Polymicrogyria-associated epilepsy: a multicenter phenotypic study from the Epilepsy Phenome/Genome Project

Abstract

Purpose: Polymicrogyria (PMG) is an epileptogenic malformation of cortical development. We describe the clinical epilepsy and imaging features of a large cohort with PMG-related epilepsy.

Methods: Participants were recruited through the Epilepsy Phenome/Genome Project, a multicenter collaborative effort to collect detailed phenotypic data on individuals with epilepsy. We reviewed phenotypic data from participants with epilepsy and PMG.

Key findings: We identified 87 participants, 43 female and 44 male, with PMG and epilepsy. Median age of seizure onset was 3 years (range <1 month to 37 years). Most presented with focal epilepsy (87.4%), some in combination with seizures generalized from onset (23.0%). Focal seizures with dyscognitive features were most common (54.3%). Of those presenting with generalized seizure types, infantile spasms were most prevalent (45.2%). The most common topographic pattern was perisylvian PMG (77.0%), of which the majority was bilateral (56.7%). Generalized PMG presented with an earlier age of seizure onset (median age of 8 months) and an increased prevalence of developmental delay prior to seizure onset (57.1%). Of the unilateral, and asymmetric bilateral groups where PMG was more involved in one hemisphere, the majority (71.4%) of participants had seizures that lateralized to the same hemisphere as the PMG or the hemisphere with greater involvement.

Significance: Participants with PMG had both focal and generalized onset of seizures. Our data confirm the involvement of known topographic patterns of PMG and suggest that more extensive distributions of PMG present with an earlier age of seizure onset and increased prevalence of developmental delay prior to seizure onset.

Keywords: Epilepsy; Epilepsy Phenome/Genome Project; Perisylvian; Polymicrogyria.

Figure. Polymicrogyria—focal, bilateral, and generalized

We present representative images from the MRIs of three cases with PMG. First, sagittal T1-weighted (A) and axial T2-weighted (B) images from an 18-year-old young woman with unilateral right-sided PMG involving the perisylvian region are shown. Epilepsy began at 18 years with focal seizures with dyscognitive features. There had been no history of developmental delay prior to seizure onset. Sagittal (C) and axial (D) images from a 5-year-old male with bilateral perisylvian PMG. Extensive involvement of the frontal lobes can be seen in the axial image (D), and bilateral enlargement of ventricles is also present. Seizures presented at 1 year of age with focal seizures with dyscognitive features and secondary generalization. The participant had developmental delay prior to seizure onset. Finally, sagittal (E) and axial (F) images from an 18-month-old male illustrate generalized PMG. Ventricular enlargement and hypoplastic brainstem is also noted. Focal seizures with secondary generalization seizures presented at 1 month of age in the setting of severe chronic static encephalopathy.