Cerebral Diseases
Glutamate imaging to predict seizure risk after stroke
Dr John-Paul Nicolo
Royal Melbourne Hospital
Co-Investigators : Prof Terence O'Brien, Prof Patrick Kwan, A/Prof Bernard Yan, Dr Andrew Neal, Dr Bradford Moffat, Prof Patrica Desmond

Project Summary:

Stroke is an important cause of epileptic seizures in adults. While several factors associated with the development of epilepsy after stroke have been identified, predicting which patients will develop seizures remains difficult. One of the most important biological factors that may be relevant is an elevation in the concentration of glutamate, a chemical involved in electrical activity in the nervous system. Excessive glutamate activity in the brain has been implicated in several neurological disorders including epilepsy, stroke and brain injury. In particular, glutamate plays a critical role in initiating and sustaining seizure activity. Measuring brain glutamate levels may, therefore, predict which patients will develop seizures after stroke.

While glutamate can be measured directly from brain tissues and cerebrospinal fluid, these sampling methods require brain biopsy or lumbar puncture, which are not practical for widespread clinical use because they are invasive. For glutamate measurement to be more readily accessible we need an alternative measurement tool.

This study aims to develop one such method using MRI. Conventional MRI technology is not sensitive enough to measure glutamate levels. There are, however, two MRI techniques called Magnetic Resonance Spectroscopy (MRS) and GluCEST, which can more accurately measure brain glutamate levels. The advantage of GluCEST in particular is that it has very good spatial resolution and can be used to produce maps reflecting glutamate concentrations in different brain regions. GluCEST has been used to study patients with epilepsy, brain tumours and psychiatric illness, but not yet patients with stroke.

Our study will test these imaging methods to analyse brain glutamate levels in stroke patients and will explore whether measurement of glutamate levels may be able to identify people at higher risk of developing epilepsy after a stroke. If this is possible these patients may be targeted for preventative treatment with drugs that modulate glutamate levels.