Refractory Epilepsy in children

Information about Refractory Epilepsy in children

Published on August 7, 2014

Author: ksaad

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PowerPoint Presentation: 1 Refractory Epilepsy in children Khaled Saad , MD Assiut University PowerPoint Presentation: 2 I- Introduction II- Refractory Epilepsy (Definition, Predictors , Classification, Strategy Of Management). Agenda PowerPoint Presentation: (1) Spontaneous remission (20-30%) - benign epilepsy with centrotemporal spikes or childhood absences. (2) Remission on AEDs (20-30%) - most focal epilepsy and myoclonic juvenile epilepsy syndromes. (3) Persistent seizures under AEDs (30-40%). EurNeurol 2009;62:65-71 3 PROGNOSTIC GROUPS IN EPILEPSY PowerPoint Presentation: 4 PowerPoint Presentation: 5 Definitions of Refractory Epilepsy Old definitions: --Uncontrolled seizures despite plasma concentrations of AEDs within the therapeutic range (Scott, 1984). -- Uncontrolled seizures despite relevant therapy (Juul-Jensen, 1986). -- Seizures intractable to all therapeutic trials with single or combined drugs for a sufficient time (Aicardi, J. 1997) . PowerPoint Presentation: Uncontrolled seizures for at least 18 m, with a frequency of 1 fit or more/m. During that peroid at least 2 or more AEDs had to have been used as mono-or poly-therapy (Berg et al, 2006) Drug Resistant Epilepsy { ILAE 2009} : Failure of informative trials of two tolerated and appropriately chosen and used AED schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. ( Kwan et al Epilepsia 2009) 6 PowerPoint Presentation: Our definition : (a) One or more seizure per month for a period of 6 months or more. (b) No more than a 3-month seizure-free during those 6 months. (c) Failure of at least two appropriately selected AEDs with proper doses, good compliance, and within the therapeutic range of AEDs. 7 PowerPoint Presentation: Refractory epileptic patients are more prone to: *Neurological and Psychosocial retardation. *Risk of injury(seizure related). *High mortality: 1.37 per 100 person-years. Sudden unexplained death in epilepsy patients (SUDEP) is 40 times more likely among patients who continue to have seizures than in those who are seizure free. Epilepsy Res. 2005;65(1-2):101-15 & J Neurol. 2000;247(1):15. 8 How Serious Is The Problem? PowerPoint Presentation: 1- Early onset & Neonatal convulsions. 2-Mental subnormality. 3-Organic brain damage, Abnormal CT. 4- Poor initial response to AED. 5.Presentation with status epilepticus. 9 Predictors For Refractory Epilepsy PowerPoint Presentation: 6. Long duration of epilepsy before diagnosis. 7. Poor psychological and or socio-economic background. Family history of epilepsy. Abnormal neurological examination. Partial seizures at diagnosis, mixed seizure types. CNS Spectr . 2004;9:110-119 . 10 PowerPoint Presentation: 11 Aicardi, J.1988 *Medically intractable epilepsy: 1. Pseudo intractable. 2. True intractable . *Medically and surgically intractable : 3. Candidates unfit for surgery. 4. Candidates with failed surgery . Classification of Intractable Epilepsy Common Errors In Diagnosis and Treatment of Epilepsy (pseudo refractory): Physician’s Errors: * Diagnosis * Treatment 12 Common Errors In Diagnosis and Treatment of Epilepsy (pseudo refractory) Patient’s Errors: * Poor compliance *Erratic life style PowerPoint Presentation: Misdiagnosis of non-epileptic seizures. Misclassification of epileptic seizures. Unrecognized progressive brain disease. Failure to uncover precipitating factors . Misdiagnosis is common; 26% of individuals thought to have DRE were incorrectly diagnosed most often as a result of incomplete history-taking and/or EEG misinterpretation 13 Diagnostic errors PowerPoint Presentation: Improper choice of drug. Inadequate drug dose. Inappropriate combination of drugs. Drug interaction. 14 Treatment errors PowerPoint Presentation: Incorrect drug choice is most commonly a consequence of diagnostic errors. It derives from the misclassification of the type of epilepsy. e.g., carbamazepine and phenytoin will not be effective in patients with absence seizures or myoclonic seizures. 15 Incorrect drug choice PowerPoint Presentation: Patients with RE should have further testing to confirm the diagnosis of epilepsy and also to better define the epilepsy syndrome and underlying classification in order to best direct treatment. In most cases, the evaluation of RE will include video-EEG monitoring and magnetic resonance imaging. Lancet Neurol. 2008;7(6):514 16 EVALUATION PowerPoint Presentation: Video EEG monitoring combines both a video and EEG recording of clinical events. This test is used primarily to determine whether epilepsy is the cause of recurrent seizure-like events. In some series, more than 25 percent of individuals referred for monitoring for refractory epilepsy are found to have nonepileptic events. EEG monitoring can also aid in seizure classification and is used for presurgical evaluation of epilepsy patients . QJM. 1999;92(1):15. 17 PowerPoint Presentation: Neuroimaging — By the time a patient is considered to have IE, a magnetic resonance imaging (MRI) study will usually have been performed. In many cases, this should be repeated, particularly if the original study was unrevealing. In some cases, follow-up MRI reveals an etiology for epilepsy (such as cerebral neoplasm, autoimmune encephalitis) that was not seen on the initial study and requires specific therapies in addition to AEDs. Arch Neurol. 2012;69(5):582. 18 Therapeutic strategy for management of intractable epilepsy: The following measures should be considered in succession. Increase the dose of the 1 st line antiepileptic drug has been chosen for the patient, up to the maximum clinically tolerated dose N.B* we have to treat the patient not the serum level , On failure→ 19 Therapeutic strategy for management of intractable epilepsy PowerPoint Presentation: 2. Change for another drug of the first line drugs, and also increase its dose gradually up to the maximum tolerated dose , on failure → 3. Permanent addition of a second drug, on failure → 4. At that point we have to re-evaluate the patient even with previous normal investigations. 20 PowerPoint Presentation: Some questions should be asked now as: - Can too much of one drug or too many drugs may not only produce side effects, but also increase seizures frequency? - Can certain drug precipitate certain seizure types? 21 PowerPoint Presentation: Return to single drug therapy with the best clinically tolerated of the previously used antiepileptic drugs (avoid sedative and hypnotic drugs). Addition of one of the new antiepileptic drugs can be considered now as add on therapy or as monotherapy, on failure→ 22 PowerPoint Presentation: 7. We have to consider the following: A} Alternative non antiepileptic drug therapy as add on therapy under strict clinical selective criteria such as: a. Vagal nerve stimulation, b. ketogenic diet., c. Melatonin, d. Calcium antagonists, e. IV immunoglobulins.   B} Epileptic surgery . 23 Treatment Algorithm For Medical Management of Epilepsy: Treatment Algorithm For Medical Management of Epilepsy Patients with newly diagnosed, previously untreated epilepsy Monotherapy (drug 1) Consider withdrawal after 2- years of complete seizure control Alternative monotherapy (drug 2) Consider withdrawal after 2 or more years of complete seizure control Polytherapy (drug 1 and 2) Substitution and transfer to monotherapy with drug 3 Presurgical evaluation? Diagnostic re-evaluation Success Failure Success Failure Success Failure Success Failure Months of treatment 0 4 8 12 16 Consider withdrawal after 2-5 years (with patient considerations) Consider withdrawal after 2-5 years

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