Abstract
Introduction: Symptoms following a mild traumatic brain injury (mTBI) usually resolve quickly but may persist past 3 months in up to 15% of children. Mechanisms of mTBI recovery are poorly understood, but may involve alterations in cortical neurophysiology. Transcranial Magnetic Stimulation (TMS) can non-invasively investigate such mechanisms, but the time course of neurophysiological changes in mTBI are unknown.Objective/Hypothesis: To determine the relationship between persistent post-concussive symptoms (PPCS) and altered motor cortex neurophysiology over time.Methods: This was a prospective, longitudinal, controlled cohort study comparing children (8–18 years) with mTBI (symptomatic vs. asymptomatic) groups to controls. Cortical excitability was measured using TMS paradigms at 1 and 2 months post injury. The primary outcome was the cortical silent period (cSP). Secondary outcomes included short interval intracortical inhibition (SICI) and facilitation (SICF), and long-interval cortical inhibition (LICI). Generalized linear mixed model analyses were used to evaluate the effect of group and time on neurophysiological parameters.Results: One hundred seven participants (median age 15.1, 57% female) including 78 (73%) with symptomatic PPCS and 29 with asymptomatic mTBI, were compared to 26 controls. Cortical inhibition (cSP and SICI) was reduced in the symptomatic group compared to asymptomatic group and tended to increase over time. Measures of cortical facilitation (SICF and ICF) were increased in the asymptomatic group and decreased over time. TMS was well tolerated with no serious adverse events.Conclusions: TMS-assessed cortical excitability is altered in children following mild TBI and is dependent on recovery trajectory. Our findings support delayed return to contact sports in children even where clinical symptoms have resolved.
Highlights
Symptoms following a mild traumatic brain injury usually resolve quickly but may persist past 3 months in up to 15% of children
The pediatric population is at the highest risk of incurring a Mild traumatic brain injury (mTBI) [5, 6] and ∼30% of children will go on to have prolonged symptoms lasting 4 weeks or longer [7], referred to as Persistent PostConcussive Symptoms (PPCS) [8,9,10]
Generalized linear mixed-effects model demonstrated shorter cortical silent period (cSP) durations (18.84 (SD 2.82) ms) in the symptomatic group compared to asymptomatic group at the initial timepoint [F(1, 167) = 4.838, p = 0.029], with a trend for cSP duration to increase over time (11.36 (SD 2.60) ms; [F(1, 84.51) = 3.27, p = 0.074]
Summary
Symptoms following a mild traumatic brain injury (mTBI) usually resolve quickly but may persist past 3 months in up to 15% of children. Mechanisms of mTBI recovery are poorly understood, but may involve alterations in cortical neurophysiology. Current understanding of the pathophysiology of mTBI includes a cascade of cellular damage that may result in excitotoxicity, neuronal death, and cellular energy crisis [13,14,15]. Underlying many of these consequences are changes to ion concentration [16, 17] and resting membrane potential [17]. Alterations to membrane potential in broader cortical regions may have a global effect on cortical excitability
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