Lissencephaly in Shih Tzu dogs

Abstract

Background: Lissencephaly is a brain malformation characterized by smooth and thickened cerebral surface, which may result in structural epilepsy. Lissencephaly is not common in veterinary medicine. Here, we characterize the first cases of lissencephaly in four Shih Tzu dogs, including clinical presentations and findings of magnetic resonance imaging of lissencephaly and several concomitant brain malformations. Case presentation: Early-onset acute signs of forebrain abnormalities were observed in all dogs, which were mainly cluster seizures and behavioral alterations. Based on neurological examination, the findings were consistent with symmetrical and bilateral forebrain lesions. Metabolic disorders and inflammatory diseases were excluded. Magnetic resonance imaging for three dogs showed diffuse neocortical agyria and thickened gray matter while one dog had mixed agyria and pachygyria. Other features, such as internal hydrocephalus, supracollicular fluid accumulation, and corpus callosum hypoplasia, were detected concomitantly. Antiepileptic drugs effectively controlled cluster seizures, however, sporadic isolated seizures and signs of forebrain abnormalities, such as behavioral alterations, central blindness, and strabismus persisted. Conclusions: Lissencephaly should be considered an important differential diagnosis in Shih Tzu dogs presenting with early-onset signs of forebrain abnormalities, including cluster seizures and behavioral alterations. Magnetic resonance imaging was appropriate for ante-mortem diagnosis of lissencephaly and associated cerebral anomalies.

Malformation of the Cortical Development Associated with Severe Clusters of Epileptic Seizures

“…In humans, type II lissencephaly results from the overmigration of neural cells beyond the external glial limitans, whilst type I is linked to a primitive neuronal migration failure to reach the cortical plate, typically seen in dogs, such as Lhasa Apsos [ 7 , 8 ] and others [ 9 , 10 , 11 , 12 ].…”

“…Only a few reports of lissencephaly are reported in cats [ 13 , 14 ] and although many genetic mutations are recognized for human lissencephaly [ 25 , 26 , 27 ], genetic mutations have been suspected in dogs but not yet described [ 12 ]. Non-genetic causes, such as hypoxia and hypoperfusion, an intrauterine viral infection and metabolic disorders, are reported instead [ 28 ].…”

“…Epileptic seizures have been usually recorded in young affected animals and they seem to be responsive to antiepileptic drugs, in most cases [ 9 , 10 , 11 , 12 , 13 , 14 ]. The cat in our study seemed to have intractable epilepsy, as documented in humans.…”

“…Other clinical signs reported, both in humans and in veterinary patients, are motor disability, neuro-ophtalmological abnormalities, and behavioral changes, including difficulty learning. In dogs and cats, aggressiveness and vocalizations are also observed [ 12 ].…”

“…Reports of focal cortical dysplasia cases showing difficult to treat seizures, included a Pekingese dog with an associated necrotizing meningoenchephalitis [ 3 ], a Shi-Tzu with a concurrent porencephaly [ 4 ], a Golden Retriever with bilateral temporal cortical lesions [ 5 ], and a mixed breed dog with an associated granulomatous meningoenchepalitis [ 6 ]. Lissencephaly has been described as associated with epileptic seizure activity in few cases, that included four Lasha Apsos [ 7 , 8 ], a Pekingese [ 9 ], a mixed breed dog [ 10 ], an Australian Kelpie [ 11 ], a Shi-Tzu [ 12 ], a Wire-haired Fox Terrier [ 13 ] an Irish Setter [ 13 ], a domestic cat [ 14 ], and two litters of Korat cats [ 13 ]. Here we describe the clinical and neuropathological features of three cases of young animals with a MCD, affected with severe clusters of epileptic seizures, despite the starting of antiepileptic drugs (AEDs).…”