The Pathogenesis of Tumour Associated Epilepsy

Abstract

Tumour associated epilepsy (TAE) is a poorly understood manifestation of many gliomas, meningiomas and metastatic brain tumours that has important clinical and social implications. Etiological mechanisms underlying tumour associated epilepsy include theories invoking peritumoural amino acid disturbances, local metabolic imbalances, cerebral oedema, pH abnormalities, morphological changes in the neuropil, changes in neuronal and glial enzyme and protein expression and altered immunological activity. It has also been suggested that the pathology involves perturbations in distribution and function of the NMDA subclass of glutamate receptors. The often capricious response of the seizure disorder following removal of the causative neoplasms suggests multiple factors are involved. Further understanding about the pathogenesis of TAE will await the development and characterisation of suitable animal models that demonstrate the clinical manifestations and physiological changes comparable to those seen in human cerebral tumours. With such a model it is hoped that progress may one day be made in understanding and subsequently treating this debilitating clinical problem.

Independent component analysis reveals dynamic ictal BOLD responses in EEG-fMRI data from focal epilepsy patients

“…In the case of cerebral tumors, the mechanisms of epileptogenesis are not fully understood, but it is known that tumors induce multiple structural changes in adjacent cortex, altering the balance between excitatory and inhibitory activity (Beaumont and Whittle, 2000;Wolf et al, 1996). Resection of the epileptogenic peritumoral cortex is often required to obtain seizure freedom (Cascino, 1990).…”

Clinical multifactorial analysis of early postoperative seizures in elderly patients following meningioma resection

“…Compression of peritumoral brain tissue may destroy the neural network structure; however, neuronal shortcuts leading to a histological basis for interictal epileptiform discharges may appear following pathological reconstruction of the network (16,17). Intracalvarial invasion by a meningioma produces mechanical compression and localized damage to the brain, and the incidence of seizures increases with the volume occupied.…”

“…Tumor-evoked compression or stimulation of brain tissue results in gliosis, which later causes PTBE, tumidness, insufficient blood supply, anoxia, gradual brain atrophy, cerebral sclerosis, proliferation of glial cells and fibers, loss of partial ganglion cells and the formation of fine insular phagocyte-like lesions. The membranes of these altered pathological nerve cells can stimulate allergic reactions and cause clinical seizures by sudden and transient neuronal discharges induced by endogenous or exogenous stimuli (16). According to Lieu and Howng (5), clinically significant seizures can be caused by supratentorial or convexity meningiomas complicated with severe PTBE.…”

Different Aquaporin-4 Expression in Glioblastoma Multiforme Patients with and without Seizures

“…The pathogenesis of the seizures in these patients is unknown but is likely imputable to a number of different factors (16). These include alterations in extracellular pH, bleeding and modified synthesis and catabolism of neurotransmitters (2,16,17). Cortical location of GBM is a risk factor for seizures.…”