Research recently published in Annals of Neurology says that preventative treatment with the use of vigabatrin could alter the natural history of seizures in infants with tuberous sclerosis complex.
TSC is typically severe and resistant to being treated with anti-epilepsy medications. It causes infantile spasms and focal seizures in around 80% of infants who have TSC. The young patients who have this form of epilepsy will also often have neurodevelopmental comorbidities, as well. This could include autism and intellectual disability, according to the researchers.
The guidelines that are currently in place say that doctors should administer antiepileptic treatment after the patient has two unprovoked clinical seizures, or after a single seizure if the patient is a high risk for having recurrent seizures. Having antiepileptic treatment immediately after the onset of seizures can reduce the risk of the aforementioned neurodevelopmental complications. However, it’s not perfect, by any means. There are still 50% to 60% of children who will develop an intellectual disability.
Katarzyna Kotulksa, MD, Ph.D., and colleagues at the Department of Neurology and Epileptology at the Children’s Memorial Health Institute in Poland presented a recent study that could provide some relief. The researchers conducted their trial from March 2014 to October 2018 across nine locations in Europe, along with one location in Australia.
During the trial, the researchers used monthly EEGs to monitor 94 infants, all of which were four months old or younger. They all had TSC and no history of seizures. The participants in the trial “received vigabatrin at either 100 mg/kg/day or 150 mg/kg/day either as conventional antiepileptic treatment, after the first electrographic or clinical seizure, or preventively, when the researchers identified epileptiform EEG activity before a clinical seizure.”
They assigned patients to treatment in a 1:1 ratio in a randomized clinical trial at six of the sites. At four of the locations, the treatment allocation was fixed and was considered an open-label trial. The study followed each of the patients until they were two years old. The primary endpoint was considered the time to the first clinical seizure.
Researchers discovered that in 54 of the patients, there were epileptiform EEG abnormalities before the onset of seizures. 27 of the patients were in the random clinical trial and 27 were in the open-label trial.
They noticed that preventative treatment meant that there was a much longer time to the first clinical seizure when compared with the usual, conventional treatments being offered. Ultimately, those patients who received the preventative treatment were “about three times more likely to remain free from clinical seizures throughout the study period compared with participants in the conventional method.”
Those who had the preventative treatment had fewer days with seizures. In both of the trials, patients who had the treatment did not develop infantile spasms. However, those who were receiving conventional treatment did. 31% of patients in the random clinical trial and 50% of patients in the open-label trial had infantile spasms. No one in the study developed a severe intellectual disability during the course of the trial.
The researchers said the patients in the trial who received preventative treatment did not have any adverse events due to that treatment. One patient died of cardiac arrest during their epilepsy surgery. This patient was undergoing conventional treatment at the time.
A Sign of Hope
The use of the vigabatrin is a sign of hope for the epilepsy community. It shows that it could be possible to change the way that severe infantile epilepsy develops and could provide better outcomes for patients in the future.