Brain Surgery for Medically Intractable Epilepsy

This review covers the broad topic of brain surgery in the treatment of pediatric intractable epilepsy. The authors review the latest advancements in the presurgical workup as well as the mandatory tests needed to explore the epilepsy workup in these children. They describe the different types of epilepsy from a surgical standpoint (temporal, extratemporal, multifocal, and hemispheric epilepsies) and various surgical procedures that can be proposed depending on the clinical scenario: lesionectomies, lobectomies, hemispherectomies, neuromodulation, and palliative surgeries. They also describe the key differences of the pediatric patient as compared with the adult patient in such pathologic conditions.

Key points

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  Children suffering from drug-resistant epilepsy must be quickly referred to a comprehensive pediatric epilepsy center for a thorough presurgical evaluation.

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  Early referral allows for early treatment, which reduces the risk of secondary epileptic focus and increases the possibility of greater functional neuroplasticity following resective surgery.

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  Hemispheric, lobar, or lesional epilepsies are often amenable to complete resection, which increases chances of seizure freedom after surgery.

• •

  Bihemispheric and generalized epilepsies can benefit from palliative surgeries or from neuromodulation.

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  Neuromodulation techniques infrequently allow for seizure freedom but can significantly reduce seizure burden and increase quality of life.

 

 

Introduction

In North America, an estimated 100/100,000 children are diagnosed each year with epilepsy [

], which is defined as recurrent seizures, and affects between 0.5% and 1% of the population. Of those patients, 50% will be controlled by a first antiepileptic drug (AED) and 15% will be controlled by a second AED [ ]. After 2 AED, the chance of seizure control drops significatively, meaning that 15% to 30% of children [ ] will be pharmaco-resistant [

] and suffer from intractable epilepsy.

Patients suffering from intractable epilepsy are more at risk of injury [

], low self-esteem [ ], and even death [ ] (sudden unexpected death in epilepsy or SUDEP). Since the first randomized clinical trial (RCT) [ ] in adults demonstrating that temporal lobectomy could allow better seizure control than AED in certain cases, tremendous progress has been made to better define patient and surgical procedures that could help achieve seizure freedom. In a recent RCT by Dwivedi and colleagues [

], surgical management of various epilepsy disorders in children led to 77% seizure freedom at 12 months compared with 7% with medical treatment.

The most important steps are patient selection and procedure definition. This is achieved through the presurgical workup, which will classify, roughly, the patient between focal epilepsy (temporal lobe epilepsy [TLE] or extratemporal lobe epilepsy [ETLE]) versus generalized epilepsy as well as lesional versus nonlesional epilepsy. Once the epilepsy type has been well described, surgical procedures can be tailored to the patient and the epileptic region.

The authors divided the article as follows:

• •

  Presurgical workup

  • ○

    Noninvasive investigations

  • ○

    Invasive investigations

  • ○

    Timing of surgery

   

• •

  TLE

• •

  ETLE

• •

  Multifocal and generalized epilepsy

  • ○

    Palliative procedures

  • ○

    Neuromodulation

   

 

Presurgical workup

Noninvasive investigations

Once epilepsy has been diagnosed and failure of 2 AED has been noted, the diagnosis of intractable epilepsy is given [

]. At that point, patients should be referred to a comprehensive epilepsy center. The first step will be to confirm drug resistance. Indeed, the 2 AED given to the patient might have been inadequate for the epilepsy type [

].

Once drug resistance is confirmed, a complete workup is undergone to best define the epileptic zone based on anatomicoelectroclinical findings.

• •

  Since the development of electroencephalography (EEG) in 1950, seizure diagnosis has always relied on it. This test can detect interictal or ictal epileptiform activity but can be negative in up to 50% [

• ] of cases because of its short duration. With improvement of technology and data-storage capacities, video-EEG was developed, which allows recordings of EEG activities and clinical manifestations simultaneously over several days. Those recordings allow better electroclinical correlation and determination of the epilepsy type based on semiology and electric origin.

• •

  As opposed to the video-EEG, which has good temporal accuracy but poor spatial accuracy, the field of intractable epilepsy has also significantly benefited from the progress in MRI. This diagnosis tool is the gold standard for epilepsy assessment that facilitates identification of an epileptogenic lesion, such as focal cortical dysplasia (FCD), glioneuronal tumors, or mesiotemporal sclerosis. The evolution to the 3-T magnet has increased spatial resolution and increased lesional diagnosis to 65% [

]. With the emergence of the 7-T magnet, one can expect even better spatial definition and increased diagnostic yield with as much as 43% more lesional cases identified [

• ].

Although these tests are sufficient for a subset of patients, others require more advanced technologies to help identify and delineate the epileptogenic focus.

• •

  PET-computed tomography and ictal– single-photon emission computed tomography rely on abnormal brain metabolism secondary to the seizure focus during the interictal or ictal phase, respectively. This is usually used to confirm the affected lobe when MRI and EEG are incongruent, or when the lesion is subtle.

• •

  Magnetoencephalography (MEG) detects magnetic dipole parallel to the brain surface. Its advantage compared with the EEG is the absence of artifacts generated by the skull and the scalp, but the depth resolution is poor. Unfortunately, very few centers have access to MEG. However, this technology is a good add on when EEG cannot well define the boundaries of epileptogenic cortex.

• •

  Functional MRI and tractography are advanced MRI sequences that allow visualization of eloquent brain regions as well as main white matter tracts. Those sequences are useful when epileptic zones are near or in eloquent cortex.

• •

  A more thorough neuropsychological testing , especially in TLE, might also prove useful to better localize cognitive dysfunction, such as memory and language deficits.

• •

  Biological and genetic testing might help in refining the diagnosis and establishing a prognosis for the patient as well as a treatment strategy. These tests are improving each year, and more than 265 genes [

• ] have already been linked to various epilepsy syndromes.

Once the workup has been completed, a multidisciplinary meeting is organized involving epileptologists, neurosurgeons, neuroradiologists, neuropsychologists, and nursing staff. The purpose of this meeting is to answer 2 questions: (1) Can the epileptogenic zone be identified? and if so, (2) Is it safe to remove that region of the brain? In other words, does the deficit associated with removing that region of the brain result in an acceptable deficit to the patient? The best treatment plan is then defined in regard to all that information. Table 1 lists frequent diagnoses [

] and epilepsy type related to it.