Stroke is one of the most important causes of acquired
epilepsy in the adult population. While factors such as cortical involvement and haemorrhage have been associated with increased seizure risk, the mechanisms underlying the development of
epilepsy after
stroke remain unclear. One hypothesised mechanism is an excitotoxic effect of abnormal
glutamate release following a
stroke. Cerebral extracellular
glutamate levels are known to rise in the setting of
acute stroke, and numerous studies have implicated
glutamate in the pathogenesis of
seizures and
epilepsy, both through direct measurement of
glutamate from the epileptic brain and by analysis of receptors and transporters central to
glutamate homeostasis. While experimental evidence suggests the cellular injury induced by
glutamate exposure may lead to development of an epileptic phenotype, there is little direct data linking the rise in
glutamate during
stroke with the later development of
epilepsy. Clinical research in this field has been hampered by the lack of non-invasive methods to measure cerebral
glutamate. However, with the increasing availability of 7T MRI technology, Magnetic Resonance Spectroscopy is able to better resolve
glutamate from other chemical species at this field strength, and
Glutamate Chemical Exchange Saturation Transfer (GluCEST) imaging has been applied to localise epileptic foci in non-lesional
focal epilepsy. This review outlines the evidence implicating a pivotal role for cerebral
glutamate in the development of post-
stroke epilepsy, and exploring the role of MRI in studying
glutamate as a
biomarker and therefore its suitability as a molecular target for anti-epileptogenic
therapies. We hypothesise that the rise in
glutamate levels in the setting of
acute stroke is a clinically relevant
biomarker for the development of post-
stroke epilepsy.