Assessment of metabolic brain damage and recovery following mild traumatic brain injury: a multicentre, proton magnetic resonance spectroscopic study in concussed patients

Abstract

Concussive head injury opens a temporary window of brain vulnerability due to the impairment of cellular energetic metabolism. As experimentally demonstrated, a second mild injury occurring during this period can lead to severe brain damage, a condition clinically described as the second impact syndrome. To corroborate the validity of proton magnetic resonance spectroscopy in monitoring cerebral metabolic changes following mild traumatic brain injury, apart from the magnetic field strength (1.5 or 3.0 T) and mode of acquisition, we undertook a multicentre prospective study in which a cohort of 40 athletes suffering from concussion and a group of 30 control healthy subjects were admitted. Athletes (aged 16-35 years) were recruited and examined at three different institutions between September 2007 and June 2009. They underwent assessment of brain metabolism at 3, 15, 22 and 30 days post-injury through proton magnetic resonance spectroscopy for the determination of N-acetylaspartate, creatine and choline-containing compounds. Values of these representative brain metabolites were compared with those observed in the group of non-injured controls. Comparison of spectroscopic data, obtained in controls using different field strength and/or mode of acquisition, did not show any difference in the brain metabolite ratios. Athletes with concussion exhibited the most significant alteration of metabolite ratios at Day 3 post-injury (N-acetylaspartate/creatine: -17.6%, N-acetylaspartate/choline: -21.4%; P < 0.001 with respect to controls). On average, metabolic disturbance gradually recovered, initially in a slow fashion and, following Day 15, more rapidly. At 30 days post-injury, all athletes showed complete recovery, having metabolite ratios returned to values detected in controls. Athletes self-declared symptom clearance between 3 and 15 days after concussion. Results indicate that N-acetylaspartate determination by proton magnetic resonance spectroscopy represents a non-invasive tool to accurately measure changes in cerebral energy metabolism occurring in mild traumatic brain injury. In particular, this metabolic evaluation may significantly improve, along with other clinical assessments, the management of athletes suffering from concussion. Further studies to verify the effects of a second concussive event occurring at different time points of the recovery curve of brain metabolism are needed.

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

“…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.…”

“…In addition, in our previous article, data obtained from different neuroradiological centers and using the single-or multivoxel technique gave overlapping values. 27 In follow-up studies, the exact repositioning of the voxel on the same acquisition plane obtained in the previous MRI study was achieved by using dedicated software (SameScan; Philips Medical Systems, Philips Healthcare, Best, The Netherlands). Postprocessing of spectral data allowed us to calculate the area under the peaks of NAA, Cho, and Cr, using common criteria for peak integration.…”

“…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.…”

Rapid number naming in chronic concussion: eye movements in the King–Devick test

“…While up to 90% of concussions resolve in 7–10 days, recovery time may be longer 2. The time to recover may reflect the extent of microscopic neuronal shearing3 and the impairment of cellular and metabolic function 4, 5. While these insights help elucidate the neurophysiology of acute concussive injuries, chronic concussion is still poorly understood and mechanisms explaining the neurobiology over a protracted time scale have not been well characterized.…”