Aberrant neuronal migration in the brainstem of Fukuyama-type congenital muscular dystrophy

Abstract

We examined the brainstem of 10 patients with Fukuyama-type congenital muscular dystrophy (FCMD). In the midbrain we noted leptomeningeal glioneuronal heterotopia (LGH) (n = 9) and intramural "micropolygyria" (n = 1) in the tectum, as well as tyrosine hydroxylase-positive ectopic neurons/fibers ventral to the cerebral peduncle (n = 3). In the pontomedullary region, glial fibrillary acidic protein-positive subpial tissue intermingled with neurons and myelinated fibers was present in the ventrolateral pontine surface in all cases and extended over the lateral surface of the upper medulla oblongata. This subpial gliotic band was often contiguous with the extra-pial LGH tissues. The gliotic band protruded from the ventrolateral pontine surface in 3 cases and appeared to include ectopic neurons of the pontine nucleus. Disarrangement of the arcuate nuclei (n = 3) was also noted in the medulla oblongata. We hypothesize that both the radial and tangential neuronal migration systems are disrupted in the FCMD brainstem in addition to altered neuronal migration in the cerebral and cerebellar cortex. Fukutin protein may play a part in the morphogenesis of certain neuronal structures in the brainstem and the dysplastic structure termed "aberrant pyramidal tract" in previous reports may essentially result from an ectopic migration of pontine nucleus neurons.