Neurocritical Care

, Volume 19, Issue 2, pp 183–191 | Cite as

Impact of Methamphetamine on Regional Metabolism and Cerebral Blood Flow After Traumatic Brain Injury

  • Kristine O’Phelan
  • Thomas Ernst
  • Dalnam Park
  • Andrew Stenger
  • Katherine Denny
  • Deborah Green
  • Cherylee Chang
  • Linda Chang
Original Article



Substance abuse is a frequent comorbid condition among patients with traumatic brain injury (TBI), but little is known about its potential additive or interactive effects on tissue injury or recovery from TBI. This study aims to evaluate changes in regional metabolism and cerebral perfusion in subjects who used methamphetamine (METH) prior to sustaining a TBI. We hypothesized that METH use would decrease pericontusional cerebral perfusion and markers of neuronal metabolism, in TBI patients compared to those without METH use.


This is a single center prospective observational study. Adults with moderate and severe TBI were included. MRI scanning was performed on a 3 Tesla scanner. MP-RAGE and FLAIR sequences as well as Metabolite spectra of NAA and lactate in pericontusional and contralateral voxels identified on the MP-RAGE scans. A spiral-based FAIR sequence was used for the acquisition of cerebral blood flow (CBF) maps. Regional CBF images were analyzed using ImageJ open source software. Pericontusional and contralateral CBF, NAA, and lactate were assessed in the entire cohort and in the METH and non-METH groups.


Seventeen subjects completed the MR studies. Analysis of entire cohort: pericontusional NAA concentrations (5.81 ± 2.0 mM/kg) were 12 % lower compared to the contralateral NAA (6.98 ± 1.2 mM/kg; p = 0.03). Lactate concentrations and CBF were not significantly different between the two regions; however, regional CBF was equally reduced in the two regions. Subgroup analysis: 41 % of subjects tested positive for METH. The mean age, Glasgow Coma Scale, and time to scan did not differ between groups. The two subject groups also had similar regional NAA and lactate. Pericontusional CBF was 60 % lower in the METH users than the non-users, p = 0.04; contralateral CBF did not differ between the groups.


This small study demonstrates that tissue metabolism is regionally heterogeneous after TBI and pericontusional perfusion was significantly reduced in the METH subgroup.


Adult brain injury MRI Blood flow Metabolism Alcohol and drug abuse 



This work was supported by NIH R03DA24199 (I START).

Conflict of interest


Supplementary material

12028_2013_9871_MOESM1_ESM.pdf (662 kb)
Supplementary material 1 (PDF 662 kb)


  1. 1.
    Jennett B, Snoek J, Bond MR, Brooks N. Disability after severe head injury: observations on the use of the Glasgow Outcome Scale. J Neurol Neurosurg Psychiatry. 1981;44(4):285–93.PubMedCrossRefGoogle Scholar
  2. 2.
    Langlois J, Rutland-Brown W, Thomas K. Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths. Atlanta: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; 2004.Google Scholar
  3. 3.
    Corso P, Finkelstein E, Miller T, Fiebelkorn I, Zaloshnaja E. Incidence and lifetime cost of injuries in the United States. Inj Prev. 2006;12(4):212–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Andelic N, Jerstad T, Sigurdardottir S, Schanke A, Sandvik L, Roe C. Effects of acute substance use and pre-injury substance abuse on traumatic brain injury severity in adults admitted to a trauma centre. Journal of Trauma Management and Outcomes. 2012;4:6.CrossRefGoogle Scholar
  5. 5.
    Kolakowsky-Hayner SA, Gourley EV 3rd, Kreutzer JS, Marwitz JH, Cifu DX, McKinley WO. Pre-injury substance abuse among persons with brain injury and persons with spinal cord injury. Brain Inj. 1999;13(8):571–81.PubMedCrossRefGoogle Scholar
  6. 6.
    Corrigan JD. Substance abuse as a mediating factor in outcome from traumatic brain injury. Arch Phys Med Rehabil. 1995;76(4):302–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Parry-Jones BL, Vaughan FL, Miles CW. Traumatic brain injury and substance misuse: a systematic review of prevalence and outcomes research (1994–2004). Neuropsychological Rehabilitation. 2006;16:537–60.PubMedCrossRefGoogle Scholar
  8. 8.
    Thompson PM, Hayashi KM, Simon SL, Geaga JA, Hong MS, Sui Y, Lee JY, Toga AW, Ling W, London ED. Structural abnormalities in the brains of human subjects who use methamphetamine. J Neurosci. 2004;24(26):6028–36.PubMedCrossRefGoogle Scholar
  9. 9.
    Chang L, Ernst T, Speck O, Patel H, DeSilva M, Leonido-Yee M, Miller EN. Perfusion MRI and computerized cognitive test abnormalities in abstinent methamphetamine users. Psychiatry Res. 2002;114(2):65–79.PubMedCrossRefGoogle Scholar
  10. 10.
    Villemange V, Yuan J, Wong DF, Dannals RF, Hatzidimitriou G, Mathews WB, Ravert HT, Musachio J, McCann UD, Ricaurte GA. Brain dopamine neurotoxicity in baboons treated with doses of methamphetamine comparable to those recreationally used by humans: evidence from [11C] WIN-35,428 positron emission tomography studies and direct in vitro determinations. J Neuroscience. 1998;18(1):419–27.Google Scholar
  11. 11.
    Harvey DC, Lacan G, Tanious SP, Melega WP. Recovery from methamphetamine induced long-term nigrostriatal dopaminergic deficits without substantia nigra loss. Brain Res. 2000;871:259–70.PubMedCrossRefGoogle Scholar
  12. 12.
    Chan P, Chen JH, Lee MH, Deng JF. Fatal and non-fatal methamphetamine intoxication in the intensive care unit. JToxicology Clinical Toxicology. 1994;32(2):147–55.CrossRefGoogle Scholar
  13. 13.
    Ashwal S, Holshouser BA, Shu SK, Simmons PL, Perkin RM, Tomasi LG, Knierim DS, Sheridan C, Craig K, Andrews GH, Hinshaw DB. Predictive value of proton magnetic resonance spectroscopy in pediatric closed head injury. Pediatr Neurol. 2000;23(2):114–25.PubMedCrossRefGoogle Scholar
  14. 14.
    Marino S, Zei E, Battaglini M, Vittori C, Buscalferri A, Bramanti P, Federico A, De Stefano N. Acute metabolic brain changes following traumatic brain injury and their relevance to clinical severity and outcome. J Neurol Neurosurg Psychiatry. 2006;78(5):501–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Ross BD, Ernst T, Kreis R, Haseler LJ, Bayer S, Danielsen E, Blüml S, Shonk T, Mandigo JC, Caton W, Clark C, Jensen SW, Lehman NL, Arcinue E, Pudenz R, Shelden CH. 1H MRS in acute traumatic brain injury. J Magn Reson Imaging. 1998;8(4):829–40.PubMedCrossRefGoogle Scholar
  16. 16.
    Schuhmann MU, Stiller D, Skardelly M, Bernarding J, Klinge PM, Samii A, Samii M, Brinker T. Metabolic changes in the vicinity of brain contusions: a proton magnetic resonance spectroscopy and histology study. J Neurotrauma. 2003;20(8):725–43.PubMedCrossRefGoogle Scholar
  17. 17.
    Hattori N, Huang SC, Wu HM, Liao W, Glenn TC, Vespa PM, Phelps ME, Hovda DA, Bergsneider M. PET investigation of post-traumatic cerebral blood volume and blood flow. Acta Neurochir Suppl. 2003;86:49–52.PubMedGoogle Scholar
  18. 18.
    Ali SF, Newport GD, Slikker W Jr. Methamphetamine-induced dopaminergic toxicity in mice. Role of environmental temperature and pharmacological agents. Ann N Y Acad Sci. 1996;801:187–98.PubMedCrossRefGoogle Scholar
  19. 19.
    Krimer LS, Muly EC, Williams GV, Goldman-Rakic PS. Dopaminergic regulation of cerebral cortical microcirculation. Nat Neurosci. 1998;1:286–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Brain Trauma Foundation & American Association of Neurological Surgeons, Joint Section on Neurotrauma and Critical Care. Management and Prognosis of Severe Traumatic Brain Injury (Part I and II). 2000;17(6/7):286.Google Scholar
  21. 21.
    Provencher S. Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed. 2001;14:260–4.PubMedCrossRefGoogle Scholar
  22. 22.
    Kim SG. Quantification of relative cerebral blood flow change by flow-sensitive alternating inversion recovery (FAIR) technique: application to functional mapping. Magn Reson Med. 1995;34(3):293–301.PubMedCrossRefGoogle Scholar
  23. 23.
    Yang Y, Gu H, Zhan W, Xu S, Silbersweig DA, Stern E. Simultaneous perfusion and BOLD imaging using reverse spiral scanning at 3T: characterization of functional contrast and susceptibility artifacts. Magn Reson Med. 2002;48:278–89.PubMedCrossRefGoogle Scholar
  24. 24.
    Buxton RB, Frank LR, Wong EC, Siewert B, Warach S, Edelman RR. A general kinetic model for quantitative perfusion imaging with arterial spin labeling. Magn Reson Med. 1998;40(3):383–96.PubMedCrossRefGoogle Scholar
  25. 25.
    Rasband R. W.S. ImageJ. U.S. National Institutes of Health: Bethesda; 1997–2011.
  26. 26.
    Steiner LA, Coles JP, Johnston AJ, Czosnyka M, Fryer TD, Smielewski P, Chatfield DA, Salvador R, Aigbirhio FI, Clark JC, Menon DK, Pickard JD. Responses of posttraumatic pericontusional cerebral blood flow and blood volume to an increase in cerebral perfusion pressure. J Cereb Blood Flow Metab. 2003;23(11):1371–7.PubMedCrossRefGoogle Scholar
  27. 27.
    Giza CC, Hovda DA. The neurometabolic cascade of concussion. J Athletic training. 2001;36(3):228–35.Google Scholar
  28. 28.
    Vespa P, Bergsneider M, Hattori N, Wu HM, Huang SC, Martin NA, Glenn TC, McArthur DL, Hovda DA. Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study. J Cereb Blood Flow Metab. 2005;25(6):763–74.PubMedCrossRefGoogle Scholar
  29. 29.
    Nordahl TE, Salo R, Natsuaki Y, Galloway GP, Waters C, Moore CD, Kile S, Buonocore MH. Methamphetamine users in sustained abstinence: a proton magnetic resonance spectroscopy study. Arch Gen Psychiatry. 2005;62(4):444–52.PubMedCrossRefGoogle Scholar
  30. 30.
    Urenjak J, Williams SR, Gadian DG, Noble M. Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. J Neurosci. 1993;13(3):981–9.PubMedGoogle Scholar
  31. 31.
    Dautry C, Vaufrey F, Brouillet E, Bizat N, Henry PG, Condé F, Bloch G, Hantraye P. Early N-acetylaspartate depletion is a marker of neuronal dysfunction in rats and primates chronically treated with the mitochondrial toxin 3-nitropropionic acid. J Cereb Blood Flow Metab. 2000;20(5):789–99.PubMedCrossRefGoogle Scholar
  32. 32.
    Baslow MH. N-acetylaspartate in the vertebrate brain: metabolism and function. Neurochem Res. 2003;28(6):941–53.PubMedCrossRefGoogle Scholar
  33. 33.
    Xu S, Zhou J, Racz J, Shi D, Roys S, Fiskum G, Gullapalli R. Early microstructural and metabolic changes following controlled cortical impact injury in rat: a magnetic resonance imaging and spectroscopy study. Journal of Neurotrauma. 2011;28:2091–102.PubMedCrossRefGoogle Scholar
  34. 34.
    Kety SS, Schmidt CF. The determination of cerebral blood flow in man by use of nitrous oxide in low concentrations. American J of Physiology. 1945;143:53–66.Google Scholar
  35. 35.
    Bergsneider M, Hovda DA, Shalmon E, Kelly DF, Vespa PM, Martin NA, Phelps ME, McArthur DL, Caron MJ, Kraus JF, Becker DP. Cerebral hyperglycolysis following severe traumatic brain injury in humans: a positron emission tomography study. J Neurosurg. 1997;86(2):241–51.PubMedCrossRefGoogle Scholar
  36. 36.
    Hattori N, Huang SC, Wu HM, Liao W, Glenn TC, Vespa PM, Phelps ME, Hovda DA, Bergsneider M. Acute changes in regional cerebral F-FDG kinetics in patients with traumatic brain injury. J of Nuclear Medicine. 2004;45:775–83.Google Scholar
  37. 37.
    Hwang J, Lyoo IK, Kim SJ, Sung YH, Bae S, Cho SN, Lee HY, Lee DS, Renshaw PF. Decreased cerebral blood flow of the right anterior cingulate cortex in long-term and short-term abstinent methamphetamine users. Drug Alcohol Depend. 2006;82(2):177–81.PubMedCrossRefGoogle Scholar
  38. 38.
    Soustiel JF, Sviri GE, Mahamid E, Shik V, Abeshaus S, Zaaroor M. Cerebral blood flow and metabolism following decompressive craniectomy for control of increased intracranial pressure. Neurosurgery. 2010;67(1):65–72.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Kristine O’Phelan
    • 1
  • Thomas Ernst
    • 2
  • Dalnam Park
    • 3
  • Andrew Stenger
    • 2
  • Katherine Denny
    • 4
  • Deborah Green
    • 5
  • Cherylee Chang
    • 2
    • 6
  • Linda Chang
    • 2
  1. 1.Department of NeurologyMiller School of Medicine, University of MiamiMiamiUSA
  2. 2.Neuroscience and MR Research Program, Department of Medicine, John A Burns School of MedicineUniversity of Hawaii at ManoaHonoluluUSA
  3. 3.School of MedicineOregon Health and Science UniversityPortlandUSA
  4. 4.Miller School of MedicineUniversity of MiamiMiamiUSA
  5. 5.Department of NeurologyBoston Medical Center, Boston University School of MedicineBostonUSA
  6. 6.Neuroscience InstituteThe Queens Medical CenterHonoluluUSA

Personalised recommendations