Table 3.
Prognostic and diagnostic biomarkers for epileptogenesis, post-traumatic epilepsy, and tissue epileptogenicity after TBI
| Modality | Analysis platform | Species | Group comparisons | Tissue | Biomarker | Statistics | Reference |
|---|---|---|---|---|---|---|---|
| Prognostic & diagnostic biomarker for post-traumatic epileptogenesis | |||||||
| Molecular | Luminex bead array | Human | Patients with vs. without epilepsy after TBI | Serum, CSF | Elevated CSF/serum IL-1β ratio during the 1st post-injury week |
Cox multivariate model Hazard ratio 1.34 (CI 1.08–1.67, p = 0.008) |
[73] Diamond et al. |
|
CLARIOstar multimode plate reader (FD4) ELISA (LPS) |
Rat | Non-epileptic vs. epileptic rats with lateral FPI | Plasma | Elevated plasma FD4 and LPS levels in rats with PTE | Mann–Whitney |
[74] Mazarati et al. |
|
| Imaging |
T2-w DTI MRI |
Rat | Rats with vs. without increased seizure susceptibility in the PTZ test after TBI | Amygdala, hippocampus, thalamus |
T1σ in S1 cortex T1σ in perirhinal cortex T2 in thalamus T1σ in hippocampus |
ROC analysis (AUC) 0.881 0.929 0.893 0.857 |
[75] Pitkänen and Immonen |
| Large-deformation high-dimensional mapping of T2-w-MRI | Rat | Non-epileptic vs. epileptic rats with lateral FPI | Hippocampus | Deformation of lateral aspects of the hippocampal surface at 1 wk post-TBI | Multivariate regression model |
[43] Shultz et al. |
|
| 18F-FDG PET | Rat | Non-epileptic vs. epileptic rats with lateral FPI | Hippocampus | Worsened hypometabolism at 1 wk, 1 month, and 3 months post-TBI | Multivariate regression model |
[43] Shultz et al. |
|
| T2-w and DTI MRI | Rat | Non-epileptic vs. epileptic rats with lateral FPI | Thalamus | T2 and diffusion changes in the ventroposterior nucleus | Logistic regression | [76] Manninen et al. | |
| MRI T2 | Human | Patients with vs. without epilepsy after TBI | Cerebral cortex | Hemorrhagic contusion with gliosis wall incompletely surrounding hemosiderin dregs |
Cox regression analysis Hazard ratio 6.61 vs. complete gliosis wall |
[77] Messori et al. |
|
| Gadolinium-MRI | Human | Patients with vs. without epilepsy after TBI | Cerebral cortex | Area of gadolinium leakage around cortical lesion after TBI |
ROC analysis (AUC) 0.850 |
[78] Data by A Friedman in Pitkänen et al. |
|
| Electrophysiology | 10–20 scalp EEG | Human | Patients with vs. without epilepsy after TBI | Brain | Epileptiform activities and focal slowing |
Multivariate logistic regression Epileptiform abnormalities OR 3.16 (CI 0.99–11.68) EDs OR 4.57 (1.60–21) Focal slowing OR 2.67 (0.97–10.1) |
[79] Kim et al. |
| Continuous EEG monitoring | Human | Patients with vs. without epilepsy after TBI | Brain | Occurrence of early seizures |
Generalized linear model p = 0.026 |
[80] Tubi et al. |
|
| Sleep-EEG | Rat | Rats with epilepsy vs. no epilepsy after lateral fluid-percussion induced TBI | Brain | Shortening of the duration of sleep spindles occurring at transition from N3 to REM |
ROC analysis (AUC) 0.907 |
[81] Andrade et al. |
|
| EEG | Rat | HFOs differentiate rats which develop epilepsy after lateral fluid-percussion injury from those that will not | Brain | Presence of HFOs during the first 2 post-injury weeks | No data |
[82] Bragin et al. |
|
| Physiology | - | Rat | Non-epileptic vs. epileptic rats with lateral FPI | Body weight | Decrease in body weigh between D0 and D4 |
ROC analysis (AUC) 0.679 |
[83] Lapinlampi et al. |
| Behavioral | - | Mouse | Non-epileptic vs. epileptic mice with CCI | Simple assessment of asymmetric behavior test (SNAP test) | Recovery between 1 wk and 2 months | 0.870 |
[84] Di Sapia et al. |
| Prognostic & diagnostic biomarkers for epileptogenicity | |||||||
| Electrophysiology | Intracerebral recordings | Rat | Non-epileptic vs. epileptic rats with lateral FPI | Brain | Occurrence of HFOs | No data |
[85] Bragin et al. |
| iEEG or icSEEG | Human | Seizure onset zone vs. other brain areas in humans evaluated for epilepsy surgery | Brain |
Stereotypical HFOs with waveform similarity Spikes x HFO |
No data |
[86] Liu et al. [87] Roehri et al. |
|
AUC area under curve; CI confidence interval; CCI controlled cortical impact; CSF cerebrospinal fluid; D day; DTI diffusion tensor imaging; EEG electroencephalogram; ELISA enzyme-linked assay; FD4 fluorescein isothiocyanate–labeled dextran; FDG fluorodeoxyglucose; FPI fluid-percussion injury; HFO high-frequency oscillation; iEEG intracranial electroencephalogram; icSEEG intracerebral stereoelectroencephalograhy; iHC intrahippocampal; LPS lipopolysaccharide; MRI magnetic resonance imaging; PET positron emission tomography; PTE post-traumatic epilepsy; PTZ pentylenetetrazol; ROC receiver operating characteristic