Evaluation and management of drug-resistant epilepsy

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1 Evaluation and management of drug-resistant epilepsy Fateme Jahanshahifar Supervised by: Professor Najafi

2 INTRODUCTION 20 to 40 % of patients with epilepsy are likely to have refractory epilepsy. a substantive ti proportion of annual cost for patients with epilepsy greatest burden of epilepsy-related disabilities

3 DEFINITION Because of the need to individualize therapy, no rigid set of guidelines can be applied to determine medical intractability Traditionally, therapeuticti failure of three antiepileptic drugs defined intractability With many new AEDs it might have been expected that more drug trials would be recommended before determining intractability

4 Response to treatment With the first drug trial, 49 % became seizure-free A second medication trial produced remission in an additional 13 % only a further 4 % became seizure-free on a third medication regimen

5 A task force of the International League against Epilepsy proposed : failure of adequate trials of two tolerated, appropriately chosen and administered antiepileptic drugs (monotherapy or in combination) to achieve seizure freedom. They also recommended replacing the term intractable with drugresistant epilepsy (DRE).

6 Some patients who meet this definition of DRE subsequently achieve prolonged (12 months or more) periods of seizure remission. However, the risk of seizure relapse in these individuals remains high,greater than 70 percent in one series.

7 Even infrequent seizures can have a large impact Frequency and severity of seizures are less commonly included in a definition of DRE(important when weighing treatment options) It is important to understand the impact of seizures in the context of the individual's life, job, and other psychosocial circumstances

8 burden of adverse effects of AEDs Less often considered, but also important, is the burden of adverse effects of AEDs that a patient experiences. If seizures can be controlled but only at doses that produce disabling side effects, then it may also be reasonable to consider that as a DRE

9 EPIDEMIOLOGY Because of unstandardized definitions as well as misdiagnoses, the incidence and prevalence of DRE are somewhat uncertain. vary between 20 and 40 %

10 Risk factors A. response to the first AED trial B. A high number of seizures prior to diagnosis and treatment C. underlying etiology and seizure classification D. Other findings more variably associated with the risk of DRE E. age at presentation the most important and consistently cited predictive factor among both populationbased and hospital-based studies and in both adult and pediatric populations AED failure due to lack of efficacy is a stronger predictor of DRE than failure due to intolerance or side effects ١٠ With each number of failed AED trials, the risk of DRE increases

11 Risk factors A. response to the first AED trial B. A high number of seizures prior to diagnosis and treatment C. underlying etiology and seizure classification D. Other findings more variably associated with the risk of DRE E. age at presentation another consistently identified risk factor for DRE ١١

12 Risk factors A. response to the first AED trial B. A high number of seizures prior to diagnosis and treatment C. underlying etiology and seizure classification D. Other findings more variably associated with the risk of DRE E. age at presentation ١٢ Idiopathic syndromes have a better prognosis than symptomatic epilepsy in both pediatric and adult almost intractable neonatal myoclonic encephalopathy early infantile epileptic encephalopathy Lennox Gastaut Rasmussen encephalitis vascular lesions may be more treatment responsive than those with mesial temporal sclerosis, cortical dysgenesis, or dual pathology

13 Risk factors A. response to the first AED trial B. A high number of seizures prior to diagnosis and treatment C. underlying etiology and seizure classification D. Other findings more variably associated with the risk of DRE E. age at presentation ١٣ 1. presentation with status epilepticus 2. longer duration of epilepsy 3. history of febrile convulsions 4. abnormal EEG 5. abnormal neurologic examination 6. developmental delay

14 Risk factors A. response to the first AED trial B. A high number of seizures prior to diagnosis and treatment C. underlying etiology and seizure classification D. Other findings more variably associated with the risk of DRE E. age at presentation ١٤ seizure onset in later childhood or adolescence more likely associated with DRE than seizures with onset between the ages of 5 and 10 Onset in the neonatal time period has been associated with DRE in at least one series Individuals who develop epilepsy later in life (>65 years) appear to be less likely to develop DRE than younger adults The varying risk of DRE by age group likely relates to the underlying pathogenesis of epilepsy that also varies by age.

15 The studies cited above have generally been performed in studies examining a patient's response to initial AED trials. However, a smaller percentage of patients with epilepsy p enter remission early in their course and develop DRE later, after a period of remission that in some cases is a long as several years. Factors that predict a later development of DRE are not well defined. However, this phenomenon of delayed intractability is most commonly described in the setting of mesial temporal sclerosis.

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