Authors :
Presenting Author: Ariel Sacknovitz, MS – New York Medical College
Isaac Thorman, ScM – New York Medical College
Michael Schubert, PT, PhD – Johns Hopkins University
Patricia McGoldrick, NP – Boston Children's Health Physicians
Steven Wolf, MD, FAES – Boston Children's Health Physicians
Carrie Muh, MD – Westchester Medical Center
Rationale:
Traumatic brain injury (TBI) is a major cause of morbidity and mortality for children in the United States. Among survivors, post-traumatic seizures and epilepsy are feared complications. Anti-seizure medications (ASMs) have long been used as seizure prophylaxis in TBI patients, but the evidence supporting this practice is weak. Recent guidelines from the Neurocritical Care Society make a weak recommendation with “low quality of evidence” that ASMs may be used in moderate-severe adult TBI. Further, few studies have analyzed the use of ASMs as seizure prophylaxis in pediatric TBI. The objective of this study is to evaluate the efficacy of administering ASMs after a mild-moderate pediatric TBI in preventing post-traumatic epilepsy, seizures and mortality.Methods:
This retrospective study included 9,507 patients 21 years old or younger with TBI and Glascow Coma Scale (GCS) 9-15, indicated by ICD-10 codes, from the TriNetX Research Network. Propensity score matching was used to control for demographics, intracranial pathology (e.g., epidural, subdural, and subarachnoid hemorrhages), and Glascow Coma Scale (GCS). Cox proportional hazard models assessed the relative hazards of seizures and mortality associated with ASMs.
Results:
Across 15 years of follow-up, patients receiving ASMs had a significantly increased hazard of seizure development than patients receiving no ASMs (HR=4.26, [3.05, 5.95). The relationship held in both patients with GCS 13-15 (HR=3.11, [2.17, 4.45]) and GCS 9-12 (HR=2.98, [1.64, 5.40]). Among patients with no intracranial pathologies, ASMs were associated with increased hazards of seizure development among patients with GCS 13-15 (HR=19.79, [4.74, 82.66]) and GCS 9-12 (HR=11.25, [1.44, 87.93]). In a competing risk analysis of patients who did not develop seizures, patients receiving ASMs did not significantly affect mortality relative to patients receiving no ASMs (HR=0.79, [0.36, 1.73]). Levetiracetam accounted for 82% of prescriptions and had a significantly increased hazard of seizure development (HR=4.32, [3.04, 6.14]) compared to patients with no ASMs. ASMs were associated with significantly increased hazards of newly diagnosed anxiety disorders (HR=1.29, [1.06, 1.58]) and metabolic disorders (HR=1.55, [1.30, 1.85]). Levetiracetam was additionally associated with significantly increased hazards of impaired memory, cognitive functions, and awareness (HR=1.20, [1.01, 1.43]) and thrombocytopenia (HR=1.96, [1.12, 3.45]).
Conclusions:
Our findings show no evidence supporting the use of ASMs as seizure and mortality prophylaxis in mild-moderate pediatric TBI. Significant adverse effects of ASMs included anxiety and metabolic disorders. Levetiracetam, the most commonly used medication, had additional hazards of cognitive impairment and thrombocytopenia. Due to the lack of efficacy and risk profile, our results strongly indicate that ASMs generally, and levetiracetam in particular, should not be given to children following a mild-moderate TBI. Further prospective research is needed to elucidate these results. Funding: This study was unfunded.