2024 Fetal Care Center Frontiers in Fetal Neurology Day 2 - Hour 1 Q&A

Fetal MRIs at 27 and 32 weeks in the twin case showed no specific findings consistent with tuberous sclerosis.

The more severely affected twin had an MRI at 2 months of age showing one small cortical dysplasia.

Both twins have had normal EEGs up to the time of discussion.

Cardiac rhabdomyomas will regress and shrink on their own without treatment.

Treatment duration for TSC rhabdomyomas is individualized based on tumor regression and family preference, with no fixed endpoint.

mTOR inhibitors are viewed as targeted therapy for the entire TSC disease, not just cardiac lesions.

Current clinical trials use pharmacokinetic teams rather than physicians to determine dosing based on the infant's individual pharmacokinetics.

Historically, it took two months to reach therapeutic mTOR inhibitor range in infants; with early level monitoring, therapeutic range can be achieved within two weeks of life.

Fetal dosing is complicated by rapid maternal blood volume changes at 26-32 weeks gestation.

mTOR inhibitors are known to increase triglycerides, but untangling pregnancy-related from drug-related elevation may not be possible without a placebo group.

Subependymal nodules and tubers can be reliably identified on fetal MRI and confirm TSC diagnosis.

Cardiac rhabdomyomas are not required for enrollment in TSC treatment studies; risk of TSC or clinical diagnosis with brain MRI is sufficient.

One case report describes a congenital subependymal giant cell astrocytoma (SEGA) found on prenatal ultrasound that was treated with an mTOR inhibitor and showed size reduction.

Maternal side effects of prenatal mTOR inhibitor treatment appear minimal.

Early genetic testing can confirm TSC diagnosis prenatally.

The heart TSC protocol follows patients from the prenatal period through 5 years of age, including echocardiograms and developmental assessments.

Postnatal TSC treatment trials follow children until 2 years of age.