Interval-censored survival analysis of mild traumatic brain injury with outcome based neuroimaging clinical applications

Abstract

Objective The purpose of this study was to assess the relationship between MRI findings and clinical presentation and outcomes in patients following mild traumatic brain injury (mTBI). We hypothesize that imaging findings other than hemorrhages and contusions may be used to predict symptom presentation and longevity following mTBI. Methods Patients (n = 250) diagnosed with mTBI and in litigation for brain injury underwent 3T magnetic resonance imaging (MRI). A retrospective chart review was performed to assess symptom presentation and improvement/resolution. To account for variable times of clinical presentation, nonuniform follow-up, and uncertainty in the dates of symptom resolution, a right censored, interval censored statistical analysis was performed. Incidence and resolution of headache, balance, cognitive deficit, fatigue, anxiety, depression, and emotional lability were compared among patients. Image findings analyzed included white matter hyperintensities (WMH), Diffusion Tensor Imaging (DTI) fractional anisotropy (FA) values, MR perfusion, auditory functional MRI (fMRI) activation, hippocampal atrophy (HA) and hippocampal asymmetry as defined by NeuroQuant ® volumetric software. Results Patients who reported LOC were significantly more likely to present with balance problems (p < 0.001), cognitive deficits (p = 0.010), fatigue (p = 0.025), depression (p = 0.002), and emotional lability (p = 0.002). Patients with LOC also demonstrated significantly slower recovery of cognitive function than those who did not lose consciousness (p = 0.044). Patients over the age of 40 had significantly higher odds of presenting with balance problems (p = 0.006). Additionally, these older patients were slower to recover cognitive function (p = 0.001) and less likely to experience improvement of headaches (p = 0.007). Abnormal MRI did not correlate significantly with symptom presentation, but was a strong indicator of symptom progression, with slower recovery of balance (p = 0.009) and cognitive deficits (p < 0.001). Conclusion This analysis demonstrates the utility of clinical data analysis using interval-censored survival statistical technique in head trauma patients. Strong statistical associations between neuroimaging findings and aggregate clinical outcomes were identified in patients with mTBI.

Loss of Consciousness and Righting Reflex Following Traumatic Brain Injury: Predictors of Post-Injury Symptom Development (A Narrative Review)

“…The duration of LOC in women, but not men, was positively correlated with loss of balance, poor coordination, fatigue, and overall vestibular impairment score on the NSI in a study comparing male and female veterans [22]. Additionally, LOC was associated with balance problems, fatigue, and headache; interestingly, every patient with LOC in this study reported headache [25]. In military personnel, LOC was associated with greater levels of plasma interleukin (IL)-6, a pro-inflammatory cytokine, and greater self-reported pain levels [20].…”

“…The presence and duration of LOC are associated with cognitive deficits after mTBI. LOC was associated with cognitive deficits and slow recovery of cognitive function [25]. Among military personnel and civilian contractors, longer duration of LOC was associated with a greater decline in accuracy on the Automated Neuropsychological Assessment Metric (ANAM), which measures reaction time, learning, and memory, between baseline and post-injury tests [11].…”

“…LOC after mTBI is associated with the development of psychiatric disorders, including post-traumatic stress disorder (PTSD) and major depressive disorder (MDD). One study reported that LOC was associated with MDD and emotional lability, a condition characterized by exaggerated and rapidly fluctuating emotions [25]. Among patients stratified by age, sex, and LOC status, LOC was associated with development of anxiety, suicidal ideation, and MDD within a 180-day period after admission for mTBI [27].…”

Updated Review of the Evidence Supporting the Medical and Legal Use of NeuroQuant® and NeuroGage® in Patients With Traumatic Brain Injury

“…Brain volume abnormalities correlated with acute measures of injury (including greater duration of posttraumatic amnesia and lower GCS score) and presence of diffuse axonal injury (Brezova et al, 2014). Vanier et al (Vanier et al, 2020) divided a sample of mild TBI patients into those with and without MRI brain abnormalities, including hippocampal atrophy or asymmetry based on NeuroQuant R analyses; patients with MRI abnormalities had slower recovery from balance and cognitive deficits. In a study of pediatric patients with TBI, Wright et al found that increased volumes of white matter hyperintensities measured by NeuroQuant R correlated with decreased cognitive processing speed (Wright et al, 2020).…”

Patients with chronic mild or moderate traumatic brain injury have abnormal longitudinal brain volume enlargement more than atrophy

“…These include multiple studies that found that NeuroQuant V R is reliable for measuring brain volume in normal subjects, patients with TBI, and other neuropsychiatric patients 8,[29][30][31][32][33][34][35] and valid for assessing brain volume in patients with TBI. 4,5,8,12,16,19,25,33,[35][36][37][38][39][40][41] Neuroquant V R automated brain MRI segmentation. The brain MRI grayscale images for each patient and NeuroGage V R normal control V R were uploaded to the NeuroQuant V R server, which processed and analyzed the brain imaging data.…”