Dataset Information

Antiepileptic Drug Withdrawal after Surgery in Children with Focal Cortical Dysplasia: Seizure Recurrence and Its Predictors.

ABSTRACT:

Background and purpose

This study investigated the seizure recurrence rate and potential predictors of seizure recurrence following antiepileptic drug (AED) withdrawal after resective epilepsy surgery in children with focal cortical dysplasia (FCD).

Methods

We retrospectively analyzed the records of 70 children and adolescents with FCD types I, II, and IIIa who underwent resective epilepsy surgery between 2004 and 2015 and were followed for at least 2 years after surgery.

Results

We attempted AED withdrawal in 40 patients. The median time of starting the AED reduction was 10.8 months after surgery. Of these 40 patients, 14 patients (35%) experienced seizure recurrence during AED reduction or after AED withdrawal. Half of the 14 patients who experienced recurrence regained seizure freedom after AED reintroduction and optimization. Compared with their preoperative status, the AED dose or number was decreased in 57.1% of patients, and remained unchanged in 14.3% after surgery. A multivariate analysis found that incomplete resection (p=0.004) and epileptic discharges on the postoperative EEG (p=0.025) were important predictors of seizure recurrence after AED withdrawal. Over the mean follow-up duration of 4.5 years after surgery, 34 patients (48.6% of the entire cohort) were seizure-free with and without AEDs.

Conclusions

Children with incomplete resection and epileptic discharges on postoperative EEG are at a high risk of seizure recurrence after drug withdrawal. Complete resection of FCD may lead to a favorable surgical outcome and successful AED withdrawal after surgery.

SUBMITTER: Choi SA

PROVIDER: S-EPMC6325372 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

Antiepileptic Drug Withdrawal after Surgery in Children with Focal Cortical Dysplasia: Seizure Recurrence and Its Predictors.

Choi Sun Ah SA Kim Soo Yeon SY Kim Woo Joong WJ Shim Young Kyu YK Kim Hunmin H Hwang Hee H Choi Ji Eun JE Lim Byung Chan BC Chae Jong Hee JH Chong Sangjoon S Lee Ji Yeoun JY Phi Ji Hoon JH Kim Seung Ki SK Wang Kyu Chang KC Kim Ki Joong KJ

Journal of clinical neurology (Seoul, Korea) 20190101 1

<h4>Background and purpose</h4>This study investigated the seizure recurrence rate and potential predictors of seizure recurrence following antiepileptic drug (AED) withdrawal after resective epilepsy surgery in children with focal cortical dysplasia (FCD).<h4>Methods</h4>We retrospectively analyzed the records of 70 children and adolescents with FCD types I, II, and IIIa who underwent resective epilepsy surgery between 2004 and 2015 and were followed for at least 2 years after surgery.<h4>Resul ...[more]

PMID: 30618221

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Project description:Focal cortical dysplasias are a common subtype of malformation of cortical development, which frequently presents with a spectrum of cognitive and behavioural abnormalities as well as pharmacoresistant epilepsy. Focal cortical dysplasia type II is typically caused by somatic mutations resulting in mammalian target of rapamycin (mTOR) hyperactivity, and is the commonest pathology found in children undergoing epilepsy surgery. However, surgical resection does not always result in seizure freedom, and is often precluded by proximity to eloquent brain regions. Gene therapy is a promising potential alternative treatment and may be appropriate in cases that represent an unacceptable surgical risk. Here, we evaluated a gene therapy based on overexpression of the Kv1.1 potassium channel in a mouse model of frontal lobe focal cortical dysplasia. An engineered potassium channel (EKC) transgene was placed under control of a human promoter that biases expression towards principal neurons (CAMK2A) and packaged in an adeno-associated viral vector (AAV9). We used an established focal cortical dysplasia model generated by in utero electroporation of frontal lobe neural progenitors with a constitutively active human Ras homolog enriched in brain (RHEB) plasmid, an activator of mTOR complex 1. We characterized the model by quantifying electrocorticographic and behavioural abnormalities, both in mice developing spontaneous generalized seizures and in mice only exhibiting interictal discharges. Injection of AAV9-CAMK2A-EKC in the dysplastic region resulted in a robust decrease (∼64%) in the frequency of seizures. Despite the robust anti-epileptic effect of the treatment, there was neither an improvement nor a worsening of performance in behavioural tests sensitive to frontal lobe function. AAV9-CAMK2A-EKC had no effect on interictal discharges or behaviour in mice without generalized seizures. AAV9-CAMK2A-EKC gene therapy is a promising therapy with translational potential to treat the epileptic phenotype of mTOR-related malformations of cortical development. Cognitive and behavioural co-morbidities may, however, resist an intervention aimed at reducing circuit excitability.

Project description:ObjectiveFluorine-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) is routinely used for presurgical evaluation in many epilepsy centers. Hypometabolic characteristics have been extensively examined in prior studies, but the metabolic patterns associated with specific pathological types of drug-resistant epilepsy remain to be fully defined. This study was developed to explore the relationship between metabolic patterns or characteristics and surgical outcomes in type I and II focal cortical dysplasia (FCD) patients based on results from a large cohort.MethodsData from individuals who underwent epilepsy surgery from 2014 to 2019 with a follow-up duration of over 3 years and a pathological classification of type I or II FCD in our hospital were retrospectively analyzed. Hypometabolic patterns were quantitatively identified via statistical parametric mapping (SPM) and qualitatively analyzed via visual examination of PET-MRI co-registration images. Univariate analyses were used to explore the relationship between metabolic patterns and surgical outcomes.ResultsIn total, this study included data from 210 patients. Following SPM calculations, four hypometabolic patterns were defined including unilobar, multi-lobar, and remote patterns as well as cases where no pattern was evident. In type II FCD patients, the unilobar pattern was associated with the best surgical outcomes (p = 0.014). In visual analysis, single gyrus (p = 0.032) and Clear-cut hypometabolism edge (p = 0.040) patterns exhibited better surgery outcomes in the type II FCD group.ConclusionsPET metabolic patterns are well-correlated with the prognosis of type II FCD patients. However, similar correlations were not observed in type I FCD, potentially owing to the complex distribution of the epileptogenic region.Plain language summaryIn this study, we demonstrated that FDG-PET was a crucial examination for patients with FCD, which was a common cause of epilepsy. We compared the surgical prognosis for patients with different hypometabolism distribution patterns and found that clear and focal abnormal region in PET was correlated with good surgical outcome in type II FCD patients.

Dataset Information

Antiepileptic Drug Withdrawal after Surgery in Children with Focal Cortical Dysplasia: Seizure Recurrence and Its Predictors.

Background and purpose

Methods

Results

Conclusions

Publications

Antiepileptic Drug Withdrawal after Surgery in Children with Focal Cortical Dysplasia: Seizure Recurrence and Its Predictors.

Similar Datasets

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