traumatic brain injury (TBI), even a mild type, can lead to post-traumatic epilepsy (PTE) up to a year after the head injury occurs, new research suggests.

Results from a multicenter, prospective cohort study showed 2.7% of nearly 1500 participants with TBI reported also having PTE, and these patients had significantly worse outcomes than those without PTE.

“Post-traumatic epilepsy is common even in so-called mild TBI, and we should be on the lookout for patients reporting these kinds of spells,” co-investigator Ramon Diaz-Arrastia, MD, PhD, professor of neurology and director of the TBI Clinical Research Center, University of Pennsylvania, Philadelphia, told Medscape Medical News.

Diaz-Arrastia added he dislikes the term “mild TBI” because many of these injuries have “pretty substantial consequences.”

The findings were published online December 29 in JAMA Network Open.

Novel Study

Seizures can occur after TBI, most commonly after a severe brain injury, such as those leading to coma or bleeding in the brain or requiring surgical intervention. However, there have been “hints” that some patients with milder brain injuries are also at increased risk for epilepsy, said Diaz-Arrastia.

To investigate, the researchers assessed data from the large, multicenter Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) database.

The study included patients with relatively mild TBI (GCS score, 13-15), which is a “novel feature” of the study, the authors note. Most prior studies of PTE focused on moderate to severe TBI.

The researchers also included two sex- and age-matched control groups. The orthopedic trauma control (OTC) group consisted of patients with isolated trauma to the limbs, pelvis, and/or ribs. The “friend” or peer control group had a similar background and lifestyle as those with TBI but had no history of TBI, concussion, or traumatic injury in the previous year.

The analysis included 1885 participants (mean age, 41.3 years; 65.8% men). Of these, 1493 had TBI, 182 were in the OTC group, and 210 were in the friends group.

At 6- and 12-month follow-ups, investigators administered the Epilepsy Screening Questionnaire (ESQ), developed by the National Institute of Neurological Disorders and Stroke (NINDS).

Confirmatory Data

Participants were asked about experiencing uncontrolled movements, unexplained changes in mental state, and repeated unusual attacks or convulsions, and whether they had been told they had epilepsy or seizures. If they answered yes to any of these questions, they received second-level screening, which asked about seizures.

Patients were deemed to have PTE if they answered affirmatively to any first-level screening item, experienced seizures 7 days after injury, and were diagnosed with epilepsy.

The primary outcome was rate of positive PTE diagnoses. At 12 months, 2.7% of those with TBI reported a PTE diagnosis compared to none of either of the control groups (< .001).

This rate is consistent with prior literature and is “pretty close to what we expected,” said Diaz-Arrastia.

Among those with TBI and PTE, 12.2% had GCS scores of 3-8 (severe), 5.3% had scores of 9-12 (moderate), and 0.9% had scores of 13-15 (mild). That figure for mild TBI is not insignificant, said Diaz-Arrastia.

“Probably 90% of all those coming to the emergency room with a brain injury are diagnosed with mild TBI not requiring admission,” he noted.

The risk for PTE was higher the more severe the head injury, and among those with hemorrhage on head CT imaging. In patients with mild TBI, hemorrhage was associated with a two- to threefold risk of developing PTE.

“This prospective observational study confirms the epidemiologic data that even after mild brain injury, there is an increased risk for epilepsy,” said Diaz-Arrastia.

Universal Screening?

The researchers also looked at whether seizures worsen other outcomes. Compared to those who had TBI but not PTE, those with PTE had significantly lower Glasgow Outcome Scale Extended (GOSE) scores (mean, 4.7 vs 6.1; < .001), higher Brief Symptom Inventory (BSI) scores (58.6 vs 50.2; = .02), and higher Rivermead Cognitive Metric (RCM) scores (5.3 vs 3.1; = .002) at 12 months after controlling for age, initial GCS score, and imaging findings.

Higher GOSE and RCM scores reflect better outcomes, but a higher score on the BSI, which assesses overall mood, reflects a worse outcome, the investigators note.

Previous evidence suggests prophylactic use of antiepileptic drugs in patients with TBI does not reduce risks. These drugs “are neither 100% safe nor 100% effective,” said Diaz-Arrastia. He added some studies showed that certain agents actually worsen outcomes.

What the field needs instead are anti-epileptogenic drugs — those that interfere with the maladaptive synaptic plasticity that ends up in an epileptic circuit, he noted.

The new results suggest screening for PTE using the NINDS-ESQ “should be done pretty much routinely as a follow-up for all brain injuries,” Diaz-Arrastia said.

The investigators plan to have study participants assessed by an epileptologist later. A significant number of people with TBI, he noted, won’t develop PTE until 1-5 years after their injury — and even later in some cases.

A limitation of the study was that some patients reporting PTE may have had psychogenic nonepileptiform seizures, which are common in TBI patients, the investigators note.

The study was supported by grants from One Mind, National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS, and Department of Defence. Diaz-Arrastia reported receiving grants from the NIH NINDS, and DOD during the conduct of the study.

JAMA Network Open. Published December 29, 2021.

Source: by Pauline Anderson