resection effective for drug-resistant temporal
lobe epilepsy?
Summary
The effectiveness and safety of temporal lobe resection have been established for drug-resistant temporal lobe
epilepsy, and it is a treatment that should be considered for complex partial seizures that impede daily living. This
treatment is particularly effective when localized temporal lobe lesions are depicted on MRI.

Comment
The results of surgical treatment for temporal lobe epilepsy have been accumulated from major epilepsy centers around theworld since the 1990’s1). In 2001, the superiority of surgical treatment to drug treatment was demonstrated by a randomized
controlled trial (RCT)2). In 2003, the American Academy of Neurology together with the American Epilepsy Society andthe American Association of Neurological Surgeons published guidelines stating that “Patients with disabling complex
partial seizures, with or without secondarily generalized seizures, who have failed appropriate trials of first-line antiepileptic
drugs should be considered for referral to an epilepsy surgery center”3).
The rate of freedom from seizures that impede daily living in patients who underwent surgery was 60–80% if MRI
detected localized temporal lesions related to seizures, and the rate was approximately 50% if MRI detected no lesions4).
Apart from hippocampal sclerosis, localized lesions responsible for epilepsy include benign tumors such as ganglioglioma,
dysembryoplatsic neuroepithelial tumor and diffuse astrocytoma; cavernous malformations; and cerebral cortical dysplasia.
Postoperative complications such as speech disturbance, memory impairment, hemiparesis, and visual field defect may
occur, but the incidence is low5). Memory impairment after medial temporal lobe resection may involve various degrees ofverbal memory loss if there is no hippocampal atrophy on the language dominant side, but in patients with hippocampal
atrophy and below average preoperative memory, there is no change in verbal memory after surgery3).
Temporal lobe resection has been shown to be highly effective and safe in patients with drug-resistant temporal lobe
epilepsy, and is an established therapy. However, it takes more than 10 years on average from diagnosis to surgery. To
address this issue, epileptologists in the United States performed a randomized controlled trial (RCT) and recommended
that when two trials with appropriate antiepileptic drugs failed, surgery should be conducted at an early stage without
waiting for years6).
Comparison between surgical and medical treatments involves an inherent limitation of the low level of evidence. The
evaluation bias always occurs because blinding of medical and surgical treatments is impossible (see Systematic Review
Digest on page 148). If surgical treatment is believed to be clearly effective, randomization becomes an ethical concern.
Furthermore, we often have further difficulty in accomplishing a clinical trial since subject recruitment is challenging. Thisis shown by the fact that the randomized trial of Engel et al.6) was terminated prematurely. No comparative trials have beenreported, probably because long-term comparative studies are especially difficult to complete. In a case series report, the rateof seizure recurrence after surgery was several percent per year, and the seizure-free rate was approximately 50% after 10
years7).
Regarding the surgical methods, in addition to the classical standard anterior temporal lobe resection, various
approaches to the medial temporal lobe have been proposed. Anterior temporal lobectomy is superior to selective
amygdalohippocampectomy in seizure outcome8), 9). The superiority of selective resection for postoperative cognitive function
has not been shown so far. For patients with high risk of postoperative memory impairment, new therapies such as multiple
hippocampus transection, laser ablation and hippocampal electrical stimulation therapy have been proposed, and evaluationof these methods is awaited.

Chapter 977▪ References
1) McIntosh AM, Wilson SJ, Berkovic SF. Seizure outcome after temporal lobectomy: current research practice and findings. Epilepsia. 2001; 42(10):1288-1307.
2) Wiebe S, Blume WT, Girvin JP, et al. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med. 2001; 345(5): 311-318.
3) Engel J Jr, Wiebe S, French J, et al. Practice parameter: temporal lobe and localized neocortical resections for epilepsy: report of the Quality
Standards Subcommittee of the American Academy of Neurology, in association with the American Epilepsy Society and the American Associationof Neurological Surgeons. Neurology. 2003; 60(4): 538-547.
4) Téllez-Zenteno JF, Hernández Ronquillo L, Moien-Afshari F, et al. Surgical outcomes in lesional and non-lesional epilepsy: a systematic review andmeta-analysis. Epilepsy Res. 2010; 89(2-3): 310-318.
5) Hader WJ, Tellez-Zenteno J, Metcalfe A, et al. Complications of epilepsy surgery: a systematic review of focal surgical resections and invasive EEG
monitoring. Epilepsia. 2013; 54(5): 840-847.
6) Engel J Jr, McDermott MP, Wiebe S, et al. Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial. JAMA. 2012; 307(9):922-930.
7) de Tisi J, Bell GS, Peacock JL, et al. The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study.
Lancet. 2011; 378(9800): 1388-1395.
8) Hu WH, Zhang C, Zhang K, et al. Selective amygdalohippocampectomy versus anterior temporal lobectomy in the management of mesial temporal
lobe epilepsy: a meta-analysis of comparative studies. J Neurosurg. 2013; 119(5): 1089-1097.
9) Josephson CB, Dykeman J, Fiest KM, et al. Systematic review and meta-analysis of standard vs selective temporal lobe epilepsy surgery. Neurology.
2013; 80(18): 1669-1676.

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CQ 9-3What are the indications for chronic intracranial EEG(long-term intracranial EEG) in presurgical evaluation?
Summary
There is no clear criterion for the indication of chronic intracranial EEG as a presurgical evaluation for epilepsy
surgery. The current consensus is described below, but it may be changed by the advances and widespread use of otherpresurgical examinations.

Comment
Although there is no clear criterion for the indication of chronic intracranial EEG, this examination has been regarded asa gold standard for determining the epileptogenic zone and the extent of resection area since over 50 years ago1).
The consensus to date for the indications includes: (1) patients with partial epilepsy diagnosed by seizure symptoms andother noninvasive examinations (including positron emission tomography and magnetoencephalography) even without any
localized lesion detected by MRI; (2) patients with localized lesions demonstrated by MRI, which are inconsistent with theepileptogenic zones localized by other noninvasive examinations, or in whom multiple epileptogenic zones are suggested bynoninvasive examinations; (3) regardless of the presence or absence of localized lesions on MRI, patients with epileptogenic
lesions near the functional area, in whom high-resolution focus localization and brain function mapping are required1, 2).
Chronic subdural EEG recording is often omitted when noninvasive examination results are consistent with anatomical
findings in patients with mesial temporal lobe epilepsy associated with unilateral hippocampal sclerosis or partial epilepsy
with localized neocortical lesions. Also, this examination is often omitted in a standard extensive resection (including
callosotomy) (especially in children). Furthermore, this examination is usually not done before corpus callosotomy for
generalized seizures.
There are two types of intracranial electrodes: subdural electrodes that are placed on the brain surface and depth electrodes
placed inside the brain. In the former case, electrodes are placed by craniotomy; and in the latter, electrodes are stereotaticallyimplanted. We have no conclusion about their superiority, and both are used when necessary3).
Even though the required recording period has not been established, the recording is done for usually 1–4 weeks in many
institutions. While it usually takes more than two weeks to perform an adequate examination, the incidence of wound
infection or intracranial infection increases as the placement period increases. Complications of chronic intracranial EEG
recording include infection, cerebrospinal fluid leak, and focal neurologic symptoms. The incidence rate is 8.3% (7.7% cured
within 3 months, 0.6% prolonged)4).
In EEG analyses, in addition to conventional visual inspection, new analytical methods are available using signal
processing for a broader frequency range. For functional brain mapping, in addition to the classical electrical stimulation
method, new method is available to identify the high-frequency oscillations during a task. However, the superiority of these
new analytical methods has not been established5, 6).

▪ References
1) Nair DR, Burgess R, McIntyre CC, et al. Chronic subdural electrodes in the management of epilepsy. Clin Neurophysiol. 2008; 119(1): 11-28.
2) Wetjen NM, Marsh WR, Meyer FB, et al. Intracranial electroencephalography seizure onset patterns and surgical outcomes in nonlesional
extratemporal epilepsy. J Neurosurg. 2009; 110(6): 1147-1152.
3) Taussig D, Montavont A, Isnard J. Invasive EEG explorations. Neurophysiol Clin. 2015; 45(1): 113-119.
4) Hader WJ, Tellez-Zenteno J, Metcalfe A, et al. Complications of epilepsy surgery: a systematic review of focal surgical resections and invasive EEG
monitoring. Epilepsia. 2013; 54(5): 840-847.
5) Gloss D, Nolan SJ, Staba R. The role of high-frequency oscillations in epilepsy surgery planning. Cochrane Database Syst Rev. 2014; (1): CD010235.
6) Ryvlin P, Cross JH, Rheims S. Epilepsy surgery in children and adults. Lancet Neurol. 2014; 13(11): 1114-1126.

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79

CQ 9-4

How to determine the timing of considering surgical treatment?
Summary
When seizures have continued even after two or more regimens of appropriately selected antiepileptic drugs given
as monotherapy or combination therapy, classify such epilepsy with uncontrolled seizures for a certain period as
drug-resistant epilepsy, and consider surgical treatment. The “certain period” of persistent seizures is considered to
be one year or longer (or a period at least three times the pre-treatment interval between seizures). Earlier surgery
should be considered in children.

Comment
The ILAE1) defines drug-resistant epilepsy as “failure of adequate trials of two tolerated, appropriately chosen and usedantiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom for anadequate period”. An adequate period without seizures may be considered as at least one year (or a minimum of three times
the pre-treatment inter-seizure interval) without seizure recurrence. For adults, surgical treatment should be considered
promptly when epilepsy is judged to be drug resistant. For childhood, early surgery is desirable considering functional andsurvival outcomes. The ILAE Commission on Neurosurgery2) also recommends early surgery. The goal of surgical treatment
is not only to eliminate seizures but also to improve quality of life. Intellectual impairment and psychiatric disorder are notexclusion criteria for surgical indication. In children, it is known that psychomotor development improves when seizures arecontrolled after surgical treatment (treatable epileptic encephalopathy)3).

▪ References
1) Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission
on Therapeutic Strategies. Epilepsia. 2010; 51(6): 1069-1077.
2) Binnie CD, Polkey CE. Commission on Neurosurgery of the International League Against Epilepsy (ILAE) 1993-1997: recommended standards.
Epilepsia. 2000; 41(10): 1346-1349.
3) Berkovic SF, Arzimanoglou A, Kuzniecky R, et al. Hypothalamic hamartoma and seizures: a treatable epileptic encephalopathy. Epilepsia. 2003;
44(7): 969-973.

80Part IThe Clinical Practice Guidelines for Epilepsy 2018

CQ 9-5

Is surgical treatment effective even for drug-resistant epilepsies
in children?
Summary
The surgical treatment is widely used for children with drug-resistant epilepsy and is recommended as a treatment
by international experts despite no high-grade evidence supporting its efficacy. Epilepsy syndromes in children are
diverse, and poorly controlled epileptic seizures may affect cognitive and behavioral developments. Therefore,
presurgical evaluation should be performed at an appropriate timing in a specialized hospital or center.

Comment
The outcome of surgical treatment for drug-resistant epilepsy in children is better than that in adults, especially when alesion is confirmed pathologically or by MRI1). However, there is no high-grade evidence for it, and the ILAE recommends
the treatment based on expert consensus2).
The conspicuous features of epilepsy surgery in children include a high proportion of multilobar resection andhemispherectomy (including callsotomy), and cerebral cortical dysplasia as a common etiology. Surgical resection of localized
cortical dysplasia results in a high rate of seizure-free outcome3, 4).
Children are affected by diverse epilepsy syndromes, and poor control of epileptic seizures has a risk of worsening cognitiveand behavioral developments. Therefore, presurgical evaluation should be performed at an appropriate timing in a specialized
hospital or center3). Good seizure control by surgery sometimes improves developmental outcomes, especially in the case of
infants treated with hemispherectomy4).
In children with severe epilepsy showing localized lesions or hemispheric lesions, good outcome may be obtained evenwhen EEG demonstrates extensive bilateral epileptic abnormalities.

▪ References
1) Téllez-Zenteno JF, Hernández Ronquillo L, Moien-Afshari F, et al. Surgical outcomes in lesional and non-lesional epilepsy: a systematic review andmeta-analysis. Epilepsy Res. 2010; 89(2-3): 310-318.
2) Cross JH, Jayakar P, Nordli D, et al. Proposed criteria for referral and evaluation of children for epilepsy surgery: recommendations of the
Subcommission for Pediatric Epilepsy Surgery. Epilepsia. 2006; 47(6): 952-959.
3) Ryvlin P, Cross JH, Rheims S. Epilepsy surgery in children and adults. Lancet Neurol. 2014; 13(11): 1114-1126.
4) Spencer S, Huh L. Outcomes of epilepsy surgery in adults and children. Lancet Neurol. 2008; 7(6): 525-537.

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CQ 9-6

What is the risk of psychiatric symptoms after epilepsy surgery?
Summary(1) The risk of psychiatric symptoms after epilepsy surgery is high in patients with a past history or a family historyof psychiatric symptoms (including anxiety, depression, and psychosis) before epilepsy surgery, and in those inwhom seizures persist after surgery.
(2) Explain to patients before surgery the possibility of psychiatric symptoms after epilepsy surgery.
(3) For early detection and early treatment of psychiatric symptoms, we should follow the patients carefully for
approximately 6 months to 1 year.

Comment
It is desirable that all patients treated with epilepsy surgery should receive psychiatric evaluation before surgery1). A pasthistory of psychiatric disease is not a contraindication for surgery under the condition that psychiatric intervention is given.
The frequency of de novo postsurgical psychiatric symptoms such as anxiety, depression and psychosis, including mild
conditions such as adaptation disorder, is 1.1‒18.2%2). Presurgical psychiatric complications frequently exacerbate or recur
up to one year after surgery. Regular close psychiatric follow-up after surgery leads to good outcome.
Risk factors for psychiatric symptoms such as anxiety, depression, and psychosis after epilepsy surgery are residual seizures
after surgery and presence of a family history or past history of psychiatric condition before surgery. In surgically treatedpatients with temporal lobe epilepsy, the rate of de novo depression after surgery is 4‒18%, occurring 3‒12 months after
surgery and lasting for 1 to 11 months. The rate of de novo anxiety disorder occurring after surgery is 3–26%, showing apeak in the first month after surgery. The rate of de novo psychiatric disorders developing after surgery is 1.1%, and theoccurrence of psychiatric disorders is not related to the postsurgical seizure control or laterality of the resected hemisphere3).
In patients with favorable seizure outcome (seizure-free) after surgery, the outcome of psychiatric symptoms is alsofavorable, but in rare cases adaptation disorder may occur. A hypothesis of “burden of normality” has been proposed to
explain this phenomenon. It may be a kind of reaction of cured epilepsy patients to their new situation, that they should takeon various social obligations that have been neglected while they were affected by epilepsy4).
Treatment is basically the same as the usual treatment for psychiatric symptoms. In patients who did not receive any
explanation about the risk of postsurgical psychiatric symptoms before surgery, the patients and families often react to or
resist the involvement of psychiatrists after surgery. Therefore, participation of a psychiatrist in the treatment team before
surgery is desirable.

▪ References
1) Kerr MP, Mensah S, Besag F, et al. International consensus clinical practice statements for the treatment of neuropsychiatric conditions associatedwith epilepsy. Epilepsia. 2011; 52(11): 2133-2138.
2) Macrodimitris S, Sherman EM, Forde S, et al. Psychiatric outcomes of epilepsy surgery: a systematic review. Epilepsia. 2011; 52(5): 880-890.
3) Cleary RA, Baxendale SA, Thompson PJ, et al. Predicting and preventing psychopathology following temporal lobe epilepsy surgery. Epilepsy
Behav. 2013; 26(3): 322-334.
4) Ferguson SM, Rayport M. The adjustment to living without epilepsy. J Nerv Ment Dis. 1965; 140: 26-37.

▪ Search formula and secondary reference sources
Search formula
epilepsy [majr] AND mental disorders [majr] AND therapy [sh] Filters: Clinical Trial; Meta-Analysis; Multicenter Study; Randomized Controlled
Trial; Publication
PubMed = 86

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CQ 9-2

Should temporal lobe resection be added to drug therapy in
drug-resistant temporal lobe epilepsy?
Recommendation
We recommend temporal lobectomy in addition to drug therapies in patients with drug-resistant epilepsy (GRADE
2D) (weak recommendation, very low level of evidence).
• Supplementary note: In the GRADE system, when the evidence level is “very low”, in principle it is not possible
to grade “strong recommendation”. Since temporal lobe resection is highly effective with a low incidence ofadverse effects, almost all the panelists supported “strong recommendation”, but due to the constraint of the
GRADE system, the final grading was “weak recommendation”.

1. Background, priority of the problem
For drug-resistant epilepsy, adding further new drugs has limited effect. The temporal lobe resection is expected to achieve
seizure-free condition despite its invasiveness.

2. Comment

Evidence summary
There were 2 randomized controlled trials (RCTs) (total 118 patients) on the effectiveness of temporal lobe resection versus
medical therapy for drug-resistant epilepsy1, 2). With regard seizure outcome, the relative risk was 20.57 (95% confidence
interval 4.24‒99.85) and the number needed to treat (NNT: indicating the number of persons needed to treat to achieve theoutcome for one person) was 4, showing superiority of temporal lobe resection. Neither of the two RCTs mentioned decreaseof antiepileptic drugs after surgery. Death rate did not differ between two groups.
The relative risk of surgical complications was 12.33 (95% confidence interval 1.67‒90.89), and was higher in the temporal
lobe resection group. Death, memory impairment, and psychiatric symptoms were not significantly different between thetwo groups. Quality of life (QOL) improvement was superior in the temporal lobe resection group.

3. Panel meeting

3-1. What is the overall quality of evidence across outcomes?
Since it was not possible to mask the intervention, the risk of bias was high overall in the collected studies. Bias for death
was considered not serious, while that for the other outcomes was considered serious and was downgraded one rank.
Inconsistency and non-directness of the results were without question and considered not serious. For imprecision, confidence
intervals crossed the clinical decision threshold in many items, and was downgraded one or two ranks. Publication bias could
not be judged because of the small number of studies. Consequently, the level of evidence for the outcomes was as follows:“low” for seizure freedom, death, surgical complications, and quality of life improvement; and “very low” for memory
impairment and psychiatric symptoms. The overall level of evidence was “D (very low)”.
* For surgical therapy, since blinding of the control group is difficult, the level of evidence is generally low.

3-2. How is the balance between benefits and harms?
Temporal lobe resection can be expected to control seizures. As a result, antiepileptic drugs are possibly reduced although
it is not shown in RCT. The incidence of serious adverse effects was low. Therefore, the risk of temporal lobe resection isconsidered to be smaller as compared to its benefit.

3-3. What about patients’ values and preference?
Some patients may feel resistance in to receive invasive surgical therapy, but the beneficial effect of seizure-free producedby the surgery outweighs the resistance to the invasive procedure. There is perhaps no significant uncertainty or variability
in value among the patients.

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3-4. What is the balance between net benefit and cost or resources?
The medical insurance fee scale for epilepsy surgery using a microscope (including temporal lobe resection) is 131,630
points (as of January 11, 2018). The surgery is conducted under general anesthesia and requires neurosurgeons.
However, through reducing antiepileptic drugs, decreasing hospitalization duration accompanying reduced seizures, andenabling more active social activities, epilepsy surgery is expected to lead to saving in the long term. For this reason, the cost
can be considered negligible.

3-5. Recommendation grading
During the discussions at the panel meeting, temporal lobe resection was expected to eliminate seizures, and overall thecost of the surgery could be considered negligible. Even taking the adverse effects into account, the surgery was supported
by panelists.
At the panel meeting, many panelists supported a recommendation grade of “strong recommendation”. However, in the
GRADE system, when the evidence level is “very low”, in general we are not able to grade “strong recommendation”. For thisreason, the final grading was “weak recommendation”.

4. Descriptions in other related guidelines
In Japan, the Japan Epilepsy Society published the “Guideline on indications for epilepsy surgery”3) in 2008, and“Guideline on diagnosis and surgical indications of mesial temporal lobe epilepsy”4) in 2010.
The “Guideline on indications for epilepsy surgery” recommends surgical treatment for mesial temporal lobe epilepsy at asuitable timing, stating that “since surgical results are superior in cases of mesial temporal lobe epilepsy with a localizedorganic lesion or with extensive lesions in unilateral hemisphere, consider surgical treatment from an early stage and do not
miss the timing of surgery”. The “Guideline on diagnosis and surgical indications of mesial temporal lobe epilepsy” also
follows the above recommendation, stating that “patients should be selected in accordance with the guideline on indications
for epilepsy surgery”.
In overseas countries, the Quality Standards Subcommittee of the American Academy of Neurology, the American
Epilepsy Society, and the American Association of Neurological Surgeons published a guideline5) in 2003. The guideline
states that “drug-resistant epilepsy should be considered for referral to an epilepsy surgery center” and that “patients whomeet established criteria for an anteromesial temporal lobe resection and who accept the risks and benefits of this procedure
should be offered surgical treatment”.

5. Treatment monitoring and evaluation
Monitoring and evaluation during the perioperative period of treatment are generally performed by a neurosurgeon. After
this period, although a neurosurgeon is not necessarily required to monitor and evaluate the patients, follow-up and support
for the patients should be provided.

6. Possibility of future researchSome memory-preserving or minimally invasive surgery may be developed in the future. In addition, we would like toknow the surgical outcomes and adverse events over a longer follow-up period because the observation periods of the two
RCTs were 1 year1) and 2 years2).

7. RCT reports reviewed for this CQ
Wiebe 20011), Engel 20122)

8. List of appendices (to be shown later)
Appendix CQ9-2-01. Flow diagram and literature search formula
Appendix CQ9-2-02. Risk of bias summary
Appendix CQ9-2-03. Risk of bias graphAppendix CQ9-2-04. Forest plot
Appendix CQ9-2-05. Summary of findings (SoF) table
Appendix CQ9-2-06. Evidence-to-decision table

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▪ References
1) Wiebe S, Blume WT, Girvin JP, et al. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med. 2001; 345(5): 311-318.
2) Engel J Jr, McDermott MP, Wiebe S, et al. Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial. JAMA. 2012; 307(9):922-930.
3) Mihara T, Fujiwara T, Ikeda A, et al. Guideline on indications for epilepsy surgery. Tenkan Kenkyu. 2008; 26(1): 114-118 (in Japanese).
4) Watanabe E, Fujiwara T, Ikeda A, et al. Guideline on diagnosis and surgical indications of mesial temporal lobe epilepsy. Tenkan Kenkyu. 2006;
27(3): 412-416 (in Japanese).
5) Engel J Jr, Wiebe S, French J, et al. Practice parameter: temporal lobe and localized neocortical resections for epilepsy: report of the Quality
Standards Subcommittee of the American Academy of Neurology, in association with the American Epilepsy Society and the American Associationof Neurological Surgeons. Neurology. 2003; 60(4): 538-547.

Chapter 985