A 36 y/o male with PMHx of IDDM is admitted to ICU for DKA and subsequently has a first time seizure. After resolution of what does appear to be a seizure and not a convulsive syncopal event, do you start this patient on an anti-epileptic drug (AED)? This answer is one of a few questions to be addressed in any patient with a first time seizure.

Based on a review of the literature, there are no strict guidelines so here is a review of my interpretation of the literature.

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How do you classify first time seizures?

Many classifications exist (ex based on movement types tonic/clonic vs clonic, etc), but the classification definition appropriate for determining initiation of AEDs can be summarized as follows:

Provoked (Acute Symptomatic) Seizures

• A seizure due to an identified insult with timing occurs at or close to the time of the identified insult. These generally carry a lower risk for future epilepsy.
• Differentials for identifiable insults are broad and include:
  • Metabolic: hypoxia, etc.
  • Infectious: mengingitis, encephalitis
  • Structural: ischemia, hemorrhage, TBI, etc.
  • Toxic: ex. Drug/Alcohol withdrawal

If you didn’t notice already, the differentials are pretty similar to the poplar MIST mnemonic for altered mental status.  Most apply to differentials for insults causing a new onset seizure. Check out a great visualization of the MIST mnemonic for an approach to AMS by the team at Clinical Problem Solvers.

• Timing can be more explicitly specified as:
  • Within 24 hours of severe metabolic derangement
  • During active phase of CNS infection
  • Within 1 week of CVA, TBI, anoxic encephalopathy event or intracranial surgery
  • At first identification of subdural hematoma

Unprovoked Seizures

• seizure of unknown etiology OR
• Remote Symptomatic Seizure
  • one that occurs in relation to preexisting brain lesion or progressive nervous system disorder ex. TBI, previous infection
  • these carry a higher risk of future epilepsy compared to acute symptomatic seizures.

Epilepsy

The Internal League Against Epilepsy (ILEA) task force defines epilepsy as:

• At least two unprovoked / reflex seizures occurring > 24 h apart
• One unprovoked / reflex seizure and a probability of further seizures similar to the general recurrence risk ( ≥ 60%) after two unprovoked seizures, occurring over the next 10 years
• Diagnosis of an epilepsy syndrome
  • an umbrella term for a wide range of specific types of seizures based on clinical features, signs, and symptoms that together define a specific seizure disorder

Yes, it is complicated.

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On whom should you start an AED?

The rationale for starting an AED immediately after a first seizure is simply based on the risk of recurrence. This is where the above classification and determination of an underlying cause plays a critical role.

Provoked (Acute Symptomatic) Seizures

Determine the risk of recurrence based on severity and persistence of the underlying cause. To better understand:

• Ex 1: Critically ill patients or those with prolonged / refractory seizures, ie status, are likely to remain critically ill until the underlying condition is treated so could therefore be loaded with the AED IV
• Ex 2: Metabolic derangements are less likely to persist so can therefore hold off on starting AEDs
  • however if the underlying disturbance is severe or prolonged, then the risk of recurrence is higher and warrants temporary AEDs

Unprovoked Seizures

The decision is more complex and the risk factors for recurrence are based on risk factors that would pose a near to or higher than 60% chance of recurrence, thereby meeting criteria for epilepsy according to the International League Against Epilepsy (ILAE).

I remember the risk factors using the mnemonic SHINE:

• first seizure occurred during Sleep
• Remote Symptomatic Cause identified on History
• Remote Symptomatic Cause identified on neuro-Imaging
• abnormal Neurologic exam including FNDs and intellectual disability
• epileptiform abnormalities on EEG

If the patient has none of the above criteria, starting an AED may be deferred until a second unprovoked seizure.

As always, engage in shared decision making with the patient / their family / the neurologist regarding risk of recurrence / benefits of AEDs / harm of AEDs

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In summary…

• categorize the seizure as provoked v unprovoked
• provoked: determine severity and duration of underlying cause
• unprovoked: determine risk factors for recurrence that would increase risk of this being epilepsy

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References

1. Epilepsia. 2010.; 51(4):671. Beghi E, Carpio A, Forsgren L, et al. Recommendation for a definition of acute symptomatic seizure.
2. Epilepsia. 2014; 55(4): 475. Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE official report: a practical clinical definition of epilepsy.
3. Neurology. 2015; 84(16):1705. Krumholz A, Wiebe S, Gronseth GS, et al. Evidece-based guideline: Management of an unprovoked first seizure in adults: Report of the Guideline Developmental Subcommittee of the American Academy of Neurology and American Epilepsy Society.

Post reviewed and edited by @udaygulati

• Neurology