Standing up to the challenge of refractory epilepsy

In neurology, the word ‘refractory‘ is almost exclusively used in relation seizures. It may apply to drug-resistant epilepsy (DRE), or to rampaging status epilepticus.’Refractory’ doesn’t sound good in whatever context it is used, typically connoting a situation beyond redemption. But this is not the case with epilepsy. Rather than a bell tolling in despair, refractory is used in epilepsy as a bugle calling to arms.

Ask Not For Whom the Bell Tolls...Vicky Vinch ON/OFF on FLikr
Ask Not For Whom the Bell Tolls…Vicky Vinch ON/OFF on Flikr

Refractory epilepsy

If anyone was asked to imagine refractory epilepsy, they would surely picture a case that has failed to respond to the heavy arsenal of anti-epileptic drugs (AEDs). They would visualise a patient who has failed Lamotrigine, Carbamazepine, Valproate, and Levetiracetam. They would envisage subsequent failures with Zonisamide, Eslicarbazepine, Oxcarbazepine, and Lacosamide. They would clearly see a neurologist desperately hoping that the seizures would respond to the new AEDs on the block such as PerampanelBrivaracetam or Retigabine.

Hands of Desperation. Chris Kueh on Flikr.
Hands of Desperation. Chris Kueh on Flikr.

They would be very wrong. Rather than a failure of all AEDs, refractory epilepsy is defined by the International League Against Epilepsy (ILEA) as the failure of two well-chosen and tolerated AEDs. The chances of achieving seizure freedom in this situation are slim, and the sooner non-drug interventions are considered, the better. ‘Refractory’, in the context of epilepsy, is therefore a red flag for the neurologist to prevent years of juggling partially effective drugs. It is an early warning system to consider non-drug interventions such as surgery and neuromodulation. This point was strongly made in an article in European Neurological Review titled Treating Drug-resistant Epilepsy – Why are we Waiting? Well worth a read!

Red Flags on the Railway Line. Evelyn Simak on geograph.
Red Flags on the Railway Line. Evelyn Simak on Geograph.

Refractory status epilepticus

Refractory is also used in the context of status epilepticus where it describes the failure of two different anti-status medications. In this case, ‘refractory’ tells us that it’s time to use anaesthetic agents to put the patient to sleep, and essentially wait for things to settle. The real challenge comes when this strategy fails. What name do we give this conundrum that goes beyond refractory, and is there anything we can do about it?

By Vaikoovery - Own work, CC BY 3.0,
By Vaikoovery – Own work, CC BY 3.0,

The experts ingeniously named this scenario super-refractory status epilepticus! And this super duper name doesn’t scare them from trying to treat it. In their enlightening and hope-raising critical review of super refractory status epilepticus, published in the journal Brain, epilepsy experts Simon Shorvon and Monica Ferlisi offer a surprisingly long list of interventions for super refractory status epilepticus. These include magnesium, steroids, IVIg, plasma exchange, hypothermia, the ketogenic diet, and Rufinamide. The review is a must-read for anyone who manages status epilepticus (or they could look up the condensed version in neurochecklists!)


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