Authors :
Presenting Author: Rafael Villalobos, MD – University of Texas Rio Grande Valley
Elida De Leon, MA – Pediatric Neurology – Pediatric Neurology of South Texas PC; Affonso Duran, Research assistant – Pediatric Neurology – Pediatric Neurology of South Texas PC; Gilberto Mauricio-Suarez, Research assistant – Pediatric Neurology – Pediatric Neurology of South Texas PC; Santiago Vidaurri, Research Assistant – Texas A & M University
Rationale:
IQSEC2 is a genetic condition that causes intellectual disability and other physical, neurological, or psychiatric symptoms. People with this condition can have seizures that are often difficult to control with anticonvulsants. Other symptoms may include motor and language development delay, regression of learning abilities, autistic-like behavior, characteristic hand movements, and behavioral problems. We wanted to evaluate the different treatments and response to medications or epilepsy surgery in a pediatric epilepsy clinic, as the the population disease estimate is fewer than 1,000 people in the U.S. clinical studies are needed for selection of treatment.
Methods:
The
IQSEC2 gene epilepsy related patients were identified in the epilepsy clinic by a gene comprehensive epilepsy panel done. The cases were selected on the basis of intractable epilepsy and developmental regression. Both cases were refractory to more than three anti epileptic medications. Only one case underwent epilepsy surgery (vagal nerve stimulation) that was replaced with a latest model that included auto stimulation. Both cases were evaluated in the clinic as often as every three months due to recurrent seizures and associated complications. Neurophysiology monitoring included EEG and Video-EEG, all cases had imaging by MRI and CT scan of the brain.
Results:
The age of symptom onset in our patients was from two to four years of age. Both patients were male and both had developmental delay and regression of motor skills as the the epilepsy symptoms progressed. All cases were intractable and placed on multiple seizure medications. The EEG findings included bi-hemispheric focal discharges with a side predominance. Imaging findings included cortical volume loss and ex vacuo ventricle dilation. Patients showed severe impairment in motor function and spasticity, abnormal posture and joint contractures. One patient was implanted with a vagal nerve stimulation device (that had a rejection reaction and was eventually implanted with a new stimulator). The medications used included levatiracetam, valproic acid, topiramate, lamotrigine, zonizamide, vigabatrin, and rufinamide. The most significant improvements were seen with topiramate administration. There was a mild improvement in seizure frequency when the vagal nerve stimulation was started on the auto-stimulation mode.
Conclusions:
The patients with
IQSEC2 gene related epilepsies are unique as the presentation is variable, but usually related to refractory seizures if epilepsy is present to our view. The response to medications is in general poor. Most cases are not inherited from a parent but are caused by a new (de novo) genetic change. When the condition is inherited, the pattern is called X-linked recessive. Seizure medications such as lamotrigine and rufinamide have been reported to control seizures in some people. To our experience the most improvements were seen with addition of topiramate and vagal nerve stimulation. A patient on the device that was re-implanted demonstrated greater reduction of the events with the auto-stimulation capabilities. Further patient case studies are needed to better understand the best potential treatment anticonvulsant options.
Funding: None.