Teaching Case

A 15-year old female patient was brought to the hospital due to a recent episode of generalised tonic-clonic seizure. She had experienced recurrent seizures during her infancy, but was asymptomatic since then until the recent attack. She had mild intellectual delay, but was otherwise physically normal. Birth and family history were unremarkable.

MRI of the brain showed a complete band of gray matter in the subcortical region of the cerebral hemispheres. It followed the signal intensity of normal cortex on all sequences. It was separated from the gyriform cerebral cortex by a thin layer of white matter, producing a “double cortex” appearance. The cerebral cortex appeared thinner than usual. (See Figures 1 and 2)

Gray matter heterotopias may be categorised into three pathologic forms—namely nodular, laminar and band heterotopias. The nodular form comprises mainly of subependymal nodules of gray matter which are usually bilateral. The laminar form is seen as isolated islands of gray matter interspersed within the hemispheric white matter, but may also involve the entire hemisphere between the ventricular surface and cortex. Lastly, band heterotopias, also known as double cortex syndrome, are distinguished by their symmetric and diffuse nature [2, 4].

Band heterotopia is a rare cortical malformation secondary to an early arrest of neuronal migration, which may be familial. The majority of the known cases are women. This abnormality is most commonly due to a missense mutation in the doublecortin (DCX) (Xq22.3-q23) gene with X-linked dominant pattern of inheritance. In some cases, though less often, this condition may be also caused by a small deletion on the LIS1 (17p13.3) gene of the chromosome 17. In rare occasions, men could also be affected and it is usually due to DCX gene somatic mosaicism or hemizygous mutations. Clinical symptoms typically include recurrent seizures and intellectual delay. Seizure attacks begin in the first decade of life, and may vary from partial to generalised forms. Usually, there are no other congenital and/or developmental anomalies [1, 3, 6].

MRI is superior to CT in the identification and characterisation of heterotopias, and is also useful in ruling out other congenital structural anomalies of the brain. The characteristic appearance of band heterotopia consists of a smoothly marginated layer of gray matter, coursing parallel to the lateral ventricle, and separated from the overlying cortex and underlying ventricle by layers of white matter. This has been described as the “double cortex” appearance. This layer or band is neither convoluted nor contiguous with the overlying cortex, and is further distinguished by the absence of blood vessels and cerebrospinal fluid. Worse disability and developmental delay occur with a thicker band of heterotopic neurons [1, 5].

Currently, treatment is mainly symptomatic and may include antiepileptics, although some cases may be refractory to medical therapy. Surgical resection may be suggested for intractable partial seizures; however, even in the presence of some early improvement, there is no certainty of decreasing seizure frequency and severity in the long run [3].