Team:Unimelb/Description

Description

Identifying issues in Stroke Diagnosis

Identifying issues in Stroke Diagnosis Our team investigated the current diagnosis and treatment of strokes and identified two areas that could be improved.

  1. Detection of ischaemic vs. hemorrhagic stroke

    Stroke is either ischaemic, caused by blood flow being blocked to the brain, or haemorrhagic when there is bleeding in or around the brain. The treatment options for these stroke types differ significantly and so it is essential to determine the type of stroke early on. This is currently done using a CT scan which is very expensive and potentially inaccessible within the timeframe required for effective treatment. A faster, cheaper method of detecting the type of stroke would help inform patient care and improve survival rates of these strokes.

  2. Monitoring Early Neurological Deterioration (END)

    Early Neurological Deterioration (END) is the worsening of a patient’s neurological condition 48-72hrs after stroke. It occurs in up to a third of stroke patients and has been associated with worse outcomes [1]. Early detection of END would allow faster treatment to be given that could potentially improve patient outcomes.


Identifying potential solutions

Biomarkers:

  1. Glutamate

    Glutamate is a potential biomarker for ischaemic stroke. An antibody that binds to a subunit of glutamate had 97% sensitivity [2]. Plasma and cerebrospinal fluid (CSF) glutamate levels are also elevated in patients who experience END [3, 4]. This is thought to occur due to increased brain lesion volume causing glutamate to leak from neurons into the blood and interstitial fluid which can then be detected [3]. For hemispheric strokes, plasma glutamate concentration of >200umol/L had a 92% END prediction accuracy while CSF glutamate concentration of 8.2umol/L had 93% END prediction accuracy [2].

  2. GABA

    For lacunar infarctions, END is predicted by plasma glutamate concentration >200 umol/L (67%) and plasma GABA concentration < 240 nmol/l (84%). Low plasma GABA can predict END with a probability of 84%.

Detection System:

We decided to develop a bacterial detection system for glutamate and GABA. A ratio of plasma glutamate to GABA greater than 106 correctly predicted END in 85% of patients and glutamate is a potential biomarker for ischaemic stroke. Additionally, as they are the two common neurotransmitters, a bacterial system that detects them would be useful in applications ranging from detecting neuronal growth in culture to food processing. Our goal is to integrate detection of multiple biomarkers into a single bacterial cell that will emit different colours based on detection of the biomarker above a given threshold.


Bibliography

  1. Siegler, J. and Martin-Schild, S. (2011). Early Neurological Deterioration (END) after Stroke: The END Depends on the Definition. International Journal of Stroke, 6(3), pp.211-212.

  2. Jickling, G. and Sharp, F. (2011). Blood Biomarkers of Ischemic Stroke. Neurotherapeutics, 8(3), pp.349-360.

  3. Dávalos, A., Castillo, J., Serena, J. and Noya, M. (1997). Duration of Glutamate Release After Acute Ischemic Stroke. Stroke, 28(4), pp.708-710

  4. Davalos, A., Castillo, J., Marrugat, J., Fernandez-Real, J., Armengou, A., Cacabelos, P. and Rama, R. (2000). Body iron stores and early neurologic deterioration in acute cerebral infarction. Neurology, 54(8), pp.1568-1574

  5. Jickling, G. and Sharp, F. (2011). Blood Biomarkers of Ischemic Stroke. Neurotherapeutics, 8(3), pp.349-360.