Two-year longitudinal and prospective electroencephalographic follow-up in patients with TBI: can early EEG and CT findings predict post-traumatic epilepsy?

Abstract

Introduction: Traumatic brain injury (TBI), caused by external force to the head, leads to anatomical or functional damage to cranial structures. It is a leading cause of morbidity and mortality in adults worldwide, with substantial economic burden. Post-traumatic epilepsy (PTE) is a significant complication of TBI, posing immense challenges to rehabilitation and exacerbating socioeconomic burdens. The incidence of PTE varies widely, underscoring the need for early detection and treatment.

Objective: Through prospective electroencephalography (EEG) evaluations over a two-year period, our study aims to identify electrographic patterns indicative of PTE development, offering crucial insights for timely intervention and improved patient outcomes.

Methods: Seventy-three adult participants with acute TBI, admitted to a reference hospital in Brazil between 2018 and 2020, were recruited based on eligibility criteria. EEG evaluations monitored seizure occurrence with follow-ups for up to 24 months post-TBI, though these were disrupted by the COVID-19 pandemic. Analyses included established EEG protocols, examining factors such as background activity and epileptiform paroxysms. Relative risk (RR), Multiple Correspondence Analysis (MCA), logistic regression, and Generalized Estimating Equations (GEE) were employed to predict variables associated with PTE development.

Results: Both PTE and NO-PTE (no post-traumatic epilepsy) patients showed improving background activity over 2 years. EEG recordings revealed that injuries in the temporal region, diffuse theta waves and abnormal bilateral sleep elements indicated a higher risk of PTE development. Additionally, multiple lesions were also associated with PTE.

Conclusion: This comprehensive approach provides valuable insights for clinical management and sheds light on the complex interplay of factors influencing TBI outcomes.

Keywords: EEG; biomarker; electroencephalography; post-traumatic epilepsy; seizure; traumatic brain injury.

Figure 1

Flowchart of selected patients and EEG. (A) *Inclusion criteria comprised patients of both sexes, aged between 18 and 75 years, who provided signed informed consent (either by the patient or a legal guardian), and had a diagnosis of acute TBI confirmed by head CT showing intracranial hemorrhage and/or cerebral contusion. Eligible patients had a GCS score between 6 and 12 upon admission, or a GCS < 6 if sedation was present at the time of evaluation. (B) EEG summary follow-ups.

Figure 2

Predominant frequency observed during awake or stimulated and its evolution over 24 months of follow-up in PTE group.

Figure 3

Multiple Correspondence Analysis (MCA) of clinical and neuroimaging. Variables in relation to post-traumatic epilepsy. (A) Two-dimensional MCA plot illustrating the associations among categorical clinical, neuroimaging, and Electrophysiological variables in relation to the presence or absence of post-traumatic epilepsy (PTE) during the first month. The first two dimensions explain 41.3% of the total variance (Dimension 1: 23.4%, inertia 0.34; Dimension 2: 17.9%, inertia 0.26). The red circle represents the profile called PTE, and the blue circle represents the profile called No-PTE. (B) Two-dimensional MCA plot illustrating the associations among electrophysiological variables about the presence or absence of post-traumatic epilepsy (PTE) over time. The first two dimensions explain 22.75% of the total variance (Dimension 1: 14.8%, inertia 0.51; Dimension 2: 7.95%, inertia 0.27). The red circle represents the profile called PTE, and the blue circle represents the profile called No-PTE. For Background Activity meanings: Dis dif theta: Disorganized diffused theta waves, Dis dif theta/delta: Disorganized diffused theta/delta; Dis theta/delta: Disorganized theta/delta Dis dif pred theta; Disorganized diffused predominant theta. Dis dif: Disorganized and diffused. Dis dif pred theta and rare delta; Disorganized diffused predominant theta and rare delta. Dis theta ant right hemisphere: Disorganized theta in the anterior right temporal.

Figure 4

Unimodal associations between EEG features and post-traumatic epilepsy (PTE) risk. Unimodal analysis of EEG predictors for PTE development. (A) Background activity. (B) Sleep spindle (C) Delta wave presence in PTE versus No-PTE cases. Data derived from a GEE model [log link, AR(1) correlation; QIC = 10.18] with Bonferroni-corrected significance. The graph is a histogram of the two variables with a shadowgram style. Stars denote statistical significance. The corrected Significance of every variable is in the text.