Polymicrogyria: pathology, fetal origins and mechanisms.

Waney Squier,Anna Jansen

doi:10.1186/s40478-014-0080-3

Abstract

Polymicrogyria (PMG) is a complex cortical malformation which has so far defied any mechanistic or genetic explanation. Adopting a broad definition of an abnormally folded or festooned cerebral cortical neuronal ribbon, this review addresses the literature on PMG and the mechanisms of its development, as derived from the neuropathological study of many cases of human PMG, a large proportion in fetal life. This reveals the several processes which appear to be involved in the early stages of formation of polymicrogyric cortex. The most consistent feature of developing PMG is disruption of the brain surface with pial defects, over-migration of cells, thickening and reduplication of the pial collagen layers and increased leptomeningeal vascularity. Evidence from animal models is consistent with our observations and supports the notion that disturbance in the formation of the leptomeninges or loss of their normal signalling functions are potent contributors to cortical malformation. Other mechanisms which may lead to PMG include premature folding of the neuronal band, abnormal fusion of adjacent gyri and laminar necrosis of the developing cortex. The observation of PMG in association with other and better understood forms of brain malformation, such as cobblestone cortex, suggests mechanistic pathways for some forms of PMG. The role of altered physical properties of the thickened leptomeninges in exerting mechanical constraints on the developing cortex is also considered.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-014-0080-3) contains supplementary material, which is available to authorized users.

Highlights

The name polymicrogyria (PMG) implies cortical gyri which are too many and too small, but the pathology, imaging and clinical manifestations of PMG are heterogeneous [1]
We suggest that fusion may be defined only when there is additional evidence of trapped remnants of the leptomeninges between the folds of the festooned neuronal band
Disruption of the pial basement membrane is identified in the majority of cases of PMG of all causes [Jansen A, Robitaille Y, Honavar M, Figure 6 Undulating band heterotopia; fetus of 23 weeks. a: A slice of the fixed brain shows large ventricle and a thin cortical mantle in which the undulating cortical neuronal band can just be made out. b: H&E stained section shows a festooned band of neurones sweeping from the brain surface (L) to the ventricular zone where germinal matrix (GM) separates it from the ventricular wall

Summary

Introduction

The name polymicrogyria (PMG) implies cortical gyri which are too many and too small, but the pathology, imaging and clinical manifestations of PMG are heterogeneous [1]. Mechanisms of PMG Taking a broadly inclusive approach, and accepting as PMG any case where one or more cortical layers shows abnormal folding or festooning, the most common pathology is of disruption of the cortical surface and its interaction with the leptomeninges. Abnormal leptomeninges are seen overlying human PMG [22], and leptomeningeal thickening with vascular proliferation, pial defects and over-migration, are seen in over 80% of cases of PMG, both of genetic and destructive origin [Jansen A, Robitaille Y, Honavar M, Mullatti N, Leventer RJ, Andermann E, Andermann F, Squier W (forthcoming) The histopathology of polymicrogyria: a series of 71 brain autopsy studies] (Figure 3).

Results

Conclusion