Relationship of seizure duration and neurological outcome


Status epilepticus is variably defined as

  • 5 minutes or more of continuous seizure activity, or two seizures with no intervening recovery of consciousness. (Oh's Manual; also 2012 Guidelines)
  • A continuous state of seizures, or multiple seizures, without return to baseline, resulting in observable or even subjectively perceived sensory, motor, and/or cognitive dysfunction for at least 30 minutes (Question 16 from the second paper of 2014)

“Refractory” status epilepticus is defined as any sort of seizure activity which fails to respond to the usual bolus dose of benzodiazepines and first-line antiepileptics.

Status epilepticus is further divided into “convulsive” and “non-convulsive" categories. Predictably, the distinction rests on the motor manifestations. Non-convulsive status epilepticus is a weird animal – these people are typically described as confused; consciousness is not completely lost as in a grand mal tonic-clonic seizure – but rather, it is altered, to the extent that the patient no longer “acts normal” in some (potentially very subtle) way. This bizarre disorder accounts for a quarter of the cases; the rest display bog-standard convulsive features.

The importance of seizure duration

Why do we care? Well. After 30 minutes or so of continuous seizures, even in the absence of hypoxia and aspiration, there is a serious risk of neuronal damage. We know this because brave heroes from the 1970s subjected a small tribe of paralyzed and ventilated baboons to injections of bicuculline, a plant-derived competitive GABAA-antagonist. Obviously, the baboons were not anaesthetised. Ischaemic changes in neurons were noted in the animals;  perhaps this is not surprising, given that the epileptic activity carried on for many hours.

The take home message from this is not that we can allow seizure activity to continue for many hours before brain damage develops, but that treatment should be considered after five minutes or so of seizure activity, because a seizure which has gone on for this long is unlikely to just stop spontaneously.

The pathophysiology of seizure-induced neuronal excitotoxicity

The key feature of excititoxic brain damage is glutamate excess. As the chief excitatory neurotransmitter, glutamate becomes overabundant during an episode of seizure. Somehow, this leads to an increase of intracellular calcium. One might remember that calcium is an uimportant intracellular messenger. An in this specific case, the message is carried directly to the mitochondrie, which promptly self-destruct, taking the neuron with them. The induction of apoptotic mechanisms by glutamate excess is the major pathophysiological mechanism of seizure-induced excitotoxicity.

Another mechanism, which may play a lesser role, is essentially exhausted starvation. Neurons which are put upon to pump frantically for minutes on end will end up exhausting their ioxygen supply, and with thus run out of ATP. To be sure, blood flow to the brain increases during a seizure, but this is not enough to compensate for the unnaturally large expenditure of energy in each involved neuron. In the absence of ATP, predictable havoc ensues. Ionic concentration gradients break down and intracellular chaos develops, with apoptosis and necrosis again the only possible outcome.

Outcome of status epilepticus: influence on mortality and morbidity

The 2012 Guidelines for Management etc etc contain within them a huge table (Table 4) on Page 7, which patiently lists the mortality statistics. The Table itself is huge; some of the more interesting features are reproduced below for the purpose of rapid revision. Nobody is going to remember any of this for their CICM SAQ paper, so the utility of even mentioning this here is very limited.

Status Epilepticus


  • At hospital discharge: 9–21 %
  • At 30 days: 19–27 %
  • At 90 days: 19 %

Features associated with poor outcome:

  • Older age
  • Unconsciousness
  • Duration of seizures,
  • Focal neurological signs
  • Medical complications

Non-convulsive status


  • At hospital discharge: 18-52%
  • At 30 days: 65%

Time-critical diagnosis:

  • Diagnosis within 30 min of seizure onset: mortality 36 %
  • Diagnosed 24 hr after seizure onset: mortality 75 %

Features associated with poor outcome:

  • Severe mental status impairment
  • Longer seizure duration
    • Less than 10hrs: 10% mortality
    • More than 20hrs: 85% mortality
  • Unknown cause

Refractory status


  • At hospital discharge: 23–61 %
  • At 3 months: 39 %

Features associated with poor outcome:

  • Older age (e.g., >50 years)
  • long seizure duration
  • high APACHE-2 scale scores
Outcome Statistics for Status Epilepticus



Oh's Intensive Care manual:

Chapter 49   (pp. 549) Disorders  of  consciousness  by Balasubramanian  Venkatesh

Chapter   50   (pp. 560) Status  epilepticus  by Helen  I  Opdam

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