Clinical and imaging heterogeneity of polymicrogyria: a study of 328 patients

Abstract

Polymicrogyria is one of the most common malformations of cortical development and is associated with a variety of clinical sequelae including epilepsy, intellectual disability, motor dysfunction and speech disturbance. It has heterogeneous clinical manifestations and imaging patterns, yet large cohort data defining the clinical and imaging spectrum and the relative frequencies of each subtype are lacking. The aims of this study were to determine the types and relative frequencies of different polymicrogyria patterns, define the spectrum of their clinical and imaging features and assess for clinical/imaging correlations. We studied the imaging features of 328 patients referred from six centres, with detailed clinical data available for 183 patients. The ascertainment base was wide, including referral from paediatricians, geneticists and neurologists. The main patterns of polymicrogyria were perisylvian (61%), generalized (13%), frontal (5%) and parasagittal parieto-occipital (3%), and in 11% there was associated periventricular grey matter heterotopia. Each of the above patterns was further divided into subtypes based on distinguishing imaging characteristics. The remaining 7% were comprised of a number of rare patterns, many not described previously. The most common clinical sequelae were epileptic seizures (78%), global developmental delay (70%), spasticity (51%) and microcephaly (50%). Many patients presented with neurological or developmental abnormalities prior to the onset of epilepsy. Patients with more extensive patterns of polymicrogyria presented at an earlier age and with more severe sequelae than those with restricted or unilateral forms. The median age at presentation for the entire cohort was 4 months with 38% presenting in either the antenatal or neonatal periods. There were no significant differences between the prevalence of epilepsy for each polymicrogyria pattern, however patients with generalized and bilateral forms had a lower age at seizure onset. There was significant skewing towards males with a ratio of 3:2. This study expands our understanding of the spectrum of clinical and imaging features of polymicrogyria. Progression from describing imaging patterns to defining anatomoclinical syndromes will improve the accuracy of prognostic counselling and will aid identification of the aetiologies of polymicrogyria, including genetic causes.

D-Bifunctional Protein Deficiency: A Cause of Neonatal Onset Seizures and Hypotonia

“…These findings are present in other D-bifunctional protein deficiency reported cases and resemble those of Zellweger syndrome [9][10] . Recent data indicate that this overlap with Zellweger syndrome may not be due to deficiencies of substrate degradation by the D-bifunctional protein enzyme, but rather to other secondary peroxisomal deficiencies that occur as a consequence of the DBP defect 6,7 .…”

Abnormal development of the human cerebral cortex

“…Different patterns of PMG have been described, including a number of bilateral PMG syndromes (Leventer et al 2010). PMG is a highly heterogeneous malformation, resulting from both genetic and destructive events, including infection, hypoxia-ischaemia, and trauma (Jansen & Andermann, 2005).…”

The Prevalence of Malformations of Cortical Development in a Pediatric Hereditary Hemorrhagic Telangiectasia Population

“…20 The genetic basis for HHT is abnormal vascular development related to various mutations in the transcription growth factor-␤ pathway. Three of our cases provide circumstantial support of abnormal vascular development being associated with PMG by virtue of spatial proximity.…”