Vague protrusions of cortical tissues called verrucous dysplasia can be seen in some areas. Heterotopic neurons are scattered in the white matter. In the cerebrum of fetal cases, the glia limitans formed by astrocytic endfeet is

disrupted, and varying degrees of glioneuronal tissues overmigrate through the defects depending on the severity of the defects. The verrucous dysplasia in post-natal cases resembles an over-migrated lesion observed in fetal cases (9). The cerebellum and brainstem are also affected from fetal to adult cases. The cerebellar cortex is dysplastic, usually focal in the dorsal part of the hemisphere. In the brainstem, heterotopic glioneuronal tissues are observed. The pyramidal tract Inhibitors,research,lifescience,medical and brainstem nuclei are abnormal in some cases (10). The spinal cord generally exhibits a normal configuration, but focal Inhibitors,research,lifescience,medical disruptions

of the glia limitans are found in severe cases. The glia limitans is formed by closely apposed astrocytic endfeet. Normally, the structure is detected as a find more linear contour of the astrocytic cell membrane and a linear double layer, lamina lucida and lamina densa, of the basement membrane, by electron microscopy. In FCMD cases, both the basement membrane and astrocytic cell membrane show abnormal configurations (9). Inhibitors,research,lifescience,medical Even in areas where disruptions are not detected by light microscopy, the three-layered Inhibitors,research,lifescience,medical structure of the cell membrane and basement membrane are discontinuously ambiguous, and minute defects less than several µm in size can be seen. Morphological findings suggest that major

malformative lesions such as cortical dysplasia are caused by the abnormal glia limitans due to an impairment of astrocytes. This hypothesis is consistent with the observations in embryos of fukutin-deficient chimeric mice (11). The glia limitans is disrupted with the reduction of glycosylated α-DG, but neither neuronal migration nor extension of radial glial fibers is affected in these chimeric mice (11). However, an impairment of immature neurons could be speculated from some minor findings Inhibitors,research,lifescience,medical observed in FCMD cases, such as heterotopic neurons in the cerebral white matter, which may indicate neuronal migration arrest (9). Astrocytes and neurons can be involved in the CNS malformation of FCMD, but the magnitude of involvement is probably more in astrocytes (Fig. ​(Fig.2).2). In addition to malformative lesions, there are some other lesions such as corpora Metalloexopeptidase amylacea and neurofibrillay tangles in post-natal FCMD, especially in patients surviving for a long time. These structures can generally be seen in normal aged people, but are exceptional in children and young adults. The aging process seems to be accelerated in FCMD. To consider the genesis of these structures, both primary and secondary events should be borne in mind, since astrocytes and neurons are closely related to each other.