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Concussions in Athletics pp 89–112Cite as

The Relevance of Assessing Cerebral Metabolic Recovery for a Safe Return to Play Following Concussion

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Abstract

Concussion, a peculiar type of mild traumatic brain injury (mTBI) frequently encountered in sports medicine, is characterized by complex molecular alterations of various important functions of neuronal cells, including mitochondrial-related energy supply, ionic homeostasis, neurotransmitters, N-acetylaspartate (NAA) homeostasis, and even gene expression. Most of these molecular and metabolic derangements are of limited duration (spontaneous recovery of metabolism and cell functions), representing the bases of the metabolic brain vulnerability occurring after mTBI. In this chapter, we describe results of experimental studies evidencing the connections among mTBI, energy metabolism, mitochondrial dysfunctions, and NAA, as well as we summarize results of clinical studies demonstrating that the monitoring of brain metabolism (NAA and creatine) by proton magnetic resonance spectroscopy (1H-MRS) is a useful tool to increase the safety of return to play of athletes after a concussion. The application of 1H-MRS in concussed athletes shows that clinical symptoms clear much faster than normalization of brain metabolism. 1H-MRS allows to measure objective parameters of biochemical relevance and is suitable to determine the end of the period of brain vulnerability. This information cannot otherwise be obtained with clinical tests of current use and is important to minimize the risks related to an early return on the field of concussed athletes.

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References

  1. de Kruijk JR, Twijnstra A, Leffers P. Diagnostic criteria and differential diagnosis of mild traumatic brain injury. Brain Inj. 2001;15:99–106.

    PubMed  Google Scholar 

  2. Bruns J, Hauser WA. The epidemiology of traumatic brain injury: a review. Epilepsia. 2003;44 Suppl 10:2–10.

    PubMed  Google Scholar 

  3. Roozenbeek B, Maas A, Menon DK. Changing patterns in the epidemiology of traumatic brain injury. Nat Rev Neurol. 2013;9:231–6.

    PubMed  Google Scholar 

  4. van der Naalt J. Prediction of outcome in mild to moderate head injury: a review. J Clin Exp Neuropsychol. 2001;23:837–51.

    PubMed  Google Scholar 

  5. Vos PE, Battistin L, Birbamer G, Gerstenbrand F, Potapov A, Prevec T, et al. EFNS guideline on mild traumatic brain injury report of an EFNS task force. Eur J Neurol. 2002;9:207–19.

    CAS  PubMed  Google Scholar 

  6. Kushner D. Mild traumatic brain injury toward understanding manifestations and treatment. Arch Intern Med. 1998;158:1617–24.

    CAS  PubMed  Google Scholar 

  7. McCrea M, Kelly JP, Randolph C, Cisler R, Berger L. Immediate neurocognitive effects of concussion. Neurosurgery. 2002;50:1032–42.

    PubMed  Google Scholar 

  8. Esselman PC, Uomoto JM. Classification of the spectrum of mild traumatic brain injury. Brain Inj. 1995;9:417–24.

    CAS  PubMed  Google Scholar 

  9. Aubry M, Cantu R, Dvorak J, Graf-Baumann T, Johnston K, Kelly J, et al. Summary and agreement statement of the first international conference on concussion in sport, Vienna 2001. Recommendations for the improvement of safety and health of athletes who may suffer concussive injuries. Br J Sports Med. 2002;36:6–10.

    CAS  PubMed  Google Scholar 

  10. McCrory P, Johnston K, Meeuwisse W, Aubry M, Cantu R, Dvorak J, et al. Summary and agreement statement of the 2nd international conference on concussion in sport, Prague 2004. Br J Sports Med. 2005;39:196–204.

    CAS  PubMed  Google Scholar 

  11. McCrory P, Meeuwisse W, Johnston K, Dvorak J, Aubry M, Molloy M, et al. Consensus statement on concussion in sport 3rd international conference on concussion in sport held in Zurich, November 2008. Clin J Sport Med. 2009;19:185–200.

    PubMed  Google Scholar 

  12. Meehan WP, Bachur RG. Sport-related concussion. Pediatrics. 2009;123:114–23.

    PubMed  Google Scholar 

  13. Maroon JC, Lovell MR, Norwig J, Podelek K, Powell JW, Hartl R. Cerebral concussion in athletes: evaluation and neuropsychological testing. Neurosurgery. 2000;47:659–69.

    CAS  PubMed  Google Scholar 

  14. Sinson G, Bagley LJ, Cecil KM, Torchia M, McGowan JC, Lenkinski RE, McIntosh TK, Grossman RI. Magnetization transfer imaging and proton MR spectroscopy in the evaluation of axonal injury: correlation with clinical outcome after traumatic brain injury. AJNR Am J Neuroradiol. 2001;22:143–51.

    CAS  PubMed  Google Scholar 

  15. Johnson B, Zhang K, Gay M, Horovitz S, Hallett M, Sebastianelli W, et al. Alteration of brain default network in subacute phase of injury in concussed individuals resting-state fMRI study. Neuroimage. 2012;59:511–8.

    PubMed Central  PubMed  Google Scholar 

  16. Zhang K, Johnson B, Pennell D, Ray W, Sebastianelli W, Slobounov S. Are functional deficits in concussed individuals consistent with white matter structural alterations combined FMRI and DTI study. Exp Brain Res. 2010;204:57–70.

    CAS  PubMed Central  PubMed  Google Scholar 

  17. Lipton ML, Gellella E, Lo C, Gold T, Ardekani BA, Shifteh K, et al. Multifocal white matter ultrastructural abnormalities in mild traumatic brain injury with cognitive disability, a voxel-wise analysis of diffusion tensor imaging. J Neurotrauma. 2008;25:1335–42.

    PubMed  Google Scholar 

  18. Kou Z, Wu Z, Tong KA, Holshouser B, Benson RR, Hu J, et al. The role of advanced MR imaging findings as biomarkers of traumatic brain injury. J Head Trauma Rehabil. 2010;25:267–82.

    PubMed  Google Scholar 

  19. Farkas O, Lifshitz J, Povlishock JT. Mechanoporation induced by diffuse traumatic brain injury: an irreversible or reversible response to injury? J Neurosci. 2006;26:3130–40.

    CAS  PubMed  Google Scholar 

  20. Barkhoudarian G, Hovda DA, Giza CC. The molecular pathophysiology of concussive brain injury. Clin Sports Med. 2011;30:33–48.

    PubMed  Google Scholar 

  21. Faden AI, Demediuk P, Panter SS, Vink R. The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science. 1989;244:798–800.

    CAS  PubMed  Google Scholar 

  22. Katayama Y, Becker DP, Tamura T, Hovda DA. Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J Neurosurg. 1990;73:889–900.

    CAS  PubMed  Google Scholar 

  23. Reger ML, Poulos AM, Buen F, Giza CC, Hovda DA, Fanselow MS. Concussive brain injury enhances fear learning and excitatory processes in the amygdala. Biol Psychiatry. 2012;71:335–43.

    PubMed Central  PubMed  Google Scholar 

  24. Smith SL, Andrus PK, Zhang JR, Hall ED. Direct measurement of hydroxyl radicals, lipid peroxidation, and blood-brain barrier disruption following unilateral cortical impact head injury in the rat. J Neurotrauma. 1994;11:393–404.

    CAS  PubMed  Google Scholar 

  25. Vagnozzi R, Marmarou A, Tavazzi B, Signoretti S, Di Pierro D, Del Bolgia F, et al. Changes of cerebral energy metabolism and lipid peroxidation in rats leading to mitochondrial dysfunction after diffuse brain injury. J Neurotrauma. 1999;16:903–13.

    CAS  PubMed  Google Scholar 

  26. Zoratti M, Szab I. The mitochondrial permeability transition. Biochim Biophys Acta. 1995;1241:139–76.

    PubMed  Google Scholar 

  27. Paradies G, Paradies V, Ruggiero FM, Petrosillo G. Changes in the mitochondrial permeability transition pore in aging and age-associated diseases. Mech Ageing Dev. 2013;134:1–9.

    CAS  PubMed  Google Scholar 

  28. Schinder AF, Olson EC, Spitzer NC, Montal M. Mitochondrial dysfunction is a primary event in glutamate neurotoxicity. J Neurosci. 1996;16:6125–33.

    CAS  PubMed  Google Scholar 

  29. Lifshitz J, Friberg H, Neumar RW, Raghupathi R, Welsh FA, Janmey P, et al. Structural and functional damage sustained by mitochondria after traumatic brain injury in the rat: evidence for differentially sensitive populations in the cortex and hippocampus. J Cereb Blood Flow Metab. 2003;23(2):219–31.

    CAS  PubMed  Google Scholar 

  30. Yoshino A, Hovda DA, Kawamata T, Becker DP. Dynamic changes in local cerebral glucose utilization following cerebral conclusion in rats: evidence of a hyper and subsequent hypometabolic state. Brain Res. 1991;561:106–19.

    CAS  PubMed  Google Scholar 

  31. Kawamata T, Katayama Y, Hovda DA, Yoshino A, Becker DP. Administration of excitatory amino acid antagonists via microdialysis attenuates the increase in glucose utilization seen following concussive brain injury. J Cereb Blood Flow Metab. 1992;12:12–24.

    CAS  PubMed  Google Scholar 

  32. Andersen BJ, Marmarou A. Post-traumatic selective stimulation of glycolysis. Brain Res. 1992;585:184–9.

    CAS  PubMed  Google Scholar 

  33. Marklund N, Sihver S, Hovda DA, Långström B, Watanabe Y, Ronquist G, et al. Increased cerebral uptake of [18F] fluoro-deoxyglucose but not [1-14C] glucose early following traumatic brain injury in rats. J Neurotrauma. 2009;26:1281–93.

    PubMed  Google Scholar 

  34. Di Pietro V, Amin D, Pernagallo S, Lazzarino G, Tavazzi B, Vagnozzi R, et al. Transcriptomics of traumatic brain injury gene expression and molecular pathways of different grades of insult in a rat organotypic hippocampal culture model. J Neurotrauma. 2010;27:349–59.

    PubMed  Google Scholar 

  35. Di Pietro V, Amorini AM, Tavazzi B, Hovda DA, Signoretti S, Giza CC, et al. Potentially neuroprotective gene modulation in an in vitro model of mild traumatic brain injury. Mol Cell Biochem. 2013;375:185–98.

    CAS  PubMed  Google Scholar 

  36. Tavazzi B, Vagnozzi R, Signoretti S, Amorini AM, Belli A, Cimatti M, et al. Temporal window of metabolic brain vulnerability to concussions oxidative and nitrosative stresses—part II. Neurosurgery. 2007;61:390–6.

    PubMed  Google Scholar 

  37. Harris LK, Black RT, Golden KM, Reeves TM, Povlishock JT, Phillips LL. Traumatic brain injury-induced changes in gene expression and functional activity of mitochondrial cytochrome C oxidase. J Neurotrauma. 2001;18:993–1009.

    CAS  PubMed  Google Scholar 

  38. Tavazzi B, Signoretti S, Lazzarino G, Amorini AM, Delfini R, Cimatti M, et al. Cerebral oxidative stress and depression of energy metabolism correlate with severity of diffuse brain injury in rats. Neurosurgery. 2005;56:582–9.

    PubMed  Google Scholar 

  39. Wu A, Ying Z, Gomez-Pinilla F. The salutary effects of DHA dietary supplementation on cognition, neuroplasticity, and membrane homeostasis after brain trauma. J Neurotrauma. 2011;28:2113–22.

    PubMed  Google Scholar 

  40. Giza CC, Hovda DA. The neurometabolic cascade of concussion. J Athl Train. 2001;36:228–35.

    PubMed Central  PubMed  Google Scholar 

  41. Moffett JR, Ross B, Arun P, Madhavarao CN, Namboodiri AM. N-acetylaspartate in the CNS: from neurodiagnostics to neurobiology. Prog Neurobiol. 2007;81:89–131.

    CAS  PubMed Central  PubMed  Google Scholar 

  42. Rigotti DJ, Kirov II, Djavadi B, Perry N, Babb JS, Gonen O. Longitudinal whole-brain N-acetylaspartate concentration in healthy adults. AJNR Am J Neuroradiol. 2011;32:1011–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  43. Moffett JR, Arun P, Ariyannur PS, Garbern JY, Jacobowitz DM, Namboodiri AM. Extensive aspartoacylase expression in the rat central nervous system. Glia. 2011;59:1414–34.

    PubMed Central  PubMed  Google Scholar 

  44. Wiame E, Tyteca D, Pierrot N, Collard F, Amyere M, Noel G, et al. Molecular identification of aspartate N-acetyltransferase and its mutation in hypoacetylaspartia. Biochem J. 2010;425:127–36.

    CAS  Google Scholar 

  45. Baslow MH. Brain N-acetylaspartate as a molecular water pump and its role in the etiology of Canavan disease: a mechanistic explanation. J Mol Neurosci. 2003;21:185–90.

    CAS  PubMed  Google Scholar 

  46. Baslow MH. N-acetylaspartate in the vertebrate brain: metabolism and function. Neurochem Res. 2003;28:941–53.

    CAS  PubMed  Google Scholar 

  47. Satrústegui J, Contreras L, Ramos M, Marmol P, del Arco A, Saheki T, et al. Role of aralar, the mitochondrial transporter of aspartate-glutamate, in brain N-acetylaspartate formation and Ca(2+) signaling in neuronal mitochondria. J Neurosci Res. 2007;85:3359–66.

    PubMed  Google Scholar 

  48. Kaul R, Gao GP, Aloya M, Balamurugan K, Petrosky A, Michals K, et al. Canavan disease mutations among Jewish and non-Jewish patients. Am J Hum Genet. 1994;55:34–41.

    CAS  PubMed Central  PubMed  Google Scholar 

  49. Elpeleg ON, Shaag A. The spectrum of mutations of the aspartoacylase gene in Canavan disease in non-Jewish patients. J Inherit Metab Dis. 1999;225:315–34.

    Google Scholar 

  50. Di Pietro V, Gambacurta A, Amorini AM, Finocchiaro A, D’Urso S, Ceccarelli L, et al. A new T677C mutation of the aspartoacylase gene encodes for a protein with no enzymatic activity. Clin Biochem. 2008;41:611–5.

    PubMed  Google Scholar 

  51. Tavazzi B, Lazzarino G, Leone P, Amorini AM, Bellia F, Janson CG, et al. Simultaneous high performance liquid chromatographic separation of purines, pyrimidines, N-acetylated amino acids, and dicarboxylic acids for the chemical diagnosis of inborn errors of metabolism. Clin Biochem. 2005;38:997–1008.

    CAS  PubMed  Google Scholar 

  52. Cozzolino M, Augello B, Carella M, Palumbo O, Tavazzi B, Amorini AM, et al. Chromosomal 17p13.3 microdeletion unmasking recessive Canavan disease mutation. Mol Genet Metab. 2011;104:706–7.

    CAS  PubMed  Google Scholar 

  53. Rigotti DJ, Inglese M, Gonen O. Whole-brain N-acetylaspartate as a surrogate marker of neuronal damage in diffuse neurologic disorders. AJNR Am J Neuroradiol. 2007;2818:43–9.

    Google Scholar 

  54. Signoretti S, Marmarou A, Tavazzi B, Lazzarino G, Beaumont A, Vagnozzi R. N-acetylaspartate reduction as a measure of injury severity and mitochondrial dysfunction following diffuse traumatic brain injury. J Neurotrauma. 2001;18:977–91.

    CAS  PubMed  Google Scholar 

  55. Lazzarino G, Di Pierro D, Tavazzi B, Cerroni L, Giardina B. Simultaneous separation of malondialdehyde, ascorbic acid, and adenine nucleotide derivatives from biological samples by ion-pairing high-performance liquid chromatography. Anal Biochem. 1991;197:191–6.

    CAS  PubMed  Google Scholar 

  56. Tavazzi B, Vagnozzi R, Di Pierro D, Amorini AM, Fazzina G, Signoretti S, et al. Ion-pairing high-performance liquid chromatographic method for the detection of N-acetylaspartate and N-acetylglutamate in cerebral tissue extracts. Anal Biochem. 2000;277:104–8.

    CAS  PubMed  Google Scholar 

  57. Benedetti B, Rigotti DJ, Liu S, Filippi M, Grossman RI, Gonen O. Reproducibility of the whole-brain N-acetylaspartate level across institutions, MR scanners, and field strengths. AJNR Am J Neuroradiol. 2007;287:2–5.

    Google Scholar 

  58. Cohen BA, Inglese M, Rusinek H, Babb JS, Grossman RI, Gonen O. Proton MR spectroscopy and MRI-volumetry in mild traumatic brain injury. AJNR Am J Neuroradiol. 2007;28:907–13.

    CAS  PubMed  Google Scholar 

  59. Govindaraju V, Gauger G, Manley G, Ebel A, Meeker M, Maudsley AA. Volumetric proton spectroscopic imaging of mild traumatic brain injury. AJNR Am J Neuroradiol. 2004;25:730–7.

    PubMed  Google Scholar 

  60. Govind V, Gold S, Kaliannan K, Saigal G, Falcone S, Arheart KL, et al. Whole-brain proton MR spectroscopic imaging of mild-to moderate traumatic brain injury and correlation with neuropsychological deficits. J Neurotrauma. 2010;27:483–96.

    PubMed  Google Scholar 

  61. Vagnozzi R, Tavazzi B, Signoretti S, Amorini AM, Belli A, Cimatti M, et al. Temporal window of metabolic brain vulnerability to concussions: mitochondrial-related impairment—part I. Neurosurgery. 2007;61:379–89.

    PubMed  Google Scholar 

  62. Hovda DA, Badie H, Karimi S, Thomas S, Yoshino A, Kawamata T. Concussive brain injury produces a state of vulnerability for intracranial pressure perturbation in the absence of morphological damage. In: Avezaat CJJ, van Eijndhoven JHM, Maas AIR, Tans JT, editors. Intracranial pressure VIII. New York: Springer; 1983. p. 469–72.

    Google Scholar 

  63. Longhi L, Saatman KE, Fujimoto S, Raghupathi R, Meaney DF, Davis J, et al. Temporal window of vulnerability to repetitive experimental concussive brain injury. Neurosurgery. 2005;56:364–74.

    PubMed  Google Scholar 

  64. Vagnozzi R, Signoretti S, Tavazzi B, Cimatti M, Amorini AM, Donzelli S, et al. Hypothesis of the postconcussive vulnerable brain experimental evidence of its metabolic occurrence. Neurosurgery. 2005;57:164–71.

    PubMed  Google Scholar 

  65. Bowen AP. Second impact syndrome: a rare, catastrophic, preventable complication of concussion in young athletes. J Emerg Nurs. 2003;29(3):287–9.

    PubMed  Google Scholar 

  66. Cantu RC. Second-impact syndrome. Clin Sports Med. 1998;17:37–44.

    CAS  PubMed  Google Scholar 

  67. Cobb S, Battin B. Second-impact syndrome. J Sch Nurs. 2004;20:262–7.

    PubMed  Google Scholar 

  68. Logan SM, Bell GW, Leonard JC. Acute subdural hematoma in a high school football player after 2 unreported episodes of head trauma: a case report. J Athl Train. 2001;36:433–6.

    PubMed Central  PubMed  Google Scholar 

  69. Mori T, Katayama Y, Kawamata T. Acute hemispheric swelling associated with thin subdural hematomas: pathophysiology of repetitive head injury in sports. Acta Neurochir Suppl. 2006;96:40–3.

    CAS  PubMed  Google Scholar 

  70. Saunders RL, Harbaugh RE. The second impact in catastrophic contact-sports head trauma. JAMA. 1984;252:538–9.

    CAS  PubMed  Google Scholar 

  71. Laurer HL, Bareyre FM, Lee VM, Trojanowski JQ, Longhi L, Hoover R, et al. Mild head injury increasing the brain’s vulnerability to a second concussive impact. J Neurosurg. 2001;95:859–70.

    CAS  PubMed  Google Scholar 

  72. Prins ML, Hales A, Reger M, Giza CC, Hovda DA. Repeat traumatic brain injury in the juvenile rat is associated with increased axonal injury and cognitive impairments. Dev Neurosci. 2010;32:510–8.

    CAS  PubMed  Google Scholar 

  73. Prins ML, Alexander D, Giza CC, Hovda DA. Repeated mild traumatic brain injury: mechanisms of cerebral vulnerability. J Neurotrauma. 2013;30:30–8.

    PubMed  Google Scholar 

  74. Doberstein CE, Hovda DA, Becker DP. Clinical considerations in the reduction of secondary brain injury. Ann Emerg Med. 1993;22:993–7.

    CAS  PubMed  Google Scholar 

  75. Kurca E, Sivk S, Kucera P. Impaired cognitive functions in mild traumatic brain injury patients with normal and pathologic magnetic resonance imaging. Neuroradiology. 2006;486:61–9.

    Google Scholar 

  76. Hunt T, Asplund C. Concussion assessment and management. Clin Sports Med. 2010;29:5–17.

    PubMed  Google Scholar 

  77. McCrea M, Guskiewicz KM, Marshall SW, Barr W, Randolph C, Cantu RC, et al. Acute effects and recovery time following concussion in collegiate football players: the NCAA Concussion Study. JAMA. 2003;290:2556–63.

    CAS  PubMed  Google Scholar 

  78. Schatz P, Pardini JE, Lovell MR, Collins MW, Podell K. Sensitivity and specificity of the ImPACT Test Battery for concussion in athletes. Arch Clin Neuropsychol. 2006;21:9–19.

    Google Scholar 

  79. Broglio SP, Macciocchi SN, Ferrara MS. Sensitivity of the concussion assessment battery. Neurosurgery. 2007;60:105–8.

    Google Scholar 

  80. Register-Mihalik JK, Mihalik JP, Guskiewicz KM. Balance deficits after sports-related concussion in individuals reporting posttraumatic headache. Neurosurgery. 2008;63:76–80.

    PubMed  Google Scholar 

  81. Galbraith RA, Furukawa M, Li M. Possible role of creatine concentrations in the brain in regulating appetite and weight. Brain Res. 2006;1101:85–91.

    CAS  PubMed  Google Scholar 

  82. Seidl R, Stöckler-Ipsiroglu S, Rolinski B, Kohlhauser C, Herkner KR, Lubec B, Lubec G. Energy metabolism in graded perinatal asphyxia of the rat. Life Sci. 2000;67:421–35.

    CAS  PubMed  Google Scholar 

  83. Barker PB, Soher BJ, Blackband SJ, Chatham JC, Mathews VP, Bryan RN. Quantitation of proton NMR spectra of the human brain using tissue water as an internal concentration reference. NMR Biomed. 1993;6:89–94.

    CAS  PubMed  Google Scholar 

  84. Friedman SD, Brooks WM, Jung RE, Chiulli SJ, Sloan JH, Montoya BT, Hart BL, Yeo RA. Quantitative proton MRS predicts outcome after traumatic brain injury. Neurology. 1999;52:1384–91.

    CAS  PubMed  Google Scholar 

  85. Brooks WM, Stidley CA, Petropoulos H, Jung RE, Weers DC, Friedman SD, Barlow MA, Sibbitt Jr WL, Yeo RA. Metabolic and cognitive response to human traumatic brain injury: a quantitative proton magnetic resonance study. J Neurotrauma. 2000;17:629–40.

    CAS  PubMed  Google Scholar 

  86. Garnett MR, Blamire AM, Corkill RG, Cadoux-Hudson TA, Rajagopalan B, Styles P. Early proton magnetic resonance spectroscopy in normal-appearing brain correlates with outcome in patients following traumatic brain injury. Brain. 2000;123:2046–54.

    PubMed  Google Scholar 

  87. Brooks WM, Friedman SD, Gasparovic C. Magnetic resonance spectroscopy in traumatic brain injury. J Head Trauma Rehabil. 2001;16:149–64.

    CAS  PubMed  Google Scholar 

  88. Mitsumoto H, Ulug AM, Pullman SL, Gooch CL, Chan S, Tang MX, et al. Quantitative objective markers for upper and lower motor neuron dysfunction in ALS. Neurology. 2007;68:1402–10.

    CAS  PubMed  Google Scholar 

  89. Signoretti S, Marmarou A, Aygok GA, Fatouros PP, Portella G, Bullock RM. Assessment of mitochondrial impairment in traumatic brain injury using high-resolution proton magnetic resonance spectroscopy. J Neurosurg. 2008;108:42–52.

    CAS  PubMed  Google Scholar 

  90. Vagnozzi R, Signoretti S, Tavazzi B, Floris R, Ludovici A, Marziali S, et al. Temporal window of metabolic brain vulnerability to concussion: a pilot 1H-magnetic resonance spectroscopic study in concussed athletes—part III. Neurosurgery. 2008;62:1286–96.

    PubMed  Google Scholar 

  91. Vagnozzi R, Signoretti S, Cristofori L, Alessandrini F, Floris R, Isgr E, et al. Assessment of metabolic brain damage and recovery following mild traumatic brain injury: a multicentre, proton magnetic resonance spectroscopic study in concussed patients. Brain. 2011;33:3232–42.

    Google Scholar 

  92. Vagnozzi R, Signoretti S, Manara M, Tavazzi B, Floris R, Amorini AM, et al. The importance of restriction from physical activity in the metabolic recovery of concussed brain. In: Agrawal A, editor. Brain injury: pathogenesis, monitoring, recovery and management. Rijeka, Croatia: InTech; 2012. p. 501–22. ISBN 978-953-51-0265-6.

    Google Scholar 

  93. Cantu RC, Gean AD. Second-impact syndrome and a small subdural hematoma uncommon catastrophic result of repetitive head injury with a characteristic imaging appearance. J Neurotrauma. 2010;27:1557–64.

    PubMed  Google Scholar 

  94. Signoretti S, Lazzarino G, Tavazzi B, Vagnozzi R. The pathophysiology of concussion. PM R. 2011;3 Suppl 2:S359–68.

    PubMed  Google Scholar 

  95. Vagnozzi R, Signoretti S, Floris R, Marziali S, Manara M, Amorini AM, et al. Decrease in N-acetylaspartate following concussion may be coupled to decrease in creatine. J Head Trauma Rehabil. 2013;28(4):284–92. doi:10.1097/HTR.0b013e3182795045.

    PubMed  Google Scholar 

  96. Signoretti S, Di Pietro V, Vagnozzi R, Lazzarino G, Amorini AM, Belli A, D’Urso S, Tavazzi B. Transient alterations of creatine, creatine phosphate, N-acetylaspartate and high-energy phosphates after mild traumatic brain injury in the rat. Mol Cell Biochem. 2010;333:269–77.

    CAS  PubMed  Google Scholar 

  97. Tachikawa M, Fujinawa J, Takahashi M, Kasai Y, Fukaya M, Sakai K, et al. Expression and possible role of creatine transporter in the brain and at the blood cerebrospinal fluid barrier as a transporting protein of guanidinoacetate, an endogenous convulsant. J Neurochem. 2008;107:768–78.

    CAS  PubMed  Google Scholar 

  98. Beard E, Braissant O. Synthesis and transport of creatine in the CNS: importance for cerebral functions. J Neurochem. 2010;115:297–313.

    CAS  PubMed  Google Scholar 

  99. Royes LF, Fighera MR, Furian AF, Oliveira MS, Fiorenza NG, Ferreira J, et al. Neuromodulatory effect of creatine on extracellular action potentials in rat hippocampus: role of NMDA receptors. Neurochem Int. 2008;53:33–7.

    CAS  PubMed  Google Scholar 

  100. Johnson B, Gay M, Zhang K, Neuberger T, Horovitz SG, Hallett M, et al. The use of magnetic resonance spectroscopy in the subacute evaluation of athletes recovering from single and multiple mild traumatic brain injury. J Neurotrauma. 2012;29:2297–304.

    PubMed  Google Scholar 

  101. Randolph C. Baseline neuropsychological testing in managing sport-related concussion. Does it modify risk? Curr Sports Med Rep. 2011;10:21–6.

    PubMed  Google Scholar 

  102. Mayers LB, Redick TS. Clinical utility of ImPACT assessment for postconcussion return-to-play counseling psychometric issues. J Clin Exp Neuropsychol. 2012;34:235–42.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurosciences—Head and Neck Surgery, Division of Neurosurgery, San Camillo Hospital, Circonvallazione Gianicolense 87, Rome, 00152, Italy

    Stefano Signoretti M.D., Ph.D.

  2. Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Largo F. Vito 1, Rome, 00168, Italy

    Barbara Tavazzi Ph.D.

  3. Department of Biology, Geology and Environmental Sciences, Division of Biochemistry and Molecular Biology, University of Catania, Viale A. Doria 6, Catania, 95125, Italy

    Giuseppe Lazzarino Ph.D.

  4. Department of Biomedicine and Prevention, Section of Neurosurgery, University of Rome Tor Vergata, Via Montpellier 1, Rome, 00133, Italy

    Roberto Vagnozzi M.D., Ph.D.

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  1. Stefano Signoretti M.D., Ph.D.
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Correspondence to Giuseppe Lazzarino Ph.D. .

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Editors and Affiliations

  1. Professor, Director of Center for Sports Concussion Research and Services, Penn State - Hershey Medical College, University Park, Pennsylvania, USA

    Semyon M. Slobounov

  2. Kalenak Professor in Orthopaedics, Director of Athletic Medicine, Penn State - Hershey Medical College, University Park, Pennsylvania, USA

    Wayne J. Sebastianelli

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Signoretti, S., Tavazzi, B., Lazzarino, G., Vagnozzi, R. (2014). The Relevance of Assessing Cerebral Metabolic Recovery for a Safe Return to Play Following Concussion. In: Slobounov, S., Sebastianelli, W. (eds) Concussions in Athletics. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0295-8_6

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  • DOI: https://doi.org/10.1007/978-1-4939-0295-8_6

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