Developmental aspects of type II lissencephaly

Abstract

We report neuropathological studies of five cases of type II lissencephaly from three fetuses and two infants. This comparative study allowed us to determine the developmental course of the cerebral lesions. Two distinct developmental events seem to generate this type of brain malformation: firstly, an early disturbance in cortex formation, which results both from a disorder of radial migration and a pial barrier disruption; secondly, a late perturbation of cerebral surface organization, resulting in fusion of the cerebral surface. All these features can be related to a primitive meningeal pathology, and more generally, to a neurocristopathy. Accordingly to our observations, this brain malformation appears during both migrational and post-migrational stages and may be considered more like a polymicrogyria than a lissencephaly.

Brain pathology of lissencephaly type 2 with an ISPD pathogenic variant

“…However, we consider this pathogenesis a less likely explanation for the observed ventral brainstem lesion, and the lack of haemosiderin deposition or calcification, which would support an encephaloclastic process, is noteworthy. Some of the other abnormalities seen in the present case, including the hypoplastic cerebellar vermis and small brainstem, have been previously described in the context of lissencephaly type 2 [8,9].…”

Developmental disorders of the midbrain and hindbrain

“…In Gpr56 deficient mice, glial processes extend through and granule cells migrate through the aforementioned gaps in the glia limitans into the subarachnoid space (Koirala et al, 2009). In human studies, the effects upon the MB-HB vary considerably (Aida et al, 1994; Gelot et al, 1995; van der Knaap et al, 1997; Barkovich, 1998; Clement et al, 2008), with some patients having normal cerebella and others having mild dysgenesis resulting in mild vermian hypoplasia with some alteration of foliation; of note, the severity of cortical dysgenesis is sometimes similar in the cerebrum and cerebellum but the involvement may be discrepant, suggesting that some gene products have different roles in the forebrain and HB. Moderately severe cerebellar dysgenesis consists of a significantly dysmorphic cortex containing cyst-like structures that contain mesenchymal tissue (Figures 3B–F) and are connected to the surface via spaces containing penetrating blood vessels (Takada and Nakamura, 1990).…”

Polymicrogyria: pathology, fetal origins and mechanisms

“…Friede’s definition of PMG included “large sinusoidal vessels marking the seams between adjacent fused gyri” [45]. However, large vessels may merely be a part of a field malformation and cannot in themselves be an indication of fusion; they are identified in cobblestone cortex where fusion is not a mechanism [11,46,47]. 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.…”

“…In recent years the distinction between cobblestone malformation and PMG has become blurred and focal PMG is frequently seen together with cobblestone lissencephaly [1,24,53,46,47]. The cobblestone malformation is the prototype of cortical overmigration into the leptomeninges in association with defects in the pial surface of the brain [11].…”