Abstracts

Viral infections of the CNS are associated with a significantly increased risk for seizures and epileptogenesis. Up to 50% of adult-onset epilepsy cases in developing countries are associated with CNS infection. To our knowledge, no available animal model accurately reproduces the pathology of human encephalitis-induced epilepsy. We have established an animal model where infection of C57BL/6 (B6) mice with Theiler[apos]s murine encephalomyelitis virus (TMEV) leads to the development of seizures during the acute encephalomyelitis phase of infection. Stage 4 /5 seizures (Racine, Electroenceph. Clin. Neurophys. 32: 281-94, 1972) occur in approximately 50% the mice between 3-10 days post infection and appear to remit as the infection clears. The present study tested the hypothesis that seized mice have altered seizure thresholds post inoculation, which increases their risk for the development of spontaneous seizures., B6 mice were infected intracerebrally with the Daniel[apos]s strain of TMEV (TMEV-DA). Animals were monitored for the development of seizures and separated into two groups: seized versus non-seized. Two months after infection with 3 x 10⁵ PFU TMEV-DA, minimal clonic and maximal tonic hindlimb extension (THE) seizure thresholds of seized and non-seized mice were assessed by electroconvulsive seizure testing (EST). Additionally, the rate of corneal kindling acquisition (number of stimulations required to reach fully kindled state, i.e., 3 consecutive Stage 5 seizures) was assessed to determine whether TMEV inoculation leads to an increased rate of kindling., At two months post infection, seized mice had a significantly lower minimal clonic seizure threshold compared to the non-seized mice (seized CC[sub]50 [/sub]= 6.7 mA, non-seized CC[sub]50 [/sub]= 7.8 mA, p [lt] 0.01). In contrast, there was no significant difference in maximal THE seizure thresholds between the seized and non-seized mice (seized and non-seized CC[sub]50[/sub] = 13.5 mA, p [lt] 0.99). In a preliminary study to assess acquisition rate of corneal kindling, 8/ 8 seized mice displayed fully generalized Stage 5 seizures, versus 5/8 non-seized mice. Furthermore, seized mice had much shorter latencies to generalized seizures than non-seized mice., The results obtained in the present study demonstrate altered seizure susceptibility following recovery from seizures associated with TMEV- induced encephalitis. Furthermore, they suggest that these animals may be more susceptible to epileptogenesis following subsequent challenges. Although preliminary, these results further support this as a model of encephalitis- induced hyperexcitability., (Supported by Robert and Joyce Rice Epilepsy Fellowship (KAS); Max Abrams Memorial Fellowship from Epilepsy Foundation of America (KAS).)