Focal nonconvulsive seizures during detoxification for benzodiazepine abuse

Focal nonconvulsive seizures during detoxification for benzodiazepine abuse.
Epilepsy Behav. 2012 Feb;23(2):168-70
Albiero A, Brigo F, Faccini M, Casari R, Quaglio G, Storti M, Fiaschi A, Bongiovanni LG, Lugoboni F.
Department of Medicine D, Addiction Unit, University of Verona, Verona, Italy.

The authors report on two cases focal seizure activity that occurred during flumazenil treatment of benzodiazepine withdrawal.  Low-dose flumazenil was given by IV infusion (0.5 mg/day) for 14 hours daily over 10 days, with discontinuation during the night. On the same day of admission, the abused BDZ was replaced with clonazepam, which was progressively tapered over the next 3 days, so that on 4th day the patient was no longer receiving BDZs. 


The episodes were confirmed by EEG. One is described as 

On the 8th day she suddenly developed behavioral changes characterized by impairment of consciousness (the patient was able to perform simple tasks such as open her eyes), sometimes with upper limb automatisms, lasting several minutes and alternating with long periods of normal behavior. No posturing, rotation, or clonic movements occurred. There were no secondarily generalized tonic–clonic seizures. 

And for the other patient:

On the 9th day she suddenly developed behavioral changes characterized by clusters of episodes with confusion, disorientation, fear, and partial impairment of consciousness (the patient was able to perform only simple tasks), lasting several minutes and alternating with periods of normal behavior. No limb or oroalimentary automatisms, posturing, rotation, or clonic movements were observed. There were no secondarily generalized tonic–clonic seizures. 

The first patient was on Depakote at a dose of 500 mg BID with a level of 54 mg/L.  Episodes continued until least day 11 when EKG changes were demonstrated.  The patient was changed to carbamazepine and discharged at the high dose of 400 mg TID.

The second patient was on oxcarbazepine (Trileptal) at 600 mg/day when the episodes began.  Her episodes recurred days 12, 13, 14, 15.  One the 15th day EEG changes were noted during an episode. Her oxcarbazepine was increased to 900 mg/day.

The authors note a 2.8% incidence of generalized seizures among the 286 patients they have treated with flumazenil. The article implies an anticonvulsant was used in these patients generally but does not specify which one, what dose or serum levels.

What should we conclude from this?  Localized seizures can occur during benzodiazepine withdrawal just at generalized seizures do.  That is the significant new finding.

The presence of one of these episodes with a valproic acid level of 54 contradicts our experience that seizures don't occur when therapeutic levels of valproate are present.  It is possible that this assumption incorrect but also possible that the level of 54 mg/L was inadequate to prevent seizures.

I have seen one patient with focal seizure activity that progressed over several hours to a generalized tonic clonic seizure.  This patient had sub-therapeutic carbamazepine  hen the episode occurred. They did not recur when carbamazepine was dosed adequately.