Occurrence of seizure clusters and status epilepticus during inpatient video-EEG monitoring.

OBJECTIVE: To investigate the occurrence of status epilepticus and seizure clusters, and the duration until first seizure at epilepsy monitoring units in the United States. METHODS: The authors examined the inpatient video-EEG monitoring reports of 514 consecutive patients admitted to five comprehensive epilepsy centers during the year 2000. Time to first seizure, seizure clustering, and seizure duration were ascertained from reports and entered into a database. RESULTS: In 169 admissions with complex partial seizures (CPSs) or secondarily generalized tonic-clonic (2GTC) seizures, there were 5 (3.0%) patients with status epilepticus, 30 (17.8%) with 4-hour seizure clusters, and 82 (48.5%) with 24-hour seizure clusters. There were no statistically significant differences between centers, except that seizure clusters were observed to be less common at the one center with a formal drug withdrawal protocol. The average time to CPS or 2GTC seizure was 2.1 days; the average number of days to nonepileptic event was 1.2 days (p = 0.001). CONCLUSIONS: Although status epilepticus is uncommon at epilepsy monitoring units, clusters of seizures are common. Intensive monitoring with drug withdrawal must be performed in a highly supervised, hospitalized setting. Inpatient video-EEG monitoring is efficient, with recording of the first epileptic or nonepileptic events in 2 days or less.

Effect of divalproex-lamotrigine combination therapy in frontal lobe seizures.

CONTEXT: Patients with intractable frontal lobe seizures represent a difficult subclass of patients with epilepsy. When medications fail, surgical outcomes typically have not been as successful as medial temporal lobe resections. The combination therapy of valproic acid (divalproex sodium) and lamotrigine has shown promising results in patients with uncontrolled seizures. OBJECTIVE: To determine outcome in patients with intractable frontal lobe seizures who were treated with the combination of divalproex and lamotrigine. DESIGN: A nonrandomized, open-label, add-on trial. SETTING: Outpatients evaluated and treated at a tertiary care referral facility. PATIENTS: Twenty-one patients between 16 and 65 years old were studied. Patients were required to have failed at least 3 prior trials with antiepilepsy drugs. Criteria for frontal lobe onset included 1 or more of the following: frontal lesion on scan, positive ictal single-photon emission computed tomographic scan, symptoms consistent with frontal lobe onset, or an electroencephalogram (surface or invasive) consistent with frontal lobe onset. INTERVENTION: Patients were treated with divalproex-lamotrigine combination therapy for 1 year. MAIN OUTCOME MEASURES: The main outcome measured was seizure reduction. Safety and tolerability were also evaluated. RESULTS: Four patients discontinued therapy. Ten of the remaining 17 became completely free of seizures. Two rashes occurred, but did not lead to discontinuation of therapy. The most common adverse events were tremor and weight gain. CONCLUSION: Divalproex-lamotrigine combination therapy is a reasonable alternative in intractable frontal lobe epilepsy.

Abnormal Wada and neuropsychological testing results due to topiramate therapy.

A 46-year-old man experienced intractable seizures since childhood. Due to lack of response to antiepilepsy drugs (AEDs), he underwent a surgical evaluation that was consistent with seizure onset in the left medial temporal lobe. While on topiramate and carbamazepine, his preoperative neuropsychological scores and sodium amytal (Wada) scores were low and may have excluded him from surgery. Repeat testing on lamotrigine and carbamazepine showed improvement in his scores, allowing him to undergo surgery. Physicians must therefore be cautious in evaluating such test scores while a patient is on topiramate.

New anti-epileptic drugs for the 21st century.

Prior to 1993, there were only six major drugs available in the US for the treatment of patients with epilepsy. These included phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), primidone (PRIM), valproic acid/sodium valproate (VPA) and ethosuximide (ESX). Of these drugs, VPA has the broadest spectrum of activity and ESX the most limited. Despite these six agents, as well as several secondary drugs, it is estimated that over 30% of patients have inadequate seizure control, while others, whose disease is adequately controlled, suffer from bothersome adverse events (AEs). Since 1993, ten new drugs have entered the worldwide market (not all in the US). Those released include felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LVT), zonisamide (ZNS), clobazam (CLB) and vigabatrin (VGB). The purpose of this article is to review each of the above drugs, looking at efficacy, safety, tolerability and where they may play a role in the current treatment of epilepsy.

Levels of tropinone-reductase activities influence the spectrum of tropane esters found in transformed root cultures of Datura stramonium L.

The nortropane sulphur analogues 8-thiabicyclo[3.2.1] octan-3-one, 8-thiabicyclo[3.2.1]octan-3a-ol and 8-thiabicyclo[3.2.1]octan-3ß-ol have been found to have differential effects in vitro on the activities of tropinone reductase I and tropinone reductase II from Datura stramonium L. It has been demonstrated that only tropinone reductase I is able to metabolise 8-thiabicyclo[3.2.1]octan-3-one and that only this enzyme is inhibited by 8-thiabicyclo[3.2.1]octan-3α-ol and 8-thiabicyclo[3.2.1]octan-3ß-ol. A K m of 0.035 mM was determined for 8-thiabicyclo[3.2.1]octan-3-one and I50 values of 0.081 mM and 0.021 mM for 8-thiabicyclo[3.2.1]octan-3α-ol and 8-thiabicyclo[3.2.1]octan-3ß-ol, respectively. The influence that these differential interactions might have on metabolism was investigated in transformed root cultures of D. stramonium. It was found that when these cultures were grown in the presence of either 8-thiabicyclo[3.2.1]octan-3-one or 8-thiabicyclo[3.2.1]octan-3ß-ol the spectrum of alkaloids that accumulated was altered from that found in control roots in the manner predicted from the observed effects of these inhibitors on the isolated reductases. The effect could be mimicked by feeding pseudotropine, the product of tropinone reductase II. It is concluded that the relative levels of activity of the two tropinone reductases might play an important role in regulating the balance of tropan-3α-ols to tropan-3ß-ols seen in the spectrum of tropane-alkaloid-producing plants.