Abstracts

Rationale: Paradoxical worsening or activation of seizures caused by anti-seizure drugs (ASD) is a known phenomenon in idiopathic generalized epilepsies. While benzodiazepines (BZD) is a group of ASDs commonly used to treat acute seizures including status epilepticus, it's rare for this group of ASDs to cause worsening of seizures. We present two cases of adult focal (frontal lobe) epilepsy patients, whose seizures were aggravated by BZD use during their epilepsy monitoring unit (EMU) stay at our institution. Methods: Case 1:A 23-year old man with seizures since age 13. His seizures were documented to be sleep-activated, focal frontal lobe seizures. Patient’s seizure medications were held, and on the third night, he was noted to have a cluster of seven nocturnal seizures prompting IV diazepam use for a total of 15mg.The patient continued to have seizures requiring additional BZDs, total of 12mg of IV lorazepam and 4mg of IV midazolam over the course of 7 – 8 hours. Despite receiving BZDs and being loaded with IV levetiracetam, patient’s seizures continued to worsen in frequency to one seizure every 3-5 minutes. Clinically it appeared the more BZDs were given the more seizures the patient had. Approximately, three hours after the administration of the last BZD dose, the seizure frequency improved to one seizure every 10 minutes. Seven hours after the last BZD dose, the seizure frequency improved to one seizure every 20 – 60 minutes and eventual cessation of all seizures the next morning. The EMU stay was continued for three more days with no additional seizures.Case 2:A 20-year-old man with history of nocturnal seizures since age 11 had EMU documented sleep activated focal frontal lobe seizures. His ASDs were continued at home doses (brivaracetam 100mg TID, carbamazepine 600-400-400, and perampanel 18mg QHS). At presentation, his average seizure frequency was 1-2 per night. Clobazam 5mg qhs was added to his regimen on day 3. On days 4 and 5, his seizure frequency increased to 4 - 6 every night. At that point his clobazam was stopped and switched to zonisamide and his seizure frequency decreased to 0-1 per night. Results: Discussion:ASD induced seizure exacerbation is generally related to either incorrect diagnosis of epilepsy syndrome, inappropriate ASDs for particular seizure type. Here we present two cases of paradoxical worsening of seizures with BZD use. BZDs are highly effective anti-seizure agents often used for rescue. They are known to at times worsen drop seizures in LGS however to our knowledge there are no reports of BZDs worsening frontal lobe seizures. The mechanism of this paradoxical effect is unknown but it could be hypothesized that perhaps by their sedative and sleep inducing effects they can provoke sleep activated seizures such as frontal lobe seizures.  Conclusions: Paradoxical worsening of frontal lobe seizures with benzodiazepine usage can occur. BZDs still remain the first line for acute seizure treatment, however additional precautions should be taken when used for sleep activated frontal lobe seizures. Funding: No funding