In Children and Youth with Mild and Moderate Traumatic Brain Injury, Glial Fibrillary Acidic Protein Out-Performs S100β in Detecting Traumatic Intracranial Lesions on Computed Tomography

Papa, Linda; Mittal, Manoj K.; Ramirez, José; Ramia, Michelle M.; Kirby, Sara; Silvestri, Salvatore; Giordano, Philip; Weber, Kurt; Braga, Carolina F.; Tan, Ciara N.; Ameli, Neema J.; López, Marco Antonio; Zonfrillo, Mark R.

doi:10.1089/neu.2015.3869

Cited by 49 publications

(49 citation statements)

References 28 publications

(49 reference statements)

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“…15,18 Moreover, GFAP out-performed S100β in the setting of multiple trauma when extracranial fractures were present. 18,20 More studies evaluating its performance in children and youth in an acute trauma setting are needed.…”

Section: Introductionmentioning

confidence: 99%

Performance of Glial Fibrillary Acidic Protein in Detecting Traumatic Intracranial Lesions on Computed Tomography in Children and Youth With Mild Head Trauma

Papa

Zonfrillo

Ramirez

et al. 2015

Academic Emergency Medicine

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Objectives This study examined the performance of serum glial fibrillary acidic protein (GFAP) in detecting traumatic intracranial lesions on computed tomography (CT) scan in children and youth with mild and moderate traumatic brain injury (TBI), and assessed its performance in trauma control patients without head trauma. Methods This prospective cohort study enrolled children and youth presenting to three Level I trauma centers following blunt head trauma with Glasgow Coma Scale (GCS) scores of 9 to 15, as well as trauma control patients with GCS scores of 15 who did not have blunt head trauma. The primary outcome measure was the presence of intracranial lesions on initial CT scan. Blood samples were obtained in all patients within six hours of injury and measured by ELISA for GFAP (ng/ml). Results A total of 257 children and youth were enrolled in the study and had serum samples drawn within 6 hours of injury for analysis: 197 had blunt head trauma and 60 were trauma controls. CT scan of the head was performed in 152 patients and traumatic intracranial lesions on CT scan were evident in 18 (11%), all of whom had GCS scores of 13 to 15. When serum levels of GFAP were compared in children and youth with traumatic intracranial lesions on CT scan to those without CT lesions, median GFAP levels were significantly higher in those with intracranial lesions (1.01, IQR 0.59 to 1.48) than those without lesions (0.18, IQR 0.06 to 0.47). The area under the receiver operating characteristic (ROC) curve (AUC) for GFAP in detecting children and youth with traumatic intracranial lesions on CT was 0.82 (95% CI = 0.71 to 0.93). In those presenting with GCS scores of 15, the AUC for detecting lesions was 0.80 (95% CI = 0.68 to 0.92). Similarly, in children under five years old the AUC was 0.83 (95% CI = 0.56 to 1.00). Performance for detecting intracranial lesions at a GFAP cutoff level of 0.15 ng/ml yielded a sensitivity of 94%, a specificity of 47%, and a negative predictive value of 98%. Conclusions In children and youth of all ages, GFAP measured within 6 hours of injury was associated with traumatic intracranial lesions on CT and with severity of TBI. Further study is required to validate these findings before clinical application.

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Section: Introductionmentioning

confidence: 99%

Performance of Glial Fibrillary Acidic Protein in Detecting Traumatic Intracranial Lesions on Computed Tomography in Children and Youth With Mild Head Trauma

Papa

Zonfrillo

Ramirez

et al. 2015

Academic Emergency Medicine

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“…Similar to adult literature evaluating mild to moderate TBI, our study found that GFAP was able to distinguish between patients with OI and those with mTBI. 6,7 Recently GFAP has been shown to outperform the serum biomarker S100B in identifying intracranial lesions in children with mild to moderate TBI, 26,27 although none of the children in our study had abnormal CT neuroimaging. Non-specific white matter signal foci were identified by MRI in 16.3% of all subjects, with no difference in prevalence between injury types.…”

Section: Discussionmentioning

confidence: 64%

Are UCH-L1 and GFAP promising biomarkers for children with mild traumatic brain injury?

Rhine¹,

Babcock²,

Zhang³

et al. 2016

Brain Injury

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Objectives Compare serum biomarker levels between children with mild traumatic brain injury (mTBI) and orthopaedic injury (OI), following injury. Secondarily, to explore the association between biomarker levels and symptom burden over one month post injury. Methods Prospective cohort study of children ages 11-16 years who presented to the emergency department within six hours of sustaining mTBI or isolated extremity OI. Serum was drawn at time of study enrollment, and levels of ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) and glial fibrillary acid protein (GFAP) were analysed. Symptom burden was assessed by the Post-Concussion Symptom Scale (PCSS) acutely following injury and at three subsequent time points over one month. Results Twenty-five children with mTBI and 20 children with OI were enrolled. The average age for the overall cohort was 13 (±1.6) years, and the majority was male and injured playing sports. GFAP and PCSS scores were significantly higher acutely following mTBI versus OI (p<0.01). There was no significant group difference in UCH-L1. Neither GFAP nor UCH-L1 was predictive of PCSS over the one month post-injury. Conclusions GFAP may be a promising diagnostic tool for children with mTBI. Additional approaches are needed to predict symptom severity and persistence.

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“…20, 31 Unfortunately, its utility in the setting of multiple trauma remains controversial because it is also elevated in trauma patients with peripheral trauma without direct head trauma. 32, 33 Several studies have found increased serum levels of S100β in the absence of head injury in soccer players and marathon runners, and individuals participating in vigorous exercise. 19, 28, 34, 35 …”

Section: Biofluid Biomarkers Of Astroglial Injurymentioning

confidence: 99%

“…4, 32, 33, 52–55 GFAP is released into serum following a MTBI within an hour of injury and remains elevated for several days after injury. 33, 52, 55 Unlike S100β, GFAP is elevated in MTBI patients with axonal injury as evidenced by MRI at 3 months post-injury.…”

Section: Biofluid Biomarkers Of Astroglial Injurymentioning

confidence: 99%

“…4 In adults and children, serum GFAP levels distinguish MTBI patients from trauma patients without TBI and detect intracranial lesions on CT with a sensitivity of 94%–100%. 32, 33, 52, 54 Moreover, GFAP out-performs S100β in detecting CT lesions in the setting of multiple trauma when extracranial fractures are present. 33, 54 GFAP also predicts the need for neurosurgical intervention in patients with MTBI.…”

Section: Biofluid Biomarkers Of Astroglial Injurymentioning

confidence: 99%

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Potential Blood-based Biomarkers for Concussion

Papa

2016

Sports Medicine and Arthroscopy Review

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Mounting research in the field of sports concussion biomarkers has led to a greater understanding of the effects of brain injury from sports. A recent systematic review of clinical studies examining biomarkers of brain injury following sports-related concussion established that almost all studies have been published either in or after the year 2000. In an effort to prevent CTE and long-term consequences of concussion, early diagnostic and prognostic tools are becoming increasingly important; particularly in sports and in military personnel, where concussions are common occurrences. Early and tailored management of athletes following a concussion with biomarkers could provide them with the best opportunity to avoid further injury. Should blood-based biomarkers for concussion be validated and become widely available, they could have many roles. For instance, a point-of-care test could be used on the field by trained sport medicine professionals to help detect a concussion. In the clinic or hospital setting, it could be used by clinicians to determine the severity of concussion and be used to screen players for neuroimaging (CT and/or MRI) and further neuropsychological testing. Furthermore, biomarkers could have a role in monitoring progression of injury and recovery and in managing patients at high risk of repeated injury by being incorporated into guidelines for return to duty, work or sports activities. There may even be a role for biomarkers as surrogate measures of efficacy in the assessment of new treatments and therapies for concussion.

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In Children and Youth with Mild and Moderate Traumatic Brain Injury, Glial Fibrillary Acidic Protein Out-Performs S100β in Detecting Traumatic Intracranial Lesions on Computed Tomography

Cited by 49 publications

References 28 publications

Performance of Glial Fibrillary Acidic Protein in Detecting Traumatic Intracranial Lesions on Computed Tomography in Children and Youth With Mild Head Trauma

Performance of Glial Fibrillary Acidic Protein in Detecting Traumatic Intracranial Lesions on Computed Tomography in Children and Youth With Mild Head Trauma

Are UCH-L1 and GFAP promising biomarkers for children with mild traumatic brain injury?

Potential Blood-based Biomarkers for Concussion

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