Surgery for epilepsy

Focal epilepsies are caused by abnormal electrical discharges in specific (localised) parts of the brain. In most people the resulting epileptic seizures can be controlled with medication. 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 from 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) findings (recording of electrical activity along the scalp) the person should be offered the chance of having the epileptogenic zone removed. We studied the factors (characteristics of the people undergoing surgery and details of surgery type) that might be linked to the best chance of surgical cure of epileptic seizures.

We examined evidence from 177 included studies reporting the experience of 16,253 people of all ages. In total, 10,518 people (65% of the total who had surgery in all studies) experienced a good outcome from surgery, defined as freedom from epileptic seizures.

One randomised controlled trial (RCT) established the superiority of surgery over continuing to try different medication in drug-resistant (intractable) epilepsy for the individuals in this trial. Three RCTs compared different types of surgery. No difference in seizure outcome was found in two trials; one removing 2.5 cm or 3.5 cm of the anterior temporal lobe (ATL, a part of the brain in which the epileptogenic zone is often located) or surgically removing the ATL with or without an additional procedure to sever the nerves that connect the two halves (hemispheres) of the brain. In the third trial, completely removing the hippocampus (a part of the brain in which the epileptogenic zone is often located) was found to be superior to only removing part of the hippocampus.

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

We identified some factors that predicted a better outcome from surgery. These were: a well-defined lesion (abnormality) on the MRI scan that corresponded with what was expected from the description of the seizures and the EEG findings, complete surgical removal of the lesion and a history of febrile seizures (a seizure 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 diffuse (spread out) brain abnormalities that might be associated with brain injury (from trauma or otherwise) 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. what would be the effect on outcome if a person has a history of febrile seizures, trauma and an MRI lesion altogether), however the studies did not report enough information to allow this.

We recommend that future studies should have a prospective design (a design where individuals are recruited before surgery has taken place, which identifies factors of interest before surgery and follows up individuals after surgery to record the outcome). Studies should examine the collective effect of factors that may predict the outcome of surgery using appropriate statistical methods. Future studies should use pre-operative investigations to guide the selection of the best candidates for surgery and the best surgical approach, use clearly defined methods to measure the result of surgery at specific time points and include pre- and postoperative cognitive and mental state assessment. Deaths during or after surgery, and complications and side effects from surgery, should be clearly recorded.

Authors' conclusions: 

The 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 outcome. Future research should be of high quality, have 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 the extent of resection. Prognostic factors related to the outcome of surgery should be investigated via multivariable statistical regression modelling, where variables are selected for modelling according to clinical relevance and all numerical results of the prognostic models are fully reported. Protocols should include pre- and postoperative measures of speech and language function, cognition and social functioning along with a mental state assessment. Journal editors should not accept papers where adverse events from a medical intervention are not recorded. Improvements in the development of cancer care over the past three to four decades have been achieved 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.

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Background: 

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 according to the age of the participants and which focal epilepsies are included, but have been reported as at least 20% and in some studies 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.

The secondary objectives are to assess the overall outcome of epilepsy surgery according to non-randomised evidence and to identify the factors that correlate to remission of seizures postoperatively.

Search strategy: 

We searched the Cochrane Epilepsy Group Specialised Register (June 2013), the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 6), MEDLINE (Ovid) (2001 to 4 July 2013), ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) for relevant trials up to 4 July 2013.

Selection criteria: 

Eligible studies were randomised controlled trials (RCTs), cohort studies or case series, with either a prospective and/or retrospective design, including at least 30 participants, a well-defined population (age, sex, seizure type/frequency, duration of epilepsy, aetiology, magnetic resonance imaging (MRI) diagnosis, surgical findings), 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 relating to postoperative seizure control.

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 proportion 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 (RR) and 95% confidence intervals.

Main results: 

We identified 177 studies (16,253 participants) investigating the outcome of surgery for epilepsy. Four studies were RCTs (including one that randomised participants to surgery or medical treatment). The risk of bias in the RCTs was unclear or high, limiting our confidence in the evidence that addressed the primary review objective. Most of the remaining 173 non-randomised studies had a retrospective design; they were of variable size, were conducted in a range of countries, recruited a wide demographic range of participants, used a wide range of surgical techniques and used different scales used to measure outcomes. We performed quality assessment 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 the domains.

In terms of freedom from seizures, one RCT found surgery to be superior to medical treatment, two RCTs found no statistically significant difference between anterior temporal lobectomy (ATL) with or without corpus callosotomy or between 2.5 cm or 3.5 cm ATL resection, and one RCT found total hippocampectomy to be superior to partial hippocampectomy. We judged the evidence from the four RCTs to be of moderate to very low quality due to the lack of information reported about the randomised trial design and the restricted study populations.

Of the 16,253 participants included in this review, 10,518 (65%) 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 the recording of adverse events to be very poor.

In total, 118 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: an abnormal pre-operative MRI, no use of intracranial monitoring, complete surgical resection, presence of mesial temporal sclerosis, concordance of pre-operative MRI and electroencephalography (EEG), 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 or presence of postoperative discharges were prognostic factors of outcome. We observed variability between studies for many of our analyses, likely due to the small study sizes with unbalanced group sizes, variation in the definition of seizure outcome, definition of the prognostic factor and the influence of the site of surgery, all of which we observed to be related to postoperative seizure outcome. Twenty-nine studies reported multivariable models of prognostic factors and the direction of association of factors with outcome was generally the same as found in the univariate analyses. However, due to the different multivariable analysis approaches and selective reporting of results, meaningful comparison of multivariate analysis with univariate meta-analysis is difficult.

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