Starting, Stopping Antiepileptic Medications in Acute Symptomatic Seizures

Stephen Hantus, MD

Stephen Hantus, MD, Director of the cEEG and Epilepsy Consult Service at the Cleveland Clinic Epilepsy Center, spoke with NeurologyLive at the American Epilepsy Society’s annual meeting in New Orleans, Louisiana, to provide additional insight on the steps to reduce medications for patients with acute symptomatic seizures in order to improve quality of life, keeping them seizure free and without side effects.

Hantus explained that it’s important for clinicians to treat acute symptomatic seizures short term and that it takes several medicines to stop the seizures and status epilepticus but it takes less medicine to maintain them.

NeurologyLive: What do we know about stopping seizure medications?

Stephen Hantus, MD: One in 10 people will have a seizure throughout their lifetime, but only 1 in a hundred people actually develop epilepsy. It's pretty clear that in the acute phase of an illness, when you have an acute symptomatic seizure maybe from a stroke, a subdural hemorrhage, encephalitis or sometimes even a blood infection, it can lead to a seizure. In the acute phase, patients need to be treated short term, but the question is, who needs to stay on seizure medicines and what are the seizure medicines to start and how do you get them back off?

There is some evidence from randomized controlled trials on which medicines we should use, there is Class I Level A evidence for aggressive use of benzodiazepines and, unfortunately, this is the step that most of us miss, and so giving 2 mg of lorazepam is a very fraction of the dose that's actually required to stop acute symptomatic seizures. Often the clinical seizure that we see is only the tip of the iceberg and there's a lot more epilepsy going on underneath, which we have revealed by doing continuous EEG of patients in the ICU.

What are the current recommendations for stopping acute symptomatic seizures and status?

What we recommend is established by the randomized control trial and the VA cooperative trial, which is 0.1 mg/kg of lorazepam which generally turns out to be 7 mg—9 mg of lorazepam. Then patients can also be given other benzodiazepines such as midazolam, this was established in the RAMPART trial and also randomized controlled trial with Class I Level A evidence. Outside of that, we really don't have a lot of guidance as far as which medicines to use and so we know all of the medicines we use require a significant delay, you have to get them from the pharmacy and those type of things, and they have to be run in over some period of time, but we want the balance mechanisms when we do that so I like to think of the sodium channel drugs, the SV2A mechanism drugs, the calcium channels, and the GABAergic drugs—so by balancing the mechanisms of these different drugs, I think you can get the best effect of antiepileptic drugs.

After these are added, often we have to go rapidly to anesthesia and so midazolam drip is the most often used anesthesia, but pentobarbital can also be used but frequently it takes a lot more to stop a status epilepticus than it does to maintain them to be seizure free. Stopping acute symptomatic seizures and status is usually the hardest step.

How should clinicians stop acute symptomatic seizure medications?

First, you get the medicines on, then we're going to keep the medications on until we can wean off the anesthesia and then we want to have the patient to remain without seizures and to wake up, and so this often requires first the insight of when to wean the anesthesia. Our group has done some work on highly epileptiform bursts and so if your burst suppression or your suppressed EEG under anesthesia contains these highly epileptiform bursts, the chances that you're going to be able to wean successfully is very small so typically we need to continue the anesthesia, continue adjusting antiepileptic drugs until those highly epileptiform bursts are dissolved.

Is there an order in which the medications should be stopped?

The next steps in this are once we get the anesthesia weaned, we get the person without seizures, then we want to start removing the medications in a rational fashion so in order to get the medicines off, we'd like to go in the order that would most likely allow the patient to wake up—phenobarbital often comes off first, valproate maybe next, levetiracetam may be limited, and then other medicines phenytol, lacosamide may also be limited to doses that would be more appropriate for waking up, but also maintaining seizures.

What determines the risk of a patient needing seizure medications again?

The next phase is basically, are we going to be having recurrent seizures or are we going to never need seizure medicines again? We want to know the risk going into that and so there are a number of things that determine this risk. If you have continuous EEG seizures, particularly continuous EEG seizures with PLEDs, or periodical idolized epileptiform discharges, then your chances of having long-term epilepsy is 48%.

This is some of work we’ve conducted with Vineet Punia, MD, and our group where we looked at follow-up of these patients leaving the ICU who had continuous EEG and we found a high proportion of epilepsy in the patients with continuous EEG implants, so that's one important factor. Second is that they have MRI structural lesions from the acute symptomatic lesion, so, for example, if you have a stroke and you have residual encephalomalacia from the stroke your chances of having long-term epilepsy is higher, if you have a brain tumor your chances is higher versus if you have PRES, or posterior reversible encephalopathy syndrome, your chances are smaller as long as you don't incur any structural damage, if you have a low sodium and you don't have any changes in your brain, your chances are much less of developing epilepsy, if you have persistent epileptiform discharges on your EEG that also determines if you will have seizures long-term.

Follow-up EEG is another thing that we do in the clinic to see if you still have sharp waves on your EEG after discharge, because if so, your chances of having seizures long-term is greater. Continuous EEG findings from your acute stay, the structural changes from the acute symptomatic period and then that follow-up EEG are the main factors that would determine if we can attempt to wean off your medicines in 6 months, which would be for a lot of patients, or that we should continue with long-term medication.

What is the main takeaway for clinicians starting and stopping antiepileptic medications in acute symptomatic seizures?

I think it is important to note that it takes a lot of medicines to stop acute symptomatic seizures and status epilepticus, however, it takes much less medicine to maintain them. Many patients get discharged from the hospital on a lot of medicines that can be reduced and reducing those medicines often improves the quality of life, and so we want to get patients to the least amount of medicines that will keep them seizure free and without side effects.

Transcript edited for clarity.