Epilepsy associated with pediatric brain tumors: the neuro-oncologic perspective

doi:10.1016/S0887-8994(03)00233-9

Pediatric Neurology

Volume 29, Issue 3, September 2003, Pages 232-235

https://doi.org/10.1016/S0887-8994(03)00233-9 Get rights and content

Abstract

The aim of the study was to correlate the onset of epilepsy with the disease stage in children with brain tumors through treatment and follow-up in the oncologic department. The study sample consisted of a heterogenous group of 219 children who were aged 6 months to 11 years, manifested brain tumors, and had been treated and monitored in the Department of Pediatric Oncology of the Schneider Children’s Medical Center of Israel since 1991. The overall rate of epilepsy was 14.6%, which rose to 38% in those with cortical tumors. Two major causes of epilepsy were evident: tumor-related and treatment-related. The first group could be further divided into epilepsy starting at or before diagnosis of brain tumor, epilepsy associated with tumor progression, and epilepsy starting at end-stage disease. The second group could be divided into epilepsy caused by radiation damage to the brain and epilepsy related to another postoperative state. The data emphasize the significance of striving for complete tumor resection and the potential damage from the use of radiotherapy to the brain. The authors suggest that a change in local neurotransmitter balance may be the mechanism underlying tumor-related epilepsy.

Introduction

Although brain tumors account for only 1% of epilepsy cases, epilepsy is much more frequent in patients with brain tumors. In adults with brain neoplasms, epilepsy may occur at 35% to 40%, but in children with supratentorial tumors, the reported percentage is even higher [1]. Brain tumors were the most common pathology (30%) in 42 children who underwent temporal lobectomy for intractable epilepsy [2] and were reported in 86.4% of 550 patients aged 4 to 75 years after stereotactic biopsy for an intracranial mass [3]. The relationship between epilepsy and brain tumors is generally investigated from the aspect of the epilepsy, with the brain tumor studied as an etiologic factor or as a factor in the management of epilepsy. The aim of the present study was to correlate the onset of epilepsy with the disease stage in children with brain tumors, from diagnosis to various stages of treatment. For this purpose, epilepsy was examined from the aspect of a clinical abnormality the neuro-oncologist has to treat during treatment of the brain tumor. With such a perspective, the clinical finding becomes multifactorial, influenced by the type of antitumoral treatments given and their complications, as well as the type of tumor itself.

Section snippets

Patients and methods

The frequency of epilepsy was studied retrospectively in 219 children aged 6 months to 18 years who had been treated and followed up for brain tumor in the Department of Pediatric Oncology of Schneider Children’s Medical Center of Israel since January 1991. Epilepsy was defined as a chronic tendency to recurrent seizures (as opposed to acute seizures provoked by fever, infection, acute intracranial bleeding, a vascular event, or a biochemical abnormality) which necessitated antiepileptic

Results

Thirty-three (14.6%) of the 219 children with brain tumors manifested epilepsy. One of them, a patient being monitored for cerebellar astrocytoma, exhibited a 3-Hz spike and wave-absence epilepsy, which was most likely a coincidental abnormality unrelated to the tumor or its treatment; this patient was therefore excluded from the study. The distribution of epilepsy by tumor type is summarized in Table 1.

The highest rate of epilepsy was demonstrated, as expected, in patients with supratentorial

Discussion

In the present study of a group of children treated and monitored for brain tumor in a single tertiary center, the overall rate of epilepsy was 14.6%. The rate rose to 38% in patients with supratentorial cortical tumors (glial, primitive neuroectodermal tumor, and others), and was 0% in patients with specific types of tumors, such as a brainstem glioma. In one patient with cerebellar pilocytic astrocytoma, absence seizures were observed with typical 3-Hz spike and wave patterns on

Acknowledgements

The authors wish to thank Gloria Ginzach and Marian Propp for their editorial and secretarial assistance.

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Seizures in Pediatric Patients With Primary Brain Tumors
2019, Pediatric Neurology
Citation Excerpt :
Brain tumors are the second most common malignancies among pediatric patients, just after acute lymphocytic leukemia, and the most frequent solid tumors.1 Seizures are a presenting symptom in 10% to 15% of children with primary brain tumors.2-6 Moreover, patients with brain tumors can have seizures secondary to surgery, radiation, metabolic abnormalities, tumor progression, or hydrocephalus or in end-stage illness.7,8
Seizures are one of the most common symptoms of pediatric brain tumors. The purpose of this study was to define seizures related to primary central nervous system tumors and to identify risk factors predictive of seizure occurrence and recurrence.
We reviewed the records of children treated from January 1, 2004, to January 1, 2018 and collected data including age, gender, tumor location, histology, extent of initial resection, seizure characteristics, treatment modalities, recurrence, and seizure control. A binomial logistic regression was performed to determine the risk factors of seizure occurrence.
During the observation period, 348 children were diagnosed with a primary brain tumor. The median age at diagnosis was 7.8 years, and the median follow-up interval was 3.9 years. There were 196 boys (56.3%). In our cohort, a total of 70 children (20.1%) experienced seizures. Most of them (64.3%) had cortical tumors. All patients with dysembryoplastic neuroepithelial tumors and 81.8% of patients with glioneuronal tumors presented seizures. Risk factors associated with an increased risk for seizures included cortical location, tumor recurrence, and age at diagnosis. Thirty-nine (86.7%) patients with seizures at diagnosis were seizure free at last follow-up (Engel 1). Significantly more patients (69.6%) with a gross total resection were withdrawn from their antiepileptic drugs when compared with those with subtotal resection (27.3%, P = 0.007).
Our study is the largest cohort in children with tumor-related seizures and brings new insight in terms of seizure risk according to tumor types and evolution following treatment.
Seizure characteristics and the use of anti-epileptic drugs in children and young people with brain tumours and epileptic seizures: Analysis of regional paediatric cancer service population
2018, Seizure
Citation Excerpt :
In this cohort we found a relationship between tumour site (cerebral hemisphere compared with other localizations) and seizure occurrence. This has been reported before: Wilne et al reported seizures to be particularly associated with supratentorial tumours (in 38%) [3], as did Ullrich (in 53%) [5], and Shuper (25%) [18]. Regarding histopathologic type, several studies have shown a relationship between low grade glioma, DNET, pleomorphic astrocytoma, oligodendroglioma, ganglioglioma and seizure occurrence [19].
Epileptic seizures complicate the management of childhood brain tumours. There are no published standards for clinical practice concerning risk factors, treatment selection or strategies to withdraw treatment with antiepileptic drugs (AED).
we undertook a case note review of 120 patients with newly diagnosed brain tumours, referred to a regional paediatric cancer service.
data was available on 117/120 (98%) children <18 years: median age at tumour presentation was 8.1 years (IQR ^25°−75°: 3.6–12.7), median follow up was 33 months (IQR ^25°−75°: 24–56), and 35/117 (29%) experienced seizures.
A cortical tumour location was associated with the highest risk of seizures (OR: 7.1; CI 95% 2.9–17.3). At a median follow up of 24 months (IQR^25°−75°: 15–48), 22/35 (63%) with seizures, had a single seizure episode, 15/35 (43%) were seizure free (SF) on AEDs, 13/35 (37%) were SF off AEDs, and 7/35 (20%) experienced continuing epileptic seizures. Overall 34/35 (97%) were treated with AEDs after a seizure, of whom 12/35 (35%) withdrew from AED medication, and although 4/35 (12%) had seizure relapse, all were after further acute events. The median duration of AED before withdrawal was 11 months (IQR^25°−75° 5–14 months), and the median follow up after withdrawal was 15 months (IQR^25°−75° 5–34 months).
Seizures affect about 1/3rd of children and young people presenting with and being treated for brain tumours particularly when the tumour is in the cerebral cortex.
The low risk of recurrent seizures after AED treatment justifies consideration of early withdrawal of AED after seizure control.
Brain-Tumor-Related Epilepsy in Children
2015, Epilepsy and Brain Tumors
Biology, epidemiology, presentation, optimal management, and outcomes of brain tumors change throughout the lifespan. The most rapid changes occur in the first two decades of life. Brain tumors have a lower incidence in children than adults, but represent a higher overall proportion of childhood cancer. Despite a relatively low incidence of high-grade primary tumors and metastases, brain and other central nervous system tumors account for a substantial burden of childhood cancer morbidity and mortality. Seizures are an equally common manifestation of supratentorial tumors in children and adults, but tumors are a less common cause of seizures and epilepsy in childhood. Initial presentation with seizures portends a longer survival. Thus, seizures are often among the primary considerations for management. Optimal management strategies that account for the unique challenges of these combined diagnoses in the pediatric patient are evolving.
Epilepsy surgery after treatment of pediatric malignant brain tumors
2012, Seizure
Citation Excerpt :
Surgical treatment for epilepsy associated with low-grade tumor is well established either at the time of first surgery or in the setting of intractable epilepsy in survivors. High grade brain tumors can be associated with epilepsy requiring aggressive medical management,8,38–40 yet surgical options in survivors is rarely reported, even in series focusing on brain tumors and epilepsy.11–14,20 Unfortunately, seizure control appears to be incomplete in many of these patients.
Epilepsy surgery is common in the face of benign brain tumors, but rarely for patients with a history of malignant brain tumors. Seizures are a common sequelae in survivors of malignant pediatric brain tumors. Medical management alone may not adequately treat epilepsy, including in this group. We report four cases of patients who previously underwent gross total resection, radiation therapy, and chemotherapy for successful treatment of malignant brain neoplasia, yet suffered from medically intractable seizures. All underwent surgery for treatment of epilepsy with extension of the original resection. Despite the aggressive primary treatment of the neoplasm, and the potential for diffuse cerebral insults, all benefited from focal surgical resection. Aggressive surgical management of intractable epilepsy can be considered in survivors of malignant brain tumors.
Epilepsy associated with supratentorial brain tumors under 3 years of life
2009, Epilepsy Research
To investigate the clinical features and outcome of epilepsy in children under 3 years of age with supratentorial brain tumors.
Patients under 3 years with primary supratentorial hemispheric brain tumors were collected during a 10-year period through a database including demographic and clinical features, neuroimaging, tumor location, developmental outcome, pharmacological and surgical treatment, and tumor histology. Postoperative outcome was assessed according to Engel classification.
Among 28 children evaluated, twenty (71.4%) suffered from epilepsy. Mean age at seizure onset was 18.7 months (range: 1–60). In fifteen (75%) children, epilepsy was an early manifestation or the presenting symptom of the tumor; seizures were focal in 8 (53.3%) and generalized in 7 (46.7%) individuals. Three (15%) children presented with an epileptic encephalopathy and continuous spike-waves during sleep. Of the five children with epilepsy onset after surgery, four had focal seizures. Post-surgical follow-up ranged from 4 to 10 years (mean: 7.6 ± 3.74). The outcome of epilepsy was generally good, with most children (76.4%) being seizure free (Engel I) or showing >90% improvement in seizure frequency (Engel II) after surgery. However, in about 20% of the cases, epilepsy persisted despite surgery and different AEDs regimen. Best epilepsy outcome was observed in patients with low-grade tumors (p < 0.01) and without neurological deficits after surgery (p < 0.001).
Epilepsy is a common and early symptom in infants with brain tumors. Its outcome is negatively influenced by high tumor malignancy and by the persistence of neurological deficits after surgery. Treatment of these patients needs a multidisciplinary approach.
The Use of Antiepileptic Drugs in Pediatric Brain Tumor Patients
2009, Pediatric Neurology
Citation Excerpt :
A substantial proportion of children in the present study (31%) developed seizure after tumor diagnosis, often in association with tumor progression. Although epilepsy associated with brain tumors is often reported to be intractable, this largely depends on pathology and location of the tumor, which will also determine the extent of possible surgery and adjuvant therapies [2,3,7]. In the present series, 39% of patients became seizure free, and only 26% of patients were considered intractable.
Antiepileptic drugs are frequently used in children with brain tumors. This retrospective study reviewed chronic use of antiepileptic drugs in children with brain tumors at two children's hospitals between 2000 and 2007. Antiepileptic drugs were used in 32/334 pediatric brain tumor patients (10%). Almost all (94%) had supratentorial tumors, of which 78% were glial tumors. The most common localization was temporal (70%). The most frequently used initial antiepileptic drugs were phenytoin (n = 14) and oxcarbazepine (n = 7). Initial antiepileptic drugs were frequently changed, because of lack of efficacy and adverse effects, as well as concerns about possible drug interactions. At last follow-up, the most common antiepileptic drugs were oxcarbazepine (n = 11) and levetiracetam (n = 10). Levetiracetam was more likely to be used in children who received chemotherapy or radiation therapy (8/14, or 57%) than in those who did not receive adjuvant therapies (3/18, or 17%) (P = 0.03). The patients started on newer-generation antiepileptic drugs (levetiracetam, oxcarbazepine, lamotrigine) tended to remain on the same antiepileptic drugs more than did patients on older-generation antiepileptic drugs (valproic acid, phenytoin, phenobarbital) (73% vs 28%) (P = 0.04). Newer antiepileptic drugs, especially those without significant drug-drug interactions, may be a more appropriate first choice in children with brain tumors and seizures.

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Original articleEpilepsy associated with pediatric brain tumors: the neuro-oncologic perspective

Abstract

Introduction

Section snippets

Patients and methods

Results

Discussion

Acknowledgements

Epilepsy Res

Pediatr Neurol

Neoplastic diseases

Pathology and neuroimaging in pediatric temporal lobectomy for intractable epilepsy

Pediatr Neurosurg

Stereotactic biopsy for intracranial space-occupying lesionsClinical analysis of 550 cases

Stereotact Funct Neurosurg

Original article
Epilepsy associated with pediatric brain tumors: the neuro-oncologic perspective