FROM PEDIATRICS
An early diagnosis of tuberous sclerosis complex (TSC) may be possible in many infants with an echocardiogram for cardiac rhabdomyomas and a skin examination for hypomelanotic macules, noninvasive tests that do not require sedation, said Peter E. Davis, MD, of Boston Children’s Hospital, and his associates on behalf of the Tuberous Sclerosis Complex Autism Center of Excellence Research Network.
“Early TSC diagnosis in infants opens a window of opportunity to treat before the onset of epilepsy or other neurodevelopmental disorders and allows for close surveillance for sequelae of TSC,” the researchers said. “However, this window may be as small as a few months.”
In two concurrent, prospective, longitudinal, observational studies at five medical centers of 130 infants meeting a genetic or clinical diagnosis of TSC, cardiac rhabdomyomas, and hypomelanotic macules were the most common initial presenting features, occurring in 59% and 39% of infants, respectively; 85% of infants had either or both. In terms of prevalence, hypomelanotic macules and tubers or other cortical dysplasias were the most prevalent TSC features both occurring at 94%, followed by subependymal nodules (SENs) at 90%, and cardiac rhabdomyomas at 82%. Every infant had at least one of these diagnostic criteria, and 61% had all four of them, the investigators reported.
Neuroimaging results were available in 115 infants, of whom 94% had tubers or cortical dysplasias, 90% had SENs, and 89% had both; 6% had subependymal giant cell astrocytomas. Seizure onset occurred in 15% of infants before or when other TSC criteria were recorded, “suggesting that seizure was an initial presenting symptom.” Seizure onset occurred within 3 months after initial presentation in 17% of infants, within 6 months in 39%, and within 12 months in 57%. Ultimately, 57% of the infants had infantile spasms, 55% had focal seizures, and 12% had another seizure type, Dr. Davis and his associates said.
“Early, prospective use of EEGs may enable risk stratification in studies of epilepsy prevention in infants with TSC. The antiepileptic medication vigabatrin is particularly effective in treating infantile spasms in TSC and has mTOR [mechanistic target of the rapamycin]–inhibiting effects. Vigabatrin is currently in clinical trials to determine its efficacy at preventing epilepsy in patients with TSC,” they said, although the drug is not currently recommended for infants. “mTOR inhibitors have been successfully used to treat multiple TSC manifestations and have shown some efficacy as adjunctive treatment of refractory epilepsy,” they wrote, adding that studies are needed “to determine the safety and efficacy of mTOR inhibitors in this age group.”
Read more at Pediatrics. 2017;140(6):e20164040 (doi: 10.1542/peds.2016-4040).
