What is break through seizures
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Breakthrough Seizure
A breakthrough seizure is a seizure that occurs in a patient with a known, previously controlled seizure disorder despite being on antiseizure medication (ASM) - i.e., a seizure "breaks through" an existing treatment regimen that was otherwise working.
Most common cause
The single most common cause of a breakthrough seizure is a subtherapeutic anticonvulsant drug level, most often due to medication noncompliance (missed or reduced doses) - Tintinalli's Emergency Medicine, p. 3465-3469.
Other recognized triggers/mechanisms
- Altitude changes - epileptic patients on stable therapy can have a breakthrough seizure at altitude; standard seizure workup is warranted, and acetazolamide 125-250 mg twice daily may be used prophylactically in this setting - Rosen's Emergency Medicine.
- Drug interactions or pharmacokinetic changes that lower effective ASM levels (e.g., altered absorption, enzyme induction/inhibition, illness, pregnancy).
- Pharmacoresistance - ASM not reaching the epileptogenic zone (e.g., due to multidrug transporters pumping the drug out of neurons) or the drug target becoming less sensitive to the ASM.
- Tolerance - established with chronic benzodiazepine use, and possibly with other ASMs.
- Paradoxical seizure aggravation - some ASMs can actually worsen seizure control or provoke new seizure types (e.g., myoclonic/absence seizures) even at therapeutic levels - documented with carbamazepine, oxcarbazepine, phenytoin, tiagabine, gabapentin, vigabatrin, and even levetiracetam in some patients.
- ASM-induced encephalopathy or sedation (e.g., valproate-induced encephalopathy) can also exacerbate seizures rather than control them.
- Common non-pharmacologic triggers in clinical practice also include sleep deprivation, alcohol use/withdrawal, fever/illness, and significant stress, though the textbook emphasis here is on drug-level and pharmacologic causes. (Bradley and Daroff's Neurology in Clinical Practice, p. 1592-1608)
Clinical work-up
When a breakthrough seizure occurs in a patient with known epilepsy:
- Check a serum anticonvulsant drug level (a very low level strongly suggests noncompliance).
- Routine repeat drug levels aren't otherwise necessary in stable patients - they're mainly indicated after a breakthrough seizure, and the new level is compared to the patient's prior baseline.
- Additional labs (glucose, electrolytes, calcium, magnesium, toxicology, pregnancy test) are guided by clinical context, especially if the seizure history or presentation is unclear.
In short: it's a seizure happening despite ongoing antiseizure treatment, most often signaling a drug-level problem (usually nonadherence) but sometimes reflecting true pharmacoresistance, tolerance, or a paradoxical drug effect.
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