Discriminative Utility of Transcranial Magnetic Stimulation-Derived Markers of Cortical Excitability for Transient Ischemic Attack

Abstract

Several guidelines currently recommend acute diffusion weighted imaging (DWI) for the detection of ischemia in transient ischemic attack (TIA). However, DWI hyperintensities resolve early and only 30%-50% with clinically defined TIA show acute DWI positivity. A recent meta-analysis reported an unexplained 7-fold variation in DWI positivity in TIA across studies, concluding that DWI does not provide a consistent basis for defining ischemia. Intracortical excitability, measured using transcranial magnetic stimulation (TMS), has previously been shown to be altered after TIA and associated with ABCD2 scores; however, whether altered cortical excitability is associated with clinical and DWI-based definitions of TIA remains unclear. Individuals with TIA symptoms (N = 23; mean age = 61 ± 12) were prospectively recruited and underwent DWI and paired-pulse TMS. Multivariate linear regression was used to estimate associations between TMS-derived excitability thresholds, and clinical TIA diagnosis, and imaging-based evidence of cerebral ischemia (DWI positivity). Area under the curve (AUC) analyses was used to compare the discriminability of TMS-derived thresholds and clinical TIA diagnoses. Thresholds for intracortical inhibition in the TIA-unaffected hemisphere were significantly associated with the clinical diagnosis of TIA. No associations between TMS-derived thresholds and DWI positivity were observed. TMS thresholds showed low-moderate discriminability and values differed by age (65+) and sex. In this small sample, TMS-derived markers of intracortical excitability were associated with clinical TIA diagnoses but not DWI positivity. Our results provide preliminary evidence for the potential discriminative utility of TMS for the diagnosis of TIA and highlight the need for future work in larger cohorts.