4.5 Article

Acute thalamic damage as a prognostic biomarker for post-traumatic epileptogenesis

Journal

EPILEPSIA
Volume 62, Issue 8, Pages 1852-1864

Publisher

WILEY
DOI: 10.1111/epi.16986

Keywords

EEG; epilepsy; MRI; traumatic brain injury

Funding

  1. Sigrid Juseliuksen Saatio
  2. Academy of Finland [2285733-9, 272249, 273909, 275453, 284544, 312686, 316258]
  3. FP7 Health [602102]
  4. Academy of Finland (AKA) [284544, 312686, 284544, 273909, 273909, 312686] Funding Source: Academy of Finland (AKA)

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This study aimed to identify MRI biomarkers for post-traumatic epilepsy in Sprague-Dawley rats with traumatic brain injury. The researchers found that a combination of T-2 relaxation time and diffusion tensor data could distinguish rats with and without epilepsy, and even a single time-point measurement could significantly enrich the epilepsy rate within the study population.
Objective To identify magnetic resonance imaging (MRI) biomarkers for post-traumatic epilepsy. Methods The EPITARGET (Targets and biomarkers for antiepileptogenesis, epitarget.eu) animal cohort completing T-2 relaxation and diffusion tensor MRI follow-up and 1-month-long video-electroencephalography monitoring included 98 male Sprague-Dawley rats with traumatic brain injury and 18 controls. T-2 imaging was performed on day (D) 2, D7, and D21 and diffusion tensor imaging (DTI) on D7 and D21 using a 7-Tesla Bruker PharmaScan MRI scanner. The mean and standard deviation (SD) of the T-2 relaxation rate, multiple diffusivity measures, and diffusion anisotropy at each time-point within the ventroposterolateral and ventroposteromedial thalamus were used as predictor variables in multi-variable logistic regression models to distinguish rats with and without epilepsy. Results Twenty-nine percent (28/98) of the rats with traumatic brain injury (TBI) developed epilepsy. The best-performing logistic regression model utilized the D2 and D7 T-2 relaxation time as well as the D7 diffusion tensor data. The model distinguished rats with and without epilepsy (Bonferroni-corrected p-value < .001) with a cross-validated concordance statistic of 0.74 (95% confidence interval [CI] 0.60-0.84). In a cross-validated classification test, the model exhibited 54% sensitivity and 91% specificity, enriching the epilepsy rate within the study population from the expected 29% to 71%. A model using the D2 T-2 data only resulted in a 73% enriched epilepsy rate (regression p-value .007, cross-validated concordance 0.70, 95% CI 0.56-0.80, sensitivity 29%, specificity 96%). Significance An MRI parameter set reporting on acute and subacute neuropathologic changes common to experimental and human TBI presents a diagnostic biomarker for post-traumatic epileptogenesis. Significant enrichment of the study population was achieved even when using a single time-point measurement, producing an expected epilepsy rate of 73%.

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