Tuberous sclerosis complex
Tuberous sclerosiscomplex (TSK) is a multisystem disease caused by mutations in the TSC1 and TSC2 genes. As a result, tumors can form in multiple human organs (e.g.: brain, heart, skin, kidney, etc.). During routine ultrasound examinations of the fetus, the disease is more frequently diagnosed prenatally.
TSK is one of the most common medical causes of severe epilepsy, which is resistant to current medications. Furthermore, neurological comorbidities such as intellectual impairment or autism may also occur in children with TSK. Current guidelines recommend an antiepileptic procedure after two unprovoked clinical epileptic seizures or after one seizure in patients at risk for periodic spasms associated with epilepsy. Despite such treatments minimizing the risk of complications in children with TSK, up to 60% of them may develop mental impairment.
Most people with TSK experience an asymptomatic seizure or electroclinical seizures prior to a clinical seizure. In this case, EEG seizure patterns (i.e., detectable on the electroencephalogram) develop in addition to clinical seizure symptoms. Based on recent research confirming that antiepileptic treatments provided better outcomes after immediate EEG detection of such seizure symptoms in children as young as two years of age compared to treatment only after clinical seizures, guidelines now recommend video EEG monitoring in infants.
Currently, epilepsy is diagnosed only after a clinical seizure. Until recently, physicians informed parents of infants with TSK about the risk of seizures and asked them to contact a neurologist as soon as a seizure occurred. However, in doing so, the potential for asymptomatic seizures means that one can be missed, which in turn can lead to significant delays in diagnosis and treatment.
To explore the safety and efficacy of preventive treatment for epilepsy, the controlled multicenter study published in November 2020, in the medical journal Annals of Neurology, compared this procedure with conventional doctoring.
Children aged four months or less with a clear TSK diagnosis (with consensus criteria) were studied. These had no prevalent asymptomatic seizures or electroclinical seizures detectable on video-EEG at baseline. Exclusion criteria were as follows:
- No definite TSC diagnosis
- past epileptic seizure
- past treatment with antiepileptic drugs
- Existing medical condition that could interfere with study participation.
A total of 94 newborns with TSC without prior seizures were monitored monthly with a video EEG while receiving vigabatrin- either as conventional treatment or after first electroclinical seizure or preventively if epileptic EEG activity was detected prior to a seizure. Vigabatrin is a seizure suppressant drug used in the treatment of epilepsy. The neonates were divided into two groups with the respective treatments in a randomized controlled trial at a total of 6 sites, while in an open-label trial at 4 sites, the treatment was fixed. The observation period was conducted until the second year of life, with the primary end goal at all sites being time to first clinical seizure.
A total of 54 newborns recorded detectable EEG activity before seizures, of which 27 were included in the randomized controlled trial and 27 in the open-label trial. There was a noticeable difference in the time to first clinical seizure between the two treatments. While the preventive treatment took a mean of 364 days to the first clinical episode, the conventional treatment took 124 days in the randomized controlled subjects. In the open-label trial, it took 426 days with preventive treatment and 106 days with conventional. After 2 years of observation, analysis showed that preventive treatment reduced the risk of clinical seizures by 79%. For drug-resistant epilepsy, the figure is 77%. No adverse events were identified in association with the preventive measure.
According to the study, preventive treatment with the drug vigabatrin significantly reduced the risk and severity of epileptic seizures in newborns diagnosed with TSK. The WHO and IBE (i.e. International Bureau of Epilepsy) also highlight the unmet need for research on the prevention of epilepsy. Regular video EEG monitoring from the diagnosis of TSK in newborns and immediate antiepileptic treatment with the seizure suppressing drug when electroclinical seizures occur could significantly prevent the risk for many children and could be discussed more frequently in medical circles.