Tuberous Sclerosis

 

This CT and MRI study of brain shows:
Multiple dense nodular calcifications along enpendymal lining of bilateral lateral ventricle best seen on CT. Cortical tubers seen as small multi focal cortical and sub cortical white matter patchy hypodensities on CT and T2 hyper intensities on MRI. No obvious obstructive hydrocephalus.

The lesion at right caudo thalamic groove not calcified on CT but shows avid enhancement on post contrast, needs follow up imaging as it may turn out to be a sub ependymal giant cell astrocytoma leading to obstructive hydrocephalus. However as of now there is not obvious obstructive hydrocephalus.

Imaging diagnosis : Tuberous Sclerosis.

TUBEROUS SCLEROSIS

Syn: Tuberous sclerosis complex (TSC), Bourneville-Pringle Syndrome.
A inherited tumor disorder with multi-organ Hamartomas.

In CNS characterized by Subependymal nodules, Subependymal giant cell astrocytoma, Cortical/subcortical tubers.
Abnormal differentiation/proliferation of germinal matrix cells, Migrational arrest of dysgenetic neurons appears to be the pathogenesis behind the lesions.
Histopathology and microscopic features are Balloon cells, Myelin loss, vacuolation and gliosis, Ectopic neurons.

Imaging 

CT and MRI both are equally sensitive but MRI often shows more number of lesions.
Subependymal nodules
Seen in ~ 98%. Commonest and specific site is caudothalamic groove followed by atrial and temporal lobe white matter.
~ 50% them shows an associated calcification best depicted on CT. calcification is often progressive after 1 yr.
30-80% of SEN shows mild enhancement on post contrast study, appreciated better on MRI than CT.
SEN at foramen of Monro needs close follow. If its enlarging it is equivalent to Subependymal giant cell astrocytoma (SGCA) and can cause obstructive hydrocephalus.
Subependymal giant cell astrocytoma (SGCA)
Seen in ~15%.
Cortical/subcortical tubers, WM lesions
Seen in ~ 70-95% common in Fronto parietal followed by temporo occipital regions and Cerebellum.
Ill defined patchy hypodensites on CT +/- calcification.
Hypo intense on T1 hyper intense on T2 and FLAIR on MRI. No restricted diffusion. May show low signal intensity on T2*GRE if an associated calcification.
~12% cortical/subependymal tubers show faint enhancement on post contrast T1.
Cyst-like white matter lesions as focal lacune best seen on MRI T2w images, common in corona radiata.
An associated thickened cortex, enlarged gyri.
MRS: decreased NAA/Cr, increased ml/Cr in subcortical tubers, SENs.

Associated abnormalities

o Renal: Angiomyolipoma and cysts 40-80%
o Cardiac: Rhabdomyomas 50-65%; majority involute over time
o Lung: Cystic lymphangiomyomatosis/fibrosis
o Solid organs: Adenomas; leiomyomas
o Skin: Ash-leaf spots (majority) including scalp/hair; facial angiofibromas; shagreen patches 20-35% post pubertal
o Extremities: Subungual fibromas 15-20%; cystic bone lesions; undulating periosteal newbone formation
o Ocular: "Giant drusen" (50%)
o Dental pitting permanent teeth in most adults with TSC

DDs: 

Subependymal heterotopia : Isointense to GM, don't enhance or Ca++.
TORCH : Periventricular Ca++ , White matter lesions, Cortical dysplasia common with Cytomegalovirus (CMV).
Taylors dysplasia

Genetics

De novo = spontaneous mutation/germ-line mosaicism
Autosomal dominant, high but variable penetrance. Approximately 50% of TSC cases are inherited.

Clinical presentation

Classic clinical triad
1. Facial angiofibromas 90%;
2. Mental retardation 50-80%;
3. Seizures /  Epilepsy 80-90%

All three ("epiloia") seen in ~ 30% of cases.

More the number lesion ~ high the neurologic symptoms.
Diagnosed at any age.

First year of life commonly present with seizures, Infantile spasms like episodes.
Child present with Autistic-like behavior, mental retardation, seizures, or skin lesions.
Adult may present for first time due to a symptomatic SGCA.

Treatment

Treat seizures.
Resect isolated tubers if seizure focus or if able to identify seizure focus among many tubers.
SGCAs resected if obstructing foramen of Monro.

Reference :

Diagnostic imaging Osborn.