- Email: [email protected]
Clinical Features of Late-onset Poststroke Seizures
Clinical Features of Late-onset Poststroke Seizures Shiho Okuda, MD, PhD,* Shin Takano, MD, PhD,* Masao Ueno, MD,* Hirotoshi Hamaguchi, MD, PhD,† and Fumio Kanda, MD, PhD†
Background: Compared to the patients with early-onset seizures (ES), those with late-onset seizures (LS) have a high risk of epilepsy that is a feared complication after stroke. However, few studies have described detailed clinical features of LS in Japanese patients. Methods: To elucidate the clinical features of LS, a series of 448 stroke patients (cerebral infarction n 5 286; cerebral hemorrhage n 5 162) in our hospital were retrospectively examined in this study. Stroke location was determined by computed tomographic and/or magnetic resonance imaging scans. Lesion size was evaluated using the Alberta Stroke Program Early Computed Tomographic Score. We examined occurrence rate, onset time, and recurrence rate of LS. In addition, clinical features of the infarction of LS and non-LS group were compared on age, gender, laterality, location, and extent, respectively. Results: LS occurred in 18 patients (4.0%). Of these, 17 experienced LS within 1.5 years after stroke. While epilepsy developed in none of the patients with ES, it developed in 33% of those with LS. Patients with cortical and a larger infarction involving the middle cerebral artery had at significantly greater risk of LS (P , .05). Conclusions: Patients with cortical and a larger infarction involving the middle cerebral artery should be carefully observed because of a high risk of LS. Key Words: Stroke-related seizures—late seizures—epilepsy—infarction size—cortical infarction. Crown Copyright Ó 2012 Published by Elsevier Inc. on behalf of National Stroke Association. All rights reserved.
Epilepsy is one of the most common neurologic disorders, with an estimated prevalence of 0.5% to 1.0%.1 It may have serious consequences, including physical injuries, and can also have high mortality rates in adults.2-5 Stroke is a frequent cause of seizure and epilepsy in adults.6 The frequency of seizures after stroke is variously estimated at 8% to 10%,7-10 and epilepsy—a condition in which recurrent seizures are expected—occurs in 2.5% of stroke patients.8 Seizures after stroke are classified as early-onset seizures (ES) when occurring within 14 days after stroke or late-onset seizures (LS) when occurring more
than 14 days after stroke.7,8 Compared to patients with ES, those with LS have a high risk of epilepsy.7,8 It is important to elucidate the characteristics of LS. Although many studies of the clinical features of LS have been reported,8-10 few studies have been reported in Japanese patients.11 In the present study, we investigated occurrence rate, onset time, and recurrence rate of LS. The clinical features of the infarction of LS and non-LS groups were compared on age, gender, laterality, location, and extent, respectively.
From the *Departments of Neurology at Hyogo Rehabilitation Center Hospital; and †Kobe University Hospital, Kobe, Japan. Received November 11, 2010; revision received January 11, 2011; accepted January 19, 2011. Address correspondence to Shiho Okuda, MD, PhD, Department of Neurology, Hyogo Rehabilitation Center Hospital, 1070, Akebonocho, Nishi-ku, Kobe 651-2181, Japan. E-mail: [email protected]. 1052-3057/$ - see front matter Crown Copyright Ó 2012 Published by Elsevier Inc. on behalf of National Stroke Association. All rights reserved. doi:10.1016/j.jstrokecerebrovasdis.2011.01.006
Four hundred forty-eight consecutive patients were admitted to Hyogo Rehabilitation Center Hospital for rehabilitation after stroke between January 2008 and November 2009. Excluded were syncopes of cardiac or other origin and subarachnoid hemorrhage. The study population included 283 males with a mean age of 62.4 years (range 14-88) and 165 females with a mean age of 64.9 years (range 14-89). Two hundred eighty-six patients had cerebral infarction and 162 had cerebral hemorrhage.
Methods
Journal of Stroke and Cerebrovascular Diseases, Vol. 21, No. 7 (October), 2012: pp 583-586
583
S. OKUDA ET AL.
584
The median period of LS after stroke was 4 months, and the mean duration of follow-up after stroke was 8 months (range 1-157). Stroke location was determined by computed tomographic (CT) and/or magnetic resonance imaging (FLAIR image) scans that were taken during a chronic stage after stroke. We defined an infarction that included the cortex as cortical infarction, and those that did not include the cortex as subcortical infarction. Lesion size was expressed using the Alberta Stroke Program Early Computed Tomographic Score (ASPECTS).12 We examined onset time of LS, type of antiepileptic drugs (AEDs) prescribed, and whether the AEDs were effective. Furthermore, the infarctions of seizure and nonseizure groups were compared on extent, location, gender, and laterality. The Chi-square test was used to compare gender, laterality, and cortical or subcortical infarction. The Student t test was used for age data, and a Wilcoxon signed-rank test was used to analyze ASPECTS data. The study protocol was approved by the local ethics committee on human research. Informed consent for the use of routine clinical data was obtained from the patients.
Results Seizures occurred in 23 (5.1%) of the 448 stroke patients, most of which were secondary generalized tonic–clonic seizures. LS occurred in 18 patients (4.0%). Of these, 17 patients experienced LS within 1.5 years after stroke except 1 (Table 1). All 18 LS patients were offered AEDs, with valproic acid given as the initial treatment in 11 of 18 LS patients. Most (67%) had already begun AED administration at another hospital. Epilepsy developed in 6 (33%) of the patients with LS, including 2 patients who received anticonvulsant prophylaxis. On the contrary, epilepsy developed in none of the patients with ES (data not shown). Cerebral infarction involving the middle cerebral artery (MCA) occurred in 13 LS patients, and it was a more frequent cause of LS in this study (Table 1). We focused on infarction in the territory of the MCA and compared clinical features of the LS and non-LS groups (Table 2). The mean ASPECTS for the 13 patients with LS was 4.2. LS group with infarction in the territory of the MCA had a larger infarction. On the other hand, the mean ASPECTS for the 182 patients in non-LS group was 7.9. Those results show that the patients with a larger infarction involving the MCA had at significantly greater risk of LS (P , .05). In addition, the patients with cortical infarction involving the MCA also had a significantly greater risk of LS (P , .05). There were no differences in age, gender, and laterality observed between the LS and non-LS groups with infarction in the territory of the MCA.
Discussion Seizures occurred in 5.1% of the patients with stroke in our study, which was lower than the nearly 10% incidence
7-10
The relatively low rates reported in previous studies. frequency in our study might have been related to dissimilarities among the studies in stroke severity, which is known to be an independent predictor of development of seizures after stroke. Because of the characteristics of our rehabilitation hospital, nearly all of the patients in this study were restricted to those who were able to participate in rehabilitation. Therefore, it is possible that severe patients were excluded from our study. Another reason for the lower rate of incidence in the present study may have been the duration of follow-up examinations. The mean duration of follow-up after stroke was 8 months in our study, and it is possible that the occurrence rate of seizures after stroke would increase with longer follow-up periods. Seizures may be a more common accompaniment of cerebral hemorrhage than cerebral infarction.8-10 Although the mechanism of seizure initiation by hemorrhage is not established, products of blood metabolism, such as hemosiderin, may cause a focal cerebral irritation, leading to seizures.7 In this study, however, seizures were prone to occur with cerebral infarction more than with cerebral hemorrhage. In addition, cortical location is the most reliable risk factor for poststroke seizures,9 which are more likely to develop in patients with larger lesions involving multiple lobes of the brain than in those with single lobar involvement.13 Although few studies of the clinical features of LS have been reported in Japanese patients, Matsumura et al11 reported that patients with cortical infarction had at significantly greater risk of LS. In the present study, most patients with LS were caused by cerebral infarction, all of which involved the MCA region. Therefore, to focus on cases of cerebral infarction involving the MCA, we investigated the clinical features of the LS and non-LS groups. Our findings revealed that patients with cortical and a larger infarction involving the MCA had a significantly greater risk of LS. To the best of our knowledge, there are no other reports of clinical features of LS patients in Japan with cerebral infarction involving the MCA. The prevalence of LS after stroke varies from 1.5 to 5 years.8-10 It was approximately 1.5 years in our patients. Taken together, patients with cortical and a larger infarction involving MCA should be carefully observed for at least 5 years poststroke because of a high risk of LS. Poststroke seizures are usually well controlled with a single anticonvulsant.7 Given the typical focal onset of poststroke seizures, carbamazepine is the first-line monotherapy candidate in Japan.14 However, the patients in this study often received valproic acid (Table 1). The reason for the preferable use of valproic acid in our patients is unclear. The frequency of prescription of carbamazepine might be avoided more often than appropriate because of its severe side effects. The newer AEDs are being touted as first-line agents for elderly patients because of their effectiveness and favorable side effect profiles.7 Although many of the newer
Age/sex
Type of stroke
Location of stroke
Risk factor DM, OMI
Surgical treatment for stroke
Onset time of LS 4 mo 4 mo 4 y 1 mo 1 y 5 mo 5 mo
53/M 54/M 55/M 66/M 78/F
Infarction Infarction Infarction Infarction Infarction
L MCA, cortical R ACA, MCA, cortical L ACA, MCA, cortical L MCA, cortical L MCA, cortical
DL, DM AF, DCM, HT AF, DL, HT
No Yes No No No
79/M 76/F 73/M
Infarction Infarction Infarction
L ACA, MCA, cortical L MCA, cortical L MCA, cortical
AF, HT AF AF, DM, HT
No No No
4 mo 1 y 2 mo 5 mo
67/M 76/M 36/M 54/M 53/M 49/M 55/F 60/M 64/F 76/M
Infarction Infarction Infarction Infarction Infarction Hemorrhage Hemorrhage Hemorrhage Hemorrhage Hemorrhage
R MCA, cortical R MCA, cortical L MCA, cortical R MCA, cortical L MCA, cortical L frontal lobar L frontal lobar L parietal, occipital lobar L frontal, temporal lobar R parietal lobar
CRF, HT DL, DM, HT
Yes No No No No No Yes No Yes Yes
3 mo 4 mo 3 mo 2 mo 7 mo 2 mo 6 mo 9 mo 4 mo 1 mo
AF, HT HT DL, HT HT HT HT
Medication Antihypertensive drug, anticoagulant, antiepileptic drug (VPA) Antiplatelet, antiepileptic drug (VPA) Antiplatelet, statin, sulfonylurea drug, antiepileptic drug (VPA) Antihypertensive drugs, anticoagulant, antiepileptic drug (VPA) Antihypertensive drug, antiplatelets, anticoagulant, antiepileptic drug (VPA) Antihypertensive drugs, anticoagulant, antiepileptic drug (PB) Anticoagulant, antiepileptic drug (PHT) Antihypertensive drug, sulfonylurea drug, anticoagulant, antiepileptic drug (VPA) Antihypertensive drugs, antiplatelets, antiepileptic drug (VPA) Antiplatelets, antiepileptic drug (CBZ) Anticoagulant, antiepileptic drug (VPA) Antihypertensive drugs, antiepileptic drug (GBP) Anticoagulant, antiplatelet, antiepileptic drug (VPA) Antiepileptic drug (VPA[P]) Antihypertensive drugs, antiepileptic drug (CBZ) Antihypertensive drug, antiepileptic drug (PHT[P]) Antihypertensive drug, antiepileptic drug (VPA) Antiepileptic drug (PRM)
Recurrence of seizures No No No No No No Yes No
CLINICAL FEATURES OF LATE SEIZURES AFTER STROKE
Table 1. Clinical features of patients with late seizures
No No Yes Yes Yes Yes No Yes No No
Abbreviations: ACA, anterior cerebral artery; AF, atrial fibrillation; CBZ, carbamazepine; CRF, chronic renal failure; DCM, dilated cardiomyopathy; DL, dyslipidemia; F, female; GBP, gabapentin; HT, hypertension; L, left; M, male; MCA, middle cerebral artery; OMI, old myocardial infarction; P, prophylactic; PB, phenobarbital; PHT, phenytoin; PRM, primidone; R, right; VPA, valproic acid.
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S. OKUDA ET AL.
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Table 2. Clinical features of late-onset seizures versus non–late-onset seizures groups with infarction in the territory of the middle cerebral artery
Age, y (mean 6 SD) Sex Male Female Side Left Right Cortical infarction Subcortical infarction Evaluation of lesion size using ASPECTS (mean 6 SD)
LS group (n 5 13)
Non-LS group (n 5 182)
P*
62.5 6 13.1
67.6 6 12.6
NS
11 2
112 70
NS
9 4 13 0 4.2 6 2.2
94 88 82 100 7.9 6 2.0
NS ,.05 ,.05
Abbreviations: ASPECTS, Alberta Stroke Program Early Computed Tomographic Score; LS, late-onset seizures; NS, not significant; SD, standard deviation. *P values were computed using the Chi-square, Student t, or Wilcoxon signed-rank tests.
anticonvulsants (e.g., topiramate and lamotrigine) have been studied for refractory partial seizures in North America,15 those AEDs are available as only adjunctive agents in Japan. Gabapentin monotherapy should be approved for use in Japan because of its effectiveness and safety for late poststroke seizures.16 There are no studies concerning treatment of LS after stroke in Japan. Therefore, it is important to establish a standard protocol for AEDs in LS patients. In addition, a large cohort study of the characteristics of LS in Japanese patients will be required.
References 1. Fisher RS, van Emde Boas W, Blume W, et al. Epileptic seizures and epilepsy: Definition proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005; 46:470-472. 2. Forsgren L. Prevalence of epilepsy in adults in northern Sweden. Epilepsia 1992;33:450-458. 3. Hauser WA, Annegers JF, Kurland LT. Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935-1984. Epilepsia 1993;34:453-468. 4. Olafsson E, Ludvigsson P, Gudmundsson G, et al. Incidence of unprovoked seizures and epilepsy in Iceland and assessment of the epilepsy syndrome classification: Prospective study. Lancet Neurol 2005;4:627-634. 5. Tomson T, Nashef L, Ryvlin P. Sudden unexpected death in epilepsy: Current knowledge and future directions. Lancet Neurol 2008;7:1021-1031.
6. Slapo GD, Lossius M, Gjerstad L. Poststroke epilepsy: Occurrence, predictors and treatment. Expert Rev. Neurotherapeutics 2006;6:1801-1809. 7. Silverman IE, Restrepo L, Mathews GC. Poststroke seizures. Arch Neurol 2002;59:195-202. 8. Bladin CF, Alexandrov AV, Bellavance A, et al. Seizures after stroke: A prospective multicenter study. Arch Neurol 2000;57:1617-1622. 9. Burn J, Dennis M, Banford J, et al. Epileptic seizures after a first stroke: The Oxfordshire community stroke project. BMJ 1997;315:1582-1587. 10. De Reuck J, Sieben A, Van Maele G. Characteristics and outcomes of patients with seizures according to the time of onset in relation to stroke. Eur Neurol 2008; 59:225-228. 11. Matsumura T, Kojima S, Shiozawa R. Late onset seizures in cerebral infarction—Clinical study of late onset seizures in cortical branch infarction [in Japanese]. Clin Neurol 1993;33:95-97. 12. Pexman JH, Barber PA, Hill MD, et al. Use of the Alberta Stroke Program Early CT Score (ASPECTS) for assessing CT scans in patients with acute stroke. AJNR Am J Neuroradiol 2001;22:1534-1542. 13. Lancman ME, Golimstok A, Norscini J, et al. Risk factors for developing seizures after a stroke. Epilepsia 1993; 34:141-143. 14. Inoue Y, Nakamura F, Nishida T. Treatment guidelines for adult epilepsy. Rinsho Shinkeigaku 2004;44:861-864. 15. Akiyama T, Otsubo H. Antiepileptic drugs in North America [in Japanese]. Brain Nerve 2010;62:519-526. 16. Alvarez-Sabin J, Montaner J, Padro L, et al. Gabapentin in late-onset poststroke seizures. Neurology 2002;59: 1991-1993.
Background: Compared to the patients with early-onset seizures (ES), those with late-onset seizures (LS) have a high risk of epilepsy that is a feared complication after stroke. However, few studies have described detailed clinical features of LS in Japanese patients. Methods: To elucidate the clinical features of LS, a series of 448 stroke patients (cerebral infarction n 5 286; cerebral hemorrhage n 5 162) in our hospital were retrospectively examined in this study. Stroke location was determined by computed tomographic and/or magnetic resonance imaging scans. Lesion size was evaluated using the Alberta Stroke Program Early Computed Tomographic Score. We examined occurrence rate, onset time, and recurrence rate of LS. In addition, clinical features of the infarction of LS and non-LS group were compared on age, gender, laterality, location, and extent, respectively. Results: LS occurred in 18 patients (4.0%). Of these, 17 experienced LS within 1.5 years after stroke. While epilepsy developed in none of the patients with ES, it developed in 33% of those with LS. Patients with cortical and a larger infarction involving the middle cerebral artery had at significantly greater risk of LS (P , .05). Conclusions: Patients with cortical and a larger infarction involving the middle cerebral artery should be carefully observed because of a high risk of LS. Key Words: Stroke-related seizures—late seizures—epilepsy—infarction size—cortical infarction. Crown Copyright Ó 2012 Published by Elsevier Inc. on behalf of National Stroke Association. All rights reserved.
Epilepsy is one of the most common neurologic disorders, with an estimated prevalence of 0.5% to 1.0%.1 It may have serious consequences, including physical injuries, and can also have high mortality rates in adults.2-5 Stroke is a frequent cause of seizure and epilepsy in adults.6 The frequency of seizures after stroke is variously estimated at 8% to 10%,7-10 and epilepsy—a condition in which recurrent seizures are expected—occurs in 2.5% of stroke patients.8 Seizures after stroke are classified as early-onset seizures (ES) when occurring within 14 days after stroke or late-onset seizures (LS) when occurring more
than 14 days after stroke.7,8 Compared to patients with ES, those with LS have a high risk of epilepsy.7,8 It is important to elucidate the characteristics of LS. Although many studies of the clinical features of LS have been reported,8-10 few studies have been reported in Japanese patients.11 In the present study, we investigated occurrence rate, onset time, and recurrence rate of LS. The clinical features of the infarction of LS and non-LS groups were compared on age, gender, laterality, location, and extent, respectively.
From the *Departments of Neurology at Hyogo Rehabilitation Center Hospital; and †Kobe University Hospital, Kobe, Japan. Received November 11, 2010; revision received January 11, 2011; accepted January 19, 2011. Address correspondence to Shiho Okuda, MD, PhD, Department of Neurology, Hyogo Rehabilitation Center Hospital, 1070, Akebonocho, Nishi-ku, Kobe 651-2181, Japan. E-mail: [email protected]. 1052-3057/$ - see front matter Crown Copyright Ó 2012 Published by Elsevier Inc. on behalf of National Stroke Association. All rights reserved. doi:10.1016/j.jstrokecerebrovasdis.2011.01.006
Four hundred forty-eight consecutive patients were admitted to Hyogo Rehabilitation Center Hospital for rehabilitation after stroke between January 2008 and November 2009. Excluded were syncopes of cardiac or other origin and subarachnoid hemorrhage. The study population included 283 males with a mean age of 62.4 years (range 14-88) and 165 females with a mean age of 64.9 years (range 14-89). Two hundred eighty-six patients had cerebral infarction and 162 had cerebral hemorrhage.
Methods
Journal of Stroke and Cerebrovascular Diseases, Vol. 21, No. 7 (October), 2012: pp 583-586
583
S. OKUDA ET AL.
584
The median period of LS after stroke was 4 months, and the mean duration of follow-up after stroke was 8 months (range 1-157). Stroke location was determined by computed tomographic (CT) and/or magnetic resonance imaging (FLAIR image) scans that were taken during a chronic stage after stroke. We defined an infarction that included the cortex as cortical infarction, and those that did not include the cortex as subcortical infarction. Lesion size was expressed using the Alberta Stroke Program Early Computed Tomographic Score (ASPECTS).12 We examined onset time of LS, type of antiepileptic drugs (AEDs) prescribed, and whether the AEDs were effective. Furthermore, the infarctions of seizure and nonseizure groups were compared on extent, location, gender, and laterality. The Chi-square test was used to compare gender, laterality, and cortical or subcortical infarction. The Student t test was used for age data, and a Wilcoxon signed-rank test was used to analyze ASPECTS data. The study protocol was approved by the local ethics committee on human research. Informed consent for the use of routine clinical data was obtained from the patients.
Results Seizures occurred in 23 (5.1%) of the 448 stroke patients, most of which were secondary generalized tonic–clonic seizures. LS occurred in 18 patients (4.0%). Of these, 17 patients experienced LS within 1.5 years after stroke except 1 (Table 1). All 18 LS patients were offered AEDs, with valproic acid given as the initial treatment in 11 of 18 LS patients. Most (67%) had already begun AED administration at another hospital. Epilepsy developed in 6 (33%) of the patients with LS, including 2 patients who received anticonvulsant prophylaxis. On the contrary, epilepsy developed in none of the patients with ES (data not shown). Cerebral infarction involving the middle cerebral artery (MCA) occurred in 13 LS patients, and it was a more frequent cause of LS in this study (Table 1). We focused on infarction in the territory of the MCA and compared clinical features of the LS and non-LS groups (Table 2). The mean ASPECTS for the 13 patients with LS was 4.2. LS group with infarction in the territory of the MCA had a larger infarction. On the other hand, the mean ASPECTS for the 182 patients in non-LS group was 7.9. Those results show that the patients with a larger infarction involving the MCA had at significantly greater risk of LS (P , .05). In addition, the patients with cortical infarction involving the MCA also had a significantly greater risk of LS (P , .05). There were no differences in age, gender, and laterality observed between the LS and non-LS groups with infarction in the territory of the MCA.
Discussion Seizures occurred in 5.1% of the patients with stroke in our study, which was lower than the nearly 10% incidence
7-10
The relatively low rates reported in previous studies. frequency in our study might have been related to dissimilarities among the studies in stroke severity, which is known to be an independent predictor of development of seizures after stroke. Because of the characteristics of our rehabilitation hospital, nearly all of the patients in this study were restricted to those who were able to participate in rehabilitation. Therefore, it is possible that severe patients were excluded from our study. Another reason for the lower rate of incidence in the present study may have been the duration of follow-up examinations. The mean duration of follow-up after stroke was 8 months in our study, and it is possible that the occurrence rate of seizures after stroke would increase with longer follow-up periods. Seizures may be a more common accompaniment of cerebral hemorrhage than cerebral infarction.8-10 Although the mechanism of seizure initiation by hemorrhage is not established, products of blood metabolism, such as hemosiderin, may cause a focal cerebral irritation, leading to seizures.7 In this study, however, seizures were prone to occur with cerebral infarction more than with cerebral hemorrhage. In addition, cortical location is the most reliable risk factor for poststroke seizures,9 which are more likely to develop in patients with larger lesions involving multiple lobes of the brain than in those with single lobar involvement.13 Although few studies of the clinical features of LS have been reported in Japanese patients, Matsumura et al11 reported that patients with cortical infarction had at significantly greater risk of LS. In the present study, most patients with LS were caused by cerebral infarction, all of which involved the MCA region. Therefore, to focus on cases of cerebral infarction involving the MCA, we investigated the clinical features of the LS and non-LS groups. Our findings revealed that patients with cortical and a larger infarction involving the MCA had a significantly greater risk of LS. To the best of our knowledge, there are no other reports of clinical features of LS patients in Japan with cerebral infarction involving the MCA. The prevalence of LS after stroke varies from 1.5 to 5 years.8-10 It was approximately 1.5 years in our patients. Taken together, patients with cortical and a larger infarction involving MCA should be carefully observed for at least 5 years poststroke because of a high risk of LS. Poststroke seizures are usually well controlled with a single anticonvulsant.7 Given the typical focal onset of poststroke seizures, carbamazepine is the first-line monotherapy candidate in Japan.14 However, the patients in this study often received valproic acid (Table 1). The reason for the preferable use of valproic acid in our patients is unclear. The frequency of prescription of carbamazepine might be avoided more often than appropriate because of its severe side effects. The newer AEDs are being touted as first-line agents for elderly patients because of their effectiveness and favorable side effect profiles.7 Although many of the newer
Age/sex
Type of stroke
Location of stroke
Risk factor DM, OMI
Surgical treatment for stroke
Onset time of LS 4 mo 4 mo 4 y 1 mo 1 y 5 mo 5 mo
53/M 54/M 55/M 66/M 78/F
Infarction Infarction Infarction Infarction Infarction
L MCA, cortical R ACA, MCA, cortical L ACA, MCA, cortical L MCA, cortical L MCA, cortical
DL, DM AF, DCM, HT AF, DL, HT
No Yes No No No
79/M 76/F 73/M
Infarction Infarction Infarction
L ACA, MCA, cortical L MCA, cortical L MCA, cortical
AF, HT AF AF, DM, HT
No No No
4 mo 1 y 2 mo 5 mo
67/M 76/M 36/M 54/M 53/M 49/M 55/F 60/M 64/F 76/M
Infarction Infarction Infarction Infarction Infarction Hemorrhage Hemorrhage Hemorrhage Hemorrhage Hemorrhage
R MCA, cortical R MCA, cortical L MCA, cortical R MCA, cortical L MCA, cortical L frontal lobar L frontal lobar L parietal, occipital lobar L frontal, temporal lobar R parietal lobar
CRF, HT DL, DM, HT
Yes No No No No No Yes No Yes Yes
3 mo 4 mo 3 mo 2 mo 7 mo 2 mo 6 mo 9 mo 4 mo 1 mo
AF, HT HT DL, HT HT HT HT
Medication Antihypertensive drug, anticoagulant, antiepileptic drug (VPA) Antiplatelet, antiepileptic drug (VPA) Antiplatelet, statin, sulfonylurea drug, antiepileptic drug (VPA) Antihypertensive drugs, anticoagulant, antiepileptic drug (VPA) Antihypertensive drug, antiplatelets, anticoagulant, antiepileptic drug (VPA) Antihypertensive drugs, anticoagulant, antiepileptic drug (PB) Anticoagulant, antiepileptic drug (PHT) Antihypertensive drug, sulfonylurea drug, anticoagulant, antiepileptic drug (VPA) Antihypertensive drugs, antiplatelets, antiepileptic drug (VPA) Antiplatelets, antiepileptic drug (CBZ) Anticoagulant, antiepileptic drug (VPA) Antihypertensive drugs, antiepileptic drug (GBP) Anticoagulant, antiplatelet, antiepileptic drug (VPA) Antiepileptic drug (VPA[P]) Antihypertensive drugs, antiepileptic drug (CBZ) Antihypertensive drug, antiepileptic drug (PHT[P]) Antihypertensive drug, antiepileptic drug (VPA) Antiepileptic drug (PRM)
Recurrence of seizures No No No No No No Yes No
CLINICAL FEATURES OF LATE SEIZURES AFTER STROKE
Table 1. Clinical features of patients with late seizures
No No Yes Yes Yes Yes No Yes No No
Abbreviations: ACA, anterior cerebral artery; AF, atrial fibrillation; CBZ, carbamazepine; CRF, chronic renal failure; DCM, dilated cardiomyopathy; DL, dyslipidemia; F, female; GBP, gabapentin; HT, hypertension; L, left; M, male; MCA, middle cerebral artery; OMI, old myocardial infarction; P, prophylactic; PB, phenobarbital; PHT, phenytoin; PRM, primidone; R, right; VPA, valproic acid.
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S. OKUDA ET AL.
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Table 2. Clinical features of late-onset seizures versus non–late-onset seizures groups with infarction in the territory of the middle cerebral artery
Age, y (mean 6 SD) Sex Male Female Side Left Right Cortical infarction Subcortical infarction Evaluation of lesion size using ASPECTS (mean 6 SD)
LS group (n 5 13)
Non-LS group (n 5 182)
P*
62.5 6 13.1
67.6 6 12.6
NS
11 2
112 70
NS
9 4 13 0 4.2 6 2.2
94 88 82 100 7.9 6 2.0
NS ,.05 ,.05
Abbreviations: ASPECTS, Alberta Stroke Program Early Computed Tomographic Score; LS, late-onset seizures; NS, not significant; SD, standard deviation. *P values were computed using the Chi-square, Student t, or Wilcoxon signed-rank tests.
anticonvulsants (e.g., topiramate and lamotrigine) have been studied for refractory partial seizures in North America,15 those AEDs are available as only adjunctive agents in Japan. Gabapentin monotherapy should be approved for use in Japan because of its effectiveness and safety for late poststroke seizures.16 There are no studies concerning treatment of LS after stroke in Japan. Therefore, it is important to establish a standard protocol for AEDs in LS patients. In addition, a large cohort study of the characteristics of LS in Japanese patients will be required.
References 1. Fisher RS, van Emde Boas W, Blume W, et al. Epileptic seizures and epilepsy: Definition proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005; 46:470-472. 2. Forsgren L. Prevalence of epilepsy in adults in northern Sweden. Epilepsia 1992;33:450-458. 3. Hauser WA, Annegers JF, Kurland LT. Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935-1984. Epilepsia 1993;34:453-468. 4. Olafsson E, Ludvigsson P, Gudmundsson G, et al. Incidence of unprovoked seizures and epilepsy in Iceland and assessment of the epilepsy syndrome classification: Prospective study. Lancet Neurol 2005;4:627-634. 5. Tomson T, Nashef L, Ryvlin P. Sudden unexpected death in epilepsy: Current knowledge and future directions. Lancet Neurol 2008;7:1021-1031.
6. Slapo GD, Lossius M, Gjerstad L. Poststroke epilepsy: Occurrence, predictors and treatment. Expert Rev. Neurotherapeutics 2006;6:1801-1809. 7. Silverman IE, Restrepo L, Mathews GC. Poststroke seizures. Arch Neurol 2002;59:195-202. 8. Bladin CF, Alexandrov AV, Bellavance A, et al. Seizures after stroke: A prospective multicenter study. Arch Neurol 2000;57:1617-1622. 9. Burn J, Dennis M, Banford J, et al. Epileptic seizures after a first stroke: The Oxfordshire community stroke project. BMJ 1997;315:1582-1587. 10. De Reuck J, Sieben A, Van Maele G. Characteristics and outcomes of patients with seizures according to the time of onset in relation to stroke. Eur Neurol 2008; 59:225-228. 11. Matsumura T, Kojima S, Shiozawa R. Late onset seizures in cerebral infarction—Clinical study of late onset seizures in cortical branch infarction [in Japanese]. Clin Neurol 1993;33:95-97. 12. Pexman JH, Barber PA, Hill MD, et al. Use of the Alberta Stroke Program Early CT Score (ASPECTS) for assessing CT scans in patients with acute stroke. AJNR Am J Neuroradiol 2001;22:1534-1542. 13. Lancman ME, Golimstok A, Norscini J, et al. Risk factors for developing seizures after a stroke. Epilepsia 1993; 34:141-143. 14. Inoue Y, Nakamura F, Nishida T. Treatment guidelines for adult epilepsy. Rinsho Shinkeigaku 2004;44:861-864. 15. Akiyama T, Otsubo H. Antiepileptic drugs in North America [in Japanese]. Brain Nerve 2010;62:519-526. 16. Alvarez-Sabin J, Montaner J, Padro L, et al. Gabapentin in late-onset poststroke seizures. Neurology 2002;59: 1991-1993.