Long-term outcome in traumatic brain injury patients with midline shift: a secondary analysis of the Phase 3 COBRIT clinical trial

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Following traumatic brain injury (TBI), midline shift of the brain at the level of the septum pellucidum is often caused by unilateral space-occupying lesions and is associated with increased intracranial pressure and worsened morbidity and mortality. While outcome has been studied in this population, the recovery trajectory has not been reported in a large cohort of patients with TBI. The authors sought to utilize the Citicoline Brain Injury Treatment (COBRIT) trial to analyze patient recovery over time depending on degree of midline shift at presentation.


Patient data from the COBRIT trial were stratified into 4 groups of midline shift, and outcome measures were analyzed at 30, 90, and 180 days postinjury. A recovery trajectory analysis was performed identifying patients with outcome measures at all 3 time points to analyze the degree of recovery based on midline shift at presentation.


There were 892, 1169, and 895 patients with adequate outcome data at 30, 90, and 180 days, respectively. Rates of favorable outcome (Glasgow Outcome Scale–Extended [GOS-E] scores 4–8) at 6 months postinjury were 87% for patients with no midline shift, 79% for patients with 1–5 mm of shift, 64% for patients with 6–10 mm of shift, and 47% for patients with > 10 mm of shift. The mean improvement from unfavorable outcome (GOS-E scores 2 and 3) to favorable outcome (GOS-E scores 4–8) from 1 month to 6 months in all groups was 20% (range 4%–29%). The mean GOS-E score for patients in the 6- to 10-mm group crossed from unfavorable outcome (GOS-E scores 2 and 3) into favorable outcome (GOS-E scores 4–8) at 90 days, and the mean GOS-E of patients in the > 10-mm group nearly reached the threshold of favorable outcome by 180 days postinjury.


In this secondary analysis of the Phase 3 COBRIT trial, TBI patients with less than 10 mm of midline shift on admission head CT had significantly improved functional outcomes through 180 days after injury compared with those with greater than 10 mm of midline shift. Of note, nearly 50% of patients with > 10 mm of midline shift achieved a favorable outcome (GOS-E score 4–8) by 6 months postinjury.

ABBREVIATIONS COBRIT = Citicoline Brain Injury Treatment; CONSORT = Consolidated Standards of Reporting Trials; FITBIR = Federal Interagency Traumatic Brain Injury Research; GCS = Glasgow Coma Scale; GOS-E = Glasgow Outcome Scale–Extended; TBI = traumatic brain injury.

Article Information

Correspondence David O. Okonkwo: University of Pittsburgh Medical Center, Pittsburgh, PA. okonkwodo@upmc.edu.

INCLUDE WHEN CITING Published online August 3, 2018; DOI: 10.3171/2018.2.JNS173138.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.



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    CONSORT diagram.

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    The 30-day (A), 90-day (B), 180-day (C) postinjury GOS-E outcomes (D) by degree of midline shift.

  • View in gallery

    Recovery trajectory of the mean GOS-E score by degree of midline shift.



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