Higher Epilepsy Mortality in Posttraumatic Cases, VA Study Finds

The risk of death in patients with posttraumatic epilepsy (PTE) varies dramatically by type of brain injury, with some facing twice the mortality rate as those with other forms of epilepsy, according to a new study of Veterans Health Administration data. 

Of 210,182 veterans with epilepsy followed for a median of 6 years, those who developed PTE after diffuse cerebral injury, focal cerebral injury, or skull/facial fractures had 16% to 18% higher mortality rates than veterans with nontraumatic epilepsy (NTE) the study found. Published in Neurology, the analysis was completed by Zulfi Haneef, MBBS, MD, of Baylor College of Medicine Medical Center, and colleagues. 

Young patients who developed PTE after extracerebral hemorrhage faced the highest risk — double the mortality rate of those with NTE.

“These numbers are striking considering that the group against which these rates are compared — other causes of epilepsy — itself suffers from a high mortality rate,” Haneef said in an interview with Federal Practitioner. “Our findings argue for risk-stratified follow-up in PTE based on the underlying TBI [traumatic brain injury] mechanism and age at epilepsy onset.”

How Common is PTE?

PTE is defined as “long-term predisposition to developing recurrent and unprovoked seizures caused by a traumatic brain injury,” according to neurologist Edilberto Amorim, MD, of University of California at San Francisco Weill Institute for Neurosciences, who was not involved with the study but is familiar with its findings. “We do not fully understand why some people with a traumatic brain injury develop epilepsy and others do not, but the risk is higher with more severe types of TBI.”

PTE accounts for about 5% of all epilepsy cases, Amorim said. The study cites research linking PTE to mortality risk that’s 1.75 to 2.30 higher than in people without epilepsy. 

Haneef said the study aimed to shed light on mortality in PTE. “Although epilepsy and TBI are each linked to higher mortality, it had never been conclusively shown that PTE specifically carries higher mortality than nontraumatic epilepsy,” he said. “We set out to answer that question in a large national veterans cohort and to see whether mortality differs by the type of antecedent TBI.”

Methodology and Findings

Researchers tracked 210,182 veterans diagnosed with epilepsy from 2005 to 2022 through the end of 2024: 28,832 with PTE (mean onset age 52.6 years, 7.4% female, 74.2% White, 16.2% Black) and 181,350 with NTE (mean onset age 60.9 years, 8.5% female, 71.0% White, 21.4% Black).

Patients with PTE were defined as having had documentation of TBI within 5 years previous to receiving an epilepsy diagnosis.

Among those with NTE (median follow-up, 6.0 years), 51.1% died. In the PTE group (median follow-up, 6.4 years), 37.3% died.

After adjustment for differences in age, sex, and comorbidities, the risk of mortality in PTE was slightly higher than in NTE (adjusted hazard ratio [aHR], 1.02); the risk was lower for the concussive TBI subtype (aHR, 0.91, both P < .05). “The underlying injury in concussion

is likely to be less severe compared with structural TBI, which may have led to the lower relative mortality observed,” the authors wrote. 

However, risk of mortality in PTE was higher than in NTE for cases with underlying TBI subtypes of skull/facial fracture (aHR, 1.18), diffuse cerebral injury (aHR, 1.17), and focal cerebral injury (aHR, 1.16).

“These injuries are associated with greater structural brain damage and sustained neuroinflammation, which are factors linked to harder-to-treat (drug-resistant) epilepsy, which carries higher mortality,” Haneef said. “They may also coexist with extracranial trauma and medical comorbidity that compound long-term risk.”

Among various age groups, there was a notably higher risk of mortality linked to patients aged 18 to 39 years at onset with extracerebral PTE (aHR, 2.02, vs NTE): “In younger patients, extracerebral bleeds (eg, subdural, epidural, and subarachnoid) may reflect higher-energy trauma and more aggressive secondary cascades, amplifying epilepsy severity and longer lifetime exposure to risk. Mechanistic differences in hemorrhage types across ages may also contribute,” Haneef said. 

Perspective on Findings

Amorim said the new research is “very useful,” although it has limitations that are common in large database studies. “A key point that this study highlights is the variability in the impact of TBI type on mortality and the differential risk across different age groups,” he said. 

As for the higher risk in younger people, Amorim said this may be related to severity of injury: “Older patients often have TBI after falls, while younger patients are more frequently involved in traffic accidents or victims of violence,” he said

In the big picture, Amorim said, “studies like this highlight the importance of moving beyond a one-size-fits-all approach in epilepsy care. Understanding the nuances of posttraumatic epilepsy—how the type of injury, age, and other factors affect outcomes—can help us personalize treatment and counseling and maybe even guide future research into preventing or mitigating epilepsy after brain injury. New methods to automate review of medical records with higher resolution, such as large language models and natural language processing, may make this type of study with large databases even more comprehensive and impactful.”

Haneef said the findings highlight the importance of recognizing PTE as a higher-risk epilepsy and prioritizing early specialty care, especially after focal/diffuse brain injury or fracture. “Screen proactively for drug resistance and fast-track definitive therapies—surgery and device-based therapies—when indicated,” Haneef said. “Management should also include optimized antiseizure therapy, comorbidity control, and safety counseling, since many deaths may be preventable with coordinated multidisciplinary care.”

Haneef added that clinicians should “pay particular attention to younger PTE patients with extracerebral hemorrhage, who showed the greatest relative mortality.”

He also noted that the US Department of Veterans Affairs has comprehensive Epilepsy Centers of Excellence across the country.

The US Department of Defense (DoD) funded the study. Haneef discloses DoD funding, and another author discloses DoD and VA funding. Other authors have no disclosures. 

Amorim discloses funding from DoD, NIH, American Heart Association, Regents of the University of California, Cures Within Reach, Zoll Foundation, and Hellman Foundation.