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.

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.

Read the full 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 strategy: 

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

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