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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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Histological section of the cerebral cortex from a control (a) and lissencephalic (b) brain. Both sections were taken at the same magnification. Whereas in the control brain the whole cortex can be seen in the picture and organized in six layers (I to VI), in the lissencephalic brain only the most superficial part of the cortex is shown (aprox. 40% of the whole thickness), due to the thickening of this layer. A sparse-cellular layer underneath the piamater can be identified (*), whereas in the rest of the gray matter the neurons appear disorganized. H-E.
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Figure 3: Histological section of the cerebral cortex from a control (a) and lissencephalic (b) brain. Both sections were taken at the same magnification. Whereas in the control brain the whole cortex can be seen in the picture and organized in six layers (I to VI), in the lissencephalic brain only the most superficial part of the cortex is shown (aprox. 40% of the whole thickness), due to the thickening of this layer. A sparse-cellular layer underneath the piamater can be identified (*), whereas in the rest of the gray matter the neurons appear disorganized. H-E.

Mentions: Histopathological examination was carried out in samples from the cerebral cortex of the most severely affected area (temporo-parietal region) in all the animals. The sagittal sections of the cerebral cortex lacked the typical six-layered structure characteristic of this area, seen in the control lambs (Figure 3). Neither glial cells nor neurons were detected in the meningeal layers (Figure 3). In both HE and cresyl violet stained sections, beneath the pial surface, a cell-sparse layer containing neurons smaller than those present in the rest of the cortex and resembling morphologically the molecular or layer I of normal brains, was observed (Figure 3). Below this layer, a wide, more densely populated cellular layer was formed by neuronal bodies of different sizes, some of which had a pyramidal appearance (Figure 3). No laminar organisation or vertical linear array of neurones was identified within this wide layer. The narrow white matter layer was normally myelinated and contained heterotopic neuronal cell bodies.


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)

Histological section of the cerebral cortex from a control (a) and lissencephalic (b) brain. Both sections were taken at the same magnification. Whereas in the control brain the whole cortex can be seen in the picture and organized in six layers (I to VI), in the lissencephalic brain only the most superficial part of the cortex is shown (aprox. 40% of the whole thickness), due to the thickening of this layer. A sparse-cellular layer underneath the piamater can be identified (*), whereas in the rest of the gray matter the neurons appear disorganized. H-E.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Histological section of the cerebral cortex from a control (a) and lissencephalic (b) brain. Both sections were taken at the same magnification. Whereas in the control brain the whole cortex can be seen in the picture and organized in six layers (I to VI), in the lissencephalic brain only the most superficial part of the cortex is shown (aprox. 40% of the whole thickness), due to the thickening of this layer. A sparse-cellular layer underneath the piamater can be identified (*), whereas in the rest of the gray matter the neurons appear disorganized. H-E.
Mentions: Histopathological examination was carried out in samples from the cerebral cortex of the most severely affected area (temporo-parietal region) in all the animals. The sagittal sections of the cerebral cortex lacked the typical six-layered structure characteristic of this area, seen in the control lambs (Figure 3). Neither glial cells nor neurons were detected in the meningeal layers (Figure 3). In both HE and cresyl violet stained sections, beneath the pial surface, a cell-sparse layer containing neurons smaller than those present in the rest of the cortex and resembling morphologically the molecular or layer I of normal brains, was observed (Figure 3). Below this layer, a wide, more densely populated cellular layer was formed by neuronal bodies of different sizes, some of which had a pyramidal appearance (Figure 3). No laminar organisation or vertical linear array of neurones was identified within this wide layer. The narrow white matter layer was normally myelinated and contained heterotopic neuronal cell bodies.

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