A. C. Palmer

Temporal lobe epilepsy in a cat with a pyriform lobe oligodendroglioma and hippocampal necrosis

A 14-year-old male domestic shorthair cat presented with an acute onset of aggressive behaviour, fear and hypersalivation. Neurological examination revealed bilateral mydriasis and left-sided facial twitching and hemiparesis. Magnetic resonance imaging (MRI) showed moderate bilateral symmetrical T2-hyperintensity along the entire hippocampus and bilateral asymmetric T2-hyperintensity in the pyriform lobes. Marked bilateral contrast enhancement of the hippocampus was evident on post-contrast T1-weighted images. The partial complex seizures were refractory to medical treatment and the cat was euthanased 4 days after admission. The clinical and MRI findings were consistent with feline hippocampal necrosis (FHN). On histopathology, neuronal necrosis and astrocytosis were present in the hippocampi and pyriform lobes. In addition, an oligodendroglioma was detected in the right pyriform lobe. Contrary to previous reports of FHN in which no underlying cause could be identified, we believe that in this case the seizure focus arose from a neoplastic lesion within the right pyriform lobe. This unique case report represents the so-called ‘dual pathology’ of temporal lobe epilepsy in humans, in which an extrahippocampal lesion within the temporal lobe results in hippocampal sclerosis.

Ultrastructure of motor endplates in canine congenital myasthenia gravis.

Morphometric analysis was carried out on electron micrographs of motor endplates from three Jack Russell terriers affected with congenital myasthenia gravis (CMG) aged 10 weeks, 12 weeks and 22 weeks, respectively. Control endplates from age-matched pups and an adult Jack Russell were also examined. The results showed that postsynaptic membrane density was significantly increased in affected animals and secondary fold length was decreased. The ratio of postsynaptic to presynaptic membrane length was normal in the 10 and 12-week-old pups, but reduced in the 22-week-old CMG animal. These changes were unrelated to muscle fibre diameter and there was no evidence of a destructive process. It is suggested that the alteration in membrane folding pattern in this condition may be related to abnormal trophic influences during synaptogenesis.

A CHRNE frameshift mutation causes congenital myasthenic syndrome in young Jack Russell Terriers

Congenital myasthenic syndromes (CMSs) are a group of rare genetic disorders of the neuromuscular junction resulting in structural or functional causes of fatigable weakness that usually begins early in life. Mutations in pre-synaptic, synaptic and post-synaptic proteins have been demonstrated in human cases, with more than half involving aberrations in nicotinic acetylcholine receptor (AChR) subunits. CMS was first recognized in dogs in 1974 as an autosomal recessive trait in Jack Russell Terriers (JRTs). A deficiency of junctional AChRs was demonstrated. Here we characterize a CMS in 2 contemporary cases of JRT littermates with classic clinical and electromyographic findings, and immunochemical confirmation of an approximately 90% reduction in AChR protein content. Loci encoding the 5 AChR subunits were evaluated using microsatellite markers, and CHRNB1 and CHRNE were identified as candidate genes. Sequences of the splice sites and exons of both genes revealed a single base insertion in exon 7 of CHRNE that predicts a frameshift mutation and a premature stop codon. We further demonstrated this pathogenic mutation in CHRNE in archival tissues from unrelated JRTs studied 34 years ago.