Subpial transection surgery for epilepsy
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To determine the benefits and adverse effects of subpial transections for partial‐onset seizures and generalized tonic‐clonic seizures in children and adults.
Background
Epilepsy is a neurological condition with an estimated incidence of 50 per 100,000 people overall and a prevalence of five to 10 per 1000 in the developed world (Sander 1996). Nearly 70% of people with epilepsy have a good prognosis and their seizures can be well controlled with anti‐epileptic drugs. Up to 30% of patients with epilepsy will continue to have seizures in spite of several anti‐epileptic drug regimens (Walker 1997). Most of the healthcare costs of epilepsy are due to patients with medically refractory seizures (Murray 1994). There is no universally accepted definition of 'medically refractory' but for the purpose of this review, we will consider seizures to be drug‐resistant if they have failed to respond to a minimum of two antiepileptic drugs (AEDs) appropriate to the type of epilepsy and given in adequate doses as monotherapy or in combination. Despite newer AEDs, many people with epilepsy do not achieve seizure freedom and some of them could potentially benefit from surgery. In the early years, epilepsy surgery focussed on removal of gross structural lesions of the brain. With the addition of electroencephalography (EEG) data from pre‐operative and intra‐operative recordings, areas of removal expanded to include tissue that was grossly normal in appearance but known to give rise to epileptiform activity. Partial lobectomies and more extensive cortical resection soon took the place of small areas of resection. Surgical procedures performed for epilepsy are categorized into (a) resection techniques (lesionectomy ‐ removal of the abnormal area of the brain; lobectomy ‐ removal of the diseased lobe; hemispherectomy ‐ removal of diseased hemisphere; corticectomy ‐ removal of the cortex of the cerebrum). These generally yield the best surgical results. There are also (b) non‐resective techniques which include callosotomy (division of corpus callosum); subpial transection (a series of shallow cuts (transections) into the brain's cerebral cortex); and vagus nerve and deep brain stimulation) (Jose 2005). Temporal lobe resection is the most common surgical procedure performed in adults with refractory epilepsy, while extra‐temporal cortical resection, hemispherectomy, corpus callostomy and temporal resection are the surgical procedures performed for refractory childhood epilepsy.
In subpial transection, multiple controlled lesions are placed 5mm apart at the mid‐level of cortical gyri to prevent the spread of epileptic discharges without altering the normal function of the cortex (Kaufmann 1996).
It is believed that early surgical intervention may prevent seizures at a younger age and improve the intellectual and social status of children. In this review we plan to systematically review the benefits and adverse effects of multiple subpial transection in patients with refractory epilepsy (Dlugos 2001).
Objectives
To determine the benefits and adverse effects of subpial transections for partial‐onset seizures and generalized tonic‐clonic seizures in children and adults.
Methods
Criteria for considering studies for this review
Types of studies
(1) Randomized or quasi‐randomized parallel group studies.
(2) The studies may be blinded or non‐blinded.
Types of participants
Children or adults with refractory partial‐onset seizures (simple partial, complex partial, or secondary generalized tonic‐clonic seizures) or generalized onset tonic‐clonic seizures (with or without other generalized seizure types).
Types of interventions
(1) Subpial transections versus anti‐epileptic drug therapy (monotherapy or multi‐drug therapy).
(2) Subpial transection versus another type of epilepsy surgery or vagal nerve stimulation.
(3) Subpial transection versus sham surgery.
Types of outcome measures
(1) Seizure outcome at one year, two years and five years after surgery ‐ free of disabling seizures, completely seizure‐free, improved, not improved.
(2) Time to achieve one‐ or two‐year seizure remission.
(3) Quality of life outcome ‐ assessed by generic as well as disease‐specific validated scales.
(4) Employment outcome ‐ post‐operative unemployment, under‐employment, employment.
(5) Activities of daily living and driving.
(6) Medication ‐ post‐surgical requirement of antiepileptic medication ‐ increased, decreased, stopped, monotherapy or polytherapy.
(7) Changes in cognitive functions and behaviour following surgery (assessed by validated scales).
(8) Mortality.
(9) Morbidity ‐ infections, new neurological deficits, and other surgical complications.
Search methods for identification of studies
(1) We will search the Cochrane Epilepsy Group's Specialized Register. This register contains reports of trials identified from regular searches of the Cochrane Central Register of Controlled Trials (CENTRAL) and of MEDLINE.
Subpial transections for epilepsy:
#1 EPILEPSY*:ME
#2 EPILEP*
#3 SEIZURES*:ME
#4 SEIZURE*
#5 CONVULSIONS*:ME
#6 CONVULSION*
#7 HEMISPHERECTOMY*:ME
#8 LOBECTOMY*:ME
#9 TRANSECTION*
#10 SUBPIAL TRANSECTION OR SUB‐PIAL TRANSECTION
#11 EPILEPSY SURGERY
#12 (((((#1 or #2) or #3) or #4) or #5) or #6)
#13 (((((((((((((((((#7 or #8) or #9) or #10) or #11)
#14 (#12 and #13)
#15. RANDOMIZED‐CONTROLLED‐TRIAL in PT
#16. CONTROLLED‐CLINICAL‐TRIAL in PT
#17. explode "RANDOMIZED‐CONTROLLED‐TRIALS" / all subheadings
#18. explode "RANDOM‐ALLOCATION" / all subheadings
#19. explode "DOUBLE‐BLIND‐METHOD" / all subheadings
#20. explode "SINGLE‐BLIND‐METHOD" / all subheadings
#21. #15 or #16 or #17 or #18 or #19 or #20
#22. Human.tw.
#23. Animal.tw.
#24. #23 not #22
#25. #22 or #23 not #24
#26. #21 and #25
#27. #14 and #26
We will search for cross‐references in identified publications. We will ask colleagues and experts in the field if they know of any relevant published or unpublished studies we may have missed.
(2) We will search cross‐references from retrieved studies for additional reports of relevant studies.
(3) We will contact the original investigators, colleagues and experts in the field to help identify and trials we have not found through our searches.
We will impose no language restrictions.
Data collection and analysis
Trial identification and data collection
Two review authors (Kodeeswaran Marappan and Lakshmi Ranganathan) will assess trials for inclusion which we have identified by means of the above search strategy. We will compare the results and resolve any disagreements by discussion. The same two review authors will extract data independently using a data extraction form which we will pilot‐test initially; we will compare results and resolve any disagreements by discussion. We plan to obtain the following information for each trial which meets our inclusion criteria. If the information is not available in the published manuscript, we will contact the original investigators for further data.
Methodological data
(1) Method of randomization.
(2) Method of concealment of randomization.
(3) Stratification factors.
(4) Methods of blinding, if used.
(5) Description of withdrawals and losses to follow up.
(6) Duration of baseline period.
(7) Duration of follow up.
Patient factors
(1) Seizure type(s).
(2) Age.
(3) Sex.
(4) Presence of neurological deficit/signs at baseline.
(5) Number of seizures or seizure frequency prior to randomization.
(6) Duration of epilepsy.
(7) EEG results at baseline.
(8) Etiology of epilepsy and imaging data.
(9) Number of anti‐epileptic drugs and dosages.
(10) Side on which surgery is located.
Treatment Issues
(1) Setting (neurosurgical or specialised epilepsy centre).
(2) Country.
(3) Differences in technique, if any.
Outcomes
Outcome data as listed earlier.
Quality assessment
We will evaluate the methodological quality of the studies according to the guidelines in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2008). We will exclude studies with a high risk of bias.
Data analysis
Our primary analysis will be an intention‐to‐treat analysis of patients according to the treatment allocation, regardless of the final treatment given.
For binary outcomes, we will use risk ratio (RR) and 95% confidence intervals (CIs). For continuous outcomes we will use mean difference (MD) and 95% CIs. We will compare patient characteristics, methodological diversities, outcomes across trials, and treatment regimens to assess clinical heterogeneity and compare patient populations. We will check for statistical heterogeneity using the I2 test for heterogeneity. Provided no significant clinical or statistical heterogeneity is present, we will synthesize data using a fixed‐effect model. We plan to do a sensitivity analysis by excluding the study with the largest or smallest effect or by excluding studies with poor quality to test the robustness of the meta‐analysis.
We will describe data on neurological examinations, CT scans, MRI scans, EEG results, and adverse effects. For psychological, cognitive and behavioural outcomes, we will narratively summarize the results and only when appropriate combine the results in a meta‐analysis.
Where possible we will undertake a sub‐group analysis according to seizure type, neuroimaging data and age groups (children less than 17 years versus adults).
