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Hereditary lissencephaly and cerebellar hypoplasia in Churra lambs.

Pérez V, Suárez-Vega A, Fuertes M, Benavides J, Delgado L, Ferreras MC, Arranz JJ - BMC Vet. Res. (2013)

Bottom Line: Lissencephaly is a rare developmental brain disorder in veterinary and human medicine associated with defects in neuronal migration leading to a characteristic marked reduction or absence of the convolutional pattern of the cerebral hemispheres.The hippocampus was also markedly disorganised and the number and size of lobules were reduced in the cerebellum.Histopathological features observed in the cerebral cortex and hippocampus are consistent with a possible failure in neuronal migration during brain development.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departamento de Sanidad Animal (Anatomía Patológica), Instituto de Ganadería de Montaña (CSIC-ULE), Facultad de Veterinaria, Universidad de León, Campus de Vegazana s/n, León 24071, Spain. vperp@unileon.es

ABSTRACT

Background: Lissencephaly is a rare developmental brain disorder in veterinary and human medicine associated with defects in neuronal migration leading to a characteristic marked reduction or absence of the convolutional pattern of the cerebral hemispheres. In many human cases the disease has a genetic basis. In sheep, brain malformations, mainly cerebellar hypoplasia and forms of hydrocephalus, are frequently due to in utero viral infections. Although breed-related malformations of the brain have been described in sheep, breed-related lissencephaly has not been previously recorded in a peer reviewed publication.

Results: Here we report neuropathological findings in 42 newborn lambs from a pure Churra breed flock, with clinical signs of weakness, inability to walk, difficulty in sucking and muscular rigidity observed immediately after birth. All the lambs showed near-total agyria with only a rudimentary formation of few sulci and gyri, and a severe cerebellar hypoplasia. On coronal section, the cerebral grey matter was markedly thicker than that of age-matched unaffected lambs and the ventricular system was moderately dilated. Histologically, the normal layers of the cerebral cortex were disorganized and, using an immunohistochemical technique against neurofilaments, three layers were identified instead of the six present in normal brains. The hippocampus was also markedly disorganised and the number and size of lobules were reduced in the cerebellum. Heterotopic neurons were present in different areas of the white matter. The remainder of the brain structures appeared normal. The pathological features reported are consistent with the type LCH-b (lissencephaly with cerebellar hypoplasia group b) defined in human medicine. No involvement of pestivirus or bluetongue virus was detected by immunohistochemistry. An analysis of pedigree data was consistent with a monogenic autosomal recessive pattern inheritance.

Conclusions: The study describes the clinical and pathological findings of lissencephaly with cerebellar hypoplasia in Churra lambs for which an autosomal recessive inheritance was the most likely cause. Histopathological features observed in the cerebral cortex and hippocampus are consistent with a possible failure in neuronal migration during brain development. This report suggests that lissencephaly should be considered in the differential diagnosis of congenital neurological disease in newborn lambs showing weakness, inability to walk and difficulty sucking.

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Coronal section (fixed tissue) of normal (a) and lissencephalic (b) brains. A marked increase of thickness of the cerebral cortex is seen in the affected lamb (b). Note that the corpus callosum is normally developed.
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Figure 2: Coronal section (fixed tissue) of normal (a) and lissencephalic (b) brains. A marked increase of thickness of the cerebral cortex is seen in the affected lamb (b). Note that the corpus callosum is normally developed.

Mentions: On coronal sections of the brain, in addition to agyria, a marked pachygyria was observed in all the regions of the cerebral cortex. It was characterized by the presence of a thick grey matter layer, with a depth of 9 mm in average, with broad gyri and very shallow sulci, when present (Figure 2). The white matter was narrow, leading to an inverted grey to white matter ratio. The cerebral grey matter-white matter interface was linear and well defined with rare interdigitations. Macroscopically, the remaining areas of the forebrain (corpus callosum, cingulate gyrus (Figure 2) and hippocampus) and brain stem appeared normally developed. The posterior part of the lateral ventricles was moderately dilated in 13 lambs but no physical obstruction of CSF flow was detected. There was a substantial reduction in the depth of the cerebellar cortex and the folia were markedly decreased in size and number.


Hereditary lissencephaly and cerebellar hypoplasia in Churra lambs.

Pérez V, Suárez-Vega A, Fuertes M, Benavides J, Delgado L, Ferreras MC, Arranz JJ - BMC Vet. Res. (2013)

Coronal section (fixed tissue) of normal (a) and lissencephalic (b) brains. A marked increase of thickness of the cerebral cortex is seen in the affected lamb (b). Note that the corpus callosum is normally developed.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750509&req=5

Figure 2: Coronal section (fixed tissue) of normal (a) and lissencephalic (b) brains. A marked increase of thickness of the cerebral cortex is seen in the affected lamb (b). Note that the corpus callosum is normally developed.
Mentions: On coronal sections of the brain, in addition to agyria, a marked pachygyria was observed in all the regions of the cerebral cortex. It was characterized by the presence of a thick grey matter layer, with a depth of 9 mm in average, with broad gyri and very shallow sulci, when present (Figure 2). The white matter was narrow, leading to an inverted grey to white matter ratio. The cerebral grey matter-white matter interface was linear and well defined with rare interdigitations. Macroscopically, the remaining areas of the forebrain (corpus callosum, cingulate gyrus (Figure 2) and hippocampus) and brain stem appeared normally developed. The posterior part of the lateral ventricles was moderately dilated in 13 lambs but no physical obstruction of CSF flow was detected. There was a substantial reduction in the depth of the cerebellar cortex and the folia were markedly decreased in size and number.

Bottom Line: Lissencephaly is a rare developmental brain disorder in veterinary and human medicine associated with defects in neuronal migration leading to a characteristic marked reduction or absence of the convolutional pattern of the cerebral hemispheres.The hippocampus was also markedly disorganised and the number and size of lobules were reduced in the cerebellum.Histopathological features observed in the cerebral cortex and hippocampus are consistent with a possible failure in neuronal migration during brain development.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departamento de Sanidad Animal (Anatomía Patológica), Instituto de Ganadería de Montaña (CSIC-ULE), Facultad de Veterinaria, Universidad de León, Campus de Vegazana s/n, León 24071, Spain. vperp@unileon.es

ABSTRACT

Background: Lissencephaly is a rare developmental brain disorder in veterinary and human medicine associated with defects in neuronal migration leading to a characteristic marked reduction or absence of the convolutional pattern of the cerebral hemispheres. In many human cases the disease has a genetic basis. In sheep, brain malformations, mainly cerebellar hypoplasia and forms of hydrocephalus, are frequently due to in utero viral infections. Although breed-related malformations of the brain have been described in sheep, breed-related lissencephaly has not been previously recorded in a peer reviewed publication.

Results: Here we report neuropathological findings in 42 newborn lambs from a pure Churra breed flock, with clinical signs of weakness, inability to walk, difficulty in sucking and muscular rigidity observed immediately after birth. All the lambs showed near-total agyria with only a rudimentary formation of few sulci and gyri, and a severe cerebellar hypoplasia. On coronal section, the cerebral grey matter was markedly thicker than that of age-matched unaffected lambs and the ventricular system was moderately dilated. Histologically, the normal layers of the cerebral cortex were disorganized and, using an immunohistochemical technique against neurofilaments, three layers were identified instead of the six present in normal brains. The hippocampus was also markedly disorganised and the number and size of lobules were reduced in the cerebellum. Heterotopic neurons were present in different areas of the white matter. The remainder of the brain structures appeared normal. The pathological features reported are consistent with the type LCH-b (lissencephaly with cerebellar hypoplasia group b) defined in human medicine. No involvement of pestivirus or bluetongue virus was detected by immunohistochemistry. An analysis of pedigree data was consistent with a monogenic autosomal recessive pattern inheritance.

Conclusions: The study describes the clinical and pathological findings of lissencephaly with cerebellar hypoplasia in Churra lambs for which an autosomal recessive inheritance was the most likely cause. Histopathological features observed in the cerebral cortex and hippocampus are consistent with a possible failure in neuronal migration during brain development. This report suggests that lissencephaly should be considered in the differential diagnosis of congenital neurological disease in newborn lambs showing weakness, inability to walk and difficulty sucking.

Show MeSH
Related in: MedlinePlus