electroencephalogram prior to discontinue antiepileptic drugs - PowerPoint PPT Presentation

Discontinuation of antiepileptic drugs in two-year seizure-free epileptic children who had abnormal electroencephalogram prior to discontinue antiepileptic drugs Supachai Janjindamai, MD Pichittra Buntarickpornpan, Utcharee Intusoma Division Neurology, Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand

Discontinuation of Antiepileptic drug For the patient with well controlled epilepsy, the major concern is whether when and how the therapy can be discontinued These aspects include the following: (1) The duration of the seizure remission period before starting antiepileptic drug (AED) discontinuation (2) The duration of the AED tapering period. (3) The presence of specific risk factors for relapse

Necessary conditions for the discontinuation of AEDs  Neuropsychological performance and verbal memory improve significantly after AED withdrawal  There is no evidence that continuous AED treatment can guarantee lifelong seizure freedom  Long-term prognosis is not worsened by drug withdrawal  Considering the cost, inconvenience, and severe adverse effects of continuous AED treatment, many patients and clinical physicians tend to withdraw AED after a seizure-free period

Time to Discontinued AED  The proper time point is still unclear as different studies have reported different conclusions  Most studies and experts recommend a 2 year period of seizure free before considering AED discontinuation 1,2 1. American Academy of Neurology, Practice Parameter, 1996 2. CamfieldP, CamfieldC, Epilepsia, 2008

Risk factors for relapse after withdrawal in children  Many factors were reported as associated risk of seizure relapse  An abnormal electroencephalogram (EEG) at the time prior to discontinue AEDs is associated with an increased risk of recurring seizures in children.  Abnormal EEG warns against treatment discontinuation, especially in children with other risk factors

Objective To determine the rate of discontinuation of AEDs in epileptic children who were seizure- free for at least 2 years but had an abnormal EEG at the end of the seizure-free period and continued on AEDs

Methods  Retrospective study from the medical records at Songklanagarind Hospital, a tertiary hospital in the south of Thailand. (Jan 1 st 2003- Aug 31 st 2010)  The inclusion criteria were 1) first time seizure-free for at least 2 years 2) abnormal EEG at the end of the seizure- free period 3) remained on AEDs  EEGs were repeated every 1 to 2 years until normalized and then the AEDs were tapered and withdrawn

Results Characteristic n=59, n (%) Gender: male 37 (62.7) Family history of epilepsy 6 (10.2) Abnormal neurological examination 12 (20.4) Mental retardation 23 (39.0) Abnormal neurological imaging 5/16 (31.3) Type of epilepsy - Localization-related 49 (83.0) - Generalized 10 (17.0) Number of AEDs: 1 53 (89.8) >1 6 (10.2)

Results  Age of seizure onset was 5.8 years (IQR 1.5, 7.6)  24/59 (40%) patients returned to a normalized EEG and discontinued AEDs  The median follow-up time was 3.9 years (IQR 2.7, 5.3)

Results  The median time to return to a normalized EEG was 5.7 years (IQR 1, 2.1) Cumulative hazard plot of time to return to a normalized EEG

Results  of 24 Patients who returned to a normalized EEG the median time = 2.0 year (range 0.9, 6.8)  Median duration time of AEDs treatment before discontinuation was 5.4 years (IQR 3.5, 6.4)

Results  After discontinuation of AEDs - 6/59 (25%) of patients had seizure recurrence - 1/3 of the recurrences occurred within 6 months - 2/3 of the recurrences occurred within the first year - 20/59 (83) of patients were at least 1-year seizure-free Kaplan – Meier curve of recurrent seizure after discontinuation of antiepileptic drugs

Factors affecting the risk of relapse Discontinued Continued P value AEDs, n=24 AEDs, n=35 n (%) n(%) Male 14 (58.3) 12 (34.3) 0.837 Onset of seizure median time (year) 6.2 4.4 0.367 Family history of epilepsy 1 (4.2) 6 (17.1) 0.120 Abnormal Neurological 2 (8.3) 10 (28.6) 0.321 examination Mental retardation 6 (25.0) 17 (48.6) 0.389 Abnormal neurological 2/7 (28.6) 3/9 (33.3) 0.694 Imaging (n=16) Localization-related 22 (91.7) 27 (77.1) 0.170 >1 AEDs 1 (4.2) 5 (14.3) 0.157

Discussion  Our study intend to use EEG as an indicator to make a decision before discontinuing AEDs  40% of patient returned to a normalized EEG and discontinued AEDs  The median time to return to a normalized EEG was 5.7 years (IQR 1, 2.1)

Discussion  The seizure relapse rate after withdrawal of AEDs in children has been reported from 16% to 56%, depending on the method and design of the studies 1  In a systematic review of the literature, the relapse rate at two years was found to range from 9% to 39% in children 2  The overall relapse rate was 25% in our study 1 Verrotti A, et al, 2012 2 Specchio and Beghi, 2004

Discussion  Our study; after discontinuation of AEDs, • 83% of patients had at least 1-year seizure-free • 25% of patients had seizure recurrence • 1/3 of the recurrences occurred within 6 months • 2/3 of the recurrences occurred within the first year  Similar pattern as a meta-analysis of 25 studies, the pooled relapse risk was 25% at one year and 29% at two years Berg and Shinnar, 1994

Discussion  Our relatively lower relapse rate can be explained by all of the EEGs being normal before withdrawal and  Majority of patients were - young age at onset of seizures - normal neurological examination - absence of a neurological disease - young age at treatment withdrawal - negative family history of epilepsy which are generally associated with a low risk of recurrence 1-3 1. Hodaka O, et al. 2004 2. Altunbasak S, et al.1999 3. Braun KPJ and Schmidt D, 2014

Discussion  Although EEG plays an important role in the diagnosis of seizure disorders and may predict outcome of the treatment discontinuation  Role of EEG as a predictor of seizure recurrence after discontinuation of AEDs is still an issue of debate Italian League Against Epilepsy. Epilepsia, 2013

Discussion  The presence of EEG abnormalities, both slowing and epileptiform, correlates with a higher rate of seizure recurrence after AED withdrawal in children  In a meta-analysis of 25 published studies found that patients with abnormal EEG carry a 1.45 higher risk of relapse 1  An abnormal EEG at the time of treatment discontinuation predicted a higher risk of relapse in 21 of 37 studies and were confirmed by multivariate analysis in six studies 2 1 Berg and Shinnar,1994 2 Italian League Against Epilepsy. Epilepsia, 2013

Discussion  Some studies reported that EEG recordings after withdrawal (post-withdrawal EEG) were significantly associated with seizure recurrence Olmez et al. Seizure, 2009 Su L, et al. J Clin Neurosci. 2013

Discussion  Limitations of our study - Retrospective study - Small number of population - Did not compare to the patients who had abnormal EEG and remained on AEDs

Conclusions  Epileptic children who have seizure-free for at least 2 years but abnormal EEG at the time to consider discontinuation of AEDs and continued on AEDs had 40% chance to become normal EEG and could discontinue AEDs  The seizure recurrence was 25% and about 2/3 of recurrence occurred within one year

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