Lissencephaly is a rare developmental defect characterized by a small, smooth-appearing cerebrum with rudimentary or no gyri (agyria) or sulci present and derangement of cells of the cerebral cortex. This anomaly has been reported in Lhasa Apso dogs, in several breeds of dogs with cerebellar hypoplasia and dysplasia, including the Wire-Haired Fox Terrier, Irish Setter, and Samoyed breeds. Lissencephaly results from disturbance of neuronal migration and proliferation during development. The condition involves only the neocortex, with the hippocampal and olfactory lobes being normal. The neocortex is thicker than normal (pachygyria) and contains scattered heterotopic white matter bundles, especially in the thin superficial molecular layer and in the 4th cortical layer. Randomly arranged neurons may be seen in the deeper cortical layers, suggesting arrested migration. In affected Lhasa apso dogs in which the cerebellum was grossly normal, changes were also observed in the flocculonodular lobe of the cerebellum that were characterized by marked heterotopic changes in several folia in which Purkinje cells were irregularly dispersed within the granular layer, the molecular layer was hypercellular and nests of heterotopic glial cells were in the roof nuclei.
Clinical signs usually are detected in the first year of life and are characterized by erratic behavior patterns, including episodic aggression, growling at imaginary objects, confusion, depression, hyperactivity, visual deficits, and seizures. Behavior alterations, including self-mutilation, also occur in cats. Gait and posture are usually normal but slight hypermetria may be present when running. Postural reactions tend to be sluggish but normal, although mild proprioceptive deficits have been observed. Spinal reflexes are normal. Bilateral menace deficit may be the only deficit in cranial nerve testing. The observation that neurological abnormalities were mild or delayed in onset after birth suggests the dog is less dependent on the cerebral cortex for sensorimotor function than is man. Abnormal wave tracings are detected electroencephalographically. Neuroimaging studies in animals have demonstrated a smooth cerebral brain surface, as in humans, along with a broad cortex in relation to a narrow white matter layer.
Prognosis is guarded. Treatment is symptomatic. Seizures may be controlled with anticonvulsant therapy. Neuronal heterotopia in Lagotto Romagnolo dogs is a recently reported disorder that remains to be classified, although it may be within the spectrum of lissencephalic malformations. Clinical signs began around 7 weeks of age and included tetraparesis with hypermetria, intention tremor, and poor conscious proprioception. Mentation and spinal reflexes are normal. Affected dogs have facial dysmorphism characterized by inferior prognathia and an atypical brachycephalic skull. With time, cerebellar signs progressively improve to apparent clinical normality by 1 year of age. Gross examination of the brain is normal (including normal gyration). Microscopic lesions are characterized by diffuse abnormal neuronal migration and maturation in the cerebral cortex, cerebellum and pons. The abnormal neurons appear monomorphic with vesicular nuclei and basophilic cytoplasm. Similar cells are also present in hemispheric and cerebellar white matter.
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