Journal of Clinical Neuroscience 22 (2015) 87–91
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
Epilepsy in patients with gliomas: Incidence and control of seizures Toshihiko Iuchi ⇑, Yuzo Hasegawa, Koichiro Kawasaki, Tsukasa Sakaida Division of Neurological Surgery, Chiba Cancer Center, 666-2 Nitona-cho, Chuo-ku, Chiba, Japan
a r t i c l e
i n f o
Article history: Received 12 March 2013 Accepted 15 May 2014
Keywords: Anti-epileptic drug Brain tumor related epilepsy Epidemiology
a b s t r a c t Brain tumor-related epilepsy (BTRE) is a unique condition that is distinct from primary epilepsy. The aim of this retrospective study was to clarify the epidemiology and results of treatment of BTRE in a single institution. From a database of 121 consecutive patients with supratentorial gliomas treated at Chiba Cancer Center from 2006–2012, the incidence and control of seizures before and after surgery were retrospectively evaluated. Epilepsy occurred in 33.9% of patients before surgery. All patients received prophylactic anti-epileptic drugs (AED) during surgery; however, seizures occurred in 9.1% of patients within the first postoperative week. During follow-up, seizures occurred in 48.3% of patients. The overall incidence of seizures was 73.7% in patients with World Health Organization Grade II gliomas, 66.7% in those with Grade III and 56.8% in those with Grade IV gliomas. Levetiracetam was very well tolerated. However, carbamazepine and phenytoin were poorly tolerated because of adverse effects. AED were discontinued in 56 patients. Fifteen of these patients (26.8%) had further seizures, half occurring within 3 months and 80% within 6 months of AED withdrawal. No clinical factors that indicated it was safe to discontinue AED were identified. The unpredictable epileptogenesis associated with gliomas and their excision requires prolonged administration of AED. To maintain quality of life and to safely and effectively control the tumor, it is necessary to select AED that do not adversely affect cognitive function or interact with other drugs, including anti-cancer agents. Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction The treatment of epilepsy, a common neurological condition with many causes, should vary according to the cause. A brain tumor is one of the major causes of epilepsy; seizures may occur as the initial symptom and may also develop during tumor treatment. Although some difficulties in controlling brain tumorrelated epilepsy (BTRE) have been reported [1,2], there are little published data concerning glioma-related seizures. The aim of this retrospective study was to clarify the epidemiology and results of treatment of BTRE in a single institution. 2. Patients and methods One hundred and twenty-one consecutive patients with supratentorial gliomas treated at the Division of Neurological Surgery at the Chiba Cancer Center, Japan, between March 2006 and March 2012 were enrolled. The study included 74 male and 47 female patients with an average age of 58 years. The diagnosis was confirmed pathologically in all cases. There were 99 astrocytic and ⇑ Corresponding author. Tel.: +81 43 264 5431; fax: +81 43 465 9515. E-mail address: [email protected] (T. Iuchi). http://dx.doi.org/10.1016/j.jocn.2014.05.036 0967-5868/Ó 2014 Elsevier Ltd. All rights reserved.
22 oligodendroglial tumors. The patients’ characteristics are summarized in Table 1. Because our institution has no guidelines for the use of anti-epileptic drugs (AED), the specific AED prescribed depended on the clinician’s preferences. Prophylactic treatment with AED was routinely initiated before surgery. Because phenytoin (PHT) is the only AED available for intravenous administration in Japan, this agent was routinely selected for seizure prophylaxis during surgery. To achieve stable serum concentrations, administration of this agent was started 2 or 3 days before surgery and continued for 6 days after surgery. Patients who had adverse reactions to PHT or whose seizures were insufficiently controlled by PHT were given phenobarbital (PB) by suppository or intramuscular injection during surgery. Postoperatively, all patients with World Health Organization (WHO) Grade III or IV tumors received irradiation with concurrent and adjuvant temozolomide according to the Stupp protocol [3], whereas patients with Grade II tumors were simply observed. The clinical records were reviewed and dates of seizure onset, efficacy of seizure control and use of AED evaluated. The chisquared test and Fisher’s exact method were used to analyze differences in incidence of seizures according to histology, WHO grades, location and number of tumors, and sex and age of patients.
88
T. Iuchi et al. / Journal of Clinical Neuroscience 22 (2015) 87–91 Table 2 Incidence of seizures as the presenting symptom in patients with brain tumor
Table 1 Characteristics of 121 patients with glioma Characteristics Histology Oligodendroglioma Anaplastic oligodendroglioma Diffuse astrocytoma Anaplastic astrocytoma Glioblastoma multiforme Sex Male Female Location involved Frontal Temporal Parietal Occipital Basal ganglia Thalamus Post-surgical treatments Observation only Irradiation + temozolomide
Characteristics (n)
Number (%)
p value
36.4/23.2
0.157
WHO Grade II (19)/III (21)/IV (81)
47.4/28.6/19.8
0.017*
Sex Male (74)/Female (47)
24.3/27.7
0.676
Age
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
Epilepsy in patients with gliomas: Incidence and control of seizures Toshihiko Iuchi ⇑, Yuzo Hasegawa, Koichiro Kawasaki, Tsukasa Sakaida Division of Neurological Surgery, Chiba Cancer Center, 666-2 Nitona-cho, Chuo-ku, Chiba, Japan
a r t i c l e
i n f o
Article history: Received 12 March 2013 Accepted 15 May 2014
Keywords: Anti-epileptic drug Brain tumor related epilepsy Epidemiology
a b s t r a c t Brain tumor-related epilepsy (BTRE) is a unique condition that is distinct from primary epilepsy. The aim of this retrospective study was to clarify the epidemiology and results of treatment of BTRE in a single institution. From a database of 121 consecutive patients with supratentorial gliomas treated at Chiba Cancer Center from 2006–2012, the incidence and control of seizures before and after surgery were retrospectively evaluated. Epilepsy occurred in 33.9% of patients before surgery. All patients received prophylactic anti-epileptic drugs (AED) during surgery; however, seizures occurred in 9.1% of patients within the first postoperative week. During follow-up, seizures occurred in 48.3% of patients. The overall incidence of seizures was 73.7% in patients with World Health Organization Grade II gliomas, 66.7% in those with Grade III and 56.8% in those with Grade IV gliomas. Levetiracetam was very well tolerated. However, carbamazepine and phenytoin were poorly tolerated because of adverse effects. AED were discontinued in 56 patients. Fifteen of these patients (26.8%) had further seizures, half occurring within 3 months and 80% within 6 months of AED withdrawal. No clinical factors that indicated it was safe to discontinue AED were identified. The unpredictable epileptogenesis associated with gliomas and their excision requires prolonged administration of AED. To maintain quality of life and to safely and effectively control the tumor, it is necessary to select AED that do not adversely affect cognitive function or interact with other drugs, including anti-cancer agents. Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction The treatment of epilepsy, a common neurological condition with many causes, should vary according to the cause. A brain tumor is one of the major causes of epilepsy; seizures may occur as the initial symptom and may also develop during tumor treatment. Although some difficulties in controlling brain tumorrelated epilepsy (BTRE) have been reported [1,2], there are little published data concerning glioma-related seizures. The aim of this retrospective study was to clarify the epidemiology and results of treatment of BTRE in a single institution. 2. Patients and methods One hundred and twenty-one consecutive patients with supratentorial gliomas treated at the Division of Neurological Surgery at the Chiba Cancer Center, Japan, between March 2006 and March 2012 were enrolled. The study included 74 male and 47 female patients with an average age of 58 years. The diagnosis was confirmed pathologically in all cases. There were 99 astrocytic and ⇑ Corresponding author. Tel.: +81 43 264 5431; fax: +81 43 465 9515. E-mail address: [email protected] (T. Iuchi). http://dx.doi.org/10.1016/j.jocn.2014.05.036 0967-5868/Ó 2014 Elsevier Ltd. All rights reserved.
22 oligodendroglial tumors. The patients’ characteristics are summarized in Table 1. Because our institution has no guidelines for the use of anti-epileptic drugs (AED), the specific AED prescribed depended on the clinician’s preferences. Prophylactic treatment with AED was routinely initiated before surgery. Because phenytoin (PHT) is the only AED available for intravenous administration in Japan, this agent was routinely selected for seizure prophylaxis during surgery. To achieve stable serum concentrations, administration of this agent was started 2 or 3 days before surgery and continued for 6 days after surgery. Patients who had adverse reactions to PHT or whose seizures were insufficiently controlled by PHT were given phenobarbital (PB) by suppository or intramuscular injection during surgery. Postoperatively, all patients with World Health Organization (WHO) Grade III or IV tumors received irradiation with concurrent and adjuvant temozolomide according to the Stupp protocol [3], whereas patients with Grade II tumors were simply observed. The clinical records were reviewed and dates of seizure onset, efficacy of seizure control and use of AED evaluated. The chisquared test and Fisher’s exact method were used to analyze differences in incidence of seizures according to histology, WHO grades, location and number of tumors, and sex and age of patients.
88
T. Iuchi et al. / Journal of Clinical Neuroscience 22 (2015) 87–91 Table 2 Incidence of seizures as the presenting symptom in patients with brain tumor
Table 1 Characteristics of 121 patients with glioma Characteristics Histology Oligodendroglioma Anaplastic oligodendroglioma Diffuse astrocytoma Anaplastic astrocytoma Glioblastoma multiforme Sex Male Female Location involved Frontal Temporal Parietal Occipital Basal ganglia Thalamus Post-surgical treatments Observation only Irradiation + temozolomide
Characteristics (n)
Number (%)
p value
36.4/23.2
0.157
WHO Grade II (19)/III (21)/IV (81)
47.4/28.6/19.8
0.017*
Sex Male (74)/Female (47)
24.3/27.7
0.676
Age
