Prospective study of myelin water fraction changes after mild traumatic brain injury in collegiate contact sports

Abstract

<jats:sec><jats:title>OBJECTIVE</jats:title><jats:p>Mild traumatic brain injury (mTBI) in athletes, including concussion, is increasingly being found to have long-term sequelae. Current imaging techniques have not been able to identify early damage caused by mTBI that is predictive of long-term symptoms or chronic traumatic encephalopathy. In this preliminary feasibility study, the authors investigated the use of an emerging magnetic resonance imaging (MRI) technique, multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT), in visualizing acute and chronic white matter changes after mTBI in collegiate football and rugby players.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>This study was a nonrandomized, nonblinded prospective trial designed to quantify changes in the myelin water fraction (MWF), used as a surrogate MRI measure of myelin content, in a group of male collegiate football and rugby players, classified here as a contact sport player (CSP) cohort, at the time of mTBI diagnosis and 3 months after injury when the acute symptoms of the injury had resolved. In addition, differences in the MWF between the CSP cohort and a control cohort of noncontact sport players (NCSPs) were quantified. T-tests and a threshold-free cluster enhancement (TFCE) statistical analysis technique were used to identify brain structures with significant changes in the MWF between the CSP and NCSP cohorts and between immediately postinjury and follow-up images obtained in the CSP cohort.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>Brain MR images of 12 right-handed male CSPs were analyzed and compared with brain images of 10 right-handed male NCSPs from the same institution. A comparison of CSP and NCSP baseline images using TFCE showed significantly higher MWFs in the bilateral basal ganglia, anterior and posterior corpora callosa, left corticospinal tract, and left anterior and superior temporal lobe (p &lt; 0.05). At the 3-month follow-up examination, images from the CSP cohort still showed significantly higher MWFs than those identified on baseline images from the NCSP cohort in the bilateral basal ganglia, anterior and posterior corpora callosa, and left anterior temporal lobe, and also in the bilateral corticospinal tracts, parahippocampal gyrus, and bilateral juxtapositional (previously known as supplemental motor) areas (p &lt; 0.05). In the CSP cohort, a t-test comparing the MWF at the time of injury and 3 months later showed a significant increase in the overall MWF at follow-up (p &lt; 0.005). These increases were greatest in the bilateral basal ganglia and deep white matter. MWF decreases were seen in more superficial white matter (p &lt; 0.005).</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p>In this preliminary study, MWF was found to be increased in the brains of CSPs compared with the brains of controls, suggesting acute/chronic MWF alterations in CSPs from previous injuries. Increases in the MWF were also demonstrated in the brains of CSPs 3 months after the players sustained an mTBI. The full clinical significance of an increased MWF and whether this reflects axon neuropathology or disorderly remyelination leading to hypermyelination has yet to be determined.</jats:p></jats:sec>

Post-acute white matter microstructure predicts post-acute and chronic post-concussive symptom severity following mild traumatic brain injury in children

“…As expected, no statistically robust (i.e., significant after correcting for multiple comparisons using FDR) difference in post-acute white matter microstructure was observed between children with mild TBI and those with OI. The limited finding of reduced microstructure of bilateral thalamic radiation white matter in mild TBI should be interpreted with caution given that it did not survive correction for multiple comparison, although similar reductions have previously been reported in post-acute pediatric mild TBI (Mayer et al., 2012; Myer et al., 2016; Spader et al., 2018). Post-acute diffusion metrics also did not differentially predict PCS in the two injury groups, with the exception of left cingulum hippocampus and thalamic radiation MD values, which only predicted cognitive PCS at 3 months post-injury in children with OI.…”

“…With few exceptions, most studies have compared children with mild TBI to typically developing children. Some studies have included non-concussed athletes or athletes who participate in noncontact sports (Mustafi et al., 2018; Spader et al., 2018). Less commonly, children with mild TBI have been compared to children with mild extracranial or orthopedic injuries (OI; Babcock et al., 2015; Ewing-Cobbs et al., 2019).…”

Structural abnormalities in thalamo-prefrontal tracks revealed by high angular resolution diffusion imaging predict working memory scores in concussed children

“…A study on mouse models of mTBI examined progression of white matter pathology and found a pattern of acute myelin loss at 3 days followed by a pattern of remyelination at 1 week and excessive myelination by 6 weeks (Mierzwa, Marion, Sullivan, McDaniel, & Armstrong, 2015). In a recent study, Spader et al (2018) used multicomponent driven equilibrium single pulse observation of T1 and T2, a quantitative myelin imaging technique, to study 27 collegiate athletes. They found that athletes had higher myelin water fraction (MWF), a measure of myelin content, when compared to healthy controls at 72 hours after injury.…”

Estudo da correlação entre a razão de transferência de magnetização e a volumetria em pacientes com lesão axonal traumática

“…Na fase crônica após o trauma, há maior consenso, com a maioria dos estudos mostrando redução da FA na substância branca dos pacientes (Nakayama et al, 2006;Sidaros et al, 2008;Xu et al, 2007;Ljungqvist et al, 2011) e aumento das difusividades média, paralela e perpendicular (Ljungqvist et al, 2011). (Spader et al, 2018). Assim, há sólidas evidências sobre a alta sensibilidade dessa técnica à mielinização, com estudos evidenciando significativa redução da fração da água mielínica com a idade (Dean et al, 2016;Dean et al, 2017), em doenças neurodegenerativas como o Alzheimer (Dean et al, 2017) e a esclerose lateral primária (Kolind et al, 2012), e em pacientes com esclerose múltipla (Kolind et al, 2012;Li et al, 2014).…”

“…Em relação ao TCE, estudos evidenciam uma redução nas primeiras semanas (Wright et al, 2016), com posterior aumento (Wright et al, 2016;Spader et al, 2018). (Does et al, 1998).…”