Focal cortical dysplasia (FCD) is a localized malformation of the brain cortex that occurs during fetal development. Although congenital, FCD often continues into adulthood, where it is a leading cause of drug-resistant epilepsy. For adult patients, this diagnosis explains a long history of seizures that have not responded to standard medical treatments. FCD signifies a structural cause for the epilepsy, requiring specialized diagnostic and treatment approaches.
The Developmental Origin of Cortical Dysplasia
FCD arises from an error in cell proliferation and migration during the second and third trimesters of pregnancy, preventing the formation of the normal six-layered cerebral cortex structure. This structural abnormality is a failure of the brain’s organization, resulting in cortical tissue with disorganized layers and abnormal cell types that are intrinsically prone to generating seizures.
The most severe forms, FCD Type II, are characterized by distinctly abnormal cells. These include dysmorphic neurons, which are abnormally large and misshapen, and balloon cells, which are enormous, non-neuronal cells. These balloon cells and dysmorphic neurons are believed to originate from radial glial cells. This structural pathology disrupts the normal flow of electrical signals, creating a highly epileptogenic zone that is refractory to standard anti-seizure medications.
Recognizing Adult Clinical Manifestations
The primary clinical manifestation of FCD in adults is drug-resistant epilepsy, defined as the failure of two or more appropriate anti-epileptic medications to control seizures. FCD is the third most common cause of epilepsy in adults undergoing surgery for this condition. Most adults with FCD had epilepsy onset in childhood, often presenting with complex partial or focal seizures that may generalize into tonic-clonic seizures.
Patients often experience a high seizure burden, with many reporting daily seizures. This uncontrolled electrical activity significantly impacts quality of life, affecting the ability to drive, maintain employment, and participate in social activities. The chronicity of seizures can also lead to secondary mental health issues, such as anxiety and depression.
Refractory seizures also impact cognitive function, leading to impairments and associated neuropsychiatric disorders. The degree of gray-white matter blurring, a sign of the dysplasia, correlates with decreased general cognitive abilities, suggesting the structural abnormality itself contributes to difficulties in areas like executive function, attention, and processing speed. Achieving complete seizure freedom after treatment can lead to stabilization or improvement in cognitive domains.
Diagnostic Imaging and Classification
Diagnosis and treatment planning for FCD rely on identifying and precisely localizing the lesion, primarily using high-resolution magnetic resonance imaging (MRI). Neurologists look for subtle structural signs of the dysplasia on the MRI scan. Characteristic findings often include localized thickening of the cerebral cortex and blurring of the boundary between the gray matter and the underlying white matter.
A telling sign of FCD Type II is the “transmantle sign,” which appears as a funnel-shaped area of high signal intensity extending from the cortex to the ventricle. While common in Type II FCD, some lesions, particularly Type I, can be visually elusive or “MRI-negative” on routine scans. In these challenging cases, functional imaging techniques like Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) or ictal Single-Photon Emission Computed Tomography (SPECT) are used to pinpoint the area of abnormal brain metabolism or blood flow corresponding to the seizure focus.
The classification of FCD is essential for determining prognosis and guiding treatment, using the current Blumcke classification.
FCD Type I
This type features architectural abnormalities, such as abnormal cortical lamination, but lacks highly dysmorphic cells.
FCD Type II
This type is characterized by the presence of dysmorphic neurons (Type IIa) or both dysmorphic neurons and balloon cells (Type IIb).
FCD Type III
This type describes FCD that occurs in association with another principal lesion, such as hippocampal sclerosis, a tumor, or a vascular malformation.
Treatment Strategies for Adults
The initial management approach involves anti-epileptic drugs (AEDs); however, the intrinsic epileptogenicity of the dysplastic tissue means these medications frequently fail. Only about 20% of people with FCD achieve seizure freedom with medication alone. If seizures remain uncontrolled after trials of two appropriate AEDs, patients should be referred for a comprehensive pre-surgical evaluation to assess candidacy for epilepsy surgery.
Epilepsy surgery is considered the best therapeutic option for adults with refractory FCD, offering the potential for a cure. The pre-surgical evaluation is a multi-modal process including long-term video-EEG monitoring to localize seizures, advanced imaging (like fMRI) to map functional areas, and neuropsychological testing. The goal of surgery is to completely remove the epileptogenic zone (the entire dysplastic tissue) through procedures such as a lesionectomy or lobectomy.
Surgical success depends on the completeness of the resection, with long-term seizure freedom rates ranging from 50% to 75%. Patients with FCD Type II generally have better outcomes than those with Type I, as Type II lesions are often more clearly defined on imaging, allowing for more complete removal. If FCD is located in an area responsible for important functions (like language or movement) where complete removal risks causing a deficit, alternative options like vagus nerve stimulation (VNS) or laser interstitial thermal therapy (LITT) may be considered.