Background: Cases of chronic traumatic encephalopathy in athletes who have had repeated subconcussive exposures, in the absence of concussion, has alarmed not only athletes but also military service members due to the repeated subconcussive blast exposure (RSCBE) that may occur in war or military training. Special Operations personnel participate in heavy weapons training (HWT) that can repeatedly expose them to blast overpressure at levels that may affect the brain. Section 734 of the National Defense Authorization Act (NDAA) for FY 2018 identified the need to document medical consequences of blast exposure. The INVICTA Study is funded by the Defense Health Agency to define the relationship between RSCBE and clinical and physiologic outcomes, as well as evidence of dose-response patterns. INVICTA quantifies blast overpressure exposure, and employs a wide range of innovative methods to serially assess the corresponding cognitive, biomarker, cerebrovascular, audiologic, vestibular, oculomotor, tactile, electroencephalographic (EEG), and neuroimaging effects at acute, subacute, and chronic time points after SO HWT.
Methods: INVICTA is a prospective, longitudinal study enrolling 300 participants: 100 range safety officers (RSOs), 100 SOs firing heavy weapons, 50 SO controls, and 50 Navy non-SO controls. Study assessments are conducted at baseline prior to HWT, and 30 minutes; 6, 24 and 72 hours; 2 weeks; and 3 months after HWT (Carl Gustav recoilless rifle, Light Anti-Armor Weapon (LAAW), and AT-4 anti-tank rocket) or at comparable time points in controls. In addition, RSOs complete assessments at each of the same time points, as well as at 9 months following HWT, and then repeat all of the time point assessments, from baseline to 3 months, associated with another round of HWT at 18 months after their initial HWT. The RSOs all have multiple significant exposures and provide a measure of the effects of chronic exposure, to include structural and functional magnetic resonance imaging. Exposure for SOs is defined by recording a peak blast overpressure (PkOP) of >4.0 psi, while SO controls represent those who either did not fire weapons, or fired training rounds that did not produce PkOP >4.0. RSOs also complete assessments at 9 and 18-21 months, as they typically conduct ~6 courses/year for 2 years. Primary outcome measures are the Hopkins Verbal Learning Test-Revised (HVLT-R) and blood levels of ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1). Additional measures include other blood biomarkers, transcranial Doppler assessment of cerebral blood flow, BrainScope™ quantitative EEG, Neurolign Dx-100™ oculomotor and vestibular function, AccWalker balance and gait, Brain Gauge™ tactile discrimination, and audiologic assessment.
Preliminary
Results: Through the end of 2022, 158 participants have been enrolled: 32 RSOs, 78 exposed SOs, 25 SO training controls and 23 non-SO active duty Navy controls. The HVLT-R has 3 components: Total Recall, representing immediate recall of a list of 12 words, which are recited by an assessor and repeated by the participant 3 times in rapid succession; Delayed Recall, represented by free recall of the words 20-25 minutes later; and Discrimination, in which the participant must distinguish which of 24 words were on the original list and which were not. All 3 aspects of the HVLT-R manifest clinically and statistically significant declines in exposed SOs: Total Recall ability dropped from 28.3 (95% CI 27.5,29.2) of 36 words at baseline to 26.3 (25.3, 27.3) 30 minutes after HWT; Delayed Recall declined from a baseline of 10.2 (9.8,10.5) to 9.5 (9.0-10.1) at 30 minutes; and Discrimination ability declined from a baseline of 11.1 (10.9,11.4) to 10.1 (9.4,10.8) at 24 hours. Preliminary analyses demonstrate similar statistically significant differences in exposed SOs for UCH-L1 blood levels, tactile discrimination, oculomotor function, and gait/balance assessment. RSOs demonstrate a similar pattern on all of these tests, though some do not achieve statistical differences with the smaller number enrolled to date. No differences were seen in either control group.
Conclusions: Preliminary results suggest HWT measurably impairs multiple aspects of brain function in minutes to hours, with evidence of resilience in hours to days. Conduct of the full study will be vital to determine whether RSOs maintain resilience after chronic RSCBE.
Keywords: blast exposure, military training, repetitive subconcussive blast exposure, subconcussive injury, brain function
