● most cases are due to spontaneous mutation. Inherited cases are autosomal dominant. Incidence: 1 in 6K–10K live births.
● classic clinical triad: seizures, mental retardation, and sebaceous adenomas; the full clinical triad is seen in < 1/3 of cases.
● typical CNS finding: subependymal nodules (“tuber”)—a hamartoma.
● commonly associated neoplasm: subependymal giant cell astrocytoma (SEGA)
● CT shows intracerebral calcifications (usually subependymal).
Tuberous sclerosis complex (TSC), AKA Bourneville’s disease, is a neurocutaneous disorder characterized by hamartomas of many organs including the skin, brain, eyes and kidneys. In the brain, the hamartomas may manifest as cortical tubers, glial nodules located subependymally or in deep white matter, or giant cell astrocytomas. Associated findings include pachygyria or microgyria.
Subependymal giant cell astrocytomas (SEGA) are benign brain lesions occurring in up to 20% of patients with TSC.
This rare multi-system genetic disease causes benign tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin. A combination of symptoms may include seizures, intellectual disability, developmental delay, behavioral problems, skin abnormalities, lung and kidney disease.
The name, composed of the Latin tuber (swelling) and the Greek skleros (hard), refers to the pathological finding of thick, firm and pale gyri, called “tubers,” in the brains of patients postmortem. These tubers were first described by Désiré-Magloire Bourneville in 1880; the cortical manifestations may sometimes still be known by the eponym Bourneville's disease.
Autosomal dominant inheritance; however, spontaneous mutation accounts for the majority of cases.
Two distinct tumor suppressor genes have been identified: the TSC1 gene (located on chromosome 9q34) codes for TSC1 (AKA hamartin), and the TSC2 gene (on chromosome 16p13.3) codes for TSC2 (tuberin). Only 1 gene needs to be affected to develop TSC. These proteins work together to inhibit the activation of rapamycin (mTOR). Genetic counseling for unaffected parents with one affected child: 1–2% chance of recurrence 4) 5).
Subependymal nodules (“tubers”) are benign hamartomas that are almost always calcified, and protrude into the ventricles.
▶ Subependymal giant cell astrocytoma (SEGA). Almost always located at the foramen of Monro. Occurs in 5–15% of patients with TSC.
Brain MRIs of 110 TSC patients (mean age 11.5 years; age range 0.5-38 years; 52 female; 26 TSC1, 68 TSC2, 8 without mutation identified in TSC1 or TSC2, 8 not tested) were retrospectively evaluated. Signal and morphological abnormalities consistent with olfactory bulb hypo/aplasia or with olfactory bulb hamartomas were recorded. Cortical tuber number was visually assessed and a neurological severity score was obtained. Patients with and without rhinencephalon abnormalities were compared using appropriate parametric and non-parametric tests.
Eight of 110 (7.2%) TSC patients presented rhinencephalon MRI changes encompassing olfactory bulb bilateral aplasia (2/110), bilateral hypoplasia (2/110), unilateral hypoplasia (1/110), unilateral hamartoma (2/110), and bilateral hamartomas (1/110); olfactory bulb hypo/aplasia always displayed ipsilateral olfactory sulcus hypoplasia, while no TSC patient harboring rhinencephalon hamartomas had concomitant forebrain sulcation abnormalities. None of the patients showed overt olfactory deficits or hypogonadism, though young age and poor compliance hampered a proper evaluation in most cases. TSC patients with rhinencephalon changes had more cortical tubers (47 ± 29.1 vs 26.2 ± 19.6; p = 0.006) but did not differ for clinical severity (p = 0.45) compared to the other patients of the sample.
Olfactory bulb and/or forebrain changes are not rare among TSC subjects. Future studies investigating clinical consequences in older subjects (anosmia, gonadic development etc.) will define whether rhinencephalon changes are simply an imaging feature among the constellation of TSC-related brain changes or a feature to be searched for possible implications in the management of TSC subjects 6).
A novel technique is presented for the application of MRgLITT in a 6-month-old infant for the treatment of epilepsy associated with tuberous sclerosis complex (TSC) .
To Hooten et al. from the Tuberous Sclerosis Complex Clinic, Duke University, Durham, North Carolina; and University of Florida, Gainesville, knowledge this is the youngest patient treated with laser ablation. They used a frameless navigation technique with a miniframe tripod system and intraoperative reference points. This technique expands the application of MRgLITT to younger patients, which may lead to safer surgical interventions and improved outcomes for these children 7).