Focal cortical dysplasia: an update on diagnosis and treatment

ABSTRACT

Introduction

Focal cortical dysplasias (FCDs) represent the most common etiology in pediatric drug-resistant focal epilepsies undergoing surgical treatment. The localization, extent and histopathological features of FCDs are considerably variable. Somatic mosaic mutations of genes that encode proteins in the PI3K-AKTmTOR pathway, which also includes the tuberous sclerosis associated genes TSC1 and TSC2, have been implicated in FCD type II in a substantial subset of patients. Surgery is the principal therapeutic option for FCD-related epilepsy. Advanced neurophysiological and neuroimaging techniques have improved surgical outcome and reduced the risk of postsurgical deficits. Pharmacological MTOR inhibitors are being tested in clinical trials and might represent an example of personalized treatment of epilepsy based on the known mechanisms of disease, used alone or in combination with surgery.

Areas covered

This review will critically analyze the advances in the diagnosis and treatment of FCDs, with a special focus on the novel therapeutic options prompted by a better understanding of their pathophysiology.

Expert opinion

Focal cortical dysplasia is a main cause of drug-resistant epilepsy, especially in children. Novel, personalized approaches are needed to more effectively treat FCD-related epilepsy and its cognitive consequences.

KEYWORDS:

• Focal cortical dysplasia
• MRI
• EEG; MTOR pathway
• surgery

Article highlights

• Focal cortical dysplasias (FCDs) are the most common etiology in children treated with surgery for drug-resistant focal epilepsy.

• FCD type II is the best recognized subtype of dysplasia and may present as either a small and overlooked bottom-of-sulcus dysplasia or a multilobar dysplastic region.

• FCD I does not present with peculiar scalp EEG findings while FCD II is often accompanied by focal rhythmic interictal epileptiform discharges that may correlate spatially with the anatomic extent of the lesion.

• High and ultra-high field imaging has demonstrated an added value compared with conventional MRI to identify, delineate and characterize FCD in patients with epilepsy.

• FDG-PET is highly sensitive for detecting FCD, especially MRI-negative FCD II (either IIa or IIb).

• FCD type II can result from mutations in genes in the MTOR pathway and FCD type I from SLC35A2 gene variants.

• Adjunctive everolimus treatment significantly reduces seizure frequency with a tolerable safety profile compared with placebo in patients with tuberous sclerosis complex and treatment-resistant seizures.

• Novel, personalized and combined approaches are needed to effectively treat FCD-related epilepsy and its consequences.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.