Early Seizures After Traumatic Brain Injury Tied to Epilepsy, Mortality

Early post-traumatic seizures after moderate to severe traumatic brain injury (TBI) raised the risk for poor outcomes, data from a large trauma registry showed.

After adjusting for confounders, early post-traumatic seizures increased risks of death (RR 2.14, 95% CI 1.32-3.46, P=0.002) and epilepsy (RR 2.91, 95% CI 2.22-3.81, P<0.001) at 2 years after acute injury, reported Joshua Laing, BBiomedSc (Hons), MBBS, of Monash University in Melbourne, Australia, and co-authors.

Post-traumatic seizures were more common in patients with pre-injury medical comorbidities, subdural or subarachnoid hemorrhage, and higher injury severity, the researchers wrote in JAMA Neurology.

“The study highlights the importance of early post-traumatic seizures on overall morbidity and mortality, additional to that of traumatic brain injury,” Laing told MedPage Today. “This is a novel finding.”

“Further, using two separate methods, key risk factors for the development of early post-traumatic seizures are TBI severity, prior medical comorbidities, and the presence of hemorrhagic blood products of subdural hematoma and subarachnoid hemorrhage,” Laing continued. This suggests management principles, including anti-seizure prophylaxis and targeted continuous electroencephalographic (cEEG) monitoring, may need revision, he added.

“Despite the long-standing recognition of seizures as a complication of TBI, the prognostic significance of post-traumatic seizures was not clear until recently,” observed James Gugger, MD, PharmD, and Ramon Diaz-Arrastia, MD, PhD, both of the University of Pennsylvania in Philadelphia, in an accompanying editorial.

“Seizures that occur within the first 7 days after TBI are not considered epileptic seizures because they do not convey a high risk of future seizures,” they wrote. “They are categorized as early post-traumatic seizures and more broadly as acute symptomatic seizures.”

While early seizures are not epileptic, they are not benign, Gugger and Diaz-Arrastia pointed out. “This study is an important reminder to clinicians that early post-traumatic seizures portend a poor outcome,” they emphasized.

Laing and co-authors followed 15,152 patients in the Victorian State Trauma Registry in Australia with moderate to severe TBI from January 2005 to December 2019. Participants had an Abbreviated Injury Scale (AIS) head severity score of 3 to 6, indicating moderate to severe intracranial injury or skull fracture. People with pre-existing epilepsy were excluded from the study.

All cases were followed up with structured telephone interviews at 6, 12, and 24 months after injury, and Glasgow Outcome Scale-Extended (GOS-E) scores were collected. Diagnosis of post-traumatic epilepsy was determined by patient responses to the GOS-E question, “Since the injury, has the patient had any epileptic fits?”

Median age of patients in the cohort was 60, and 69% were men. A total of 416 people (2.7%) had early post-traumatic seizures, defined by ICD codes for unspecified convulsions, status epilepticus, and acute symptomatic seizures. Overall, 27 participants (0.2%) had status epilepticus.

Three of four patients (75%) eligible for 24-month follow-up had a completed GOS-E assessment. The post-traumatic epilepsy question was completed by 1,665 patients (15%). The prevalence of epilepsy in patients who had experienced early post-traumatic seizures was 11% at 2 years.

Factors predicting early post-traumatic seizures included higher Charlson Comorbidity Index scores: patients with a score of 1 or 2 had 1.76 and 3.87 times the risk, respectively, than those with a score of 0.

A subdural hematoma increased early seizure risk by 77%; a subarachnoid hemorrhage increased it by 40%. An AIS head severity score of 5 or 6 upped the risk by more than three times compared with an AIS score of 3. A fall from a height less than 1 meter had a higher risk for early seizures than a motor vehicle crash.

A model predicting early post-traumatic seizures had an area under the receiver operating characteristic curve of 0.72 (95% CI 0.66-0.79), a sensitivity of 66%, and a specificity of 73%, the researchers reported.

Early post-traumatic seizures were associated with higher risks of ICU admission, use of ventilation, length of hospital stay, and discharge to inpatient rehabilitation instead of home, but not with in-hospital mortality. Early seizures raised the risk of taking antiseizure medication (RR 2.44) in the 24 months after injury.

The study is the largest of early post-traumatic seizures, but has important limitations, the editorialists noted. Its definition of early seizures may have excluded some patients with nonconvulsive seizures that could be captured only with cEEG monitoring.

The study’s method of assessing post-traumatic epilepsy is currently the standard, “but it is insufficient,” Gugger and Diaz-Arrastia added. “For example, the high rate of comorbidity between TBI and post-traumatic stress disorder, especially among military veterans, can lead to diagnostically challenging cases and to misdiagnosis of psychogenic nonepileptic seizures as epileptic events.”