Surgical Management of Drug Resistant Epilepsy

INTRODUCTION

Epilepsy (ILAE2014): is a disease of the brain defined by any of the following conditions: at least 2 unprovoked (or reflex) seizures occurring more than 24 hours apart; one unprovoked (or reflex) seizure with relatively high recurrence risk (i.e., ≥ 60 %(, occurring over the next 10 years or diagnosis of an Epilepsy syndrome. Seizure is a chronic brain disease that is caused by various factors and characterized by recurrent, episodic and temporary central nervous system dysfunction which results from excessive discharge of brain neurons.⁵

Drug-resistant epilepsy may be defined by International League Against Epilepsy (ILAE)as failure of adequate trials of two tolerated and appropriately chosen and used AED schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom.⁷

As a serious health problem worldwide, epilepsy accounts for 1% of the world's diseases.¹⁰

Despite appropriate trials of at least two antiepileptic drugs, about a third of patients with epilepsy remain drug resistant (intractable; refractory).¹

Traditionally, therapeutic failure of three antiseizure drugs defined intractability.⁶

Epilepsy surgery offers a potential cure or significant improvement to those with focal onset drug-resistant seizures. Unfortunately, epilepsy surgery is still underutilized which might be in part because of the complexity of pre-surgical evaluation. Pre-surgical evaluation includes classifying the seizure type, lateralizing and localizing the seizure onset focus (epileptogenic zone), confirming the safety of the prospective brain surgery in terms of potential neurocognitive deficits (language and memory functions), before devising a surgical plan.

Pathogenesis of drug-resistant epilepsy

The pathogenesis of epilepsy is complex and, at present, commonly acknowledged to be caused by the excitatory and inhibitory imbalance of the central nervous system. So far, the hypotheses regarding the pathogenesis of drug-resistant epilepsy mainly include:

1- Transporter hypothesis

Most antiepileptic drugs play the antiepileptic role in the brain via the blood-brain.⁸

Moreover, the overexpression of multidrug transporters that have a role in the efflux from the capillary endothelial cells which form the blood-brain barrier may lead to increased intracellular drug efflux or isolated vesicles, resulting in decreased intracellular drug concentration or changed drug distribution; consequently, antiepileptic drugs in epileptogenic zone and surrounding tissues cannot achieve the effective drug concentration, which leads to drug resistance.⁹

2- Target hypothesis

This hypothesis proposes that antiepileptic drugs cannot inhibit the excessive discharge of neurons through binding the predetermined target when the structure or function of the target of antiepileptic drugs changes, resulting in uncontrollable epilepsy attack, which is mainly reflected by abnormal ion channel function.¹²

Surgical treatment of drug-resistant epilepsy

Although there were multiples of new-type antiepileptic drugs that have been continued to be approved for application, there still exist more than 30 percent of patients with epilepsy developed into drug-resistant epilepsy.¹

With the continuous development of related science and technology, a variety of different surgical treatment methods emerged in response to the proper time and conditions, and now surgical treatment has become a very important therapeutic tool for drug-resistant epilepsy treatment. The goal of surgery is to reduce the seizures, to avoid the adverse reaction after surgery, and to a certain extent, to improve the quality of life. In general, we need to adjust the preoperative state of patients to meet the criteria of surgery. At present, surgical treatment methods for epilepsy are divided into resective surgery, palliative surgery, neuromodulation and other surgical interventions.

The work aims to review surgical outcome for drug resistant epilepsy of different causes to identify which patient would get the most benefit.

PATIENTS AND METHODS

Prospective and retrospective study on 20 cases with drug resistant epilepsy at Al-Azhar university hospitals. All cases are subjected to history and clinical examination. (Clearance of epilepsy seminology).

-Investigation by MRI brain, EEG and CT brain.

-Surgical techniques: resective (Lesionectomy) Surgery, Corpus Callosotomy

Outcome: functional outcome, control of epilepsy, complications

Inclusion Criteria:Age: 10-50 years, all cases of epilepsy that are not controlled on 2 antiepileptic drugs (drug resistant) and all cases that cannot tolerate side effects of antiepileptics.

Exclusion Criteria:All cases that are controlled on two or less antiepileptic drugs without intolerable side effects and ages younger than 10 or older than 50 years

Statistical analysis:Recorded data were analyzed using the statistical package for social sciences, version 20.0 (SPSS Inc., Chicago, Illinois, USA). Quantitative data were expressed as mean± standard deviation (SD). Qualitative data were expressed as frequency and percentage.

RESULTS

Table (1): Distribution of the study group according to their age (n=20).

This table shows that the 20 years (25.0%) of age (years), also ranged age 10-36 with mean 17.30±9.20

Table (2): Distribution of the study group according to their sex (n=20).

This table shows that the female (50%) and male (50%) of sex.

Table (3): Distribution of the study group according to their duration of disease

This table shows that the ranged 1-8 with mean 3.60±2.28 and median 3 (3) of duration of disease

Table (4): Distribution of the study group according to their semiology of epilepsy (n=20).

This table shows that the generalized tonic colonic fits (75.0%), Left focal tonic colonic fits of upper limb & lower limb (10.0%) and Right focal fits of upper limb & lower limb with secondary generalization (10.0%) of semiology of epilepsy.

Table (5): Distribution of the study group according to their MRI findings (n=20).

This table shows that the Normal  (10.0%), Right Parietal arachnoid cyst  (10.0%), Right insular dysplasia (10.0%), Left temporoparietal arachnoid cyst (15.0%), Left temporal Oligodendroglioma grade II (10.0%), Left temporal Xanthoastrocytoma grade II (10.0%), Left temporal low grade glioma  (10.0%), Left temporal ganglioglioma grade I (10.0%), Right temporal encephalomalacia (5.0%) and Right temporal arachnoid cyst  (10.0%) of MRI findings.

Table (6): Distribution of the study group according to their EEG (n=20).

This table shows that the Right centroparietotemporal epileptic discharge (20.0%), bilateral temporal epileptogenic activity with tendency to generalization (10.0%), Left temporal epileptic discharge (45.0%), Normal (15.0%) and Right occipitoparietal epileptogenic activity (10.0%) of EEG.

Table (7): Distribution of the study group according to their antiepileptic drugs (n=20).

This table shows that the Phynetion (50.0%), Levetira cetam (80.0%), Valproate (50.0%), Barbiturate (10.0%), Carbamazepine (50.0%) and Clonazepam (10.0%) of antiepileptic drugs.

Table (8): Distribution of the study group according to their antiepileptic drugs (n=20).

This table shows that the Phenytoin & Levetiracetam 20.00%, Phenytoin & Levetira cetam & Valproate 10.00%, Phenytoin & Levetiracetam & Valproate & Clonazepam 10.00%, Phenytoin & Levetiracetam & Carbamazepine 10.00%, Levetiracetam & Valproate  10.00%, Levetiracetam & Carbamazepine 10.00%, Levetiracetam & Carbamazepine & Toperamate 10.00%, Valproate & Barbiturate & Carbamazepine 10.00% and Valproate & Carbamazepine 10.00% of Antiepileptic drugs.

Table (9): Distribution of the study group according to their surgical intervention (n=20).

This table shows that the Excision (70.0%), Excision & fenestration of cyst to subarachnoid space (10.0%) and Callosotomy (20.0%) of surgical intervention.

Table (10): Distribution of the study group according to their Engl’s class (n=20).

This table shows that the class I (60%), class II (10%), class III (10%), class IV (20%) of Engl’s class.