AB is a 22 year old female comes to the clinic with an eleven year history of medically refractory seizures as well as frequent headaches. Complete neurological exam is normal. On a head MRI, multiple small nodular lesions are noted along the lateral ventricles bilaterally. On all sequences, the signal characteristics of these lesions are typical of gray matter.

Before the advent and widespread usage of magnetic resonance imaging (MRI) gray matter heterotopia were thought to be rare occurrences, generally only found at autopsy. However, as MRI became a more frequent imaging modality of the brain, gray matter heterotopia has been found to be a relatively common brain malformation.

The term heterotopia is used to describe large collections of neurons that are found outside of their normal anatomic location. It is believed that this occurs as a result of either premature cessation of neuronal migration, thus giving rise to gray matter found in the periventricular or white matter areas, or failed apoptosis of neuroblasts within the periventricular matrix. Subependymal heterotopia (SEH), also known as periventricular nodular heterotopia, is the most common heterotopia found in clinical practice. Mutation of the gene FLNA, which codes for the protein filamin A, a protein essential to the overall process of neuronal migration, has been implicated in the development of SEH. Other clinical distributions of gray matter heterotopia are subcortical, and band (also known as “double cortex’) heterotopia.

Clinical manifestations of grey matter heterotopia vary from being asymptomatic to having intractable seizures and cognitive impairment. Seizures can be either generalized or focal in nature. Patients with SEH have an 80% chance of developing epilepsy with their first seizures typically developing in the second decade of life. Impaired cognition is more likely in patients with bilateral disease versus those with only unilateral lesions.

Diagnosis is based on MRI illustrating isointensity of periventricular nodules with normal grey matter on all sequences examined. This allows these lesions to be differentiated from those of tuberous sclerosis. Additionally, the lesions of SEH will not enhance with contrast, which the lesions of tuberous sclerosis will.

Treatment is aimed at controlling the seizures. Medical management with anti-epileptic drugs is the first line treatment, however a significant proportion of these patients will be refractory to medical therapy. At this point, the patient can be evaluated for surgical intervention, though this is controversial in the literature. Precise localization of the epileptogenic center is determined typically by utilizing MRI, video electroencephalography (vEEG) and invasive presurgical stereo-EEG (sEEG). After extensive evaluation, surgical excision of the epileptogenic center can be performed. While differing levels of success have been described in the literature, patients with unilateral disease have had the best surgical outcomes, many of which were seizure-free one year after surgery.

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