Tuberous sclerosis (TS) is an autosomal dominant,
neurocutaneous disorder that is characterized by development of hamartomatous tumors in multiple organs and neuronal migration abnormalities.
TS is a multisystem genetic disorder with specific intracranial manifestations such as cortical and cerebellar tubers,
subependymal nodules,
and SEGAs,
as well as abdominal and thoracic manifestations such as renal angiomyolipoma (AML) and lymphangioleiomyomatosis (LAM).
TS results from a mutation in the TSC1 or TSC2 genes,
with approximately one-third of cases being inherited.
The common underlying biochemical pathways have also been identified.
It is important for radiologists involved in the interpretation and care of these children and adults to be abreast of this rapidly changing field.
TS has a wide variety of clinical and radiologic manifestations.
It should be suspected when some of the common manifestations are found,
including CNS
involvement,
renal AML,
and cardiac rhabdomyoma,
even if clinical signs are not obvious.
Familiarity with the clinical course,
sites of potential involvement,
and frequency of involvement can allow correct treatment and improvement in quality of life.
Recognition of radiologic features of various organ manifestations is essential for making the correct diagnosis and is helpful for detecting additional abnormalities.
The diagnosis of TS can not be confirmed unless accompanied by characteristic CT or MRI findings of brain involvment.
Calcified subependyma nodules are the most specific CT feature,
whereas MRI is more sensitive than CT in detecting gyral tubers and,
thus,
may be better for screening family members and others in whom TS is possible.
MRI is the primary imaging modality in the diagnosis,
characterization,
and monitoring of the intracranial lesions of TSC.
Cortical tubers are considered to be closely related to the neurologic manifestations of TS,
including epilepsy,
cognitive disability,
and neurolobehavioral abnormalities.
Cortical tubers are usually present in more than 90% of patients,
and are often multiples and bilateral (65%–92%).
Certain neuroradiological features,
such as greater than 7 tubers,
9 large tuber size,
and increased tuber/brain ratio,
favor a more severe epilepsy or early onset of epilepsy as well as intellectual impairment.
Tubers with significantly higher ADCs and lower FA have increased epileptogenic potential compared with other lesions.
On MR spectroscopy,
tubers show decreased N-acetyl aspartate (NAA),
presumably from loss of neurons,
and increased myoinositol from gliosis or immature neurons.
It has been proved that there is a higher risk of severe cognitive and behavioral difficulties in patients with involvement of the temporal or occipital lobes,
particularly the left temporal lobe in right-handed patients.
Autism is commonly seen in patients with frontal and parietotemporal tubers.
The prevalence of patients with more than 10 subependymal nodules ranges from 12% to 57%.
Leung et al revealed no correlation between subependymal nodules and clinical severity of disease.
Some authors have reported that the number and location of subependymal nodules may allow prediction of neurologic manifestations.
The prevalence of white matter abnormalities is 40%–90%.
In a study on RML,
the investigators found a strong association between the frequency of RMLs and age of seizure onset and history of seizures.
Additionally,
the RML frequency was also strongly associated with the level of intelligence and rate of autistic features.
They suggested that,
in TS,
neurocognitive deficits are caused by focal migration and proliferation abnormalities.
Although the name of SGCAs may suggest that they are astrocytomas (and they are included under the astrocytoma category in the current WHO classification),
they are now thought to be of glioneuronal origin.
Different from other cerebral astrocytomas,
SGCAs are low-grade tumors (World Health Organization [WHO] grade I) and have benign biologic and pathologic features (ie,
slow growth,
minimal or no attendant brain edema,
and invasiveness).
Because surgical risk depends largely on tumor size and vascularity,
CT and MRI are useful for noninvasive evaluation.
When subependymal nodules are located near the foramen of Monro and they measure more than 5 mm in diameter,
are not or are incompletely calcified,
and are enhanced by gadolinium,
repeat MRI should be recommended to detect the growth and a transformation in SGCA.
MR spectroscopy of SGCAs shows high Cho/Cr and low NAA/Cr ratios,
which may be useful for distinguishing them from subependymal nodules.
Because early detection and treatment is critical,
periodic surveillance with imaging every 1 to 3years is recommended until the age of 25 years.
Monitoring also depends on size,
with some investigators suggesting 6-monthly screening in lesions greater than 1 cm.
Treatment options include surgical resection,
gamma knife radiosurgery,
and pharmacotherapy with mTOR inhibitors.
Surgical resection is the standard therapy for SEGAs with documented growth or if associated with obstructive hydrocephalus.
mTOR inhibitors such as everolimus may be used in patients aged 3 years and older for asymptomatic SEGAs,
when surgery is contraindicated,
or in recurrent lesions when scarring and distorted anatomy may increase morbidity and mortality from surgery.
Patients who have both cerebral and cerebellar tubers have significantly more global cortical lesions than patients without cerebellar tubers.
Cerebellar tubers are thus a marker for severity of disease.
Cerebellar tubers have been associated with more severe clinical disease.
Patients have more severe communication and social disturbances when these tubers are located in the right cerebellar hemisphere.
Other rare CNS manifestations include mild dilatation of lateral ventricles due to atrophy or dysgenesis,
cerebellar atrophy,
infarction caused by occlusive vascular disorders,
cerebral aneurysm,
dysgenesis of the corpus callosum,
Chiari malformation,
microcephaly,
macroencephaly,
arachnoid cyst,
neurofibromatosis,
and chordoma.