The patient is a 19-year-old right-handed woman with a known spontaneous TSC1 mutation. She was the product of a normal pregnancy. Seizure onset occurred at the age of 9 months and led to a diagnosis of TSC. Neuropathologic features include numerous cortical tubers and subependymal giant cell tumors (SGCT). The patient has experienced daily seizures since their onset. Multiple antiepileptic medications and other anticonvulsant treatments were tried without significant seizure control. The patient has a history of global developmental impairment.
As part of the presurgical evaluation for neurosurgical intervention, an MRI showed SGCT, multiple tubers located in bilateral frontal, parietal, and occipital lobes, and a large (22 mm) T2 hypointense calcified lesion deep to the left superior frontal sulcus (). Review of prior scans revealed that the calcified component of this lesion was not visible when the patient was 2 years 4 months old and was first visible on MRI when the patient was 4 years old (). Fluorodeoxyglucose PET revealed numerous bilateral frontal and parietal foci of cortical hypometabolism corresponding to cortical tubers on coregistered MRI. There was also a single focus of asymmetric hypermetabolism in the left middle frontal gyrus located deep to the large calcified cortical tuber described. Although the EEG was multifocal, discharges were more prominent over the left frontocentral region. At age 19, the patient underwent a left frontal craniotomy and intraoperative electrocorticography, which demonstrated frequent interictal epileptiform abnormalities in the tissue surrounding the large frontal lobe calcified tuber that had been suspected to be the source of her more problematic partial seizures. The tuber and its immediately surrounding tissue were excised. Subsequently, she has had a significant improvement in both the number and severity of seizures.
Radiologic and histopathologic findings
The resection specimen consisted of a 5.4 × 2.6 × 1.7 cm aggregate of brain tissue. A dominant fragment had a heterogenous cut surface and central mineralization (, B.a). Histology demonstrated a tuber clearly delineated from overlying white matter, which was diffusely gliotic, suggesting that the adjacent tuber tissue had chronically compressed the white matter. The area of mineralization corresponded to a 0.5 × 0.3 × 0.3 cm fragment of mature cortical-like bone surrounded by punctuate calcifications. The bone had lamellar architecture, haversian-like canals, which enclosed small capillaries, and small osteocytes with delicate canaliculi. The bone surface was sharply demarcated from adjacent gliotic white matter by a rim of flattened osteoblasts (IIB, IIC). In limited areas, small foci of woven bone extended from the surface into and encompassed some of the microscopic calcifications (IID).