CQ 9-2
Digest Edition

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 low incidence of adverse 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 (RCT) (total 118 patients) on the effectiveness of temporal lobe resection 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 the outcome for one person) was 4, showing superiority of temporal lobe resection. Neither of the two RCTs mentioned decrease of 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 the two 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 we were not able 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 is considered to be smaller compared to its benefit.

3-3. What about patients’ values and preference?

Some patients may feel resistant to receive invasive surgical therapy, but the beneficial effect of seizure-free produced by the surgery outweighs the resistance to the invasive procedure. There is perhaps no significant uncertainty or variability in value among the patients.

3-4. What is the balance between net benefit and cost or resources?

The health 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, and enabling 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 the cost 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 this reason, 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 a suitable timing, stating that “since surgical results are superior in cases of mesial temporal lobe epilepsy with a localized organic 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 who meet 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, follow-up and support should be provided to the patients.

6. Possibility of future research

Some memory-preserving or minimally invasive surgery may be developed in the future. In addition, we would like to know the surgical outcomes and adverse events over a longer follow-up period because the observation periods of the two RCT 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 graph

Appendix CQ9-2-04. Forest plot

Appendix CQ9-2-05. Summary of Findings (SoF) table

Appendix CQ9-2-06. Evidence-to-Decision table

▪ 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, 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 Association of Neurological Surgeons. Neurology. 2003; 60(4): 538-547.

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Appendix CQ 9-2-01

Flow diagram and literature search formula

Literature search

PICO

P: Patients with drug-resistant epilepsy

I: Temporal lobe resection added to drug therapy

C: Compared with drug therapy alone

O: Are seizures eliminated or reduced?

Are antiepileptic drugs reduced or discontinued?

Is there increase in death related to surgery?

Are there increases in complications (medical/neurological) related to surgery?

Is memory (IQ, memory) lowered?

Is QOL (including psychiatric symptoms) improved?

▪ Search formula

CQ9-2. Flow diagram of literature search (modified PRISMA 2009)

cq9-2-01f01
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Appendix CQ9-2-02 and -03.

Risk of bias summary 
Risk of bias graphs

cq9-2-02_03f01a cq9-2-02_03f01b cq9-2-02_03f02a cq9-2-02_03f02b cq9-2-02_03f03a cq9-2-02_03f03b
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Appendix CQ9-2-04

Forest plot

cq9-2-04f01a cq9-2-04f01b cq9-2-04f01c cq9-2-04f01d cq9-2-04f02a cq9-2-04f02b cq9-2-04f02c
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Appendix CQ9-2-05

Summary of Findings (SoF) table

cq9-2-05t01
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Appendix CQ 9-2-06

Evidence-to-Decision table

Evaluation table of recommendation decision criteria

cq9-2-06t01

Recommendation decision table

cq9-2-06t02
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