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Prediction of seizure risk following repeated mild traumatic brain injury in
             children
             Laura M. Prolo, MD, PhD, Department of
             Neurosurgery, Stanford University School of Medicine, Stanford CA
             Co-authors:  Michael  C.  Jin  BS  1  ,  Adela  Wu  MD  1  ,  Cesar  A.  Garcia  BA  1  ,
             Adrian J. Rodrigues BA 1 , Sol Savchuk BS 1 , Gabriela D. Ruiz Colón BA 1 ,
             Bina W. Kakusa MD 1 , Jonathon J. Parker MD, PhD 1 , Gerald A. Grant MD 2
             1  Department  of  Neurosurgery,  Stanford  University  School  of  Medicine,
             Stanford, CA
             2 Department of Neurosurgery, Duke University School of Medicine, Durham, NC
             Introduction: While moderate to severe traumatic brain injury is a known risk fac-
             tor for seizures, the impact of repeated mild head trauma on long-term seizure
             risk is less clear. We developed a modeling tool to determine what clinical char-
             acteristics predict long-term seizure risk following mild TBI (mTBI).
             Methods:  Utilizing  a  national  longitudinal  healthcare  claims  database,  a total  of
             156,118 children (age < 18) diagnosed with mTBI without prior seizures were
             identified  from  2003  to  2021.  Comorbidities  linked  to  epilepsy  were  collected
             during the six months  preceding the initial mTBI event. Each mTBI event was
             defined  as  a  diagnosis  code  indicating  head  injury  with  ≤1  hour  loss-of-
             consciousness.  Repeated  mTBI  was  defined  as  a  subsequent  mTBI  diagnosis
             code > one month following the prior event. Follow-up was censored at antiepi-
             leptic drug initiation, moderate or severe TBI, or loss-to-follow-up. Time-varying
             multivariable Cox regression was used to assess impact of repeat mTBI. Three
             distinct machine learning approaches were evaluated.
             Results:  Median  duration  of  follow-up  was  22.6  months  and  median  time-to-
             seizure was 306 days. Seizures among those with radiographic findings (median
             time-to-seizure  112.5  days,  IQR  5  to  526.25),  loss-of-consciousness  (80  days,
             IQR 7 to 652 or both (22 days, IQR 5 to 192) occurred earlier. Both mTBI without
             and with short loss-of-consciousness resulted in increasing seizure risk with re-
             peated events (HR=1.196, 95%CI 1.082-1.322; HR=2.025, 95%CI 1.828- 2.244;
             respectively).  The  survival  random  forest  approach  performed  best,  achieving
             fixed-time AUROCs of 0.780 and 0.777 at 30- and 90-days post-mTBI.
             Conclusion: Utilizing a machine learning approach, children with elevated seizure
             risk following mTBI can be identified. Repeated mTBI accompanied by loss-of-
             consciousness doubles the risk for future seizures and a small subset of children
             were identified with a nearly 9- fold elevated seizure risk. These results suggest a
             subset of children who have multiple mTBI events may benefit from prophylactic
             antiepileptic drugs.











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