Antiepileptic Drugs for Post Stroke Seizure

• Post‐stroke seizure and post‐stroke epilepsy are common causes of hospital admissions, either as a presenting feature or as a complication after a stroke.
• They require appropriate management and support in long term.
•  With an increasingly ageing population, and age itself being an independent risk factor for stroke, the incidence and prevalence of post‐stroke seizure and post‐stroke epilepsy is likely to increase
• The incidence of seizures after stroke has been estimated at 4-20%.
• It is also estimated that epilepsy affects 1% of patients aged over 65 and that the majority of these cases (20-40%) are secondary to cerebrovascular disease.
• There are currently no clear guidelines on use of anti-epileptic drugs (AED) in the management of seizures after a stroke. 
• There is no clear consensus on when to start an AED, which is the best AED to use and for how long to treat patients with an AED. 
• Current practice is often based on the existing guidelines for adult onset epilepsy, both idiopathic and localisation related,and individual physicians experience and preferences

 Choice of AEDs

• The risk of recurrence of post-stroke seizures is 50-90% in those with late-onset seizures

• Both NICE and SIGN guidelines recommend carbamazepine, sodium valproate, lamotrigine or oxcarbazepine as first line treatments for partial seizures and secondary generalised seizures

• The International League Against Epilepsy (ILAE) suggest that lamotrigine and gabapentin are as effective as carbamazepine in partial-onset seizures and that lamotrigine is better tolerated than carbamazepine in older people.

• Both SIGN and NICE guidelines recommend initial AED monotherapy, with trial of a second first-line agent as monotherapy if the first-line drug fails after it has been titrated to a maximum dose
• Postgrade Medical Journal suggests that  carbamazepine, lamotrigine, sodium valproate, and toppiramate as the first line AEDs for both focal (with or without generalised tonic‐clonic) seizures and generalised seizures

• The latest studies regarding post-stroke seizure treatment showed that 'new-generation' drugs, such as lamotrigine, gabapentin and levetiracetam, in low doses would be reasonable because of their high rate of long-term seizure-free periods, improved safety profile, and fewer interactions with other drugs, especially anticoagulant ones, compared with first-generation AEDs. 

• The first-generation drugs, such as phenytoin, carbamazepine and phenobarbital, have the potential to have a harmful impact on recovery, bone health, cognition and blood sodium levels and may interact with other treatments used by the elderly population

Timing to Initiate Therapy

• NICE guidelines suggests to consider AED for a patient after a first unprovoked seizure if the patient has a neurological deficit or abnormality on brain imaging, which could be said to apply to stroke patients.

• The decision to start AED therapy also depends on the perceived risk of recurrent seizures, whose associated risks outweigh the potential side effects of the medications. 

• Based on best available evidence,the recommended treatment is to treat the initial seizure post stroke if it occurs more than seven days after the event.

• The Stroke Council of American Heart Association recommends  that patients with seizure activity more than two weeks after presentation have a higher risk of recurrence and require long term anticonvulsant prophylactic therapy

• Discussion with the patient or relatives about the risks and intended benefits of AED therapy is required

Recommended Duration of Therapy

• Both guidelines suggest discontinuing AED after two years seizure free, although this is a generalised statement and not specific to post stroke seizures.

• Based on another evidence, treating with an appropriate first-line AED, such as lamotrigine or sodium valproate,is recommended for at least 1 year before considering tapering the dose

• Based on The Stroke Council of America Heart Association, early onset seizures need treatment for one month and drug treatment can be stopped if no seizure activity occurred during treatment.

• For late-onset seizures, long term treatment is recommended as the recurrent rate is higher. 

Conclusion

• Most of the guidelines and studies consistently recommend the newer generations of AEDs as the first line treatment of post stroke seizure. 

• According to preferable side effect profile, especially in elder patients,  Lamotrigine is the first option to be initiated in post stroke seizure patients among other newer generation of AEDs.

• If the first-line AED fails to control seizures after being titrated up to an optimal dose as a monotherapy, then switching to another first line agent is recommended with titration up to a maximal dose

• Combination therapy with two or more AEDs is only indicated once two first line agents have been used as monotherapy at optimal doses and should be managed under expert supervision

References

• Use of Anti-epileptic Drugs in Post-stroke Seizures: A Cross-sectional Survey Among British Stroke Physicians January/February 2011. http://www.acnr.co.uk
• Poststroke seizures in the elderly. https://www.ncbi.nlm.nih.gov/pubmed/1868406
• Post‐stroke seizure and post‐stroke epilepsy . https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585721/
• Controlling Post-Stroke Seizure. https://www.strokeassociation.org/idc/groups/stroke-public/@wcm/@hcm/@sta/documents/downloadable/ucm_312968.pdf
• Management of seizures following a stroke: what are the options?. https://www.ncbi.nlm.nih.gov/pubmed/22540349