Risk Factors Identified in TBI for Early Posttraumatic Seizures, Posttraumatic Epilepsy

Terence J. O’Brien, MD, FRACP

Newly published data from a large cohort study identified multiple clinical risk factors of traumatic brain injury (TBI) that may be used to predict early posttraumatic seizures (EPS), specifically the presence of prior medical comorbidities, subarachnoid hemorrhage (SAH) and subdural hemorrhage (SDH), and injury severity.¹

In addition to these risk factors, investigators concluded that EPS were associated with significant in-hospital mortality, poorer outcomes, and subsequent risk of mortality at 24 months on follow-up Glasgow Outcome Scale-Extended (GOS-E) score. In total, the long-term mortality rate was 14% (n = 1658) for the group of patients without EPS and 24% (n = 76) for patients who had EPS (P <.001).

"Identifying patients at high risk of developing EPS may allow a precision medicine diagnostic approach, focusing management strategies and targeting clinical trials of antiepileptogenic therapies," senior author Terence J. O’Brien, MD, FRACP, chair of medicine and head, The Central Clinical School, Monash University, and colleagues concluded.

The final sample pulled from an Australian statewide registry included 15,152 patients with moderate to severe TBI, defined as Abbreviated Injury Scale (AIS) head severity score of 3 to 6. Of that cohort, 2.7% (n = 416) of patients had EPS, identified via International Statistical Classification of Diseases, Tenth Revision, Australian Modification (ICD-10-AM)codes. The gathered cohort was used to evaluate risk factors for EPS, associated morbidity and mortality, and contribution to posttraumatic epilepsy (PTE). Conducted using patients from 2005 to 2019, the incidence of EPS decreased each year (incidence rate ratio, 0.94; 95% CI, 0.92-0.96; P <.001). Of patients with EPS, 6.5% experienced status epilepticus (0.2% of all cases).

Demographically, patients who experienced EPS were older than those who did not (median, 69 years [IQR, 44-81] vs 60 years [IQR, 35-79]). Factors such as sex, service accessibility and rurality, preexisting mental health conditions and drug misuse, or socioeconomic status had no association with EPS. Individuals with EPS demonstrated a higher Clinical Global Impression (CGI) score and had associations with preexisting alcohol misuse.

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Another significant factor of EPS was sustaining injuries in a low fall (from standing height or <1 meter). This, and the prevalence of isolated TBI, SDH, SAH, intracranial hemorrhage, epidural hematoma, and base-of-skull fracture, was higher in patients with EPS than those without. Additionally, greater severity of head injury, represented by scores on AIS or GCS, and overall injury using Injury Severity Score, were associated with EPS.

"The mechanism of injury seems less important and potentially difficult to interpret, although here low falls was associated with EPS in multivariable analysis, raising the possibility that an unwitnessed seizure caused the fall," O’Brien et al wrote. "In-hospital complications such as sepsis and metabolic derangements, not evaluated in this study, may contribute to EPS risk although are difficult to predict and attribute causality on a group level."

Using multivariable analysis, patients injured from low falls had 1.63 times the risk of EPS compared with patients injured in motor vehicle crashed. The presence of SDH increased EPS risk by 77% and an SAH by 40%. Those with baseline AIS head severity scores of 5 to 6 had more than 3 times the risk of EPS compared with those with AIS of 3. Patients with a GCS score of 3 to 8 had 1.47 times the risk of EPS compared with patients with mild head injury.

Compared with patients without EPS, a higher proportion of patients with EPS were admitted to the intensive care unit (ICU), spent longer in the ICU (median, 5 days vs 8 days), were more often ventilated and for longer times (median, 4 days vs 6 days) and spent longer in the hospital (median, 7 days vs 17 days), and a higher proportion were discharged to rehabilitation rather than home.

Among the 75% of patients eligible for 24-month follow-up who completed GOS-E assessment, a higher proportion developed EPS were severely disabled or deceased vs those who did not develop EPS. By 24 months after the injury, investigators observed a larger number of patients with EPS who developed PTE (78%; 35 of 45) than those who did not (19%; 340 of 1620; P <.001). Similarly, antiseizure medication use at that follow-up was reportedly more common in those who developed EPS (68% vs 19%; P <.001).

An adaptive least absolute shrinkage and selection operator regression prediction model developed for EPS demonstrated an overall performance of area under the ROC curve of 0.72 (95% CI, 0.66-0.79) in the test set, with a maximum value of Youden index of 0.39 at total penalized coefficient value of 1.05 (sensitivity, 66%; specificity, 73%). Preexisting CGI score of 2+ (penalized coefficient, 0.303), SDH (0.333), and AIS head severity score of 5 or 6 (0.333) were the 3 highest contributors toward association with EPS. In contrast, a lower preexisting CGI of 0 was the strongest negative predictor (–0.270) of EPS in the model.

REFERENCE
1. Laing J, Gabbe B, Chen Z, et al. Risk factors and prognosis of early posttruamtic seizures in moderate to severe traumatic brain injury. JAMA Neurol. 2022;79(4):334-341. doi:10.1001/jamaneurol.2021.5420