A Comparison of Midazolam and Thiopental Sodium in the Management of Refractory Status Epilepticus

BACKGROUND: Refractory status epilepticus (RSE) requires urgent and effective treatment. Recently, midazolam was suggested as a useful drug in controlling RSE. In order to evaluate the effectiveness and adverse effects of midazolam, we compared midazolam with thiopental sodium. METHODS: Fourteen consecutive RSE in 13 patients from January 1998 to August 1999 were treated. Two RSE were happened in one patient. When the SE was refractory as a result of standard treatment, midazolam and thiopental sodium was alternatively used as therapeutic agent. RESULTS: Out of 9 RSE treated with midazolam, 5 were resolved. Four unresolved RSE received additional thiopental sodium. Thiopental sodium was initially administered in 5 out of 14 RSE. Among the 5 RSE improved by midazolam, no one had midazo-lam- induced hypotension or pneumonia. Three patients had respiratory suppression and needed artificial ventilation. RSE was controlled in 2 out of 4 patients treated with thiopental sodium after midazolam. In these patients, hypoten-sion was developed in 3, pneumonia in 2, and respiratory suppression in all. In 5 RSE treated with thiopental sodium alone, RSE were successfully treated in 3 patients. Complications were hypotension in 2, pneumonia/unknown infec-tion in 3, and respiratory suppression in 4. CONCLUSIONS: Midazolam was comparably effective as thiopental sodium in the treatment of RSE, with less adverse effects. We suggest that midazolam be used in the treatment of RSE before thiopental sodium is administered.

Semiological and Electroencephalographic Characteristics of Kainic Acid-Induced Status Epilepticus in Rats

BACKGROUND: Status epilepticus (SE) shows stereotyped progression of electroencephalogram (EEG) and behaviors in human and some SE models. We analysed semiologic features with the electroencephalographic characteristics of kainic acid (KA)-induced SE which showed different patterns from the previously reported patterns of SE. METHODS: Seventeen male Sprague-Dawley rats weighing 150~220 grams were used. SE was induced 5~7 days after the place-ment of epidural electrodes on the rats, using 13 mg/kg kainic acid I.p.. EEGs were recorded and behaviors were contin-uously observed until the end of SE. RESULTS: After the initial akinesia which was apparent within minutes of the KA injection, limbic motor seizure (LMS) composed of facial clonus, head nodding, and akinesia were repeated. Each LMS progressed into more vigorous patterns composed of facial clonus, head nodding, bilateral upper extremity clonus and rearing, without akinesia. Each cycle was repeated as the SE progressed. Severe LMS made up of facial clonus, head nodding, bilateral upper extremity clonus, rearing, falling, and jumping was followed and reiterated. After severe LMS, rats entered subtle SE. In the EEG, repeated discrete seizures mostly consisted of low voltage regular sharp waves and spikes with flat periods. After entering into the LMS, discrete seizure, merging seizure, continuous ictal discharges & periodic epileptiform discharges (PEDs) appeared sequentially in a single cycle and also reiterated. Even during subtle SE, rhythmic cycles were composed of alternating continuous ictal discharges and PEDs. PEDs were gradually replaced by sharp waves or spikes and rats recovered from SE. CONCLUSIONS: Semiologic features and the EEG sequence of KA-induced SE were composed of a series of rhythmic cycles, which have separate EEG patterns in a single cycle. Late EEG patterns of SE were more prominent as the SE progressed.

The Effect of Benzathine Penicillin-induced Focal Interictal Epileptiform Discharges on the Expression Patterns of c-JUN Protein in the Rat Brain

BACKGROUND: Immediate early gene (IEG) is supposed to be linked in the continuous seizure induced long-term changes of specific neurons. We tried to investigate the effects of focal interictal epileptiform discharges on the c-JUN expression in the rat brain which is not clearly understood. METHODS:Epidural electrodes were placed on a male Sprague-Dawley weighing 150~230 g and benzathine penicillin (Pc) was applied cortically. After focal interictal epileptiform discharges were successfully identified, EEG was recorded regularly. Cardiac perfusion and extraction of the brain was done at 2, 4, 24 hours and 1 week after the Pc application. Sixteen rats were evenly distributed into 4 groups. Immunocytochemical staining with specific antisera (Santa Cruz) was performed. RESULTS: The epileptiform discharges were induced within an hour after topical Pc applications. At 2 hours after Pc application, c-JUN was moderately expressed in the dentate gyrus (DG) and weakly expressed in the CA3 pyramidal cell, amygdala, pyriform cortex, thalamus, and neocortex. At 4 hours, c-JUN was minimally expressed in DG and other regions. Whereas, at 24 hours, c-JUN was maximally expressed in the DG and also in the CA3 pyramidal cell, amygdala, pyriform cortex, thalamus, and neocortex. One week after Pc application, c-JUN was moderately expressed in the DG and weakly expressed in the CA3 pyramidal cell, amygdala, pyriform cortex, and neocortex. CONCLUSIONS: This data showed that even focal interictal epileptic activity can induce IEG encoded c-JUN protein in the specific distant brain regions of a rat until a late period and the expression pattern showed a synchronous and bimodal pattern.