We found that, although 8.4% (22/263) of patients with spontaneous ICH experienced seizures during the follow-up period, epilepsy was a sequela in only 0.8%, except for one patient who died. Early seizures occurred in 3.4% of patients, and late seizures occurred in 5.0% of patients. Previous studies have reported the incidence rate of seizures occurring after spontaneous ICH to be 2.8-18.7%2,4-6,8,14,19,28)
. When comparing the incidence of seizures reported in previous literatures, our study revealed consistent results.
Several previous studies examined early seizures and late seizures occurring after stroke10,28,31)
. In this current study, younger age and cortical involvement were independent factors for early seizures. Post-hemorrhagic communicating hydrocephalus and cortical involvement were independent factors for late seizures. Previous studies have reported that the cortical involvement of ICH affects the incidence of seizures5,7,8,11,17,31,33)
. The pathogenesis of seizures in cortical involvement may involve the location of the lesion in the gray-white matter interface, creating a condition similar to the surgical isolation of cortex, which results in its sustained paroxysmal activity9)
, and direct irritation of the cortex is one possible mechanism through which post-ICH seizures are provoked32)
In the present study, young age (60 years or less) and communicating hydrocephalus were risk factors for seizures after spontaneous ICH. But the exact cause was unclear. Some authors suggested younger age is one of the risk factors for seizures in ICH, however, the pathogenesis was not noted in the literature7,33)
. Communicating hydrocephalus was also suggested as one of the risk factors for seizures in ICH16,24)
. In common with age, the exact cause was also still unclear.
The effect of ICH volume on the occurrence of seizures after spontaneous ICH remains controversial. In a previous study, Yang et al.33)
stated that large ICH volumes were significantly correlated with the occurrence of early seizures. In a prospective study by De Herdt et al.7)
, ICH volume was unrelated to the occurrence of seizures. Several pathophysiological mechanisms, although requiring further elucidation, have been implicated in the occurrence of seizures after spontaneous ICH, including a combination of the sudden development of a space-occupying lesion with mass effect, focal ischemia, and blood products, which could explain the occurrence of seizures in the early phase of hemorrhagic stroke5)
. However, in this study, large ICH volume was not associated with the occurrence of seizures.
The effect of seizures on the outcomes of patients with spontaneous ICH is controversial. Arboix et al.1)
reported poor outcomes in cases of seizures following stroke. In other studies, no significant influences on outcomes were evident23)
. In this study, patients with early seizures had worse functional outcomes at both 2 weeks after the onset of ICH and the last follow-up than those patients without seizures. Regarding late seizures, there was no difference between the 2 groups at 2 weeks after the onset of ICH, but on last follow-up, poor outcomes were apparent in patients with late seizures. Although seizures did not influence the mortality, it could lead to poor functional outcome. Passero et al.23)
reported that the administration of prophylactic anticonvulsants decreases the risk of acute seizures, but Reddig et al.26)
stated that prophylactic anticonvulsants have no significant benefits. In this study, the incidence of early seizures tended to decrease in patients prescribed prophylactic anticonvulsants. However, the administration of prophylactic anticonvulsants did not prevent the occurrence of seizures, and the outcomes were rather poor in patients prescribed prophylactic anticonvulsants. The reasons or risk factors for poor functional outcomes in patients prescribed with prophylactic anticonvulsants were not identified in this study. However, adverse factors including hyperammonemia and thrombocytopenia were present in patients prescribed with prophylactic anticonvulsants. Upon review of previous studies, complications including hyperammonemia and thrombocytopenia could be caused by valproate or levetiracetam13,27)
. One study demonstrated an association between phenytoin prophylaxis and more fever, worse clinical examination, and a worse functional outcome at follow-up21)
. Based on our findings and the findings of others, the benefit of prophylactic anticonvulsant therapy would further be limited because of the relatively easy control of seizures if they did occur and the adverse effects of anticonvulsant therapy. Therefore, to balance the limited benefit and the potential serious adverse effects of antiepileptic drugs, prophylactic anticonvulsant must be used with caution only when necessary; future research may clarify protocols for the effective use of anticonvulsants and target specific populations at high risk for seizures after ICH (e.g., ICH with cortical involvement and depressed mental status).
Our study has some limitations that should be considered. First, we performed a retrospective observational study. Second, because the follow-up period was short, there may be differences in the incidence rate of late seizures. Third, although there was no significant difference between the patients receiving prophylactic anticonvulsants and those patients without medication, the surgeon's decision regarding the prescription of prophylactic anticonvulsants may have acted as a selection bias. Fourth, in this study, valproate, levetiracetam, and phenytoin were administered by selection according to the preference of the surgeon. Therefore, it may be subject to systematic bias and influence the outcome of the analysis.