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Epileptic seizures in supratentorial gliomas.
Correspondence Address:
Two hundred patients with supratentorial glioma; astrocytoma (pilocytic, fibrillary, gemistocytic) 82, mixed glioma (oligoastrocytoma) 46, oligodendroglioma 8, malignant (anaplastic) astrocytoma 33 and glioblastoma multiforme 31, surgically treated for the tumours and followed up for one to sixteen years, were retrospectively analysed for the incidence of pre and postoperative epileptic seizures. 122 patients (61%) had seizures preoperatively. 62 (50.8%) of them had at least one or more seizures during follow up. Seizures were persistent in 22 patients. Doubtful, or one or two minor seizures occurred in 19 cases. Six patients in this group had seizure only at the time of CT confirmed recurrence, after a seizure free interval of one to nine years. Amongst 78 patients who did not have seizures preoperatively, 24 (30.6%) developed seizures during the postoperative follow up period. Recurrent attacks were reported only by 5 patients while 15 patients had seizure(s) only at the time of recurrence of tumour. Two patients had a few seizures in the early postoperative period and none thereafter, while doubtful seizures were reported by two patients.
The occurrence of epileptic attacks in patients with brain tumours is well known and has been the subject of a number of studies.[1],[2],[3],[4],[5],[6],[7] The reported series have individual and institutional bias, some including patients diagnosed and treated for brain tumours, others deal with patients discovered to have a brain tumour during investigation and surgical treatment for intractable epilepsy. There are still others dealing with specific groups like children[8] or specific tumour types.[9],[10],[11] There is enough information regarding the incidence of epilepsy in different types of tumours and several publications deal with its prognostic significance.[7],[12],[13],[14],[15] There is an obvious paucity of information regarding the effect of treatment of the tumour on epilepsy.[5],[6] Somewhat more information is available on patients with brain tumours primarily treated for epilepsy.[4],[6],[9],[16],[17] It was, therefore, decided to review this subject in the light of an analysis of a random series of 200 patients of supratentorial gliomas treated in the Department of
Two hundred patients of histologically verified supratentorial gliomas, who were surgically treated for their tumour and followed up in our clinic, for a minimum of one year, were retrospectively analysed. These patients were referred to the neurosurgery clinic with a suspicion of brain tumour and not primarily for management of epilepsy. During the period of this study, more than 1000 cases of supratentorial gliomas were treated in our department. The criteria for selecting these cases were (i) patient having survived for one year after surgery (ii) availability of complete records for initial hospital admission and postoperative follow up in outpatient clinic. At each visit, besides other clinical features, history of a seizure was specifically inquired and recorded. Histological slides of all these patients were reviewed recently and the final diagnosis was astrocytoma (including pilocytic, fibrillary and gemistocytic) in 82, mixed glioma (oligoastrocytoma) in 46, oligodendroglioma in 8, malignant (anaplastic) astrocytoma in 33 and glioblastoma muliforme in 31 cases. Follow up was available for one to three years for 104, upto five years for 59, upto seven years for 22 and more than seven years for 15 cases. As a matter of policy in our department, all patients with supratentorial gliomas are submitted to radical surgical removal of the tumour without any attempt to delineate or remove the epileptogenic cortex. No pre or peroperative EEG was recorded. Lobectomy was performed for anterior frontal or temporal tumours, while tumours in and around eloquent areas were treated by intratumoural decompression.18 Except for four cases, all patients were submitted to postoperative radiotherapy from a Cobalt60 source. All patients, irrespective of preoperative history of convulsions, were given anti-epileptic medication postoperatively (diphenylhydantoin, phenobarbital or carbamazepine, alone or in combination).
Records of 200 patients (147 males and 53 females) were analysed. Their age ranged between 2 years and 65 years. However, there were only 11 patients below the age of 15. History of preoperative seizures was recorded in 122 (61%). These included simple partial seizures with (19) or without (39), secondary generalization, partial complex seizures with (4) or without (9), secondary generalization and generalized seizures (43). Eight patients had seizures of indeterminate nature. It was the only symptom in 12 (9.7%), the initial symptom in 81 patients (65.1%) and it manifested sometime during the course of illness preoperatively in 29 patients (24.3%). The incidence of epilepsy was, however, variable in different types of tumours, being more common amongst those with relatively benign tumours (ranging from 60 to 75%), less so in malignant astrocytomas (54.5%) and least amongst the patients with glioblastoma (29.0%) [Table I]. The incidence of seizures according to the site of the tumour is summarized in [Table II]. The highest incidence was in fronto parietal tumours, involving the sensorimotor cortex (90%) and lowest in tumours of the occipital lobe (20%). Analysis of the type of seizures, according to the site of tumour, did not reveal any specific features. Further analysis of the type of seizures, according to nature of the tumour revealed a relatively higher incidence of generalized seizures amongst patients with astrocytoma. Amongst those with history of preoperative seizures (122 patients), one or more seizures were reported by 62 cases (50.8%) postoperatively. A detailed analysis of these 62 cases revealed that persistent seizures were reported by only 22 patients. Doubtful or one or two minor seizures, sometime in the postoperative period, were reported by 19 patients. Six patients had a few minor attacks in the first year or two and none thereafter. One or more seizures occurred, at the time of CT confirmed recurrence in 15 patients, after they had been seizure free for one to 9 years postoperatively [Table III]. Twenty four of 78 patients, who did not give any history of preoperative seizures, developed a seizure for the first time postoperatively. The seizures heralded a recurrence (as confirmed by contrast enhanced CT) in 15 cases. Recurrent seizures were reported by only 5 patients. Two patients had a few seizures in the early postoperative period and none thereafter, while two others had one or two doubtful seizures. Thirty four patients died during the period of study, all except 3 due to the tumour related causes.
At the time of admission to the hospital, 122 out of 200 (61%) patients with supratentorial gliomas gave history of seizures. The incidence was higher among cases of relatively slow growing tumours (astrocytoma-75.5%, mixed glioma-60.8%, oligodendroglioma-62.5%) as compared to the malignant astrocytoma (54.5%) and glioblastoma (29.0%). This incidence is comparable to most of the reported series.[1],[3],[5],[6],[7] Epileptic seizures were the only symptom (12 cases) or the initial symptom (81 cases) in 46.5% of cases. Rasmussen[6] reported patients with supratentorial gliomas who presented with seizures disorder of variable period, at times extending to even 10 to 25 years. One of our patients had generalized seizures for 20 years prior to the diagnosis of the tumour. The incidence of brain tumours occurring in patients of all ages under treatment for epilepsy was reported to vary from 0.6% to 20%.[6],[20],[21],[22] It has been stated that primary intracerebral tumours, presenting with epilepsy, are relatively benign.[7] However, we observed 5 out of 33 patients with malignant astrocytomas to have seizures as the initial and only symptom for 2 to 10 years. Seizures were the initial symptom for 6 months to 18 months in 5 patients with glioblastoma. It is generally believed that seizures, which are late onset, those which change character over a period of time, show poor response to medical therapy, have prolonged post-ictal paralysis or present as a status at onset should arouse the suspicion of a neoplastic aetiology of epilepsy. On the other hand, it has been generally held that epilepsy throughout childhood, even if focal, is only rarely associated with tumour.[23],[24] Similarly, epilepsy of long duration (more than 8 to 10 years) specially generalized, particularly in younger age group, has been considered to rule out a tumour. A review of the present series and a survey of the literature leads one to the conclusion that these positive and negative criteria are only indicative and cannot be relied upon as diagnostic criterias. One of the important reasons to undertake this study was to evaluate the effect of surgery on the seizure outcome; since there are surprisingly few publications on the subject. Amongst 122 patients, who had postoperative seizures, 53 (42.4%) did not have postoperative seizures till the time of last follow up. History was equivocal in 7 patients. 19 patients had no more than one or two minor attacks and another six had a couple of seizures in the first one or two years and none thereafter. 15 patients had no seizure till the time of tumour recurrence. As a matter of fact, the recurrence of attacks after a long seizure free interval generally heralded the recurrence of tumour. Seizures persisted in 22 patients (18%) amongst those who had reported seizures preoperatively. Among 78 patients, who did not have a history of preoperative seizures, 24 patients experienced one or more seizures for the first time after the operation. Majority of these cases (15) had their seizure on the recurrence of tumour. Four patients had only a couple of seizures throughout the follow up period, while recurrent seizures developed only in 5 patients. The overall impression gathered from the present series is that the duration and frequency of preoperatively seizures were not important factors influencing the postoperative seizures status. There were number of patients with frequent seizures for as long as 5 to 10 years preoperatively, who had no seizure after surgery. Likewise, there were those with only a few seizures or none at all who had persistent seizure problem postoperatively. In general, it could be concluded that radical tumour decompression resulted in complete relief in 42.2% cases and definite improvement in seizure tendency till the time of tumour recurrence in an additional 40% of cases. In contrast, 9 out of 78, (excluding those with seizures heralding recurrence) developed recurrent seizures for the first time after surgery. Rasmussen,[6] in his series of 206 cases of cerebral astrocytoma and 35 cases of glioblastoma, whose presenting problems were seizures, and who were operated upon using the technique generally used for epilepsy surgery, reported the overall reduction of seizure, upto the time of recurrence of neoplastic growth by 60-70%. This was similar to the results in patients with focal epilepsy due to nontumoural lesions. Cascino, Lee et al and Hirsch observed worthwhile reduction in seizure activity in 80% of cases following tumour excision only.[9],[11],[17] In another publication, Cascino et al25 reported stereotactic tumour resection along with the epileptogenic area to produce worthwhile reduction in seizure tendency. All patients in the present series were prescribed antiepileptic drugs, irrespective of their seizure history. It is, therefore, not possible to state whether the relatively low incidence of postoperative seizures, 9 out of 78, (other than those heralding recurrence) was solely due to tumour excision or due to drugs. It could, therefore, be argued that patients without history of preoperative seizures need not be put on prophylactic anti-epileptic drugs, which may be restricted to only those with history of seizures. Shaw,[26] evaluating the utility of prophylactic anti-epileptic treatment for postoperative cases (of all types) did not find significant reduction in the incidence of seizures. However, if one includes all the cases who had at least one or more seizures during follow tip, including the ones associated with recurrence of tumour, these add up to a sizeable number of 86 out of 200 (43%) patients in the present series. This may justify a prophylactic antiepileptic therapy in the postoperative management of patients with brain tumours. There is a need to undertake a well controlled prospective study to objectively decide this issue.
The authors are thankful to the Chief of Neuroscience Centre and their colleagues in the Department of Neurosurgery for permitting the use of clinical material utilised in this study. Thanks are due to Dr. Dheerendra Prasad for his help in compiling the data.
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