Mild traumatic brain injury (“mTBI”) is a common cause of neurocognitive deficits. Until recently, concussions were considered minor events with no persistent damage. In recent years, researchers have recognized that structural injury and activation of pathological protein cascades that lead to functional impairment can occur in concussion. Concussion and mTBI are now considered synonymous terms.
The Centers for Disease Control and Prevention referred to mTBI as “the silent epidemic” in its 2003 Report to Congress on Mild Traumatic Brain Injury in the United States: Steps to Prevent a Serious Public Health Problem.1 It notes that about 75% of all of the then estimated 1.5 million traumatic brain injury cases reported in the U.S. each year are mTBI. Today, nearly 1.7 million Americans are seen in hospitals for some form of traumatic brain injury each year.2 It is also known that there are hundreds of thousands of unreported sports and recreation-related head injuries each year, making the actual number of TBIs as high as 3.8 million annually.3 This coupled with the estimated 320,000 service men and woman who have returned home since 2001 with a traumatic brain injury4,5, yields a staggering number of affected individuals with demonstrable neuropsychological deficits who often go unrecognized, untreated, and even misjudged.
Although most patients recover fully from mTBI, up to 33% of patients have persistent neurocognitive problems.6 As many as 15% have been reported to have disabling symptoms a year later.7 For military or civilian patients with mild or moderate TBI, approximately 25-70% will have some memory loss; impaired judgment, difficulty with concentration and with completing tasks8-12. All frontal lobe functions can be affected, leading to changes in personality, impulse control, judgment, motivation and communication13-15. Up to 40% of patients with mild or moderate TBI will have neurological symptoms, such as seizures, changes in sensations, speech impairments, headaches, dizziness, fatigue and loss of balance5,11,12.
Depression or anxiety occur much more frequently after mTBI5,11-13,16,17. Notably, the symptoms of mTBI often overlap with those of Post-Traumatic Stress Disorder (PTSD), such as headache, dizziness, irritability, memory impairment, delayed problem solving, slowed reaction time, fatigue, visual disturbances, sleep disturbances, sensitivity to light and noise, impulsivity, judgment problems, emotional outbursts, depression, and anxiety5,9,12,15,18-20. An estimated 8-19% of returning Warfighters meet criteria for PTSD,5,21,22 while approximately 20% of returning Warfighters have screened positive for a probable mTBI. It is not surprising that the RAND study estimated that roughly one third of those screening positive for mTBI also had overlapping PTSD or depression4. The differentiation of mTBI and PTSD in returning Warfighters is a critical diagnostic and programmatic need for the DoD11,23. These two overlapping populations have potentially different treatment requirements and different prognoses24. Neuropsychological testing has been unsuccessful in clearly differentiating these two disorders and facilities are struggling to adequately treat the many affected Warfighters without the benefit of adjunctive and adequate diagnostic tests11,12,25. For civilians with mTBI there are even fewer resources (see Links).
Sports is a common cause of mTBI (concussions), be it skiing, football, soccer, or wrestling. In one study, 6.3% of college football players had experienced a concussion over the course of a single season26,27. A significant proportion of those who had a concussion experienced repeated concussion and the research showed a progressive increased risk for re-injury. With one concussion the odds ratio of a repeat concussion was 1.5; with 2 concussions the odds ratio of repeat concussion increased to 2.8; and at 3 concussions, the odds ratio increased to 3.4. With each successive concussion, recovery time became more and more prolonged26,27. Research indicates that younger athletes are at higher risk of injury – a serious concern for parents of children playing football in high school, middle school, and even elementary school. Patients in my private practice who have received concussions (from football, soccer, cheerleading, or motor vehicle accidents) have experienced marked cognitive impairment – often being unable to compute simple math problems – for several weeks. Sideline assessments are inadequate to demonstrate the presence or absence of mTBI. The recent introduction of computerized assessments has resulted in a tendency to delay return-to-play until a player can be evaluated by a physician28. However, computerized assessments are not reliably predictive of long-term outcome. Computerized assessments have a positive predictive value (a positive test is predictive of protracted recovery with associated high vulnerability to repeat concussion) of about 73% and a negative predictive value (a negative test is predictive of no long-term neuropsychological symptoms) of 74%29. In contrast, a SPECT scan (see below) has a positive predictive value of 90-100% and a negative predictive value of 100% in mTBI following motor vehicle accidents30,31.
Treating Mild Traumatic Brain Injury
A wide variety of symptoms and difficulties can occur following mTBI. Each symptom or symptom cluster requires a different treatment strategy. Medications often can be helpful to stabilize neurocircuitry or systems that have become impaired as a result of injury. The frontal lobes are often damaged in mTBI and improving frontal lobe function is a critical step in treatment. Research is being vigorously pursued to find effective treatments for TBI. As yet, there is no promising treatment that repairs brain injury.
Identifying Mild Traumatic Brain Injury
Traditional brain imaging modalities such as MRI and CT have provided little assistance in identifying mTBI, let alone differentiating it from PTSD. CT and MRI certainly have their applications in helping to diagnose traumatic brain injuries (especially severe injuries). Typically, CT remains a vital first step in the assessment of any traumatic brain injury due to its superior capacity to visualize hemorrhage and skull fracture. However, SPECT has been repeatedly demonstrated to be superior to CT in localizing functional cerebral damage in traumatic brain injury.30-42 In fact, in a large series of patients with post-concussive syndrome, SPECT demonstrated a 10-fold superiority to CT in predicting clinical symptoms.36 SPECT has also been repeatedly demonstrated to be superior to MRI in localizing functional cerebral damage in traumatic brain injury.30-35,37 Indeed, new MRI applications such as diffusion-weighted MRI 43-46 and flow MRI 47,48 have utilized SPECT as the “gold standard” against which to measure results.
In evaluating mTBI, Bonne and colleagues call for a multimodal integration of clinical evaluation, neuropsychological assessment, and cerebral perfusion studies.49 SPECT brain imaging has proven to be highly sensitive for detecting regional cerebral blood flow disturbances in patients with mTBI30-42,49-60, despite a critique published over 14 years ago by the American Academy of Neurology which was based on a very small number of early studies.61 SPECT has been found to have high predictive value at 3, 6 and 12 months post injury of 90%, 100% and 100%, respectively.30,31 It is clear that patients with persistent clinical symptoms continue to have abnormal follow-up SPECT findings. As with any abnormality, the ability to determine progress over time is crucial in choosing the best treatment option. SPECT has been utilized to track neurological changes during a course of treatment, providing clear evidence of neurophysiological changes52,56-60. SPECT at 1 and 50 weeks was more predictive of functional impairment and yielded more prognostic information compared with MRI at 1 and 50 weeks in a study of traumatic brain injury.56 Laatsch and colleagues demonstrated that SPECT and neuropsychological assessment were strongly correlated.57 Neurology as a field tends to dismiss SPECT as a tool for evaluating mTBI, repeatedly citing a critique of early studies – referred to as the TTASAN report61. Neurology seems to be unaware of the wealth of research literature I have presented here and also disregard the opinions of thought leaders in Nuclear Medicine54 and Radiology53. More recent reviews62 critical of SPECT have scrupulously ignored the key powerful studies demonstrating the effectiveness of SPECT30,31,36. Oddly, Neurology also seems to miss the point that SPECT imaging can demonstrate functional changes that occur in response to treatment, making it a potent tool for assessing treatments52,57-60,63-69.
On March 19, 2014, an international team led by Dr. Theodore Henderson published a comprehensive review of the utility of SPECT neuroimaging in the evaluation and treatment of traumatic brain injury (TBI). This review published in PLos ONE, summarized data derived from research studies conducted over 30 years and involving 2,634 patients. This quantitative analysis and review found that the frontal lobe was the most common area of injury occurring in 94% of patients with TBI. The temporal lobe was the second most common area injured (77%). In studies comparing SPECT to more conventional neuroimaging techniques such as computed tomography (CT scan) or magnetic resonance imaging (MRI), SPECT proved far superior in detecting TBI in both the acute and chronic condition. Particularly in the case of mild TBI, also known as concussion, anatomical findings that can be picked up by CT or MRI are rarely present. We will have to watch to see if Neurology finally gets the message.
1. National Center for Injury Prevention and Control. Report to Congress on Mild Traumatic Brain Injury in the United States: Steps to Prevent a Serious Public Health Problem. Atlanta, GA: Centers for Disease Control and Prevention; 2003.
2. Faul M, Xu L, Wald MM, Coronado VG. Traumatic Brain Injury in the United States: Emergency Department Visits, Hospitalizations and Deaths 2002–2006. Atlanta (GA): Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; 2010.
3. Langlois JA, Rutland-Brown W, Wald M. (2006) The epidemiology and impact of traumatic brain injury: a brief overview. Journal of Head Trauma Rehabilitation; 21(5):375-8.
4. Tanielian T, Jaycox LH. (2008). Invisible wounds of war: Psychological and cognitive injuries, their consequences, and services to assist recovery. Santa Monica (CA): RAND Corp.
5. Lew HL, Vanderploeg RD, Moore DF, Schwab K, Friedman L, Yesavage J, Keane TM, Warden DL, Sigford BJ. (2008). Overlap of mild TBI and mental health conditions in returning OIF/OEF service members and veterans. J Rehabil Res Dev.;45(3):xi-xvi.
6. Rimel, R.W., Giorani B., Barth, J.T., Boll, T.J. & Jane, J.A. (1981). Disability caused by minor head injury. Neurosurgery. 9, 221-228.
7. Alexander, M.P. (1995). Mild traumatic brain injury: Pathophysiology, natural history, and clinical management. Neurology 45, 1253-1260.
8. Rao V, Lyketsos CG. (2000). Neuropsychiatric sequelae of traumatic brain injury, Psychosomatics 41: 95-103.
9. Lew HL. (2005). Rehabilitation needs of an increasing population of patients: Traumatic brain injury, polytrauma, and blast-related injuries. J. Rehabil. Res. Dev. 42, xiii-xvi.
10. Taber KH, Warden DL, Hurley RA. (2006). Blast-related traumatic brain injury: What is known? J. Neuropsychiatry Clin. Neurosci. 18, 141-145.
11. Brenner LA, Vanderploeg RD, Terrio H. (2009). Assessment and diagnosis of mild traumatic brain injury, posttraumatic stress disorder and other polytrauma conditions: Burden of adversity hyposthesis. Rehabil psychology 54:239-246.
12. Vaishanavi S, Rao V, Fann JR. (2009). Neuropsychiatric problems after traumatic brain injury: unraveling the silent epidemic. Psychosomatics 50(3):198-205.
13. Hibbard MR, Bogdany J, Uysal S, Kepler K, et al. (2000). Axis II psychopathology in individuals with traumatic brain injury. Brain Inj 14:45-61.
14. Rao V. Lyketsos CG. (2002). Psychiatric aspects of traumatic brain injury. Psychiatr Clin North Am; 25: 43-69.
15. Warden DL, Gordon B, McAllister TW, Silver JM, et al (2006).Guidelines for the Pharmacologic Treatment of Neurobehavioral Sequelae of Traumatic Brain Injury. J Neurotrauma 23:1468-1501.
16. Fann, J.R., Burington, B, Leonetti, A., Jaffe, K., Katon, W.J., Thompson, R.S. (2004). Psychiatric illness following traumatic brain injury in an adult health maintenance organization population. Arch Gen Psychiatry, Jan;61(1):53-61.
17. Jorge, R.E., Robinson, R.G., Moser, D., Tateno, A., Crespo-Facorro, B., Arndt, S. (2004). Major depression following traumatic brain injury. Arch Gen Psychiatry, Jan;61(1):42-50.
18. Okie S. (2005). Traumatic brain injury in the war zone. N. Engl. J. Med. 352, 2043-2047.
19. Kennedy JE, Jaffee MS, Leskin GA. Stokes JW, et al. (2007). Posttraumatic stress disorder and posttraumatic stress disorder-like symptoms and mild traumatic brain injury. J. Rehabil. Res. Dev. 44, 895-920.
20. Anderson R.J. Shell shock an old injury with new weapons. (2008). Molecular interventions. 8: 204-218.
21. Milliken CS, Auchterlonie JL, Hoge CW. (2007). Longitudinal assessment of mental health problems among active and reserve component soldiers returning from Iraq war. JAMA 298: 2142-2148.
22. Smith TC, Ryan MA, Wingard DL, Slymen DJ, et al. (2008). New onset and persistent symptoms of post-traumatic stress disorders self reported after deployment and combat exposures: Prospective population based US military cohort study. BMJ. 336:366-71.
23. Hill JJ III, Mobo BHP Jr., Cullen MR. (2009). Separating deployment-related traumatic brain injury and posttraumatic stress disorder in veterans: Preliminary findings from the Veterans Affairs traumatic brain injury screening program. Am J Phys Med Rehabil 88: 605-614.
24. Bremner JD. (2002). Neuroimaging studies in post-traumatic stress disorder. Current Psychiatry Reports 4: 254-263.
25. Terrio H, Brenner LA, Ivins BJ, Cho JM, et al. (2009). Traumatic brain injury screening: preliminary findings in a US Army brigade combat team. J Head Trauma Rehabil 24:14-23.
26. McCrea M, Guskiewicz KM, Marshall SW, Barr W, Randolph C, Cantu RC, Onate JA, Yang J, Kelly JP. (2003). Acute effects and recovery time following concussion in collegiate football players: the NCAA Concussion Study. JAMA. 19;290(19):2556-63.
27. Guskiewicz KM, McCrea M, Marshall SW, Cantu RC, Randolph C, Barr W, Onate JA, Kelly JP. Cumulative effects associated with recurrent concussion in collegiate football players: the NCAA Concussion Study. (2003). JAMA. 290(19):2549-55.
28. Meehan WP 3rd, d’Hemecourt P, Collins CL, Taylor AM, Comstock RD. Computerized neurocognitive testing for the management of sport-related concussions. (2012). Pediatrics. 2012 129(1):38-44.
29. Lau BC, Collins MW, Lovell MR. Sensitivity and specificity of subacute computerized neurocognitive testing and symptom evaluation in predicting outcomes after sports-related concussion. (2011). Am J Sports Med. 2011 39(6):1209-16.
30. Jacobs, A., Put, E., et al. (1994). Prospective Evaluation of Technetium-99m-HMPAO SPECT in Mild and Moderate Traumatic Brain Injury. J Nucl Med. 35(6);947-8.
31. Jacobs, A., Put, E., Ingels, M. & Bossuyt, A. (1996). One-year follow-up of Technitium-99m-HMPAO SPECT in mild head injury. The Journal of Nuclear Medicine, 37, 1605-1609.
32. Abdel-Dayem, H.M., Abu-Judeh, H., Kumar, M., Atay, S., Naddaf, S., El-Zeftawy, H., et al. (1998). SPECT brain perfusion abnormalities in mild and moderate traumatic brain injury. Clincial Nuclear Medicine, 23, 309-317.
33. Bavetta, S., Nimmon, C., et al. (1994). A prospective study comparing SPET with MRI and CT as prognostic indicators following severe closed head injury. Nucl Med Commun, Dec;15(12), 961-8.
34. Ichise, M., Chung, D.G., Wang, P., Wortzman, G., Gray, B.G., & Franks, W. (1994). Technetium-99m-HMPAO SPECT, CT and MRI in the evaluation of patients with chronic traumatic brain injury: A correlation with neuropsychological performance. Journal of Nuclear Medicine, 34, 217-226.
35. Cihiangiroglu, M., Ramsey, R.G., & Dohrmann, G.J. (2002). Brain injury: Analysis of imaging modalities. Neurological Research, 24, 7-18.
36. Newberg, A.B., Alavi, A. (2003). Neuroimaging in patients with head injury. Seminars in Nuclear Medicine, 33, 136-147.
37. Prayer, L., Wimberger, D., Oder, W., Kramer, J., Schidler, E., Podreka, I., et al. (1993). Cranial MR imaging and cerebral 99m Tc HM-PAO-SPECT in patients with subacute or chronic severe closed head injury and normal CT examinations. Acta Radiologica, 34, 593-599.
38. Gray, B.G., Ichise, M., Chung, D., Kirsh, J.C. & Franks, W. (1992). Technetium-99m-HMPAO SPECT in the evaluation of patients with a remote history of traumatic brain injury: A comparison with x-ray computed tomography. The Journal of Nuclear Medicine. 33,52-58.
39. Varney, N.R., Bushnell, D.L, Nathan, M. Kahn, D., Roberts, R., Rezai, K., et al. (1995). NeuroSPECT correlates of disabling mild head injury: Preliminary findings. Journal of Head Trauma, 10,18-28.
40. Nedd, K., Sfakianakis, G., Ganz, W., Uricchio, B., Vernberg, D., Villanueva, P., et.al. (1993). 99mTc-HMPAO SPECT of the brain in mild to moderate traumatic brain injury patients: Compared with CT-A prospective study. Brain Injury, 7, 460-479.
41. Abdel-Dayem, H.M., Sadek, S.A., Kouris, K., Bahar, R.H., Higazi, I., Erickson, S., et al. (1987). Changes in cerebral perfusion after acute head injury: Comparison of CT with Tc-99m-HM-PAO SPECT. Radiology; 165, 221-226.
42. Masdeau JC, VanHeertman RL, et al. (1994). Early single-photon emission computed tomography in mild head trauma. Am. Soc. Neuroimaging.; 4:177.
43. Ezura M; Takahashi A; Shimizu H; Yoshimoto T. (2000). Diffusion-weighted MRI and selection of patients for fibrinolytic therapy of acute cerebral ischaemia; Neuroradiology; 42(5); 379-83.
44. Sagiuchi T; Ishii K; Asano Y; Woodhams R; Yanaihara H; Kan S; Hayakawa K. (2001). Transient seizure activity demonstrated by Tc-99m HMPAO SPECT and diffusion-weighted MR imaging; Ann Nucl Med; 15(3); 267-70.
45. Chu K; Jung KH; Kim HJ; Jeong SW; Kang DW; Roh JK. (2004). Diffusion-weighted MRI and 99m Tc-HMPAO SPECT in delayed relapsing type of carbon monoxide poisoning: evidence of delayed cytotoxic edema; Eur Neurol; 51(2); 98-103.
46. Karonen Jari O; Vanninen Rivata L; Liu Yawu; Ostergaard Leif; Kuikka Jyrki; et al. (1999). Combined diffusion and perfusion MRI with correlation to single-photon emission CT in acute ischemic stroke; Stroke; 30; 1583-1590.
47. Wirestam R; Ryding E; Lindgren A; Geijer B; Holtas S; Stahlberg F. (2000). Absolute cerebral blood flow measured by dynamic susceptibility contrast MRI: a direct comparison with Xe-133 SPECT; MAGMA;11(3); 96-103.
48. Ernst T; Chang L; Oropilla G; Gustavson A; Speck O. (2000). Cerebral perfusion abnormalities in abstinent cocaine abusers: a perfusion MRI and SPECT study; Psychiatry Res; 99(2);63-74.
49. Bonne O, Gilboa A, Louzonn Y, Kempf-Sherf O, Katz M, Fishman Y, et al. (2003). Cerebral blood flow in chronic symptomatic mild traumatic brain injury. Psychiatry Res.; 30;124(3):141-52.
50. Davalos, D.B., Bennett, T.L. (2002). A Review of the Use of Single-Photon Emission Computerized Tomography as a Diagnostic Tool in Mild Traumatic Brain Injury. Applied Neuropsychology, 9(2), 92-105.
51. Abu-Judeh, H.H., Parker, R., Singh, M., el-Zeftway, H., Atay, S., Kumar, M., Naddaf, S., Aleksic, S., & Abdel-Dayem, H.M. (1999). SPET brain perfusion imaging in mild traumatic brain injury without loss of consciousness and normal computed tomography. Nucl Med Commun, 20(6),
52. Maxfield, 55th Annual Meeting of Southwestern Chapter of Society of Nuclear Medicine, 2010.
53. Graham MM. (2007). ACR Practice Guideline for the Performance of Single Photon Emission Computed Tomography (SPECT) Brain Perfusion Imaging. 823-828.
54. Tatsch, K., Asenbaum, S., Bartenstein, P., Catafau, A., Halldin, C., Pilowsky, L.S., Pupi, A. (2002). European Association of Nuclear Medicine Procedure Guidelines for brain perfusion SPECT using 99mTc-labelled radiopharmaceuticals. European Journal of Nuclear Medicine, 29,BP36-BP42.
55. Kant, R, Smith-Seemiller, L., Isaac, G., & Duffy, J. (1997). Tc-HMPAO-SPECT in persistent post-concussion syndrome after mild head injury: comparison with MRI/CT. Brain Inj, 11(2), 115-24.
56. Stamatakis EA; Wilson JT; Hadley DM; Wyper DJ. (2002). SPECT imaging in head injury interpreted with statistical parametric mapping; J Nucl Med; 43(4); 476-83.
57. Laatsch L; Pavel D; Jobe T; Lin Q; Quintana JC. (1999). Incorporation of SPECT imaging in a longitudinal cognitive rehabilitation therapy programme; Brain Inj. 13(8); 555-70.
58. Laatsch L, Jobe T, Sychra J, Lin Q, Blend M. (1997). Impact of cognitive rehabilitation therapy on neuropsychological impairments as measured by brain perfusion SPECT: a longitudinal study. Brain Inj.; 11(12):851-63.
59. Hattori N, Swan M, Stobbe GA, Uomoto JM, Minoshima S, Djang D, Krishnananthan R, Lewis DH. (2009). Differential SPECT activation patterns associated with PASAT performance may indicate frontocerebellar functional dissociation in chronic mild traumatic brain injury. J Nucl Med. 50(7):1054-61.
60. Lewis DH, Bluestone JP, Savina M, Zoller WH, Meshberg EB, Minoshima S. (2006). Imaging cerebral activity in recovery from chronic traumatic brain injury: a preliminary report. J Neuroimaging. 16(3):272-7.
61. Assessment of brain SPECT. Report of the Therapeutics and Technology Assessment Subcomeittee of the American Academy of Neurology. 1996. Neurology 46:278-285.
62. Wortzel HS, Filley CM, Anderson CA, Oster T, Arciniegas DB. Forensic applications of cerebral single photon emission computed tomography in mild traumatic brain injury. (2008). J Am Acad Psychiatry Law. 36(3):310-22.
63. Diler RS, Kibar M, Avci A. Pharmacotherapy and regional cerebral blood flow in children with obsessive compulsive disorder. Yonsei Med J. 2004 Feb 29;45(1):90-9.
64. Carey PD, Warwick J, Niehaus DJ, van der Linden G, van Heerden BB, Harvey BH, Seedat S, Stein DJ. Single photon emission computed tomography (SPECT) of anxiety disorders before and after treatment with citalopram. BMC Psychiatry. 2004 Oct 14;4:30.
65. Carey PD, Warwick J, Harvey BH, Stein DJ, Seedat S. Single photon emission computed tomography (SPECT) in obsessive-compulsive disorder before and after treatment with inositol. Metab Brain Dis. 2004 Jun;19(1-2):125-34.
66. Lee JS, Kim BN, Kang E, Lee DS, Kim YK, Chung JK, Lee MC, Cho SC. Regional cerebral blood flow in children with attention deficit hyperactivity disorder: comparison before and after methylphenidate treatment. Hum Brain Mapp. 2005 Mar;24(3):157-64.
67. Cho SC, Hwang JW, Kim BN, Lee HY, Kim HW, Lee JS, Shin MS, Lee DS. The relationship between regional cerebral blood flow and response to methylphenidate in children with attention-deficit hyperactivity disorder: comparison between non-responders to methylphenidate and responders. J Psychiatr Res. 2007 Sep;41(6):459-65.
68. Amen DG, Hanks C, Prunella J. Predicting positive and negative treatment responses to stimulants with brain SPECT imaging. J Psychoactive Drugs. 2008 Jun;40(2):131-8.
69. Richieri R, Boyer L, Farisse J, Colavolpe C, Mundler O, Lancon C, Guedj E. Predictive value of brain perfusion SPECT for rTMS response in pharmacoresistant depression. Eur J Nucl Med Mol Imaging. 2011 Sep;38(9):1715-22.
70. Raji CA, Tarzwell R, Pavel D, Schneider H, Uszler M, Thornton J, van Lierop M, Cohen P, Amen D, & Henderson T. (2014) Clinical Utility of SPECT Neuroimaging in the Diagnosis and Treatment of Traumatic Brain Injury: A Systematic Review. PLoS ONE 9(3): e91088. doi:10.1371/journal.pone.0091088)