Images below require Macromedia's Flash Player to view

Neuroradiology Case of the Week

Case 192

Samuel Madoff, MD and Per-Lennart Westesson, MD, PhD, DDS

Clinical Presentation: Patient is a 2-year-old female with seizures.

Radiological Findings: On CT there are multiple, ill-defined hypodense lesions scattered throughout the brain parenchyma. Bilateral, subependymal calcific lesions are identified adjacent to the lateral ventricles (Fig. 1). Calcifications are also noted within a left frontal lobe lesion (Fig. 2).
     On MRI, the ovoid-shaped, subependymal lesions along the lateral ventricles are hypointense on T1 and slightly iso- to hypointense on T2-weighted images (Figs. 3 and 4, respectively). Well seen on coronal images, these lesions demonstrate intense homogeneous enhancement (Fig. 5). Additionally, there are high signal lesions scattered diffusely throughout the bilateral frontal, temporal and occipital regions, left more than right (Fig. 4).

Diagnosis: Tuberous sclerosis

Discussion: Tuberous sclerosis is a disorder described classically as presenting with a clinical triad of facial angiofibromas, mental retardation and seizures (infantile spasms for example). The incidence is estimated to be in the range of 1:10,000. Clinical diagnosis is guided by scoring of major and minor criteria (see below).
     The gross pathologic underpinning of tuberous sclerosis is multi-organ hamartomas, characteristically non-invasive, benign, slow growing tumors. As a rule of thumb, hamartomas in more than two organ systems is strongly suggestive of the diagnosis.
     Upon histologic analysis, the hamartomas contain giant balloon cells. Tuberous sclerosis has been linked to mutations in the genes coding “hamartin” (chromosome 9) and “tuberin” (chromosome 16). Half of cases are estimated to be of autosomal dominant inheritance (high, but variable penetrance), while the other half are attributed to de novo mutations.
     Specific to the CNS, findings of tuberous sclerosis include subependymal nodules, cortical tubers, white matter lesions, thickened cortex with enlarged pyramidal-shaped gyral expansion and subependymal giant cell astrocytomas. Subependymal nodules occur in 98% of patients and are usually calcified (as in this case). The cortical/subcortical tubers and white matter lesions are only slightly less common (70-95%) and have a predilection for the frontal lobes (also seen in this case). White matter abnormalities may represent dysplastic areas due to hypomyelination or possibly anomalous neural migration.
     Subependymal giant cell astrocytomas occur in approximately 15% of patients and are typically located adjacent to the foramen of Monro. While they are classified as WHO grade I (low grade, slow growing, circumscribed neoplasms), the location of subependymal giant cell astrocytomas may cause significant morbidity. They may obstruct CSF outflow resulting in hydrocephaly and dangerously increased intracranial pressure.
     The short differential diagnosis of tuberous sclerosis includes Cytomegalovirus (ie. TORCH), X-linked subependymal heterotopia (no calcification and nonenhancing) and Taylors dysplasia (a single lesion thought to be an incomplete form of tuberous sclerosis).
     The abnormalities imaged in this patient include subependymal tubers demonstrating intense enhancement (Figs. 1, 3, 4 and 5) and cortical tubers associated with dysplastic white matter areas scattered throughout the brain parenchyma (Figs. 1-4). One of the tubers is calcified (Fig. 2).

Diagnostic criteria: Two major OR one major + two minor

References:

1. Castillo M. The Core Curriculum:  Neuroradiology. 1st ed. Philadelphia: Lippincott Williams & Wilkins, 2002: 48-51.
2. Loevner L. Brain Imaging: Case Review. 1st ed. St Louis: Mosby, 1999: 213-214.
3. Osborn A. Diagnostic Imaging: Brain. 1st ed. Philadelphia: W.B. Saunders, 2004: 90-93.