Contemporary Insights into Intractable Epilepsy in Children

ABSTRACT

While most children with epilepsy find their seizures manageable through medication, some continue to experience seizures despite trying multiple drugs. Failure of medical treatment often becomes apparent early on, and for these cases, it is advisable to seek further treatment options at a specialized epilepsy center. Such centers offer additional treatments like epilepsy surgery, vagus nerve stimulation, and ketogenic diets. There is no universal definition for what constitutes “medically intractable” epilepsy. A proposal by a task force from the International League Against Epilepsy suggests that drug-resistant epilepsy could be defined as the inability to control seizures even after two adequate treatment attempts with well-chosen and tolerated medications, either alone or in combination. In this review, the authors discussed the management of intractable epilepsy in children.

INTRODUCTION

Intractable epilepsy in children represents one of the most challenging aspects of pediatric neurology, affecting both the child’s quality of life and posing considerable emotional and psychological strain on families. This form of epilepsy is challenging to manage because it remains resistant to multiple antiepileptic medications, distinguishing it from more common forms of epilepsy that are usually responsive to pharmaceutical intervention.[1,2,3] There is, however, no universally accepted definition of intractable epilepsy, although an influential proposal by the International League Against Epilepsy suggests that drug-resistant epilepsy be considered as the failure to maintain seizure freedom even after two or more adequate trials of suitable antiepileptic medications, either alone or in combination.[2,3] The prevalence of intractable epilepsy in children varies by demographic factors, underlying neurological conditions, and diagnostic criteria employed. Nevertheless, it is universally acknowledged as a serious medical condition requiring specialized care. In many instances, the refractory nature of epilepsy becomes apparent early in the course of treatment. Comprehensive epilepsy centers offer an interdisciplinary approach, which is crucial for accurately diagnosing and managing this complex condition. These centers usually have specialized teams comprising neurologists, surgeons, psychologists, and dietitians who collaboratively work to develop an individualized treatment plan for the child.[3,4,5]

MANAGEMENT

When initial antiepileptic medications fail to control seizures effectively, it is crucial to reevaluate the type of seizures the patient is experiencing, and the suitability of the medication plans previously attempted. Conditions that can be mistaken for seizures include psychogenic nonepileptic seizures and other paroxysmal disorders that are not linked to epilepsy[4] as given in Table 1.

Table 1.

Conditions that mimic epilepsy

Neonates and Infants

Apnea, Jitteriness, Benign neonatal sleep myoclonus

Shuddering attacks, Breath-holding spells, Sandifer syndrome

Benign myoclonus and benign torticollis of infancy, Head banging,

Children

Breath-holding spells, Benign paroxysmal vertigo, Vasovagal syncope, Migraine

Tic disorders and Parasomnias

Adolescents and young adults

Vasovagal syncope, Periodic limb movements of sleep, Paroxysmal dyskinesia,

Narcolepsy, Tic disorders, Migraine, Psychogenic nonepileptic seizures, Hallucinations

There are several factors that could account for the ineffectiveness of treatment that do not necessarily point to true drug-resistant epilepsy. These can include incorrect diagnosis or misclassification of the type of seizure (such as confusing focal and generalized seizures), which leads to choosing an inappropriate medication that might worsen seizures as given in Table 2.

Table 2.

Spectrum of antiepileptic drugs

Broad-spectrum antiepileptic drugs (For focal and generalized seizures)	Narrow antiepileptic spectrum (For focal-onset seizures)	Narrow spectrum (absence) For absence seizures
Brivaracetam	Carbamazepine	Ethosuximide
Clobazam	Cenobamate
Felbamate	Eslicarbazepine
Lamotrigine	Gabapentin
Levetiracetam	Lacosamide
Perampanel	Oxcarbazepine
Rufinamide	Phenobarbital
Topiramate	Phenytoin
Valproate	Pregabalin
Zonisamide	Primidone
	Stiripentol
	Tiagabine
	Vigabatrin

MEDICAL THERAPY

In the realm of medical therapy for pediatric epilepsy, a pivotal consideration pertains to children who exhibit resistance to monotherapy involving antiseizure medications. This resistance can manifest either through an inadequate response to sufficient doses or an inability to tolerate efficacious doses of the prescribed medication.[2] In such cases, the logical course of action entails the initiation of a secondary antiseizure medication. However, it is crucial to note that the probability of achieving complete cessation of seizures diminishes with each successive attempt involving an alternate antiseizure medication. The prospect of success in this regard depends upon the condition’s underlying etiology.[4]

INSUFFICIENT RESPONSE TO MULTIDRUG THERAPY

Paradoxically, the initial or second antiseizure medication may have contributed to an elevation in seizure frequency, thus exacerbating the problem with the subsequent addition of more antiseizure medications.[1,5] It is pertinent to note that a proportion of patients may experience an increase in seizure frequency as a result of most antiseizure medications. In some instances, the introduction of these medications may even induce the emergence of new seizure types. Such seizures can manifest at low or therapeutic doses of certain medications, while in others, they may occur at toxic doses.[1,6] Thus, the primary strategy for managing a child experiencing refractory seizures while on multiple antiseizure medications involves gradually reducing the least efficacious medicine.

EPILEPSY SURGERY

The evaluation for epilepsy surgery involves identifying the epileptogenic zone and assessing its resectability. It includes clinical evaluation, neuropsychological testing, EEG, MRI, and advanced imaging techniques.[7,8] Surgical options range from less invasive procedures like vagus nerve stimulation to more extensive surgeries like focal resections, lobar or multilobar resections, corpus callosotomy, hemispherectomy, and multiple subpial transection. The choice of procedure depends on the type and localization of the seizures. Lesionectomy is effective for children with a well-localized epileptic focus and a visible lesion on imaging. The risk of new or worsened neurological deficits, such as hemiparesis, varies depending on the specific procedure and the patient’s preoperative neurological status, with the highest risk associated with hemispherectomy and extratemporal resections and the lowest risk with medial temporal lobectomy.[1,5,6,7,8]

CONCLUSION

Intractable epilepsy in children is a complex and multifaceted condition requiring specialized care. Though the availability of multiple treatment options offers some hope, the reality is that a substantial number of children with intractable epilepsy continue to face daily challenges that extend far beyond the medical symptoms. Advances in genetic research and technology offer new avenues for more personalized treatment, yet a significant gap remains between the existing therapies and the ideal of complete seizure control. The complexity of intractable epilepsy necessitates a multidisciplinary approach that encompasses medical interventions and psychosocial support, signaling the need for continued research and development of more effective, comprehensive treatment strategies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.