MRI of the brain in muscle-eye-brain (MEB) disease

Abstract

Muscle-eye-brain (MEB) disease belongs to the spectrum of rare congenital syndromes with migration disorders of the brain and muscular dystrophy, along with the Walker-Warburg syndrome and Fukuyama congenital muscular dystrophy. Their features overlap, and differential diagnosis presents some difficulties. We examined the brain of 10 patients with MEB using high-field MRI and found a uniform pattern consisting of a pachygyria-type cortical migration disorder, septal and corpus callosum defects and severe hypoplasia of the pons in 7 of them.

Midbrain–hindbrain involvement in lissencephalies

“…3 The pattern of cortical brain involvement in cLIS is typically different from what is seen in "cobblestone malformations" associated with defects in O-glycosylation of ␣-dystroglycan. [7][8][9][10][11]16 The agyria/pachygyria complex seen in cLIS and vLIS is mainly the result of incomplete migration of neurons, 2-6 whereas CBSC is primarily a result of overmigration of neurons, many of which pass through gaps in the glial limiting membrane. [7][8][9][10][11] Involvement of the cerebellum and the pons has been described in cLISs that were classified according to mutation analysis.…”

“…[7][8][9][10][11]16 The agyria/pachygyria complex seen in cLIS and vLIS is mainly the result of incomplete migration of neurons, 2-6 whereas CBSC is primarily a result of overmigration of neurons, many of which pass through gaps in the glial limiting membrane. [7][8][9][10][11] Involvement of the cerebellum and the pons has been described in cLISs that were classified according to mutation analysis. Some authors found hypoplasia of the cerebellar vermis to be more common in patients with DCX mutations, whereas both DCX and LIS1 sometimes had normal cerebellum and brainstem.…”

“…3 Numerous genes have been identified in association with the CBSC (also called dystroglycanopathies). [7][8][9][10][11][12] Most affected patients have symptoms of congenital muscular dystrophies (CMDs) with CNS involvement. Among these disorders, three phenotypes are well defined: Fukuyama congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), and muscle-eye-brain disease (MEB).…”

“…Among these disorders, three phenotypes are well defined: Fukuyama congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), and muscle-eye-brain disease (MEB). 1,[7][8][9][10][11] These phenotypes have been associated with mutations of multiple genes involved in O-glycosylation of ␣-dystroglycan, including FCMD, FKRP, POMT1, POMT2, LARGE, and POMGnT1. 12 The aim of our study was to determine the involvement of the midbrain and hindbrain (MHB) in these disorders, and to determine whether a correlation exists between the cerebral malformation and the MHB characteristics as determined by MRI.…”

Muscle-eye-brain Disease and Drug-resistant Seizures: Unravelling the Phenotypic Heterogeneity of Congenital Muscular Dystrophies

“…The hallmark MRI findings in dystroglycanopathies include multiple irregular small cotical gyri, cobblestone lissencephaly, fused midbrain colliculi, pontine and vermian hypoplasia, dilated fourth ventricle, lateral cerebellar cysts (which are frequently observed in POMGnT1, and FKRP mutations and have recently been described in POMT2 and LARGE patients) with or without cerebellar polymicrogyria, patchy hypomyelination and callosal hypogenesis variably [2,[4][5][6]. MRI in Walker-Warburg syndrome shows much greater degree of abnormalities with complete absence of cerebral and cerebellar myelin, hydrocephalus and severe cobblestone lissencephaly [2,3].…”