What is Focal Cortical Dysplasia?

  • Focal Cortical Dysplasia (FCD) is a term used to describe a focal area of abnormal brain cell (“neuron”) organization and development.
  • Brain cells, or “neurons” normally form into organized layers of cells to form the brain “cortex” which is the outermost part of the brain.
  • In FCD, there is disorganization of these cells in a specific brain area leading to much higher risk of seizures and possible disruption of brain function that is normally generated from this area.

There are several types of FCD based on the particular microscopic appearance and associated other brain changes.

  • FCD Type I: the brain cells have abnormal organization in horizontal or vertical lines of the cortex. This type of FCD is often suspected based on the clinical history of the seizures (focal seizures which are drug-resistant), EEG findings confirming focal seizure onset, but is often not clearly seen on MRI. Other studies such as PET, SISCOM or SPECT and MEG may help point to the abnormal area which is generating seizures, but FCD Type I is often only confirmed after that area of the seizure-generating area of the brain has been resected and is then examined under the microscope. 
  • FCD Type II: when, in addition to abnormal organization, the brain cells themselves look abnormal, with “dysmorphic neurons” or “balloon cells.” FCD type II typically presents in early childhood and is usually seen on MRI. 
  • FCD type III: when in addition to either of the above findings, there is another associated abnormality such as hippocampal atrophy, tumors, stroke or traumatic brain damage. 

What types of seizures may be seen with FCD?

  • FCD is associated with wide range of seizures depending on the exact brain region where the abnormal cells are located and the age of the patient.
  • The most common seizure types are focal-onset seizures, which may progress to generalized tonic-clonic activity. The initial symptoms of the focal seizure often provide a clue to which region of the brain is affected by the FCD.
  • Young children can also present with infantile spasms, or less commonly seizures associated with Lennox-Gastaut syndrome.

How is FCD diagnosed?

The diagnosis of FCD can often be strongly suspected based on a detailed history and physical examination. FCD often causes seizures that onset in the first 5 years of life, and the majority will have seizures by the age of 16 years. Less commonly, seizures can start in adulthood. The subtype of FCD correlates to some degree with age at onset, with FCD Type II presenting most commonly very early in childhood, and some cases of  FCD type III presenting later in life. In addition to seizures, FCD may result in clinical symptoms that result from focal disruption of brain function in the region affected by the dysplasia, such as language delays, weakness or visual concerns.

The electroencephalogram (EEG) may show slowing of the background activity in the region of the FCD, however this finding is not specific for FCD and can be seen with other causes of epilepsy. More suggestive of FCD is abnormal focal fast activity. Epileptiform discharges are also commonly seen. 

In many cases of FCD, and particularly in Type II, the MRI is abnormal, showing an abnormally bright focal area on T2 and FLAIR sequences, which often has a characteristic “tail” extending to the margins of the ventricles. However, the MRI can be normal in some cases, particularly with Type I FCD. In these cases, the diagnosis can only be made after the removal of the brain region that causes the seizures and detailed examination under the microscope. 

If the MRI is normal, other tests such as PET, SISCOM or MEG can help pinpoint the location of the brain where seizures arise. While these tests can help show the region where seizures arise, they are not able to distinguish FCD from other focal causes of epilepsy.

When considering surgery, a functional brain MRI (fMRI) can be done to evaluate which areas of the brain control specific functions. Often, with FCD, one may see atypical localization of specific functions. 

What causes FCD? 

We know that FCD is due to abnormal formation of the cell layers and brain cells during the brain formation, while the baby is still in the womb. Genetic factors likely play a role in some cases, and certain genes such as DEPDC5 can result in FCD in multiple family members. These changes usually happen in the advanced stages of the brain maturation which explains why these changes are often limited to small region of the brain. In other cases, it is thought that in utero infection may play a role in FCD. However, in most FCD cases, the cause is not known.

How is FCD treated?

The optimal treatment of FCD depends on epilepsy severity and response to antiseizure medication.  Antiseizure medication is considered first-line therapy. However, many people with FCD will have drug-resistant seizures, and only about 1 in 5 people achieve good seizure control with medication alone. 

If two or more antiseizure medications fail to result in good seizure control, epilepsy surgery should be considered, as the chance of seizure control with further medicines is very low. If the FCD is located in a focal brain region that can be safely resected without impairment in brain function, resective surgery is a good option. The success of the surgery is dependent on the type of the FCD (better outcomes with Type II) and on the ability to completely resect the abnormal area.  Overall, the surgical success can reach up to 50-60%. If the resection of the FCD was incomplete, which can occur if FCD involves eloquent cortex (brain regions responsible for important function such as language or movement), seizure-free outcome is unlikely. 

If the bulk of the FCD involves a brain region that has a critical function, then surgical removal may not be feasible - in this situation, neuromodulation with an implanted device such as RNS, DBS or VNS could reduce seizure burden but is unlikely to result in seizure freedom.

Responsive neurostimulation (RNS) is a small device that is implanted in the head with wires and strips implanted over the FCD region. It records the brain activity continuously and when it sees a seizure, it can deliver a small electrical discharge to stop the seizure.  

The deep brain stimulation (DBS) device has a generator implanted in the chest under the collar bone and wires which are implanted deep in the brain in a structure called the thalamus, which connects different brain regions and which is often utilized by seizure activity to spread to different parts of the brain. This DBS device delivers electrical discharges to modulate that activity and decrease seizures.  

The vagus nerve stimulation (VNS) is a stimulator device that is placed under the skin just below the collar bone in the chest and wires connected it to the vagus nerve in the left side of the neck. Electrical impulses are transmitted to the brain through the vagus nerve to modulate the seizure activity. Newer devices can also detect heart rate changes which may indicate seizure onset and can trigger a stimulus in response to that.

Nonsurgical options for FCD include dietary therapies such as the ketogenic diet, modified Atkins diet and low glycemic index diet, which can reduce seizures in many cases but typically do not result in seizure freedom.

What is the outlook for FCD?

Most cases of FCD are associated with seizures that are drug resistant. In such cases, persons should be evaluated for resective epilepsy surgery, as this may significantly reduce seizure burden or possibly lead to seizure freedom. 

 

Authored By: 
Omar Danoun MD
Authored Date: 
08/2020