Description of the condition
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 (AEDs). 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' (French 2006) 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 AEDs appropriate to the type of epilepsy and given in adequate doses as monotherapy or in combination.
Description of the intervention
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 focused 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 categorised into (a) resection techniques (lesionectomy- removal of the abnormal area of the brain; lobectomy- removal of 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 the corpus callosum); subpial transection (a series of shallow cuts into the brain's cerebral cortex); and (vagus nerve and deep brain stimulation) (Tellez-Zenteno 2005). Temporal lobe resection is the most common surgical procedure performed in adults with refractory epilepsy, while extra-temporal cortical resection, hemispherectomy, corpus callosotomy and temporal resection are the surgical procedures performed for refractory childhood epilepsy.
Multiple subpial transection (MST) is a novel technique, conceived and first described by (Morrell 1989 ,Dogali 1993; Shimizu 1991) and useful in those patients where the epileptogenic lesion cannot be resected because it lies in an eloquent cortical area or in regions where excision may produce major deficits. The surgical technique consists of severing horizontal intracortical fibres at intervals of 5 mm, while preserving both vertical fibres and the penetrating blood vessels. This results in reduction of the synchronised discharge from the epileptic focus and limitation of its spread without jeopardising the function of the cerebral cortex. The procedure may control seizures without producing major postoperative neurological deficit. Brain resection may also be performed in addition to MST in some patients. Hence, If epileptiform activity involves vital cortical areas or an inoperable site, subpial transection may be a preferred option in patients with medically refractory epilepsy.
How the intervention might work
Subpial transection may prevent the spread of epileptic discharges without altering the normal function of the cortex and thus prevent seizures. Sometimes the area of seizure onset can be an area where resection may produce neurological deficits and in those patients subpial transection may be beneficial. It is believed that early surgical intervention may prevent seizures at a younger age and improve the intellectual and social status of children (Dlugos 2001). The minimum volume essential to sustain synchoronous spiking has been empirically determined to be 12.5 mm. Cortical islands greater than 5 mm can support paroxysmal discharge Sawhney 1995) This is the reason why in subpial transection, multiple controlled lesions are placed 5 mm 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).
Adverse effects of the intervention
There may be a risk for surgery-related mortality, though no clear data are available. Morbidity such as aphasia or dysphasia, limb paralysis, post operative infections such as meningitis may be seen in some cases.
Why it is important to do this review
Despite new AEDs, nearly 30% of people with epilepsy do not achieve seizure reduction or seizure freedom affecting the quality of life and increasing healthcare costs. Since subpial transection is one of the surgeries performed for medically refractory epilepsy, there is an urgent need to establish precisely its efficacy and harms by a systematic review of randomised trials. Studies done previously Sawhney 1995; Orbach 2001, Schramm 2002 show good post-operative outcome after subpial transection; two-year follow-up has shown good results. Even in patients with Landau Kleffner syndrome, subpial transection resulted in improvement of communication skills in previously mute patients. It is particularly useful in terminating prolonged medically refractory seizures and seizures involving eloquent areas of cortex. It does not lead to any deficit post-operatively. A meta-analysis of 211 patients undergoing multiple subpial transections (MST) at six centres (non-randomised trials) found that 62% to 71% had > 95% seizure reduction (Tellez-Zenteno 2005).
To determine the benefits and adverse effects of subpial transections for partial-onset seizures and generalised tonic-clonic seizures in children and adults.
Criteria for considering studies for this review
Types of studies
- Randomised or quasi-randomised parallel group studies.
- 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 generalised tonic-clonic seizures) or generalised onset tonic-clonic seizures (with or without other generalised seizure types).
Types of interventions
- Subpial transections versus anti-epileptic drug therapy (monotherapy or multi-drug therapy).
- Subpial transection versus another type of epilepsy surgery or vagal nerve stimulation.
- Subpial transection versus sham surgery.
Types of outcome measures
- Seizure outcome at one year, two years and five years after surgery - free of disabling seizures, completely seizure-free, improved, not improved.
- Time to achieve one- or two-year seizure remission.
- Quality of life outcome - assessed by generic as well as disease-specific validated scales.
- Employment outcome - post-operative unemployment, under-employment, employment.
- Activities of daily living and driving.
- Medication - post-surgical requirement of antiepileptic medication - increased, decreased, stopped, monotherapy or polytherapy.
- Changes in cognitive functions and behaviour following surgery (assessed by validated scales).
- Morbidity - infections, new neurological deficits, and other surgical complications.
Search methods for identification of studies
We searched the following databases.
- Cochrane Epilepsy Group's Specialised Register (8 August 2013) using the search strategy outlined in Appendix 1.
- The Cochrane Central Register of Controlled Trials (CENTRAL, Issue 7 of 12, The Cochrane Library July 2013) using the search strategy outlined in Appendix 2.
- MEDLINE (Ovid, 1946 to 8 August 2013) using the search strategy outlined in Appendix 3.
We did not apply any language restrictions.
Data collection and analysis
Trial identification and data collection
Two review authors (BK and SR) assessed the trials for inclusion that were identified by means of the above search strategy. We compared the results and resolved any disagreements by discussion. The same two review authors planned to extract data independently using a data extraction form, which we had previously pilot-tested, and to compare the results and resolve any disagreements by discussion. In future updates of this review, we plan to obtain the following information for each trial that meets our inclusion criteria.
- Method of randomisation.
- Method of concealment of randomisation.
- Stratification factors.
- Methods of blinding, if used.
- Description of withdrawals and losses to follow-up.
- Duration of baseline period.
- Duration of follow-up up.
- Seizure type(s).
- Presence of neurological deficit/signs at baseline.
- Number of seizures or seizure frequency prior to randomisation.
- Duration of epilepsy.
- EEG results at baseline.
- Aetiology of epilepsy and imaging data.
- Number of anti-epileptic drugs and dosages.
- Side on which surgery is located.
- Setting (neurosurgical or specialised epilepsy centre).
- Differences in technique, if any.
Outcome data as listed earlier.
If studies had been identified, we would have evaluated the methodological quality of the studies according to the guidelines in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2008) and excluded studies with a high risk of bias.
Our primary analysis would have been an intention-to-treat analysis of patients according to the treatment allocation, regardless of the final treatment given.
We planned to use risk ratio (RR) and 95% confidence intervals (CIs) for binary outcomes and mean difference (MD) and 95% CIs for continuous outcomes. We would have compared patient characteristics, methodological diversities, outcomes across trials, and treatment regimens to assess clinical heterogeneity and to compare patient populations. We would have checked for statistical heterogeneity using the I
We intended to describe data on neurological examinations, computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, EEG results, and adverse effects. For psychological, cognitive and behavioural outcomes, we would have narratively summarised the results and, only if appropriate, combined the results in a meta-analysis.
If sufficient studies had been identified, we would have undertaken a subgroup analysis according to seizure type, neuroimaging data and age groups (children less than 17 years versus adults).
Description of studies
In total, we identified 282 studies through database searching. We did not consider any of the identified studies to be relevant as no single study met the inclusion criteria. Figure 1 gives the flow chart of results of studies identified from various sources and their inclusion status.
|Figure 1. Study flow diagram.|
Risk of bias in included studies
No studies were included in the review.
Effects of interventions
No studies met the inclusion criteria.
Summary of main results
Despite an exhaustive literature search, we were unable to find any study fulfilling our inclusion criteria.
Overall completeness and applicability of evidence
No study met the inclusion criteria. Hence at present there is no reliable evidence regarding the efficacy of subpial transection surgery for epilepsy.
Quality of the evidence
No studies met the inclusion criteria.
Potential biases in the review process
There may be some unpublished trials, or trials that could not be retrieved despite our exhaustive search strategy.
Agreements and disagreements with other studies or reviews
A meta-analysis of 211 patients undergoing multiple subpial transections (MST) at six centres (non-randomised trials) found that 62% to 71% had > 95% seizure reduction. MST plus cortical resections did not improve the outcome further (Spencer 2002). However, the pooled proportion of long-term seizure-free patients after subpial transection (two non-randomised studies, 74 persons) was 16% (95% CI = 8, 24) (Orbach 2001; Schramm 2002; Tellez-Zenteno 2005). Non-randomised trials may overestimate the effects of treatments compared with randomised trials (Dasheiff 1994; Devinsky 2003; Kuzniecky 2007).
This review has highlighted our knowledge gap regarding the efficacy of subpial transection as a treatment modality for persons with medically refractory epilepsy.
Implications for practice
Currently, there is insufficient evidence to support the use of subpial transection for medically refractory epilepsy.
Implications for research
There is an urgent need for randomised trials to assess the efficacy of subpial transection surgery for medically refractory epilepsy. The trials need to be multicentric to recruit sufficient numbers of participants. Blinding may not be possible for surgical intervention, but a random assignment with adequate concealment of allocation should be done. These studies can compare subpial transection with other types of surgeries or subpial transection with anti-epileptic drug therapy. The surgical procedure and technique should be as uniform as possible in case of multicentre trials to reduce the heterogeneity. These trials should assess outcomes such as quality of life; long-term intellectual and functional outcomes; seizure freedom or seizure reduction; economic aspects; surgical and epilepsy related morbidity and mortality. The outcome assessment should be validated and standardised. The follow-up must be sufficiently long to assess the long-term benefits of the surgery.
We wish to thank Dr Kodeeswaran and Dr Deiveegan for their contribution to the protocol.
Data and analyses
This review has no analyses.
Appendix 1. Epilepsy Specialised Register search strategy
#1 MeSH DESCRIPTOR Hemispherectomy Explode All WITH AE CL CT EC ED ES HI IS LJ MT MO NU PX RH ST SN TD UT VE
#4 "subpial transection" or "sub-pial transection"
#6 epilep* NEAR3 surg*
#7 #1 OR #2 OR #3 OR #4 OR #5 OR #6
#9 #7 AND #8
Appendix 2. CENTRAL search strategy
#1 MeSH descriptor Epilepsy explode all trees
#2 MeSH descriptor Seizures explode all trees
#3 (epilepsy* or seizure* or convuls*)
#4 (#1 OR #2 OR #3)
#5 MeSH descriptor Hemispherectomy explode all trees
#8 (subpial transection) or (sub-pial transection)
#10 (epilep* NEAR/3 surg*)
#11 (#5 OR #6 OR #7 OR #8 OR #9 OR #10)
#12 (#4 AND #11)
Appendix 3. MEDLINE search strategy
This strategy is based on the Cochrane Highly Sensitive Search Strategy for identifying randomized trials (Lefebvre 2011).
1. randomized controlled trial.pt.
2. controlled clinical trial.pt.
5. clinical trials as topic.sh.
8. 1 or 2 or 3 or 4 or 5 or 6 or 7
9. exp animals/ not humans.sh.
10. 8 not 9
11. exp Epilepsy/
12. exp Seizures/
13. (epilep$ or seizure$ or convuls$).tw.
14. 11 or 12 or 13
15. exp Hemispherectomy/
19. ((subpial or sub-pial) adj transection).tw.
20. (epilep$ adj3 surg$).tw.
21. 15 or 16 or 17 or 18 or 19 or 20
22. 10 and 14 and 21
Contributions of authors
BK and SR undertook the literature search and assessed trials identified by the search.
SR, LR, provided expert opinion and editorial support.
Declarations of interest
Differences between protocol and review
There were no differences between protocol and review.
Medical Subject Headings (MeSH)
MeSH check words