Diagnostic methods and treatment options for focal cortical dysplasia

Abstract

SUMMARYOur inability to adequately treat many patients with refractory epilepsy caused by focal cortical dysplasia (FCD), surgical inaccessibility and failures are significant clinical drawbacks. The targeting of physiologic features of epileptogenesis in FCD and colocalizing functionality has enhanced completeness of surgical resection, the main determinant of outcome. Electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) and magnetoencephalography are helpful in guiding electrode implantation and surgical treatment, and high-frequency oscillations help defining the extent of the epileptogenic dysplasia. Ultra high-field MRI has a role in understanding the laminar organization of the cortex, and fluorodeoxyglucose-positron emission tomography (FDG-PET) is highly sensitive for detecting FCD in MRI-negative cases. Multimodal imaging is clinically valuable, either by improving the rate of postoperative seizure freedom or by reducing postoperative deficits. However, there is no level 1 evidence that it improves outcomes. Proof for a specific effect of antiepileptic drugs (AEDs) in FCD is lacking. Pathogenic mutations recently described in mammalian target of rapamycin (mTOR) genes in FCD have yielded important insights into novel treatment options with mTOR inhibitors, which might represent an example of personalized treatment of epilepsy based on the known mechanisms of disease. The ketogenic diet (KD) has been demonstrated to be particularly effective in children with epilepsy caused by structural abnormalities, especially FCD. It attenuates epigenetic chromatin modifications, a master regulator for gene expression and functional adaptation of the cell, thereby modifying disease progression. This could imply lasting benefit of dietary manipulation. Neurostimulation techniques have produced variable clinical outcomes in FCD. In widespread dysplasias, vagus nerve stimulation (VNS) has achieved responder rates >50%; however, the efficacy of noninvasive cranial nerve stimulation modalities such as transcutaneous VNS (tVNS) and noninvasive (nVNS) requires further study. Although review of current strategies underscores the serious shortcomings of treatment-resistant cases, initial evidence from novel approaches suggests that future success is possible.

Genetic Basis of Brain Malformations

“…The histological changes in hemimegalencephaly, which can be considered as an extreme hemispheric form of FCD, are similar, if not identical, to FCD type 2, with cortical dyslamination and dysmorphic neurons, without (type 2a) or with (type 2b) balloon cells, blurred junctions between grey and white matter, and increased heterotopic neurons in white matter [De Rosa et al, 1992;Blümcke et al, 2011;Guerrini et al, 2015].…”

The relationship between morphological lesion, magnetic source imaging, and intracranial stereo-electroencephalography in focal cortical dysplasia

“…Focal cortical dysplasias (FCDs) are a common cause of pharmaco-resistant epilepsy, prompting presurgical evaluation in a large proportion of patients (Guerrini et al, 2015). Their localization, extent, and histo-pathologic presentation are highly variable, reflected in several consensus classification schemes.…”

“…Surgical treatment often requires intracranial electroencephalography recordings to localize the seizure onset zone (SOZ) and seizure propagation pathways (Fauser et al, 2015, Guerrini et al, 2015, Ryvlin et al, 2014). Moreover, the surgical outcome in FCD related epilepsy is directly related to the resection of epileptogenic tissue (Fauser et al, 2015, Fauser et al, 2008, Hong et al, 2000).…”

Nuclear Medicine Methods in Epilepsy

“…Başka bir çalışma ise çok modaliteli nöro-görüntüleme yöntemlerinin invaziv EEG'ye olan ihtiyacı ortadan kaldırarak rezeksiyon alanını da daraltabileceğini göstermiştir (19). Fokal kortikal displazi olgularında PET epileptik alanı fokal bir hipometabolizma alanı olarak MR bulgusu olan ve olmayan hastalarda tanımlamaktadır (20).…”