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Subpial transection surgery for epilepsy

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Abstract

Background

Nearly 30% of patients with epilepsy continue to have seizures in spite of using several antiepileptic drug (AED) regimens. Such patients are regarded as having refractory, or uncontrolled, epilepsy. No definition of uncontrolled, or medically refractory, epilepsy has been universally accepted, but for the purposes of this review, we will consider seizures as drug resistant if they have failed to respond to a minimum of two AEDs. It is believed that early surgical intervention may prevent seizures at a younger age, which, in turn, may improve the intellectual and social status of children. Many types of surgery are available for treatment of refractory epilepsy; one such procedure is known as subpial transection.

Objectives

To determine the benefits and adverse effects of subpial transection for partial‐onset seizures and generalised tonic‐clonic seizures in children and adults.

Search methods

We searched the Cochrane Epilepsy Group Specialised Register (29 June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; May 2015, Issue 5) and MEDLINE (1946 to 29 June 2015). We imposed no language restrictions.

Selection criteria

We considered all randomised and quasi‐randomised parallel‐group studies, whether blinded or non‐blinded.

Data collection and analysis

Two review authors (BK and SR) independently screened trials identified by the search. The same two review authors planned to independently assess the methodological quality of studies. When studies were identified for inclusion, one review author would have extracted the data, and the other would have verified the data.

Main results

We found no relevant studies.

Authors' conclusions

We found no evidence to support or refute use of subpial transection surgery for patients with medically refractory epilepsy. Well‐designed randomised controlled trials are needed to guide clinical practice.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

Subpial transection surgery for epilepsy

Nearly 30% of patients with epilepsy continue to have seizures despite taking several antiepileptic drugs (AEDs). Such patients are regarded as having refractory, or uncontrolled, epilepsy. Uncontrolled epilepsy by itself directly affects the intellectual function and social status of children. It causes considerable morbidity and mortality, affecting the person's quality of life. Some people with refractory epilepsy benefit from surgical treatment. Multiple subpial transection (MST) is a surgical technique by which connections of the epileptic focus are partially cut without resection. MST is one type of surgery that can be performed for people with medically refractory epilepsy, for whom the epileptogenic zone cannot be resected because of high risk of neurological deficits. In this review, we planned to assess benefits and adverse effects of multiple subpial transection in patients with refractory epilepsy. We found no randomised controlled trials comparing subpial transection versus antiepileptic drug therapy or subpial transection versus another type of epilepsy surgery. Therefore, evidence is insufficient for assessment of benefits or adverse effects of subpial transection; additional studies are needed.

Authors' conclusions

Implications for practice

Currently, evidence is insufficient to support the use of subpial transection for medically refractory epilepsy.

Implications for research

Randomised trials are urgently needed to assess the efficacy of subpial transection surgery for medically refractory epilepsy. These trials should be multi‐centric to recruit sufficient numbers of participants. Blinding may not be possible for surgical intervention, but random assignment with adequate concealment of allocation should be done. These studies can compare subpial transection versus other types of surgery, or subpial transection versus antiepileptic drug therapy. The surgical procedure and the technique should be as uniform as possible in multi‐centre trials to reduce heterogeneity. These trials should assess outcomes such as quality of life; long‐term intellectual and functional outcomes; seizure freedom or seizure reduction; economic aspects; and surgery‐‐ and epilepsy‐related morbidity and mortality. Outcome assessments should be validated and standardised. Follow‐up must be sufficiently long to permit assessment of the long‐term benefits of surgery.

Background

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 antiepileptic drugs (AEDs). Up to 30% of patients with epilepsy will continue to have seizures in spite of using several antiepileptic drug regimens (Walker 1997). Most of the healthcare costs of epilepsy are due to medically refractory seizures (Murray 1994). No definition of 'medically refractory' has been universally accepted (French 2006), but for the purposes of this review, we will consider seizures to be drug‐resistant if patients 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 using newer AEDs, many people with epilepsy do not achieve seizure freedom, and some could 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 preoperative and intraoperative recordings, areas of removal were expanded to include tissue that was grossly normal in appearance but was 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 can be categorised as (1) 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 approaches generally yield the best surgical results; and (2) 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 surgical procedure most commonly performed in adults with refractory epilepsy, and extratemporal cortical resection, hemispherectomy, corpus callosotomy and temporal resection are performed for refractory childhood epilepsy.

Multiple subpial transection (MST) is a novel technique that was conceived and first described by Dogali 1993, Morrell 1989 and Shimizu 1991; this approach is useful in patients for whom 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 penetrating blood vessels. This results in reduction of synchronised discharge from the epileptic focus and limitation of its spread, without jeopardised function of the cerebral cortex. The procedure may control seizures without producing major postoperative neurological deficits. Brain resection may 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, thus preventing seizures. Sometimes the area of seizure onset is one in which resection may produce neurological deficits; in these patients, subpial transection may be beneficial. It is believed that early surgical intervention may prevent seizures at a younger age, which, in turn, may improve the intellectual and social status of children (Dlugos 2001). The minimum volume essential for sustaining synchronous 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

Risk for surgery‐related mortality may be present, although no clear data are available. Morbidity such as aphasia or dysphasia, limb paralysis or postoperative infection such as meningitis may be seen in some cases.

Why it is important to do this review

Despite using new AEDs, nearly 30% of people with epilepsy do not achieve seizure reduction or seizure freedom, affecting quality of life and increasing healthcare costs. As subpial transection is one of the surgeries performed for medically refractory epilepsy, an urgent need exists to establish precisely its efficacy and harm through a systematic review of randomised trials. Studies done previously (Orbach 2001; Sawhney 1995; Schramm 2002) have reported good postoperative outcomes after subpial transection; two‐year follow‐up has shown good results. Even in patients with Landau Kleffner syndrome, subpial transection has resulted in improvement in communication skills among previously mute patients. This procedure is particularly useful for terminating prolonged medically refractory seizures and seizures involving eloquent areas of the cortex. It does not lead to postoperative deficits. A meta‐analysis of 211 patients undergoing multiple subpial transection (MST) at six centres (non‐randomised trials) found that 62% to 71% had greater than 95% seizure reduction (Tellez‐Zenteno 2005).

Objectives

To determine the benefits and adverse effects of subpial transection for partial‐onset seizures and generalised tonic‐clonic seizures in children and adults.

Methods

Criteria for considering studies for this review

Types of studies

  • Randomised or quasi‐randomised parallel‐group studies.

  • 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 transection versus antiepileptic 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 outcomes 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 outcomes ‐ assessed by generic and disease‐specific validated scales.

  • Employment outcomes ‐ postoperative unemployment, underemployment, employment.

  • Activities of daily living and driving.

  • Medication ‐ postsurgical requirement of antiepileptic medication ‐ increased, decreased, stopped, monotherapy or polytherapy.

  • Changes in cognitive function and behaviour following surgery (assessed by validated scales).

  • Mortality.

  • Morbidity ‐ infection, new neurological deficits and other surgical complications.

Search methods for identification of studies

Electronic searches

We searched the following databases.

  • Cochrane Epilepsy Group Specialised Register (29 June 2015), using the search strategy outlined in Appendix 1.

  • The Cochrane Central Register of Controlled Trials (CENTRAL; May 2015, Issue 5), using the search strategy outlined in Appendix 2.

  • MEDLINE (Ovid; 1946 to 29 June 2015), using the search strategy outlined in Appendix 3.

We applied no language restrictions.

Data collection and analysis

Trial identification and data collection

Two review authors (BK and SR) assessed trials for inclusion that were identified by means of the search strategy described above. We compared results and resolved 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 results and resolve disagreements by discussion. In future updates of this review, we plan to obtain the following information for each trial that meets our inclusion criteria.

Methodological data

  • 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.

Participant factors

  • Seizure type(s).

  • Age.

  • Sex.

  • Presence of neurological deficits/signs at baseline.

  • Number of seizures or seizure frequency before randomisation.

  • Duration of epilepsy.

  • EEG results at baseline.

  • Aetiology of epilepsy and imaging data.

  • Number of antiepileptic drugs and dosages.

  • Side on which surgery was performed.

Treatment issues

  • Setting (neurosurgical or specialised epilepsy centre).

  • Country.

  • Differences in technique, if any.

Outcomes

Outcome data as listed earlier.

Quality assessment

If studies had been identified, we would have evaluated their methodological quality according to guidelines provided in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2008), and we would have excluded studies with high risk of bias.

Data analysis

Our primary analysis would have been an intention‐to‐treat analysis of participants according to treatment allocation, regardless of the final treatment given.

We planned to use risk ratio (RRs) and 95% confidence intervals (CIs) for binary outcomes, and mean differences (MDs) and 95% CIs for continuous outcomes. We would have compared participant 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 by using the I2 test for heterogeneity. We would have synthesised data by using a fixed‐effect or a random‐effects model as appropriate. We planned to carry out a sensitivity analysis by excluding the study with the largest or smallest effect, or by excluding studies of poor quality to test the robustness of the meta‐analysis.

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, would have combined the results in a meta‐analysis.

If we had identified sufficient studies, we would have undertaken a subgroup analysis according to seizure type, neuroimaging data and age groups (children younger than 17 years vs adults).

Results

Description of studies

In total, we identified 369 studies through database searching. We considered none of the identified studies to be relevant, as no single study met the inclusion criteria. Figure 1 shows the flow chart of results of studies identified through various sources and their inclusion status.


Study flow diagram.

Study flow diagram.

Risk of bias in included studies

We included no studies in the review.

Effects of interventions

No studies met the inclusion criteria.

Discussion

Summary of main results

Despite an exhaustive literature search, we were not able to find any study that fulfilled our inclusion criteria.

Overall completeness and applicability of evidence

No study met the inclusion criteria. Hence at present, no reliable evidence supports the efficacy of subpial transection surgery for epilepsy.

Quality of the evidence

No studies met the inclusion criteria.

Potential biases in the review process

Some unpublished trials may have been conducted, or some trials might not have been retrieved, despite our exhaustive search strategy.

Agreements and disagreements with other studies or reviews

A meta‐analysis of 211 participants undergoing multiple subpial transection (MST) at six centres (non‐randomised trials) found that 62% to 71% had greater than 95% seizure reduction. MST plus cortical resection did not improve outcomes further (Spencer 2002). However, the pooled proportion of long‐term seizure‐free participants after subpial transection (two non‐randomised studies; 74 persons) was 16% (95% CI 8 to 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.

A Cochrane review reviewing all types of surgery (including subpial transections) for epilepsy has recently been published by the Cochrane Epilepsy group. This review incorporates non‐randomised trials as well as randomised controlled trials. Please refer to this review for more information (West 2015).

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.