Risk Factors and Outcomes for Post-Traumatic Seizures After Moderate to Severe Traumatic Brain Injury

Associate Professor of Neurology, Weill Cornell Medical College; Director, Weill Cornell Concussion and Brain Injury Center

SYNOPSIS: Using data collected from an Australian registry, a population-based cohort study identified risk factors for early post-traumatic seizures (EPS), associated morbidity and mortality, and contribution to development of post-traumatic epilepsy (PTE). EPS were associated with significant in-hospital morbidity, poorer outcomes, and increased risk of mortality at 24 months of follow-up. Patients with EPS had a higher risk of developing PTE.

SOURCE: Laing J, Gabbe B, Chen Z, et al. Risk factors and prognosis of early posttraumatic seizures in moderate to severe traumatic brain injury. JAMA Neurol 2022;79:334-341.

Early post-traumatic seizures (EPS) are defined as those occurring during the first six months following a traumatic brain injury (TBI). Moderate to severe TBI may be associated with EPS. The investigators in this population-based study of 15,152 patients with moderate to severe TBI (10,457 [69%] male; median age, 60 [35-79] years) identified 416 (2.7%) patients with EPS, including 27 (0.2%) with status epilepticus. On multivariate analysis, risk factors for developing EPS were younger age, higher Charlson Comorbidity Index, TBI sustained from a low fall, subdural hemorrhage, subarachnoid hemorrhage, higher Injury Severity Score, and greater head injury severity, measured using the Abbreviated Injury Scale and Glasgow Coma Scale (GCS) score.

Patients with EPS had increased intensive care unit (ICU) admission and ICU length of stay, greater likelihood of mechanical ventilation, and a longer hospital length of stay. Patients with EPS were more likely to be discharged to inpatient rehabilitation rather than home. Although in-hospital mortality rates were not different between patients with EPS and those without, TBI patients with EPS had poorer outcomes at 24 months, including an increased risk of developing long-term post-traumatic epilepsy (PTE). A higher proportion of patients who developed EPS were severely disabled or died within 24 months, compared with patients who did not develop EPS.

Commentary

Patients with moderate to severe TBI present with altered mental status and varying degrees of motor, sensory, and cerebellar deficits. Moderate TBI is defined as GCS score of 9 to 13 on presentation and may decline precipitously over a short period of time to severe TBI (GCS < 9).¹ Computed tomography scan of the head and magnetic resonance imaging of the brain show an increasing level of structural brain damage. Patients with moderate to severe TBI have a lower seizure threshold and increased propensity for seizures in the immediate aftermath of the head injury. Hence, many patients in the hospital are started on an anticonvulsant drug regimen for seizure prophylaxis. Usually, a broad-spectrum anticonvulsant, such as levetiracetam, is preferred. Levetiracetam is an efficacious broad-spectrum anticonvulsant with a favorable side-effect profile and few drug-drug interactions.² It also can be administered intravenously in the unconscious, intubated patient. In patients who do not experience seizures, anticonvulsant drugs can be tapered off after a period of seven days.

Post-traumatic seizures may be divided into immediate, early, and late, based on when they occur after the head injury.³ Immediate post-traumatic seizures, also referred to as impact seizures, occur at the time of the head injury. The etiology of these seizures is thought to be biomechanical forces experienced by the brain at the time of the initial head impact.

Immediate post-traumatic seizures usually have a good prognosis and do not lead to PTE. As a result, these patients do not warrant long-term anticonvulsant drug therapy. Seizures occurring within six months of the head injury are labeled early post-traumatic seizures. The etiology of these seizures is thought to be multifactorial, including hemorrhage, cerebral edema, and metabolic factors. These patients usually are treated with anticonvulsant drug therapy for varying periods. If they remain seizure-free, a gradual and cautious taper of the anticonvulsant is attempted.

Our current understanding is that more prolonged duration of treatment of EPS does not prevent later development of PTE. An electroencephalogram study may help in characterization and prognostication before anticonvulsant wean is attempted. Seizures may occur as far as five years out after a head injury. Patients with late PTE usually need long-term anticonvulsant therapy.⁴ In some, seizures are refractory to initial therapy, and multiple antiseizure medications are needed.

References

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2. DJohn J, Ibrahim R, Patel P, et al. Administration of levetiracetam in traumatic brain injury: Is it warranted? Cureus 2020;12:e9117.
3. Fordington S, Manford M. A review of seizures and epilepsy following traumatic brain injury. J Neurol 2020;267:3105-3111.
4. Torbic H, Forni AA, Anger KE, et al. Use of antiepileptics for seizure prophylaxis after traumatic brain injury. Am J Health Syst Pharm 2013;70:759-766.