Characteristics of patients included and enrolled in studies on the prognostic value of serum biomarkers for prediction of postconcussion symptoms following a mild traumatic brain injury: a systematic review

Abstract

ObjectiveMild traumatic brain injury (mTBI) has been insufficiently researched, and its definition remains elusive. Investigators are confronted by heterogeneity in patients, mechanism of injury and outcomes. Findings are thus often limited in generalisability and clinical application. Serum protein biomarkers are increasingly assessed to enhance prognostication of outcomes, but their translation into clinical practice has yet to be achieved. A systematic review was performed to describe the adult populations included and enrolled in studies that evaluated the prognostic value of protein biomarkers to predict postconcussion symptoms following an mTBI.Data sourcesSearches of MEDLINE, Embase, CENTRAL, CINAHL, Web of Science, PsycBITE and PsycINFO up to October 2016.Data selection and extractionTwo reviewers independently screened for potentially eligible studies, extracted data and assessed the overall quality of evidence by outcome using the Grading of Recommendations Assessment, Development and Evaluation approach.ResultsA total of 23 298 citations were obtained from which 166 manuscripts were reviewed. Thirty-six cohort studies (2812 patients) having enrolled between 7 and 311 patients (median 89) fulfilled our inclusion criteria. Most studies excluded patients based on advanced age (n=10 (28%)), neurological disorders (n=20 (56%)), psychiatric disorders (n=17 (47%)), substance abuse disorders (n=13 (36%)) or previous traumatic brain injury (n=10 (28%)). Twenty-one studies (58%) used at least two of these exclusion criteria. The pooled mean age of included patients was 39.3 (SD 4.6) years old (34 studies). The criteria used to define a mTBI were inconsistent. The most frequently reported outcome was postconcussion syndrome using the Rivermead Post-Concussion Symptoms Questionnaire (n=18 (50%)) with follow-ups ranging from 7 days to 5 years after the mTBI.ConclusionsMost studies have recruited samples that are not representative and generalisable to the mTBI population. These exclusion criteria limit the potential use and translation of promising serum protein biomarkers to predict postconcussion symptoms.

Acute findings in an acquired neurosensory dysfunction

“…[25][26][27] Perhaps the most important objective clinical feature is the nearly universal evidence of otolithic impairment; such uniformity in symptoms is uncommon in mTBI cases from other sources. 28,29 This frequency of specific vestibular findings is not seen in any control populations. In this work the authors provide the characteristics in a group of patients defined by vestibular pathology in which the clinical presentation seems most consistent with a primary localized neurotologic (largely otolithic) injury with cognitive symptoms.…”

“…In addition, the low incidence of headaches (around 25%) is unusual, as many studies of mTBI show that headache is one of the most common and persistent symptoms . Perhaps the most important objective clinical feature is the nearly universal evidence of otolithic impairment; such uniformity in symptoms is uncommon in mTBI cases from other sources . This frequency of specific vestibular findings is not seen in any control populations.…”

An integrated perspective linking physiological and psychological consequences of mild traumatic brain injury

“…Traumatic injury to neuronal, axonal, glial, and vascular structures causes the release of brain-specific proteins [ 11 ]. Promising results have been published suggesting that serum levels of brain-specific proteins, such as S100 calcium-binding protein B (S100B; primarily found in astroglial cells, but also in melanocytes), glial fibrillary acidic protein (GFAP; present in the cytoskeleton of several cells in the central nervous system, for example astrocytes), tau (protein that stabilizes microtubuli that make up the cytoskeleton of axons), neurofilament light (NF-L; protein that is also part of the cytoskeleton of neurons), and ubiquitin C-terminal hydrolase-L1 (UCH-L1; an enzyme which plays a role in the repair of neurons and axons via regulation of protein degradation), are predictive of the presence of lesions after mTBI, and poor outcome after mTBI [ 11 , 18 – 23 ]. In Scandinavia, S100B measurement in the acute phase post-injury has already been added to the Neurotrauma guidelines as a biomarker to reduce unnecessary CT-scans and associated costs [ 24 ].…”

“…The application of advanced imaging modalities, such as functional MRI (fMRI) and diffusion-weighted imaging (DWI), has provided evidence of altered brain network connectivity after mTBI, although a clear-cut mechanism underlying continued symptoms has not been found [9,10]. There is also increasing evidence that certain protein biomarkers of cellular injury in the acute phase post-injury are informative of injury severity and clinical outcome after mTBI [11,12]. However, it is unclear if these markers have a role in the pathophysiology of persistent symptoms, and how this process may be influenced by other acute physiological sequelae such as inflammation or the acute stress response.…”

S100B protein level for the detection of clinically significant intracranial haemorrhage in patients with mild traumatic brain injury: a subanalysis of a prospective cohort study

“…They have included unrepresentative populations with age and comorbidities exclusion criteria and have often used restrictive delays between the head trauma and the blood sampling, which are not generalisable to the ED's mTBI population. 14 Many studies regarding the S100B protein have focused on the detection of any intracranial lesions. 13 However, from a clinical perspective, the detection of clinically significant haemorrhage is a more useful outcome.…”