Rasmussen encephalitis (RE): Rasmussen encephalitis (RE) is a very rare neuroinflammatory disease characterized by intractable seizures and progressive neurological deficits resulting from the destruction of brain tissue. As shown in MRI scan, loss of brain tissue is restricted to one side of the brain, thus contralateral function is affected, although the seizures can affect the whole brain. RE appears to be an autoimmune disease, but what causes the immune system to attack the brain is not known. A close up of an area of affected brain tissue removed during surgery shows the presence of clusters of T lymphocytes. Currently available anti-inflammatory drugs do not provide a lasting benefit, leaving surgery the only treatment option. The REBDTB is collecting resected remnant brain tissue, peripheral blood and CSF (where possible) from RE surgeries. This initiative was established as part of the RE Children’s Research Consortium Tissue Transfer Program which is generously supported by the RE Children’s Project (http://www.rechildrens.org), a nonprofit organization founded by Seth Wohlberg after his daughter was diagnosed and treated for RE. Since inception of the Tissue Transfer Program in 2012, we are proud that RE specimens have been obtained from 33 surgeries at 19 epilepsy centers in six countries. The REBDTB is involved with studies designed to characterize the immune cells in RE brain tissue, and understand why these cells attack the brain.
Cortical Malformations: Children presenting with intractable epilepsy are often found to have a developmental malformation of the cerebral cortex. The MRI scan shows an area of abnormal cortical development that is giving rise to seizures. The seizures can severely impact the child’s intellectual and cognitive development, and surgery is often necessary to control them. The REBDTB is involved in two projects studying cortical malformations. In collaboration with Drs. Carlos Cepeda and Michael Levine at University of California, Los Angeles the physiological basis of seizures in malformed cerebral cortex is under investigation in which recordings are made of living brain cells. We are also currently recruiting participants for research studies investigating the genetic causes of pediatric neurological disorders and brain malformations such as Hemimegalencephaly (HME) and Focal Cortical Dysplasia (FCD). This work is in collaboration with Dr. Joseph Gleeson from the University of California, San Diego and Rockefeller University in New York (www.gleesonlab.org). Dr. Gleeson is a Pediatric Neurogenetics Specialist interested in identifying the genes related to abnormal brain development. The goal of this research project is to understand the factors that contribute to assembly and function of the human brain and understand which genetic mutations produce focal cortical malformations requiring surgery. The Mathern and Gleeson teams have recently identified the first genetic causes of the focal dysplasia Hemimegalencephaly, spotting mutations in the MTOR pathway. The mutations identified were found to activate the MTOR pathway, and suggest that treatment aimed at blocking this pathway may help reduce seizures and improve outcome. Patients diagnosed with a brain development disorder and their family members are eligible to participate. Blood, saliva or DNA samples from patients, parents and siblings will be collected.
Tuberous Sclerosis: Tuberous Sclerosis complex (TSC) is a genetic disorder that causes non-malignant tumors to form in many different organs, primarily in the brain, eyes and heart. While most patients with TSC do not require neurosurgery, complications from the condition occasionally require a surgical approach with resection of diseased tissue. We are currently recruiting participants for research studies investigating the genetic causes of brain lesions in TSC. This project is performed in collaboration with Dr. Joseph Gleeson from the University of California, San Diego and Rockefeller University New York (www.gleesonlab.org). The goal of this project is to identify genetic mutations, in addition to the mutations in the known TSC genes that lead to brain lesions. Patients with TSC requiring brain surgery are eligible to participate. Blood, saliva or DNA from patients, parents and siblings are requested.