Seizures after intracerebral hemorrhage; risk factor, recurrence, efficacy of antiepileptic drug

https://doi.org/10.1016/j.jns.2015.09.358Get rights and content

Highlights

  • The largest cohort of ICH and post-stroke seizure analyzed.

  • Incident rate of early seizure and late seizure were 4.3% and 2.3%.

  • Of the patients with an initial seizure, 15.7% had recurrent PSS.

  • AED treatment had a poor probability of preventing the recurrence of PSS.

Abstract

Objective: This study aimed to determine the risk factors for recurrent post stroke seizure (PSS) and the efficacy of anti-epileptic drugs (AED) in patients having intracerebral hemorrhage (ICH) with initial seizure.

Methods/subjects: A total of 1920 consecutive patients with ICH from 2004 to 2012 were investigated retrospectively. The relationships among the baseline clinical and radiological data, administration of AED, and incidence of initial and recurrent PSS were evaluated using multiple logistic regression analysis.

Results: Seizures occurred in 127 (6.6%) of the 1920 patients, displaying statistically significant relationships with cortical involvement of a cerebral lesion (P < 0.001), non-hypertensive ICH (P < 0.001), younger age (P < 0.001), and severe neurological deficits (P < 0.001). Early (4.3%) and late seizure (2.3%) had no significant relationship with the development of recurrent PSS. Larger volume of hematoma was the only independent factor associated with recurrence of PSS (OR 1.03; 95% CI 1.00–1.05; P = 0.027). A Kaplan Meier survival analysis revealed that AED treatment had a poor association with recurrence of PSS (P = 0.750).

Conclusions: Larger volume of hematoma was predictive of recurrence of PSS. AED therapy had poor association with preventing the recurrence of PSS.

Introduction

Post stroke seizures (PSS) are occasionally associated with intracerebral hemorrhage (ICH), with some patients having recurrent PSS. However, the risk factors of recurrent seizure for patients with an initial PSS after first ever ICH, and the effects of antiepileptic drugs (AED) for preventing recurrence of PSS, remains limited.

Electrographic seizures occur in 28% of patients with ICH during the initial 72 h after admission [1], and may be associated with expanding hemorrhages and periodic electrical discharges during cortical ICH [2]. PSS are commonly classified as early and late seizure (ES and LS) based on the differences of their timing after stroke. An arbitrary cut point of 1 or 2 weeks after the presenting stroke has been recognized to distinguish between them. Previous studies have reported that the incidence rate of seizures after ICH is 2.7–18.7% [3], [4], [5], [6], [7], [8], [9], with ES occurring in 2.7–17%, after ICH and the majority of seizures occurring at, or near, the onset of ICH [1], [3], [4], [5], [8]. The incidence rate of LS after ICH is reported to be 2.0–26.1%, and the wider variance is attributed to the divergent definitions of LS between studies [3], [4], [6], [9], [10], [11], [12]. Several studies report that the factors provoking seizures following ICH are related to hemorrhage volume, hemorrhage location within the cerebrum, cortical involvement, and the severity of neurological deficits [5], [11], [12], [13], [14].

There are also several previous reports on the effects of AED for seizures associated with ICH. Prophylactic administration of AED for lobar ICH reduces clinical seizures [5]. Short-term prophylactic AED therapy during the acute stage of ICH is effective for patients, because the seizures lead to additional damage such as herniation or re-bleeding [15]. However, these reports did not show the correlation between AED therapy in acute state and long-term outcome. Prospective and population-based studies do not show clear evidence for the direct influence of clinical seizures on neurological outcome or mortality [6], [9], [13], [16], which may suggest the benefit little from AED therapy. Several reports have examined the preventative effects of AED therapy on the development of recurrent PSS, which showed prophylactic AED therapy was not significantly associated with outcome [17], [28], [19]. The clinical decision about beginning and/or continuing AED therapy for an initial PSS after ICH is an important issue. This study aimed to determine the risk factors for recurrence of PSS and the efficacy of AED to prevent the recurrent PSS for patients having ICH with ES and LS.

Section snippets

Study population and design

This retrospective study analyzed hospitalized patients enrolled in our stroke registry from January 2004 to April 2012. The study sample consisted of 1920 patients with ICH. Exclusion criteria for ICH consisted of the following: (1) traumatic ICH, (2) subarachnoid hemorrhage, subdural hematoma, hemorrhagic infarct, or inflammatory vascular diseases, and (3) ICH caused by a primary or metastatic brain tumor. All records regarding subsequent hospitalization and death were reviewed. For the

Total patient cohort

The total number of patients with spontaneous ICH was 1920, comprising 1103 men (mean age 65.7 ± 13.8 years) and 817 women (mean age 71.9 ± 14.1 years). In this study, seizures occurred in 127 cases (6.6%). The interval from the onset of ICH to initial PSS was 0–78.5 months (mean 6.1 ± 13.8 months). Sixty-five cases had PSS at onset, and 72 had PSS within 24 h of onset. ES and LS were present in 83 (4.3%) and 44 cases (2.3%), respectively. Patients with PSS were significantly younger (62.1 ± 18.1 vs. 68.8 ± 

Discussion

The present study demonstrates that the incidence of PSS in 1920 patients with ICH is 6.6%, and that seizures occur frequently following a cortical hemorrhage, non-hypertensive hemorrhage, severe neurological deficits, or in young patients. ES and LS occurred in 4.3% and 2.3% of the total ICH patient cohort, respectively, and 15.7% of the patients with an initial seizure developed recurrent PSS. In the present study, ES occurred in 4.3% of patients, which is consistent with past reports [4], [5]

Conclusion

Seizures are an important neurological complication of spontaneous ICH. The incident rates of ES and LS were 4.3% and 2.3%. Initial seizures in patients with ICH significantly correlated with cortical involvement of the cerebral lesion, non-hypertensive ICH, younger age, and severe neurological deficits. Of the patients with an initial seizure, 15.7% had recurrent PSS. Larger hematoma volume was the only predictive factor for recurrence of PSS. AED therapy when administered after the initial

Conflicts of interest/disclosures

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Acknowledgments

We are grateful to Mrs. Tomoko Fukushima for providing statistical analysis and help for this study.

References (29)

  • J. De Reuck et al.

    Seizures and epilepsy in patients with a spontaneous intracerebral haematoma

    Clin. Neurol. Neurosurg.

    (2007)
  • J. De Reuck et al.

    Single seizure and epilepsy in patients with a cerebral territorial infarct

    J. Neurol. Sci.

    (2008)
  • P.M. Vespa et al.

    Acute seizures after intracerebral hemorrhage:a factor in progressive midline shift and outcome

    Neurology

    (2003)
  • J. Claassen et al.

    Electrographic seizures and periodic discharges after intracerebral hemorrhage

    Neurology

    (2007)
  • C.F. Bladin et al.

    Seizures after stroke: a prospective multicenter study

    Arch. Neurol.

    (2000)
  • T.M. Yang et al.

    Predictors and outcome of seizures after spontaneous intracerebral hemorrhage. Clinical article

    J. Neurosurg.

    (2009)
  • S. Passero et al.

    Seizures after spontaneous supratentorialintracerebral hemorrhage

    Epilepsia

    (2002)
  • K.M.1. Woo et al.

    Seizures after spontaneous intracerebral hemorrhage

    J. Korean Neurosurg. Soc.

    (2012)
  • C.Y. Sung et al.

    Epileptic seizures in intracerebral haemorrhage

    J. Neurol. Neurosurg. Psychiatry

    (1989)
  • N. Andaluz et al.

    Recent trends in the treatment of spontaneous intracerebral hemorrhage: analysis of a nationwide inpatient database

    J. Neurosurg.

    (2009)
  • J. Burn et al.

    Epileptic seizures after a first stroke: the Oxfordshire Community Stroke Project

    Br. Med. J.

    (1997)
  • C. Rossi et al.

    Incidence and predictors of late seizures in intracerebral hemorrhages

    Stroke

    (2013)
  • C. Lamy et al.

    Patent foramen ovale and atrial septal aneurysm study group: early and late seizures after cryptogenic ischemic stroke in young adults

    Neurology

    (2003)
  • V. De Herdt et al.

    Early seizures in intracerebral hemorrhage: Incidence,associated factors, and outcome

    Neurology

    (2011)
  • Cited by (40)

    • Incidence and relevant factors for seizures after spontaneous intracerebral hemorrhage: A systematic review and meta-analysis

      2022, Seizure
      Citation Excerpt :

      If the relevant factors were discussed by at least 3 studies in a consistent manner with a sample size >50, we conducted a meta-analysis, which we classified into the following 5 groups: baseline characteristics, basic diseases, lifestyle habits, clinical events, and treatments (Table 2). Our meta-analysis of age included 15 studies [6,10,11,16,19–29], which showed that elderly patients with ICH were less vulnerable to suffering seizures than young patients(SMD (95% CI)= −0.27 (−0.37, −0.16), I2= 66.80%, p<0.01). The forest plot of age is listed in Fig. 2.

    • Development and validation of a clinical score to predict late seizures after intracerebral hemorrhage in Chinese

      2021, Epilepsy Research
      Citation Excerpt :

      Multivariate analysis of our study showed patients with NIHSS 15 or more had an almost 7-fold increase in risk of late seizures. Consistent with the CAVE score and other studies we found that younger age was associated with late seizures (Haapaniemi et al., 2014; Qian et al., 2014; Roivainen et al., 2013; Tanaka et al., 2015; Neshige et al., 2015; Conrad et al., 2013). A 10-year population-based study reported a higher incidence of late seizures in patients aged <65 years than >85 years (10.7 % vs. 1.6 %)(Graham et al., 2013).

    • Preventing seizure occurrence following spontaneous intracerebral haemorrhage: A systematic review and meta-analysis of seizure prophylaxis

      2021, Seizure
      Citation Excerpt :

      Furthermore, as more studies were added, we did not observe the same efficacy. We observed that the early 3 studies also reported relatively higher ICH volumes or higher percentages of patients with IVH or both; both of these factors have been shown to be associated with a higher risk of seizures after spontaneous ICH 7,16,24]. Thus, we now hypothesize that seizure prophylaxis may be more effective in patients with more severe disease and in those at higher risk of seizure occurrence.

    View all citing articles on Scopus
    1

    Present address: Department of Clinical Neuroscience and Therapeutics, Hiroshima

    University Graduate School of Biomedical Sciences, Hiroshima, Japan.

    View full text