BrainTF11-Tuberous Sclerosis (Bourneville's disease, Pringle's disease, Epiloia)

Clinical Profile:

H/O seizures. 

Findings:

There are multiple, small, hyperintense nodules on the T1 Weighted images along the subependymal lining of the lateral ventricular walls. These appear hypointense on the T2 Weighted images. Also seen is a fairly large hypointense lesion on the T1 Weighted images at the level of the foramen of Monroe on the right. It is predominantly hypointense on the T2 Weighted images and shows fairly intense enhancement after contrast administration. Multiple, hypointense lesions on the T1 Weighted images that turn hyperintense on the T2 Weighted images are seen in the subcortical region in both cerebral hemispheres.  

Discussion: 

Tuberous sclerosis is an autosomal dominant genetic disease that involves multiple organs. The predominant lesions are the hamartomas. These are slow growing masses composed of a disorganized arrangement of cells . These cells are relatively normal and are appropriate for the site of origin. Classically tuberous sclerosis has been characterized by a  classical clinical triad (Vogt triad) of mental retardation, epilepsy and characteristic skin lesions known as adenoma sebaceum.

The intracranial abnormalities of tuberous sclerosis are postulated to result from an abnormal expression of genes within the cells of the germinal matrix of the developing brain. As a result these stem cells do not differentiate, develop or migrate properly, which results in the presence of dysplastic, disorganized cells in the subependymal region, cortex and along the curvilinear pathways between them.  

Infantile spasms or myoclonic seizures are the presenting symptoms. Patients with tuberous sclerosis can have any type of seizures.  Incidence of mental retardation ranges from 45 to 82%. Patients with more than 10 tubers have a higher incidence of mental retardation. 

Neuroimaging plays an important role in making the diagnosis. CNS abnormalities are present since birth, whereas cutaneous malformations may not develop until much later in childhood. 

Intracranial Manifestations of Tuberous Sclerosis:  

Subependymal Hamartomas:

These are the most common lesions.  They tend to be located along the ventricular surface of the caudate nuclei. Less commonly the nodules may be detected along the frontal and temporal horns, the third ventricle and/or fourth ventricle. The imaging appearance of subependymal hamartomas on CT and MR varies with age of patient. They are rarely calcified in the first year of life.  The number of calcified lesions typically increase with the age of patient. The lesions do not grow, but appear to calcify progressively. By 20 years of age, most of them are calcified. 

On MR scans, these appear as irregular subependymal nodules that protrude into the adjacent ventricles.  Their appearance changes as the signal of the surrounding white matter changes. In infants who have unmyelinated white matter, the hamartomas are relatively hyperintense on the T1 Weighted images and hypointense on the T2 Weighted images.  As the brain myelinates, the subependymal nodules gradually become isointense with the white matter.  They are most easily visualized on the T1 Weighted images. A few lesions may be hyperintense on the T1 Weighted images, related to the dispersed microcalcifications. Small nodules may not be apparent on the T2 Weighted images. Larger subependymal nodules manifest as variably low signal intensity on the T2 Weighted images, depending on the extent of calcification. A few lesions may have a target appearance, with a central hyperintensity, on the T2 Weighted images. After intravenous administration of contrast these nodules show variable enhancement, some will enhance markedly, some mildly, some not at all.  The presence or  absence of enhancement, has no clinical significance. Subependymal grey matter heterotopias do not calcify, are isointense to normal grey matter and do not enhance. 

Giant cell tumors:

Giant cell tumors is the term given to the enlarging subependymal nodules that are usually situated near the foramen of Monroe.  These tumors differ from subependymal hamartoma in their size and tendency to enlarge, which results in the clinical presentation of hydrocephalus. The incidence in tuberous sclerosis is 5-10%. Lesions having a size greater than 12 mms should be classified as a giant cell tumor. However, progressive enlargement is a more reliable criteria.

On imaging these tumors are identified by a demonstration of tumor growth on serial studies. Most of them are located near the foramen of Monroe.  However, they can occur anywhere along the ependymal surface.  Neither signal intensity nor the presence or absence of enhancement is useful in making the distinction between hamartomas and giant cell tumors. These tend to grow into the ventricle as a polypoid mass and only rarely invade the brain parenchyma. They do not seed the CSF. Occasionally degeneration into a high grade or infiltrating neoplasm, can occur.

Cerebral hamartomas (“Tubers”):

Cerebral hamartomas are most characteristic lesions of tuberous sclerosis. These are most commonly supratentorial, although 8-15% of affected patients have cerebellar lesions. The number of calcified lesions seen on CT increases with age.

The MR appearance of cortical tubers changes with age. In neonates, they appear as gyri that are hyperintense to the surrounding unmyelinated white matter on the T1 Weighted images and hypointense on the T2 Weighted images. About 20% of the affected gyri are enlarged.  The appearance changes as brain myelinates, the signal of the lesions slowly becomes isointense. After suppression of the high intensity of myelination, by application of a magnification transfer pulse, parenchymal  lesions may be more apparent than on the standard T1 and T2 Weighted images.  FLAIR images are also more sensitive in detection of parenchymal lesions in children and adults.

The tubers are predominantly subcortical, separate from the overlying cortex. The inner margin of the tuber is poorly defined on all pulse sequences. Although cortical tubers may become isointense with normal white matter on the T1 Weighted images, they usually remain hyperintense on the T2 Weighted images in the mature brain. Neoplastic degeneration of these tubers is rare. When cortical tubers calcify they may appear bright on the T1 Weighted, presumably because of the T1 shortening caused by the calcium crystals. Degenerated calcified cortical tubers may enhance after contrast administration.

White matter lesions:

Islets consisting of a group of neurons and glial cells are usually present in the white matter of. These white matter foci contain areas of hypomyelination and different type of cells. 

On MR these white matter lesions have the same characteristics as cortical tubers. In older patients, they may be difficult to see on the T1 Weighted images. They can sometimes be identified as low signal intensity regions. On the T2 weighted images, they appear as well defined areas of high signal intensity. If the lesion is calcified the calcification may appear as low or high signal intensity on the short TR images depending upon the characteristics of calcium crystals. They have short T1 and T2 relaxation times in neonates and young infants. Degenerated lesions may enhance. On the T2 Weighted, FLAIR and magnetization transfer images they will be often seen as linear or curvilinear regions of hyperintensity in the cerebral white matter, extending from the subependymal hamartomas to the cortical tubers. These are believed to represent bands of unmyelinated disordered cells, along the pathway of the linear radial glial-neuronal unit (similar to focal transmantle dysplasia-formes fruste).

Parenchymal cysts:

Cyst like structures may be seen in the cerebral white matter (usually periventricular).

Cerebellar lesions:

Cerebellar lesions are less common occurring in about 10% of patients. MR features are similar to cerebral lesions. 

Vascular lesions:

Vascular lesions are rare. Cerebral aneurysms have been seen in internal carotid arteries and the anterior cerebral artery distribution. These are usually seen in children.  

Non-Central Nervous System Manifestations:

Brain, ocular and cutaneous lesions are common. However, lesions are also seen in the heart, kidneys, liver, lungs and spleen. Renal hamartomas (angiomyolipoma) occur in 40 to 80% of patients. Benign rhabdomyomas of the heart may present as a congenital cardiomyopathy. Pulmonary involvement is usually in the form of lymphangioleiomyomatosis. Other types of visceral lesions include adenomas and lipomyomas of the liver, adenomas of the pancreas and tumors of the spleen. Bone lesions consist of multiple dense lesions in the cranium and cystic changes in the metacarpals and phalanges of the hand.