Tumor-associated epilepsy and glioma: are there common genetic pathways?

Abstract

Background: Patients with glioma exhibit a great variability in clinical symptoms apart from variations in response to therapy and survival. Many patients present with epileptic seizures at disease onset, especially in case of low-grade gliomas, but not all have seizures. A large proportion of patients develop refractory seizures. It is likely that the variability in epileptic symptoms cannot exclusively be explained by tumor-related factors, but rather reflects complex interaction between tumor-related, environmental and hereditary factors.

Material and methods: No data exist on susceptibility genes associated with epileptic symptoms in patients with glioma. However, an increasing number of candidate genes have been proposed for other focal epilepsies such as temporal lobe epilepsy. Some of the susceptibility candidate genes associated with focal epilepsy may contribute to epileptic symptoms also in patients with glioma.

Results: This review presents an update on studies on genetic polymorphisms and focal epilepsy and brings forward putative candidate genes for tumor-associated epilepsy, based on the assumption that common etiological pathways may exist for glioma development and glioma-associated seizures. Conclusion. Genes involved in the immune response, in synaptic transmission and in cell cycle control are discussed that may play a role in the pathogenesis of tumor growth as well as epileptic symptoms in patients with gliomas.

Figure 1.

MRI (T1-weighted images) of two patients with an oligodendroglioma (grade II) in the right frontal lobe, both presenting with focal epileptic seizures as the first symptoms. a) This patient became seizure-free on antiepileptic drugs after an initial seizure. b) This patient developed pharmacoresistent seizures in spite of multiple antiepileptic drugs.

Figure 2.

Immunohistochemical stainings with antibodies for the astrocytic marker GFAP (glial fibrillary acidic protein) of the peritumoural cortices of two different samples of diffuse astrocytomas (WHO grade II). a) A significant increase of reactive astrocytes is demonstrated in the peri-tumoural cortex of this patient with chronic epileptic seizures, compared to. b) the peri-tumoural cortex of a patient who did not have any epileptic seizures.