Neuroradiology

Tuberous sclerosis

(TBS), (also called Bourneville - Pringle disease), autosomal dominant disorder with variable expressivity and genetic heterogeneity (two loci are recognized: one on 9q34 and one on 16p13). The incidence is reported as between 1/10,000 and 1/150,000 births with no sexual predilection.

Only half of patients present with the classic clinical triad of mental retardation, epilepsy and sebaceous adenoma of the face. Sebaceous adenoma (histologically classified as angiofibroma) is a characteristic nodular rash brownish red in colour disseminated bilaterally over the face in the nasalinfraorbital regions. Similar lesions can occur on the trunk, gingiva and periungual regions. Other cutaneous lesions are represented by ashleaf-shaped depigmented nevi on the trunk and extremities, caf-au-lait spots, subungual fibromas, often demonstrable only under an ultraviolet light. Neurological manifestations include myoclonic seizures in infancy and early childhood that are the presenting symptoms in nearly 80% of patients, variable mental and developmental retardation, and psychiatric disorders like autistic behaviour and attention deficit. Patients who manifest seizures before the age of 5 are more likely to have mental deficits. Retinal hamartoma, usually bilateral, is present in over half of the cases.

Other frequent lesions are cardiac rhabdomyoma (80% of cardiac rhabdomyomas are associated with tuberous sclerosis), intra- and extracranial aneurysms, renal angiomyolipomas, carcinomas, pulmonary lymphangiomyomatosis, cysts, interstitial reticular infiltrates and spontaneous pneumothorax.

Various skeletal and endocrine manifestations can be present.

The four major intracranial manifestations of TBS are cortical tubers, white matter abnormalities, subependymal nodules and subependymal giant cell astrocytoma. All these lesions are postulated to represent the same defect of cell proliferation and differentiation in the germinal matrix with resulting disorders of migration and cortical organization, variably expressed all along the glioneuronal units.

Cortical tubers are the most characteristic and epileptogenic lesions of TBS. They are nodules that involve both the cortex and the underlying white matter, composed of bizarre giant astrocytic and neuronal cells, dense fibrillary gliosis and diminished, disordered myelin sheaths. As the pathological findings in cortical tuber are similar to those of focal cortical dysplasia (FCD) with balloon cells (BC), some authors believe that FCD with BC and formes frustes of TBS may in fact represent the same entity.

Imaging

CNS manifestations of TBS are investigated by CT and MR. CT shows cortical tubers as gyral expansions with low attenuation compared to the surrounding brain tissue and with variable contrast enhancement. Cortical tubers can calcify in a nodular or gyriform pattern as their age increases. Subependymal nodules are frequently seen as periventricular calcifications. Subependymal giant cell astrocytoma appears as nodular masses located near the foramen of Monro; some are calcific and enhance after contrast. They tend to grow, causing hydrocephalus.

MR imaging

MR (Fig.1) is more accurate in demonstrating the number and location of cerebral and cerebellar cortical and subcortical lesions and for screening family members. The MR appearance of cortical tubers varies with age: in neonates they appear as enlarged gyri hyperintense on T1-weighted and hypointense on T2-weighted images compared to the unmyelinated adjacent white matter. In older infants and adults they show a centre of low signal on T1-weighted and high signal on T2-weighted images, clearly separate from the overlying cortex. White matter lesions present as radial or cuneiform bands, conglomerates, or linear cerebellar bands hyperintense on T2-weighted images. Subependymal nodules indent the ventricular surface. They also vary in signal intensity with age: in infants they are relatively hyperintense on T1-weighted and hypointense on T2-weighted images and they become gradually isointense as the brain myelinates. Enhancement in subependymal nodules is variable. Giant cell astrocytomas are enlarging subependymal nodules situated near the foramen of Monro, they tend to grow in serial studies and rarely degenerate into higher grade tumour. Contrast enhancement of these tumours is not indicative of malignant degeneration. The surgical treatment of subependymal giant cell astrocytomas is controversial (Fig. 2).

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Fig.1

a. CT scan without contrast. Bilateral hyperdense calcifications in subependymal hamartomas. b, c. MR, T1-weighted image following gadolinium injection. Some of the subependymal nodules enhance. d, e. MR, T2-weighted image. Areas of hyperintensity in the subcortical white matter bilaterally represent displastic and hamartous cortex and white matter.
Tuberous sclerosis, Fig.1 (a)
Tuberous sclerosis, Fig.1 (b)
Tuberous sclerosis, Fig.1 (c)
Tuberous sclerosis, Fig.1 (d)
Tuberous sclerosis, Fig.1 (e)
Tuberous sclerosis, Fig.2 (a)
Tuberous sclerosis, Fig.2 (b)
Tuberous sclerosis, Fig.2 (c)
Tuberous sclerosis, Fig.2 (d)