Global Perspectives
| Review Articles | |
| Refractory Epilepsy | |
Epilepsy, a common neurologic disorder can be defined as the recurrence of nonprovoked epileptic seizures. A complete diagnosis of epilepsy requires differentiation of seizures from other causes of altered consciousness / behaviour, differentiation of spontaneous unprovoked seizures from provoked seizures, classification of seizures and epilepsy and determination of underlying cause. However such measures for diagnosis are rarely used outside specialist centres1.
About 70 to 80% of newly diagnosed patients with epilepsy eventually achieve remission within two years of diagnosis. The remaining 20-30% of patients continue to have seizures that cannot be completely controlled by anti-epileptic drugs. Thus medically refractory epilepsy poses a challenge for both researchers and clinicians. Over the last two decades remarkable advances have taken place in the evaluation and treatment of patients with refractory epilepsy2. Epidemiology of refractory epilepsy A study was designed by Smith D et al (1998) to assess the frequency of, factors contributing to, and consequence of an erroneous diagnosis of epilepsy, and to evaluate the effectiveness of a specialist clinic in terms of the outcome of patients referred with 'refractory epilepsy'. Of the 94 patients referred with refractory epilepsy, 13% had pseudoseizures and of the remainder, 19% were seizure free. Only 7 of the 16 patients had genuinely refractory epilepsy. The main cause for pseudo refractoriness was failure to recognize idiopathic generalized epilepsy such that these patients had never received the drug of first choice, sodium valproate1. Furthermore, whilst the prognosis is favourable, relapse of treatment is almost inevitable and failure to recognize the condition often leads to inappropriate cessation of treatment. In this study, six patients with unrecognized idiopathic generalized epilepsy became seizure free with the introduction of valproate.1 Vagus nerve stimulation for the treatment of refractory epilepsy Vagus nerve stimulation (VNS) is a new and accepted therapy for treating seizures in refractory epilepsy patients3. Ben Menachem et al assessed the long-term efficacy of vagus nerve stimulation (VNS) for up to five years in 64 refractory epilepsy patients. They observed that despite refractoriness, 44% of patients experienced a large reduction in seizure frequency and severity over longer periods of time3. Authors have thus concluded that VNS is a safe and effective treatment for refractory epilepsy3. Surgical treatment for mesial temporal lobe epilepsy (MLTE) A recent advance in surgical treatment for epilepsy is the recognition that among the medically refractory patients are identifiable subgroups who have surgically remediable syndromes. The prototypic surgically remediable syndrome is mesial temporal lobe epilepsy (MLTE). With modern techniques, 80-90% of patients with MLTE become seizure free after anteromesial temporal lobectomy2. The data presented by Semah et al suggests that MLTE is the most medically refractory localization related epilepsy syndrome, underlining the important role of surgical treatment for this disorder2,4. Intravenous valproic acid in the treatment of refractory epilepsy Since its first clinical use in France in 1963, valproic acid (VPA) has rapidly established itself world wide as one of the major anti-epileptic drugs, with a broad efficacy for treatment of both generalized and partial seizures in children and adults. Intravenous VPA also offers the opportunity to treat emergency situations as prolonged or serial seizures, or even patients with status epilepticus (SE)5. Uberall et al reported 41 children with therapy resistant SE treated with in intravenous VPA. Because of its wide spectrum of anticonvulsant activity, it has been suggested that VPA acts through a combination of several primary slow acting mechanisms. In contrast to initial expectations, current clinical evidence suggests that VPA has at least a few immediate acting anti- epileptic effects and is capable of stopping the clinical and bioelectric correlates of ongoing seizure activity, even in patients with SE refractory to commonly used epileptic drugs5. Conclusions: One of the most important risk factors for refractory epilepsy is related to the type of epilepsy. The misdiagnosis of syncope and psychogenic attacks as epilepsy and the inadequate management of genuine epilepsy are common problems1. There is a general prevalence of medically refractory MLTE that is much larger than the smaller number being treated surgically worldwide. This treatment gap can be resolved by greater attention to early diagnosis and timely consideration of epilepsy surgery2,4 . Vagus nerve stimulation (VNS) has been found to be an effective therapy of refractory epilepsy3. Intravenous valproic acid has several galenic advantages that result in an excellent local and systemic side effect profile with none of the drug related complications of other intravenous convulsants. Based on the current evidence, intravenous valproic acid seems a safe, effective and well-tolerated parenteral alternative for emergency treatment of children with epilepsy5. References:
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