Elsevier

The Lancet Neurology

Volume 6, Issue 5, May 2007, Pages 421-430
The Lancet Neurology

Review
Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management

https://doi.org/10.1016/S1474-4422(07)70103-5Get rights and content

Summary

Epilepsy is common in patients with brain tumours and can substantially affect daily life, even if the tumour is under control. Several factors affect the mechanism of seizures in brain tumours, including tumour type, tumour location, and peritumoral and genetic changes. Prophylactic use of antiepileptic drugs is not recommended, and potential interactions between antiepileptic and chemotherapeutic agents persuades against the use of enzyme-inducing antiepileptic drugs. Multidrug-resistance proteins prevent the access of antiepileptic drugs into brain parenchyma, which partly explains why seizures are frequently refractory to treatment. Lamotrigine, valproic acid, and topiramate are first-line treatments of choice; if insufficient, add-on treatment with levetiracetam or gabapentin can be recommended. On the basis of clinical studies, we prefer to start treatment with valproic acid, adding levetiracetam if necessary. Risks of cognitive side-effects with antiepileptic drugs can add to previous damage by surgery or radiotherapy, and therefore appropriate choice and dose of antiepileptic drug is crucial.

Introduction

Epilepsy is common in patients with brain tumours, and seizure control is an important part of clinical management. In the presence of a well-controlled tumour, development of convulsions adds substantial morbidity to patients with brain tumours.1 Seizures in patients with brain tumours are symptomatic and localisation-related, manifesting as simple or complex seizures with or without secondary generalisation. Several factors affect epileptogenesis in patients with brain tumours, including tumour type, tumour location, changes in the peritumoral environment, and genetic factors.

Difficulties in the medical management of epilepsy in patients with brain tumours include the refractoriness of epilepsy, which might be due to multidrug-resistance proteins; potential interactions between antiepileptic drugs and chemotherapeutic agents; and risk of cognitive side-effects from use of antiepileptic agents in addition to earlier brain damage from surgery or radiotherapy.1, 2, 3, 4

In this Review, we focus on the clinical characteristics of seizures in patients with brain tumours. We discuss the underlying mechanisms for treatment refractoriness and the interactions between antiepileptic drugs and chemotherapy, and give guidelines on appropriate management.

Section snippets

Epidemiology and presentation

The incidence of brain tumours in people with epilepsy is about 4%.5, 6 Of patients with brain tumours, the frequency of epilepsy is 30% or more depending on tumour type.7 For 30–50% of patients with brain tumours, an epileptic seizure is the presenting clinical sign of a tumour; 10–30% will develop seizures later in the disease course.5, 8, 9, 10

Patients with brain tumours who present with seizures can be divided into two groups: children and adolescents who usually show no other neurological

Epileptogenesis by brain tumours

The precise nature of epileptogenesis in patients with brain tumours is unclear. However, several mechanisms have been proposed, and its origin is probably multifactorial. In principle, the balance between intracortical inhibitory and excitatory mechanisms must shift towards that of excitation.20 Epileptogenic activity probably arises in the cortex adjacent to the tumour; lesions are usually electrically inert.21

Epilepsy in cancer

At least 4% of patients without brain metastases or primary brain tumours (ie, those with extracranial cancer) have seizures,29 which are commonly caused by metabolic encephalopathies secondary to electrolyte abnormalities or organ dysfunction, or by toxic encephalopathies induced by chemotherapeutic agents or other drugs.

Furthermore, epilepsy might be secondary to radionecrosis of the temporal lobe after radiotherapy (eg, of a laryngeal tumour).15 Also, seizures can be secondary to an

Treatment of brain tumours and seizures

Anticonvulsive treatment is an important, but nevertheless neglected, issue in patients with brain tumours because epileptologists are not often actively involved in their care, and because neuro-oncologists usually devote most of their time to cancer treatment. Therefore, prospective studies on medical treatment of epilepsy in patients with brain tumours are scarce, despite the frequent occurrence of treatment-resistant seizures in these patients. By contrast, much is known about the surgical

Localisation-related epilepsy

There are few robust data to make conclusions about the optimum treatment for epileptic seizures in patients with brain tumours. Moreover, there may be no a priori reason why treatment of epilepsy in the setting of a brain tumour should differ from that of other types of symptomatic localisation-related epilepsy. Therefore, we think it reasonable to follow treatment guidelines for symptomatic localisation-related epilepsy, and to see subsequently whether additional guidelines are needed on the

Conclusions

Epileptic seizures are common in patients with brain tumours, and epileptogenesis is probably multifactorial. Multidrug-resistance proteins might actively transport antiepileptic drugs out of the brain and contribute to the refractoriness of epilepsy, which is common in patients with brain tumours. A consensus statement has advised discouragement of antiepileptic drugs or their discontinuation after the first operative week in patients with brain tumours who have never had seizures.

Treatment of

Search strategy and selection criteria

Data for this review were identified by searches of PubMed with single or combined terms for: “brain tumour”, “epilepsy”, “incidence”, “surgery”, “chemotherapy”, “cranial radiation”, “epileptogenesis”, “treatment”, “antiepileptic drugs”, “prophylaxis”, “refractory epilepsy”, “multidrug resistance pathway”, “interactions”, “side-effects”, “anticancer agents”, and “dexamethasone”. Original research papers, clinical series, case reports, and reviews were included. Our search covered all

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