Foraminal subependymal nodules and subependymal giant cell astrocytoma in children with tuberous sclerosis

Tuberous sclerosis complex (TSC) is a genetic syndrome affecting brain and other organs caused by mutations in the TSC1 or TSC2 genes. These mutations disrupt several cellular processes by altering the mTOR pathway, stimulating cell growth and proliferation. This abnormal cellular growth can cause brain lesions called subependymal nodules (SEN) and other lesions in the kidney and in the skin. Most SEN are harmless, but some are located close to the foramina of Monro, openings that allow fluid to circulate in the brain; these are called foraminal SEN (fSEN). A small proportion of fSEN can grow to subependymal giant cell astrocytomas (SEGAs) and may block the normal fluid circulation within the brain, causing an increase in intracranial pressure. This fSEN growth makes regular imaging follow-up important to detect this SEGA volume increase and treat it before the occurrence of the neurological complications of an increased intracranial pressure. Current guidelines recommend brain imaging every 1 to 3 years in children with TSC. However, repeated MRI can be challenging, particularly for children with neurodevelopmental difficulties who may require sedation or general anesthesia to perform the imaging in good conditions. We reviewed brain imaging from 128 children with TSC and studied changes in the volume of 232 fSEN over time. Most fSEN did not grow during childhood. Among those that grew, some increased steadily, while others showed a period of accelerated growth, which could occur up to approximately 9 years of age. We suggest that the period from 5 to 9 years of age is particularly important for monitoring the brain imaging. Large fSEN (≥360 mm3) before 5 years of age, faster growth, higher number of brain tubers (other brain lesions due to TSC), and TSC2 gene variants were associated with a greater likelihood of growth.