Focal cortical dysplasia (FCD) is a brain malformation that can lead to recurrent seizures and is a frequent cause of medication-resistant epilepsy, particularly in children.
Understanding Focal Cortical Dysplasia
FCD is a condition where areas of the brain’s outer layer, the cortex, develop abnormally. The International League Against Epilepsy (ILAE) categorizes FCD into types I, II, and III, based on microscopic features and associated brain changes. Type I FCD involves disorganized brain cells in the cortex, often not clearly visible on an MRI. Type II FCD, which commonly appears in early childhood, features abnormally shaped brain cells, sometimes with “balloon cells,” and is usually detectable on MRI. Type III FCD is characterized by FCD occurring alongside other brain abnormalities, such as hippocampal atrophy, tumors, or damage from stroke or trauma.
Diagnosing FCD often involves a detailed medical history and physical examination, as well as neuroimaging techniques. Magnetic Resonance Imaging (MRI) is the preferred method for assessing FCD, though it may not always show the abnormality, especially in Type I FCD. Electroencephalography (EEG) helps identify the brain region where seizures originate. Positron Emission Tomography (PET) scans can detect areas of abnormal brain metabolism, which may indicate FCD even when an MRI appears normal. These diagnostic tools help pinpoint the dysplastic area, which is important for planning effective treatment strategies.
Medical Management
Anti-epileptic drugs (AEDs) are typically the initial treatment for controlling seizures in individuals with FCD. Broad-spectrum AEDs like levetiracetam, topiramate, and zonisamide are commonly used due to their varied mechanisms of action. While AEDs can help manage seizures, FCD often leads to drug-resistant epilepsy, meaning medications may become less effective over time.
Many patients with FCD experience drug-resistant epilepsy, where seizures persist despite trials of at least two appropriate AEDs. While some patients may experience a “honeymoon” period of seizure freedom lasting over a year with medication, often on a single AED, the long-term effectiveness of AEDs in FCD can be limited, making it necessary to consider other treatment approaches.
Surgical Treatment Options
When medication proves insufficient for FCD-related epilepsy, surgical intervention is often considered. The goal of surgery is to achieve seizure freedom by removing the abnormal brain tissue. Resective surgery, which involves directly removing the FCD, is a common approach. For more extensive or widespread FCD, procedures such as lobectomy or even hemispherectomy, which removes a large portion of one brain hemisphere, may be performed.
The success of surgery largely depends on the complete removal of the dysplastic tissue. Studies indicate that 60-70% of patients who undergo complete resection achieve seizure freedom. Overall, seizure freedom rates after surgery for FCD range from 50-75% at two years, with long-term outcomes remaining relatively stable. Surgical candidacy involves a comprehensive evaluation to localize the FCD and determine if its removal is feasible without causing significant neurological deficits.
Other and Investigational Approaches
Beyond medication and surgery, other strategies are available for managing FCD-related epilepsy. Dietary therapies, such as the ketogenic diet (a high-fat, low-carbohydrate, and low-protein diet), have shown efficacy in reducing seizures in children with drug-resistant epilepsy. This diet may modify disease progression by influencing gene expression.
Neurostimulation devices offer options when medication and surgery are not sufficient or feasible. Vagus nerve stimulation (VNS) involves implanting a device that sends electrical impulses to the vagus nerve, potentially reducing seizure frequency, with responder rates exceeding 50% for widespread dysplasias. Responsive neurostimulation (RNS) is a closed-loop neuromodulation therapy that involves implanting electrodes directly onto or within the brain to detect and respond to seizure activity, potentially aborting seizures at their onset. Investigational treatments, such as gene therapy or targeted molecular therapies (including mTOR inhibitors), are being explored. These emerging therapies aim to address the underlying molecular mechanisms of FCD, particularly in cases linked to specific genetic mutations.