Focal Cortical Dysplasia


Focal Cortical Dysplasia

Focal cortical dysplasia (FCD) is a congenital abnormality of brain development where the neurons in an area of the brain fail to develop properly. FCD is a common cause of intractable epilepsy in children. Malformations of the cerebral cortex during development are the most common cause of seizures in pediatric surgical candidates. Complete removal of the epileptogenic lesion usually prevents recurrence of seizures. To achieve this, especially in challenging cases, a staged approach that involves the use of invasive electroencephalographic monitoring is recommended. Read this review co-authored by Howard L. Dr. Weiner, Chief of Neurosurgery and a leading eileptologist at Texas Children’s Hospital, to learn about new surgical treatment options for FCD patients.

There are several subtypes of FCD but all of them result in cellular disorganization. Patients with FCD type 2b have many enlarged cells in the brain that are similar to the giant cells in Tuberous Sclerosis Complex. Consistent with this observation, researchers in the laboratories of Dr. John Swann, director and Dr. Anne Anderson in the Gordon and Mary Cain Pediatric Neurology Research Foundation Laboratories at Texas Children’s Hospital have found similar mechanisms are responsible for excessive growth in both disorders. Their research has led to the following advances in understanding cortical dysplasia -

  • Among the abnormal cell types found in FCD patients are the cytomegalic neurons, whose hyperactivity likely contributes to epilepsy. A study showed that mammalian target of rapamycin (mTOR) pathway is activated in these neurons, and is the likely cause of excessive growth and hyperactivity in cortical dysplasia patients. Read more
  • Selective suppression of PTEN, an inhibitor of the PI3K (phosphoinositide 3-kinase)-Akt-mTOR (mammalian target of rapamycin) signaling pathway, in a subset of neurons, is a good experimental model to study human FCD. This study also showed that short-term treatment with the mTOR inhibitor rapamycin strongly suppresses the severity and the duration of seizures. Read more
  • A single course of rapamycin treatment is sufficient to suppress epilepsy for several weeks before seizures recurred again in mouse models of FCD. Also, additional intermittent treatments with rapamycin can prevent this recurrence. This treatment also prolonged the survival of mice and did not affect its growth. Read more
  • Rapamycin-mediated inhibition of mTOR pathway can restore normal brain activity and increase survival even in cases of well-established, late-stage epilepsy associated with CD. Read more
  • While ERK (extracellular signal-regulated kinase) and mTOR signaling pathways are dysregulated in FCD and Tuberous Sclerosis Complex (TSC) patients, the exact molecular alterations are different in FCD I compared to FCD II or TSC. Read more
  • Pediatric patients with FCD or enlargements in the brain (megalencephaly/hemimegalencephaly) carry mutations in the mTOR pathway. The severity of symptoms varied with the type of mutation the patient carries. Read more
  • The expression of a particular subtype of voltage-gated potassium channel (Kv1.1) is altered in the brains of animals with cortical dysplasia. Read More