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Multicenter Study
. 2021 Dec 1;4(12):e2140191.
doi: 10.1001/jamanetworkopen.2021.40191.

Association of Posttraumatic Epilepsy With 1-Year Outcomes After Traumatic Brain Injury

John Burke  1   2 , James Gugger  3 , Kan Ding  4 , Jennifer A Kim  5 , Brandon Foreman  6 , John K Yue  1   2 , Ava M Puccio  7 , Esther L Yuh  2   8 , Xiaoying Sun  9 , Miri Rabinowitz  7 , Mary J Vassar  1   2 , Sabrina R Taylor  1   2 , Ethan A Winkler  1   2 , Hansen Deng  7 , Michael McCrea  10 , Murray B Stein  11 , Claudia S Robertson  12 , Harvey S Levin  13 , Sureyya Dikmen  14 , Nancy R Temkin  15   16 , Jason Barber  16 , Joseph T Giacino  17 , Pratik Mukherjee  2   8 , Kevin K W Wang  18 , David O Okonkwo  7 , Amy J Markowitz  2 , Sonia Jain  9 , Daniel Lowenstein  19 , Geoffrey T Manley  1   2 , Ramon Diaz-Arrastia  3 ; TRACK-TBI Investigators; Neeraj Badjatia  20 , Ann-Christine Duhaime  21 , V Ramana Feeser  22 , Etienne Gaudette  23 , Shankar Gopinath  24 , C Dirk Keene  25 , Frederick K Korley  26 , Christopher Madden  27 , Randall Merchant  22 , David Schnyer  28 , Ross Zafonte  29
Affiliations
Multicenter Study

Association of Posttraumatic Epilepsy With 1-Year Outcomes After Traumatic Brain Injury

John Burke et al. JAMA Netw Open. .

Abstract

Importance: Posttraumatic epilepsy (PTE) is a recognized sequela of traumatic brain injury (TBI), but the long-term outcomes associated with PTE independent of injury severity are not precisely known.

Objective: To determine the incidence, risk factors, and association with functional outcomes and self-reported somatic, cognitive, and psychological concerns of self-reported PTE in a large, prospectively collected TBI cohort.

Design, setting, and participants: This multicenter, prospective cohort study was conducted as part of the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study and identified patients presenting with TBI to 1 of 18 participating level 1 US trauma centers from February 2014 to July 2018. Patients with TBI, extracranial orthopedic injuries (orthopedic controls), and individuals without reported injuries (eg, friends and family of participants; hereafter friend controls) were prospectively followed for 12 months. Data were analyzed from January 2020 to April 2021.

Exposure: Demographic, imaging, and clinical information was collected according to TBI Common Data Elements. Incidence of self-reported PTE was assessed using the National Institute of Neurological Disorders and Stroke Epilepsy Screening Questionnaire (NINDS-ESQ).

Main outcomes and measures: Primary outcomes included Glasgow Outcome Scale Extended, Rivermead Cognitive Metric (RCM; derived from the Rivermead Post Concussion Symptoms Questionnaire), and the Brief Symptom Inventory-18 (BSI).

Results: Of 3296 participants identified as part of the study, 3044 met inclusion criteria, and 1885 participants (mean [SD] age, 41.3 [17.1] years; 1241 [65.8%] men and 644 [34.2%] women) had follow-up information at 12 months, including 1493 patients with TBI; 182 orthopedic controls, 210 uninjured friend controls; 41 patients with TBI (2.8%) and no controls had positive screening results for PTE. Compared with a negative screening result for PTE, having a positive screening result for PTE was associated with presenting Glasgow Coma Scale score (8.1 [4.8] vs.13.5 [3.3]; P < .001) as well as with anomalous acute head imaging findings (risk ratio, 6.42 [95% CI, 2.71-15.22]). After controlling for age, initial Glasgow Coma Scale score, and imaging findings, compared with patients with TBI and without PTE, patients with TBI and with positive PTE screening results had significantly lower Glasgow Outcome Scale Extended scores (mean [SD], 6.1 [1.7] vs 4.7 [1.5]; P < .001), higher BSI scores (mean [SD], 50.2 [10.7] vs 58.6 [10.8]; P = .02), and higher RCM scores (mean [SD], 3.1 [2.6] vs 5.3 [1.9]; P = .002) at 12 months.

Conclusions and relevance: In this cohort study, the incidence of self-reported PTE after TBI was found to be 2.8% and was independently associated with unfavorable outcomes. These findings highlight the need for effective antiepileptogenic therapies after TBI.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Foreman reported receiving personal fees from UCB, grants from the National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS), the Department of Defense (DOD), and National Science Foundation (NSF) outside the submitted work. Dr McCrea reported receiving grants from the University of California, San Francisco, during the conduct of the study and grants from the NIH, DOD, Centers for Disease Control and Prevention (CDC), Abbott Laboratories, National Collegiate Athletic Association (NCAA), and National Football League (NFL) outside the submitted work. Dr Stein reported owning stock in Oxeia Biopharmaceuticals outside the submitted work. Dr Robertson reported receiving grants from the NIH and DOD during the conduct of the study. Dr Temkin reported receiving grants from the NIH and DOD during the conduct of the study. Dr Giacino reported receiving grants from the NIH NINDS and NFL during the conduct of the study. Dr Mukherjee reported receiving grants from the NIH and DOD during the conduct of the study and owning a patent for 15/782,005 (pending University of California Regents) and PCT/US2020/042811 (pending University of California Regents). Ms Markowitz reported receiving grants from the DOD during the conduct of the study. Dr Manley reported receiving grants from the DOD and NIH NINDS during the conduct of the study and grants from NeuroTrauma Sciences, One Mind, and Abbott Laboratories outside the submitted work. Dr Diaz-Arrastia reported receiving grants from the NIH NIHDS and DOD during the conduct of the study. Dr Duhaime reported receiving grants from the NIH during the conduct of the study. Dr Madden reported receiving grants from the NIH during the conduct of the study. Dr Schnyer reported receiving grants from the NIH and DOD during the conduct of the study. Dr Zafonte reported serving on scientific advisory boards for Myomo, OneCare, and Biodirection and as a consultant for the Mackey White committee and the MGH Brain and Body-TRUST Program (funded by the NFL Players Association) and receiving royalties from Springer. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Diagram of Screening Questionnaire and Definition of Self-reported Diagnosis
After applying the first-level screening criteria, any patient who screened positive to questions 1a-d was given a second-level screening questionnaire. If the patient answered positively to questions 2a and 2c, and negatively to question 2b they were considered to have a self-reported diagnosis of posttraumatic epilepsy (PTE). SRD indicates self-reported diagnosis; TBI, traumatic brain injury.
Figure 2.
Figure 2.. Diagram of Exclusion Criteria and Number of Patients in the Analysis
After applying the exclusion criteria, 1493 patients with traumatic brain injury (TBI), 182 orthopedic control patients, and 210 friend control patients were analyzed.
See this image and copyright information in PMC

References

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