An unusual type of primary cerebral hemihypotrophy with signs of dysfunctional neuronal migration.

We describe the neuropathological features of a complex brain malformation characterized by cerebral hemihypotrophy with ipsilateral lissencephaly, periventricular nodular heterotopia and macrogyria. The contralateral hemisphere showed only slight alterations of the gyral pattern and a limited periventricular gray matter heterotopia. The clinical picture of the patient, who died at the age of 15 years, consisted of severe oligophrenia, intractable seizures and left hemiparesis. We discuss the nosological status of this neuronal migration disorder of apparently unknown origin.

Muscular dystrophy, mental retardation and cardiomyopathy not associated with dystrophin deficiency.

We report on a male patient aged 38, affected by a syndrome whose characteristic features include onset in early childhood, slow progression, diffuse muscle weakness, mental retardation and cardiomyopathy. Muscle biopsy showed myopathic changes compatible with muscular dystrophy. However, immunostaining for dystrophin as well as 50 and 43 kDa dystrophin-associated glycoproteins (DAGs) was normal. Genetic analysis suggested that direct involvement of the dystrophin gene was highly unlikely. No other family members were affected. Although the clinical picture is reminiscent of Duchenne/Becker muscular dystrophy, the immunologically and genetically documented lack of dystrophin involvement suggests that this particular syndrome is as yet undescribed.

Localization of merosin in the normal human brain: implications for congenital muscular dystrophy with merosin deficiency.

A particular form of congenital muscular dystrophy with merosin deficiency has recently been described. Magnetic resonance imaging has shown that affected children show brain abnormalities. We investigate the localization of merosin in the normal human brain by immunohistochemistry. Other organs, such as the kidney, lung and liver, were also included in this study. We show that in the normal central nervous system merosin is localized in the basement membrane of blood vessels. No expression of merosin was found at the level of the liver and lungs, whereas the glomerular mesangial matrix of the kidney was intensely positive. These results suggest that merosin deficiency in the basement membrane of blood vessels in the central nervous system could play an important role in the physiopathology of brain abnormalities found in children affected by the congenital muscular dystrophy associated with merosin deficiency. Furthermore, the potential absence of merosin in the glomerular mesangial matrix of the kidney suggests a multi-system involvement.

Ultrastructure and immunoreactivity of dystrophic axons indicate a different pathogenesis of Hallervorden-Spatz disease and infantile neuroaxonal dystrophy.

An immunohistochemical and ultrastructural analysis of dystrophic axons (DAs) in the brain and peripheral nerve of a patient with familial infantile neuroaxonal dystrophy (INAD) and in the brain of a patient with familial Hallervorden-Spatz Disease (HSD) revealed prevalent membrano-tubular or granulo-vesicular profiles with a graded pattern of evolution in INAD, while dense bodies, vesicles and amorphous material were present in HSD. DAs immunoreactivity with tai-protein and 200 kDa-neurofilament antibodies was stronger in HSD than in INAD. In both cases immunohistochemistry was positive for ubiquitin and negative for beta-tubulin and beta-amyloid. Distinct ultrastructural features and immunoreactivity pattern of cytoskeletal components suggest different pathogenetic mechanisms.