Periventricular gray matter heterotopia in a patient with uncontrolled seizure disorder

A 51-year-old female with seizure disorder and memory impairment presented after a witnessed focal seizure episode at home. She also had a 90-second witnessed tonic-clonic seizure in the emergency room which responded to lorazepam. Physical examination revealed rightward gaze and right-sided weakness.

Non-contrast computed tomography (CT) of the head was negative for acute intracranial process but demonstrated an abnormal contour of the posterior lateral ventricles (figures 1a, 1b). Further evaluation with magnetic resonance imaging (MRI) brain without contrast demonstrated periventricular nodularity isointense to the grey matter on both T1 and T2 weighted images in the posterior horns of the lateral ventricles (figures 2a-2c), suspicious for periventricular nodular heterotopia (PVNH). Other findings included asymmetric prominence of the right temporal horn secondary to underlying gliosis or atrophy of the right hippocampal or parahippocampal tissues. Non-emergent follow-up MRI with and without contrast showed nonenhancement of these grey matter nodularities (figures 2d-2f), compatible with PVNH.

Grey matter heterotopia (GMH) is the ectopic clumping of nerve cells caused by failure of neuronal migration during fetal development. It is not clear what causes the interruption of the migration. GMH clusters can be periventricular, subependymal, or subcortical in location, with periventricular nodular heterotopia (PVNH) being the most common [1]. PVNH is most commonly inherited through mutations in the filamin A gene. It is associated with mental retardation, developmental delay, and other neuropsychiatric diseases [2]. As many as 88% of patients with PVNH have epilepsy that is frequently difficult to control [4,5]. Epileptic features in isolated PVNH patients can begin at any age but frequently begin in adolescence. Age-corrected risk of seizures by age 5 is 14% and increases to 75% at age 25 and beyond [3]. Cortical defects predispose patients to drug-resistant seizure disorders, with GMH accounting for 40% of such cases [1]. Persistent pharmacoresistant epilepsy in both children and adults is associated with cognitive decline, with memory being particularly impacted [6].

Non-contrast CT is commonly done as initial imaging in patients presenting with seizure disorder. In this case, an abnormal contour of the posterior lateral ventricles (figures 1a, 1b) was noted, prompting further imaging workup with MRI. Non enhancing periventricular nodularities that follow gray matter signal intensity on both T1 and T2 weighted images (figures 2a-2f) are the classic and diagnostic radiologic appearance of PVNH on MRI.

In this case, the patient developed memory impairment after many years of ongoing epilepsy. She continued to have breakthrough seizures despite multiple admissions and medication optimization. While surgical treatment, such as resection or ablation of the heterotropic area, may help prevent further seizure episodes, it would not reverse developmental or memory deficits [7]. With an earlier diagnosis of PVNH, the patient could have potentially avoided repeated seizure episodes and possibly prevented developmental and memory deficits. Therefore, timely imaging is critical in diagnosing PVNH and ultimately minimizing the degree of developmental and memory impairments.

Written informed patient consent for publication has been obtained.