title: Muscle-eye-brain disease: a neuropathological study.
abstract: A combination of congenital central nervous, ocular and muscular abnormalities is characteristic of muscle-eye-brain disease (MEB), of Fukuyama congenital muscular dystrophy (FCMD), and of Walker-Warburg syndrome (WWS). The nosological relationship of these inherited malformative disorders is still unestablished, although the genetic locus for FCMD has been excluded in MEB. We present the first postmortem neuropathological study of MEB based on 2 male patients. Apart from sharply limited occipital agyric areas, their brains showed coarse gyri with an abnormally nodular surface ("cobblestone cortex"). Both the cerebral and cerebellar cortices showed a total disorganization without horizontal lamination. The haphazardly oriented cortical neurons formed irregular clusters or islands, separated by gliovascular strands extending from the pia. The ocular abnormalities included a pronounced glial preretinal membrane. Although MEB shares the cobblestone cortex-type malformation with FCMD and WWS, the cerebral and ocular manifestations are less severe than in WWS. Furthermore, a consistently weak staining for laminin alpha2 chain (merosin) was found in muscle biopsy specimens from 4 MEB patients, while normal immunoreactivity was observed for the laminin beta2 chain, reported to be severely deficient in WWS. These findings support nosological independence of MEB.
authors.affiliation: Department of Pathology, University of Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Haltia
authors.forename: I
authors.initials: I
authors.lastname: Leivo
authors.forename: H
authors.initials: H
authors.lastname: Somer
authors.forename: H
authors.initials: H
authors.lastname: Pihko
authors.forename: A
authors.initials: A
authors.lastname: Paetau
authors.forename: T
authors.initials: T
authors.lastname: Kivelä
authors.forename: A
authors.initials: A
authors.lastname: Tarkkanen
authors.forename: F
authors.initials: F
authors.lastname: Tomé
authors.forename: E
authors.initials: E
authors.lastname: Engvall
authors.forename: P
authors.initials: P
authors.lastname: Santavuori
mesh_terms: D000328:Adult; D001927:Brain Diseases / Q000473:pathology*; D002648:Child; D005128:Eye Diseases / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009133:Muscular Atrophy / Q000473:pathology*