title: Evidence for cellular damage in normal-appearing white matter correlates with injury severity in patients following traumatic brain injury: A magnetic resonance spectroscopy study.
abstract: Neuropsychological studies in patients who have suffered traumatic brain injury show that the eventual clinical outcome is frequently worse than might be predicted from using conventional (CT or T(1)/T(2)-weighted MRI) imaging. Furthermore, patients who have sustained an initial mild or moderate injury may show long-term disability. This implies that there may be abnormalities in areas of the brain that actually appear normal on conventional imaging. Proton magnetic resonance spectroscopy studies have shown that N-acetylaspartate and choline-containing compounds can provide measures of cellular injury. We report MRI and proton magnetic resonance spectroscopy studies of 19 head-injured patients performed once the patients were clinically stable (mean 11 days after injury, range 3-38 days). Proton magnetic resonance spectra were acquired from frontal white matter that on conventional MRI appeared normal. The brain N-acetylaspartate/creatine ratio was reduced [patients (mean +/- standard deviation), 1.28 +/- 0.25; controls, 1.47 +/- 0. 24; P = 0.04] and the choline/creatine ratio was increased (patients, 0.85 +/- 0.18; controls, 0.63 +/- 0.10; P < 0.001) compared with controls. When the severity of the injury was assessed using either the Glasgow coma scale or the length of post-traumatic amnesia, the increase in the choline/creatine ratio was significant even in the mildly injured group (P = 0.008 and P = 0.04, respectively). Furthermore, there was a significant correlation (P = 0.008) between the severity of head injury and the N-acetylaspartate/choline ratio. We conclude that there is an early reduction in N-acetylaspartate and an increase in choline compounds in normal-appearing white matter which correlate with head injury severity, and that this may provide a pathological basis for the long-term neurological disability that is seen in these patients.
authors.affiliation: MRC Biochemical and Clinical Magnetic Resonance Unit, Department of Biochemistry, University of Oxford, UK.
authors.forename: M R
authors.initials: MR
authors.lastname: Garnett
authors.forename: A M
authors.initials: AM
authors.lastname: Blamire
authors.forename: B
authors.initials: B
authors.lastname: Rajagopalan
authors.forename: P
authors.initials: P
authors.lastname: Styles
authors.forename: T A
authors.initials: TA
authors.lastname: Cadoux-Hudson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000647:Amnesia / Q000473:pathology; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001369:Axons / Q000473:pathology; D001923:Brain Chemistry / Q000502:physiology; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D002540:Cerebral Cortex / Q000293:injuries* / Q000378:metabolism / Q000473:pathology*; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D005260:Female; D015600:Glasgow Coma Scale; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline