Is Refractory Epilepsy Preventable?

Abstract

Summary: About a third of the patients diagnosed with epilepsy will not be fully controlled with antiepileptic drugs (AEDs), and many of them will have frequent and disabling seizures. These patients will undergo multiple drug trials, most often without complete seizure remission. Moreover, refractory epilepsy is associated with increased morbidity (from seizures and medications), social isolation, unemployment, and overall reduced quality of life. There is evidence that refractory epilepsy can be a progressive disorder, which, if controlled early, might never develop into a full syndrome with all of its associated sequelae. The difficulty lies in identifying at an early stage patients who are likely to progress to intractability. No currently known markers enable clinicians to make this identification with confidence. Advances in pharmacogenomics and our understanding of pharmacologic responsiveness in epilepsy may change this situation. Even now, we are able to identify many patients with a poor prognosis earlier than before, particularly in the pediatric population, in which syndromic classification may provide an approach to predict intractability. The early initiation of aggressive therapy may improve outcome and overall quality of life.

The benefit of active drug trials is dependent on aetiology in refractory focal epilepsy

“…The aim in the future is to recognise patients at risk of refractory epilepsy as early as possible in order to evaluate the chance of long-term seizure remission and to prevent the development and progression of intractability 3 5 7 20 – 23. The aetiology seems to influence the outcome in patients with epilepsy, which makes high-resolution MRI important for diagnosis of patients with focal epilepsy; repetition of imaging is essential in refractory patients.…”

“…The specific imaging protocol is needed; this has certain sequences and thin slices to find the smallest abnormalities, especially in patients failing to achieve remission after two consecutive drugs 9 24 25. Patients with lesional aetiologies, including HS, are potential candidates for resective surgery in medically refractory patients 3 5 13 15–17 26–29. There is no need to hesitate in evaluating the possibilities of surgery in such cases because otherwise the prognosis seems to be poor.…”

“…On the other hand, there is a report from the UK in which 28% of the patients with drug-resistant epilepsy gained seizure freedom by adding a previously unused AED 4. An established definition of refractory epilepsy requires failure of two or more AEDs, with maximally tolerated doses sequentially or in combination, and lack of seizure control after 2 years of AED therapy 1 5 6…”

Antiepileptic Drugs

“…In clinical trials, patients in whom at least 3 AEDs 40 have failed are usually classified as refractory and most of trials have been carried out in individuals with partial epilepsy, given that it is the most common form of refractory epilepsy. Classic drugs (CBZ, VPA, PHT, PB, and PRM) are considered efficacious in these epilepsies, because although they have not been specifically evaluated in randomized trials in this patient population, the experience accumulated as a result of their widespread use suggests that they are efficacious in a large proportion of patients.…”

Anticonvulsant activities of nutmeg oil of Myristica fragrans

“…It is generally estimated that up to 30% of patients are refractory to conventional AED treatment. Moreover, refractory epilepsy is associated with increased morbidity, social isolation, dependent behavior, low rates of marriage, unemployment, overall reduced quality of life and a heavy burden on society (Arroyo et al, 2002). There is thus a need for the development of better and safer AEDs with improved clinical profiles.…”