Temporal Window of Metabolic Brain Vulnerability to Concussion

Abstract

OBJECTIVE:In the present study, the occurrence of the temporal window of brain vulnerability was evaluated in concussed athletes by measuring N-acetylaspartate (NAA) using proton magnetic resonance ( 1 H-MR) spectroscopy. METHODS: Thirteen nonprofessional athletes who had a sport-related concussive head injury were examined for NAA determination by means of 1 H-MR spectroscopy at 3, 15, and 30 days postinjury. All athletes but three suspended their physical activity. Those who continued their training had a second concussive event and underwent further examination at 45 days from the initial injury. The single case of one professional boxer, who was studied before the match and 4, 7, 15, and 30 days after a knockout, is also presented. Before each magnetic resonance examination, patients were asked for symptoms of mild traumatic brain injury, including physical, cognitive, emotional, and sleep disturbances. Data for 1 H-MR spectroscopy recorded in five normal, age-matched, control volunteers, who were previously screened to exclude previous head injuries, were used for comparison. Semiquantitative analysis of NAA relative to creatine (Cr)-and choline (Cho)-containing compounds was performed from proton spectra obtained with a 3-T magnetic resonance system. RESULTS: Regarding the values of the NAA-to-Cr ratio (2.21 Ϯ 0.11) recorded in control patients, singly concussed athletes, at 3 days after the concussion, showed a decrease of 18.5% (1.80 Ϯ 0.04; P Ͻ 0.001). Only a modest 3% recovery was observed at 15 days (1.88 Ϯ 0.1; P Ͻ 0.001); at 30 days postinjury, the NAA-to-Cr ratio was 2.15 Ϯ 0.1, revealing full metabolic recovery with values not significantly different from those of control patients. These patients declared complete resolution of symptoms at the time of the 3-day study. The three patients who had a second concussive injury before the 15-day study showed an identical decrease of the NAA-to-Cr ratio at 3 days (1.78 Ϯ 0.08); however, at 15 days after the second injury, a further diminution of the NAA-to-Cr ratio occurred (1.72 Ϯ 0.07; P Ͻ 0.05 with respect to singly concussed athletes). At 30 days, the NAAto-Cr ratio was 1.82 Ϯ 0.1, and at 45 days postinjury, the NAA-to-Cr ratio showed complete recovery (2.07 Ϯ 0.1; not significant with respect to control patients). This group of patients declared a complete resolution of symptoms at the time of the 30-day study. CONCLUSION: Results of this pilot study carried out in a cohort of singly and doubly concussed athletes, examined by 1 H-MR spectroscopy for their NAA cerebral content at different time points after concussive events, demonstrate that also in humans, concussion opens a temporal window of brain metabolic imbalance, the closure of which does not coincide with resolution of clinical symptoms. The recovery of brain metabolism is not linearly related to time. A second concussive event prolonged the time of NAA normalization by 15 days. Although needing confirmation in a larger group of patients, these results show that NAA measurement by 1 H-MR spe...

Decrease in N-Acetylaspartate Following Concussion May Be Coupled to Decrease in Creatine

“…Different from what was observed in our previous studies, in which the Cho/Cr ratio remained unaltered during the whole observational period after concussion, 26,27 in the present cohort of athletes, we observed a significant increase in the Cho/Cr ratio after 3 (+33%; P < .01) and 15 (+31.5%; P < .01) days postinjury. At the third and fourth 1 H MRS scans (30 and 45 days postimpact, respectively), no difference in the Cho/Cr ratio was observed compared with controls.…”

“…Figure 3 illustrates the changes in the NAA/Cho ratio during 45 days following concussion. In accordance with our previous observations, 26,27 but in contrast to the apparent increase in NAA suggested by the increase in the NAA/Cr ratio, the NAA/Cho ratio underwent a transient decrease, particularly evident at 3 and 15 days postinjury when mean values of 1. 61 ± 0.20 and 1.55 ± 0.18 were recorded (mean value of the NAA/Cho ratio in controls = 1.94 ± 0.17; P < .01).…”

“…26,27 Significantly, we observed that the recovery of brain metabolism occurred weeks after the resolution of the self-reported postconcussive clinical symptoms. 26,27 Recently, two 1 H MRS studies reported that Cr but not NAA levels were affected by mTBI, with head injury producing a significant increase in Cr levels in different brain areas. 28,29 As indicated earlier, in our previous studies, to investigate possible changes in NAA evaluated relatively to Cr and/or Cho, we excluded patients in whom the Cho/Cr ratio did not remain unaltered.…”

“…24,25 In two longitudinal studies in which patients were scanned 3 or 4 times to perform the time course of postinjury recovery of brain metabolism, we showed that concussion, an mTBI caused by any type of acceleration-deceleration of the brain, frequently encountered in contact sports, caused a reversible decrease in NAA content of the frontal lobe white matter. 26,27 In these studies, an inclusion criterion was the constancy in the Cho/Cr ratio that allowed the semiquantitative determination of NAA relative to both Cr and Cho. 26,27 Significantly, we observed that the recovery of brain metabolism occurred weeks after the resolution of the self-reported postconcussive clinical symptoms.…”

“…26,27 In these studies, an inclusion criterion was the constancy in the Cho/Cr ratio that allowed the semiquantitative determination of NAA relative to both Cr and Cho. 26,27 Significantly, we observed that the recovery of brain metabolism occurred weeks after the resolution of the self-reported postconcussive clinical symptoms. 26,27 Recently, two 1 H MRS studies reported that Cr but not NAA levels were affected by mTBI, with head injury producing a significant increase in Cr levels in different brain areas.…”