Tuberous sclerosis complex

Dr. Amol LahotiResident, Dept of Radiodiagnosis &

ImagingNKP SIMS & LMH, Nagpur

Group of CNS disorders characterized by • brain malformations or • neoplasms • skin• eye lesions.

The term is derived from the Greek root phako, which refers to the lens

phakomatosis means -tumor-like condition of the eye (lens)

Neurocutaneous Syndromes / Phakomatoses

Neurocutaneous Syndromes

• Neurofibromatosis( types 1 and type 2)• Tuberous sclerosis• Sturge-weber syndrome• Ataxia-telangiectasia• Von hippel-lindau disease

Tuberous sclerosis complex (TSC) Bourneville or Bourneville-Pringle disease.

Characterised by classic clinical triad (vogt triad)

• Facial lesions ("adenoma sebaceum“)• Seizure• Mental retardation.

Clinically:

Epilepsy affecting 80 – 90% infantile spasms simple or complex partial seizures EEG +ve in 75 % of patients

Cognitive deficits 44 – 65%

Autism and behavioral problems

Skin EyesBrainHeart

Lung Kidney

Tuberous Sclerosis Complex (TSC)multiple benign hamartomas:

GENETICS

Autosomal dominant Incidence 1 : 6000 livebirthsMutation in

TSC-1 (Hamartin) or TSC-2 (Tuberin)

+ve family history in 7 – 40%

Cell Proliferation

complex

hamartinTSC1

tuberinTSC2

Hamartin-Tuberin complexCentral regulator of cell cycle

TSC: loss of inhibition to cell cycle

Diagnostic criteria Major Features

Identified clinically Facial angiofibromas or

forehead plaque

Non-traumatic ungual or periungual fibroma

Hypomelanotic macules

Shagreen patch

Multiple retinal nodular hamartomas

Cortical tuber Subependymal nodule Subependymal giant

cell astrocytoma Cardiac rhabdomyoma Lymphangio-

myomatosis Renal angiomyolipoma

Identified on imaging

Minor Features

Multiple pits in dental

enamel

Hamartomatous rectal

polyps

Bone cysts,

Cerebral white matter

migration lines

Gingival fibromas

Non-renal hamartoma

Retinal achromic

patch

Multiple renal cysts

DERMATOLOGICAL LESIONS:

81-95%

Fibrous plaque

Gingival fibromatosis

Diagnosis

OPHTHALMIC MANIFESTATIONS

Retinal hamartoma

Calcified hamartoma

CNS RADIOLOGY MANIFESTATIONS

Radiological major criteria

Cortical Tubers• Cortical tubers are firm, whitish, pyramid-shaped,

elevated areas of smooth gyral thickening, with or without central depressions, that grossly resemble potatoes ("tubers")

• On CT scan, Seen as hypodense cortical/subcortical masses within

broadened and expanded gyri Calcifications in cortical tubers increase with age• Tubers in older children and adults demonstrate

mixed signal intensity on T2/FLAIR

Cortical tuber

Subependymal Nodules• appear as elevated, rounded, hamartomatous lesions• located beneath the ependymal lining of the lateral ventricles,

along the course of the caudate nucleus• Are small(generally < 1.3cm) nodular "bumps" that protrude from

the walls of the lateral ventricles.• In the unmyelinated brain, SENs appear hyperintense on T1WI and

hypointense on T2WI. With progressive myelination, the SENs gradually become isointense with WM

• They often calcify with increasing age• An enhancing or enlarging SEN—especially if located near the

foramen of Monro—is suspicious for SEGA.• Calcified SENs appear variably hypointense on T2WI and are

especially easy to detect on T2* sequences

Subependymal nodules

Subependymal Giant Cell Astrocytoma

• seen almost exclusively in the setting of TSC. • well-circumscribed • solid intraventricular masses• located near the foramen of Monro. • SEGAs are WHO grade I tumors that often

cause obstructive hydrocephalus. most SEGAs are unilateral, bilateral tumors occur in 10-15% of cases

Genetic Criteria

• The identification of either a TSC1 or

TSC2 pathogenic mutation in DNA from normal tissue is sufficient to

make a Definite Diagnosis of TSC

Diagnostic features

associated with increase

morbidity

New symptoms or

papilledema

Hydrocephalu

s

Serial imagi

ng showi

ng growth of

lesions

• Cortical Tubers– Broad, expanded gyrus– CT: Initially hypodense; Ca++ ↑ with age

• 50% of patients eventually develop ≥ 1 calcified tuber(s)

– MR: Periphery isointense, subcortical portion T2/FLAIR hyperintense

• Subependymal Nodules– CT: Ca++ rare in first year; ↑ with age

• 50% eventually calcify• Don't enhance

– MR: T1 hyper-, T2 hypointense; 50% enhance• White Matter Lesions

– T2/FLAIR hyperintense radial lines/wedges• Subependymal Giant Cell Astrocytoma

– CT: Mixed-density mass at foramen of Monro, moderate enhancement

– MR: Heterogeneous signal, strong enhancement

Regression of a SEGA after ~15 months oral rapamycin therapy in a 4-year-old patient with TSC

Thank - you