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

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)

(Left) Axial graphic of typical

brain involvement in tuberous

sclerosis complex (TSC) shows

a giant cell astrocytoma ﬇ in

the left foramen of Monro,

subependymal nodules ﬊,

radial migration lines ﬉, and

cortical/subcortical tubers ﬈.

(Right) Clinical photograph of

a patient with TSC shows the

hypopigmented "ash leaf"

spots ﬈ characteristic of TSC.

(Left) Clinical photograph of a

patient with TSC shows

numerous facial

angiofibromas ﬉

characteristic of the disorder.

(Courtesy B. Krafchik, MD.)

(Right) Axial FLAIR

surveillance scan in a 14-yearold boy with known TSC shows

a well-demarcated lobulated

mass in the left frontal horn

﬊, a subependymal giant cell

astrocytoma. Note multiple

expanded gyri with poor graywhite differentiation (tubers

ſt), subcortical WM

hyperintensities.

Trauma, and Stroke

Brain: Pathology-Based Diagnoses: Malformations,

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