subkortikale Hamartome

Cortical tubers or subcortical tubers (with involvement of the underlying white matter) are a common finding in tuberous sclerosis, present in 95-100% of cases .

These benign hamartomatous lesions can be epileptogenic foci, and are important to diagnose on imaging (typically MRI) as they can affect treatment. In some cases of medically-refractory epilepsy, cortical tubers may be surgically resectable.

Epidemiology

Tuberous sclerosis typically presents in the first decade of life and has a reported incidence of 1:6000-12000 with intracranial involvement in the vast majority of patients, mainly cortical tubers or subependymal nodules.

The majority of cases of tuberous sclerosis (approximately 2/3's) are sporadic, and an autosomal dominant inheritance pattern has been demonstrated in the remainder .

Clinical presentation

There is significant variation in the presentation of tuberous sclerosis, dependent on the distribution and burden of hamartomata throughout the body.

Cortical tubers may be epileptogenic foci, presenting with partial seizures or infantile spasms. Cortical tubers may also contribute to cognitive defects or autistic/neurobehavioural traits in some patients . These symptoms were part of the original Vogt triad, and cortical tubers remain one of the major features in the diagnostic criteria for TS . There is an association with worse neurological outcome with a greater burden of cortical tubers .

Pathology

Tubers represent cortical glioneuronal hamartomas, and consist of focal distortions in cellular organization and morphology which extend into the underlying (subcortical) white matter. Distinguishing these cortical tubers from focal cortical dysplasia can be difficult, often relying on ancillary findings and immunophenotyping.

Calcification can occur in tubers, but is more commonly present in subependymal nodules. Central cystic degeneration can also occur .

The tubers have been shown to be non-functioning as they have been removed from eloquent areas with little to no long term neurological deficit .

Macroscopic appearance

Small (<1 cm) firm indistinct expansions of the gray matter and adjacent white matter , giving the appearance of an expanded gyrus or group of gyri with loss of gray-white distinction .

Cerebellar lesions are typically wedge shaped, and tend not to be epileptogenic foci. Tubers are rarely found in the brainstem (without cortex).

Microscopic appearance

Expansion and disorganization of cortical cell layering (cortical dysplasia) , and variable presence of bizarre large cells with immunohistochemical characteristics of both neuronal and glial cells . Lower myelin content has also been demonstrated in tubers.

Immunophenotype

Giant cells can demonstrate variable immunoreactivity to vimentin, S100 protein, glial fibrillary acidic protein, class III b-tubulin, nestin, neurofilament, synoptophysin .

Radiographic features

Tubers are triangular-shaped lesions centered at the cortex/juxtacortical, with apex oriented "inward" toward the ventricles . 50-90% will be found in the frontal lobes .

Tubers, and most of the CNS involvement of tuberous sclerosis, are best demonstrated on MRI.

CT

• can show areas of calcification, although this is more commonly demonstrated in subependymal nodules

MRI

• T1: low signal
• T2/FLAIR: high signal (except neonatal period, see below)
• T1 C+ (Gd): enhancement only demonstrated in <10% of cases

In neonatal brain some tubers can be isointense on T2 sequences and can be missed, and it is better to look for their relative T1 hyperintense appearance compared to the surrounding unmyelinated brain .

Occasionally radial bands relating to periventricular matter can be seen.

Treatment and prognosis

Treatment of symptoms arising from cortical tubers is usually required in the form of seizure control. If there is reduced cognitive function, supportive care should also be considered.

In medically-refractory epilepsy (50-80% of TS cases), surgical excision of the tuber can be considered with a view to improving seizure frequency and control, with possible improvement in cognitive function .

Differential diagnosis

In the clinical context of known tuberous sclerosis, the appearance is virtually pathognomonic. The presence of other findings (subependymal nodules, subependymal giant cell astrocytomas, white matter abnormalities) or extra-CNS findings will help.

Siehe auch:

• Tuberöse Sklerose
• subependymale Hamartome