Band heterotopia

Band heterotopia, also known as double cortex syndrome, is a form of diffuse grey matter heterotopia affecting almost only women. Refractory epilepsy is present in nearly all affected patients, with partial complex and atypical absence epilepsy being the most common syndromes.

On imaging, this condition is characterized by a band of grey matter located deep to and roughly paralleling the cortex, with either normal or pachygyric overlying cortex. The signal intensity is the same as normal cortex on all sequences.  

Terminology

As is the case with many cortical malformations there is some confusion as to the terminology. For example, many authors use the term synonymously with laminar heterotopia ^2,3. 

Band heterotopia is best thought of as being on the lissencephaly type I - subcortical band heterotopia spectrum, as the genetic defects are in many cases the same and result from arrested migration of neurons, such that they form a grey matter layer within the centrum semiovale or subcortical white matter.

Epidemiology

The majority of patients with double cortex syndrome are female on account of the genetic abnormality often being located on the X chromosome (see below) ⁵. The condition may be familial with X-linked dominant inheritance ².

Clinical presentation

Seizures and delayed development are the most common presentations, usually evident within the first decade ³. Some patients, however, have only minor disabilities ⁵. 

Pathology

The majority of band heterotopia syndrome cases have now been attributed to an abnormality of the DCX gene (also known as XLIS gene) located on the long arm of chromosome X. The DCX gene encodes for the protein doublecortin responsible for stabilization of microtubules, crucial in normal neuronal migration ⁵. 

LIS1 (also known as PAFAH1B1) and also seen in type I lissencephaly is also implicated in some cases. 

Approximately 10% of cases remain cryptogenic ⁵. 

Radiographic features

Although all modalities able to image the brain in cross-section (ultrasound / CT / MRI) are able to identify the abnormality, MRI is the imaging modality of choice. 

MRI

As the name suggests, this condition is characterized by a band of grey matter located deep to, and roughly paralleling, the cortex, with either normal or pachygyric overlying cortex. The band of abnormal grey matter may be complete or incomplete and may even be duplicated (i.e. two concentric bands) within the temporal lobes ⁵. 

The signal intensity is the same as normal cortex on all sequences. 

Interestingly depending on the underlying genetic abnormality the anterior-posterior gradient of heterotopia is variable:

• anterior predilection suggests mutations of DCX
• posterior predilection suggests mutations of LIS1

On MRS there is a reduction of NAA within the heterotopic grey as neurons therein are dysfunctional ⁴. 

Treatment and prognosis

Treatment is symptomatic and usually targeted at controlling epilepsy.