Platform Presentation The Joint Annual Meeting of the Stroke Society of Australasia (SSA) and Smartstrokes 2023

Discovery Lipidomics to Differentiate between Transient Ischaemic Attacks (TIAs), TIA Mimics, and Minor Stroke: A Clinical Study at the Royal Adelaide Hospital (#81)

Deeksha Sharma 1 , Marten F Snel 2 , Paul Trim 2 , Stephan Lau 1 , Mark Jenkinson 1 3 , Suzanne Edwards 1 , Austin G Milton 4 , Joshua Mahadevan 4 , Craig Kurunawai 4 , Timothy Kleinig 4 , Jim Jannes 4 , Simon A Koblar 1 , Anne Hamilton-Bruce 4
  1. The University of Adelaide, Adelaide, SA, Australia
  2. South Australian Health & Medical Research Institute, Adelaide, SA, Australia
  3. University of Oxford, Oxford, United Kingdom
  4. Central Adelaide Local Health Network, Adelaide, SA, Australia

Background: 

Transient Ischaemic Attacks (TIAs) are a key predictor for ischaemic stroke (1) but diagnosing TIAs is complicated due to overlapping symptomology with minor strokes and other mimic conditions such as migraines, and seizures (2). Investigation into lipidomic pathways to differentiate between TIAs, minor strokes, and TIA mimics could provide insight into potential diagnostic targets for TIAs and reduce the risk of subsequent ischaemic stroke.

Aims: 

To identify lipidomic pathways differentially involved in TIAs, TIA mimics, and minor strokes.

Methods: 

Patients presenting with TIA-like symptoms were recruited at the Royal Adelaide Hospital (n=50). Plasma samples (9mL) were collected within 48 hours of symptom onset and stored in line with HUPO guidelines (3). Discovery lipidomic investigation was conducted using LC-MS, with preliminary data processing undertaken on Skyline and MetaboAnalyst 5.0. A volcano plot was used to identify individual lipids of interest for further exploration using MS/MS. All patients were clinically classified independently as TIAs/TIA mimics/minor strokes by two vascular neurologists, with any disagreement resolved by a third, senior vascular neurologist.

Results: 

We enrolled 50 patients (29 Females, 21 Males) with ages ranging from 39–94 years (Median: 72y) at time of enrolment. All patients were classified based on clinical data with 56% diagnosed as a TIA mimic. A total of 467 lipids were detected in the cohort, and 15 glycerophospholipids were selected from both negative and positive ion datasets based on significance (p<0.05) and magnitude of fold change for further investigation using MS/MS.

Conclusion: 

The preliminary findings from this study have identified an initial set of 15 glycerophospholipids of interest that are currently being targeted for further investigation using MS/MS to differentiate between TIAs, TIA mimics, and minor strokes. The outcomes will be expanded to a larger sample set (n=100) with additional assessment using machine learning.

  1. 1. Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet 2007;369:283–92.doi:10.1016/S0140-6736(07)60150-0pmid:http://www.ncbi.nlm.nih.gov/pubmed/17258668
  2. 2. Fonseca AC, Canhão P. Diagnostic difficulties in the classification of transient neurological attacks. Eur J Neurol 2011;18:644–8.doi:10.1111/j.1468-1331.2010.03241.xpmid:http://www.ncbi.nlm.nih.gov/pubmed/20955353
  3. 3. Rai AJ, Gelfand CA, Haywood BC, et al. HUPO plasma proteome project specimen collection and handling: towards the standardization of parameters for plasma proteome samples. Proteomics 2005;5:3262–77.doi:10.1002/pmic.200401245pmid:http://www.ncbi.nlm.nih.gov/pubmed/16052621