Population-Based Assessment of the Long-term Risk of Seizures in Survivors of Stroke

Alexander E. Merkler, MD; Gino Gialdini, MD; Michael P. Lerario, MD; Neal S. Parikh, MD; Nicholas A. Morris, MD; Benjamin Kummer, MD; Lauren Dunn, MD; Michael E. Reznik, MD; Santosh B. Murthy, MD, MPH; Babak B. Navi, MD, MS; Zachary M. Grinspan, MD, MS; Costantino Iadecola, MD; Hooman Kamel, MD

Disclosures

Stroke. 2018;49(6):1319-1324. 

In This Article

Discussion

In 2 large, heterogeneous cohorts of patients, we found that patients who survived a stroke hospitalization faced a significant long-term risk of developing seizures, with a risk that was ≈7-fold higher than the general population. The relative risk of developing seizures was higher after hemorrhagic stroke and in younger patients.

Prior studies found that between 2.6% and 13.5% of patients with stroke subsequently developed seizures and that the risk of poststroke seizures was highest after hemorrhagic strokes.[2,10–16,18] Our study extends these findings by elucidating the long-term risk of seizures according to age, sex, race, and stroke subtype in survivors of stroke.

Age has been previously evaluated as a risk factor for the development of poststroke seizures with conflicting results.[2,3,7,8,12,13,16] In this study, we found that younger age was strongly associated with an increased relative risk of development of seizures after stroke. In addition, we found that nonwhite race was associated with the development of poststroke seizures in the multistate analysis, but not in the Medicare claims analysis where all patients were ≥66 years of age. Although to our knowledge, no previous study has found an association between race and the development of seizures in patients with stroke, a recently published study found that the incidence of epilepsy was significantly higher in black patients.[30] Prospective studies are needed to better understand the impact of race on the development of seizures.

Our study has several limitations. First, we relied on ICD-9-CM codes to identify patients with stroke and seizures, which may have led to misclassification of both our exposure and outcomes; however, we used previously validated, reliable diagnosis code algorithms to identify both stroke and seizures. Second, in our multistate analysis, we only identified seizures resulting in an emergency department visit or hospitalization which may have led to an underestimation of the risk of seizures. However, the validity of our findings is supported by the similar findings from our separate analysis of Medicare claims which included data on outpatient diagnoses. Third, we lacked data on clinical characteristics such as stroke severity, size, and location—factors that may contribute to the risk of seizures. Likewise, we lacked information about the semiology, duration, and frequency of seizures. Fourth, as patients with stroke are often in close contact with a medical professional, the association between stroke and seizures may have been affected by ascertainment bias; however, we found a similar association between stroke and out-of-hospital status epilepticus, a severe form of seizure unlikely to be affected by ascertainment bias. Last, we were unable to account for medication use, including prophylactic antiepileptics, which may have influenced the risk of developing seizures and weakened the association between stroke and poststroke seizures. However, because prophylactic antiepileptics in stroke patients are currently not recommended, the absence of data about medication use should not have significantly impacted the validity of our results.[31]

In 2 large, heterogeneous cohorts of patients, we found that ≈10% of patients with stroke went on to develop a seizure within the following decade. Hemorrhagic stroke and younger age seem to be most strongly associated with the development of poststroke seizures, although an association with nonwhite race was observed only in the multistate analysis. Further study of the epidemiology and pathophysiology of poststroke seizures may lead to improved methods of risk stratification and prevention.

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