Tuberous Sclerosis Complex

KEY FACTS

Terminology

• Tuberous sclerosis complex (TSC)

• Multisystem genetic disorder with epilepsy, multiorgan tumors, and hamartomas

  • Spectrum of CNS hamartomas; all contain dysplastic neurons and giant (balloon) cells

  • Caused by mutation in TSC1 or TSC2 gene

  • Now considered an infantile (developmental) tauopathy

    • –

      Tau abnormally expressed in many dysmorphic neurons and glial cells of TSC

    • –

      Similar to focal cortical dysplasia (FCD) 2

Imaging

• FLAIR and T1 MR most sensitive sequences for diagnosis

• Calcified subependymal nodules (SENs)

  • < 1.3 cm, often enhance (more on MR than CT)

• Subependymal giant cell astrocytoma (SEGA) (15% of TSC)

  • Most located at foramen of Monro

    • –

      > 1.3 cm; enhance strongly, enlarge over time

• Cortical/subcortical tubers (95%)

  • Early T1 ↑ but variable after myelin maturation

• Other findings

  • White matter (WM) radial migration lines

  • Cyst-like WM lesions (cystoid brain degeneration)

Top Differential Diagnoses

• Taylor-type cortical dysplasia (FCD type 2)

• X-linked subependymal heterotopia

• TORCH syndromes

  • CMV has periventricular Ca++, typical WM lesions, polymicrogyria

Pathology

• Mutations in TSC tumor suppressor genes → abnormal germinal matrix proliferation, differentiation

Clinical Issues

• Classic clinical triad = facial angiofibromas (90%), mental retardation (50-80%), seizures (80-90%) (all 3 = 30%)

Diagnostic Checklist

• SEN (< 1.3 cm) vs. SEGA (> 1.3 cm, enlarging)

TERMINOLOGY