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Rapid Cessation of Focally Induced Generalized Seizures in Rats Through Microinfusion of Lidocaine Hydrochloride into the Focus
Author(s) -
Smith Douglas C.,
Krahl Scott E.,
Browning Ronald A.,
Barea Edwin J.
Publication year - 1993
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.1993.tb02374.x
Subject(s) - epilepsy , anesthesia , lidocaine , lidocaine hydrochloride , psychology , refractory (planetary science) , temporal lobe , medicine , neuroscience , physics , astrobiology
Summary: An experimental animal model of complex partial seizures which become secondarily generalized is produced by microinfusion of the GAB A antagonist bicuculline (BIC) into the deep prepiriform cortex (DPC) of rats. In the present study, we investigated the effects of microinfusion of the local anesthetic, lidocaine hydrochloride, directly into the BIC focus in the DPC and demonstrated that direct inactivation of the focus arrested a focal seizure that was in progress. A measure of the integrated amplitude of the electrocorticogram (ECoG) and behavioral seizure scores from unanesthetized and freely moving rats were used to address this question quantitatively. Microinfusion of 2% lidocaine hydrochloride into the BIC focus significantly reduced the integrated amplitude of the ECoG to levels that did not differ from baseline in either hemisphere (mean = 112% ipsilateral, 99% contralateral), whereas saline microinfusion had no effect Epilepsy is an important neurologic disorder which affects about two million people in the United States alone (Delgado‐Escueta et al., 1986). Although many persons with epilepsy have their seizures controlled with antiepileptic drugs (AEDs), an estimated 20% of patients continue to have seizures despite AED therapy (Rimmer and Richens, 1988; Porter and Pitlick, 1989). Furthermore, even for patients for whom AED therapy is effective, drug side effects can become a significant factor (Rasmussen, 1975). Patients with complex partial seizures (CPS) are often refractory to the available pharmacologic in terventions. Such seizures begin in a localized area, usually in the temporal lobe, and involve impairment of consciousness. CPS can also become sec (mean = 175% ipisilateral, 125% contralateral). Moreover, ECoG reductions after lidocaine were present assoon as the microinfusion was complete. Behaviorally, clonic seizure severity was assessed on a rating scale of 0–5. Lidocaine microinfusion significantly reduced the seizure scores to values not different from baseline during the first postinfusion measurement period (i.e., 30 s). Microinfusion of saline alone also significantly reduced behavioral seizure severity, although to a lesser degree and not as rapidly as lidocaine. This effect suggests the need for caution in interpretation and design of studies investigating the anticonvulsant effects of various pharmacologic agents when microinfusions are used.