2007 Wolters Kluwer Health Lippincott Williams & Wilkins ... is a growing trend in functional brain

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  • J Head Trauma Rehabil Vol. 22, No. 3, pp. 141–155

    Copyright c© 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

    Objective Documentation of Traumatic Brain Injury Subsequent to Mild Head Trauma: Multimodal Brain Imaging With MEG, SPECT, and MRI

    Jeffrey David Lewine, PhD; John T. Davis, PhD; Erin D. Bigler, PhD; Robert Thoma, PhD; Dina Hill, PhD; Michael Funke, MD, PhD; John Henry Sloan, MD; Sandra Hall, PhD; William W. Orrison, MD

    Objective: To determine to what extent magnetic resonance imaging (MRI), single photon emission computed to- mography (SPECT), and magnetoencephalography (MEG) can provide objective evidence of brain injury in adult patients with persistent (>1 year) postconcussive symptoms following mild blunt head trauma. Design: A retrospec- tive and blind review of imaging data with respect to the presence of specific somatic, psychiatric, and cognitive complaints. Setting/Participants: Thirty complete data sets (with MRI, SPECT, MEG, and neuropsychological test- ing results) were collected between 1994 and 2000 from the MEG programs at the Albuquerque VAMC and the University of Utah. Main Outcome Measures: MRI data were evaluated for focal and diffuse structural abnormal- ities, SPECT data for regions of hypoperfusion, and resting MEG data for abnormal dipolar slow wave activity (DSWA) and epileptiform transients. Results: Structural MRI was abnormal for 4 patients. SPECT showed regions of hypoperfusion in 12 patients, while MEG showed abnormal activity in 19 patients. None of the imaging methods produced findings statistically associated with postconcussive psychiatric symptoms. A significant association was found between basal ganglia hypoperfusion and postconcussive headaches. For patients with cognitive complaints, abnormalities were more likely to be detected by MEG (86%) than either SPECT (40%) or MRI (18%) (P < .01). MEG also revealed significant (P < .01) associations between temporal lobe DSWA and memory problems, parietal DSWA and attention problems, and frontal DSWA and problems in executive function. Conclusions: Functional brain imaging data collected in a resting state can provide objective evidence of brain injury in mild blunt head trauma patients with persistent postconcussive somatic and/or cognitive symptoms. MEG proved to be particu- larly informative for patients with cognitive symptoms. Keywords: head trauma, magnetoencephalography, MEG, MRI, postconcussive syndromes, SPECT, traumatic brain injury

    IN the United States alone, it is estimated that emer-gency departments treat more than 2 million cases From the Department of Radiology, the University of Utah School of Medicine, Salt Lake City (Drs Lewine, Davis, Bigler, Thoma, Hill, Funke, and Orrison); Hoglund Brain Imaging Center (Drs Lewine and Hall), Department of Neurology and the Department of Psychiatry and Behavioral Sciences (Dr Lewine), and Department of Preventative Medicine and Public Health (Dr Hall), University of Kansas Medical Center, Kansas City; Department of Psychology, Brigham Young University, Provo, Utah (Dr Bigler); and Department of Psychiatry, University of New Mexico (Dr Thoma and Hill) and St. Joseph’s Rehabilitation Center, St. Joseph’s Hospital (Dr Sloan), Albuquerque, NM.

    This work was supported by research grants from NSF (CCR-0105504), The University of Kansas Research Institute, Picker International, and Neuromag Ltd to J.D.L. The authors are grateful to K. Paulson, M. Johnson, K. Hatch, D. Detmers, J. Meyer, and R. Christensen for technical support and to Michael Hartshorne for the evaluation of SPECT data. The authors also thank the reviewers and JHTR editors for their valuable and insightful comments.

    Corresponding author: Jeffrey David Lewine, PhD, Illinois MEG Center, The Alexian Neurosciences Institute, Alexian Brothers Medical Center, 800 Biesterfield Rd, Suite 610, Elk Grove Village, IL 60007 (e-mail: Jeffrey. Lewine@abbhh.net).

    of head trauma each year. When blunt trauma is se- vere, many patients will show a wide range of persistent posttraumatic problems that may include headache, fa- tigue, impaired memory, reduced concentration and at- tention, reduced information-processing capacity, poor impulse control, personality changes, depression, irri- tability, sleep disturbances, and sexual dysfunction.1,2

    Similar symptoms may be reported initially after mild head trauma (mild HT), but in most cases, all symp- toms subside within a few weeks. However, 15% to 30% of patients who suffer minor trauma report postcon- cussive symptoms that persist for many years after the traumatic incident.3–6 Given that more than 80% of all head traumas are of the mild type, this translates into 200,000 to 400,000 new patients in the United States each year with a persistent postconcussive syndrome re- sulting from mild HT. Available data suggest that many of these patients will experience vocational and inter- personal distress that place a significant economic and



    social burden on our society, with many cases giving rise to litigation.3–6

    In considering both treatment and legal ramifica- tions of head trauma, objective documentation of traumatic brain injury (TBI) subsequent to mild HT would be of utility, especially in view of the com- mon assertion that cognitive symptoms following mild HT reflect “compensation neurosis” rather than brain damage.7 In cases of moderate-severe head trauma, there is a very high likelihood of TBI, with structural brain imaging via computed tomography (CT) or mag- netic resonance imaging (MRI) often demonstrating chronic abnormalities including focal encephalomala- cia, diffuse axonal injury, ventricular dilation, and corti- cal atrophy.8,9 Consequently, many researchers and clin- icians use the term TBI interchangeably with the term head trauma. Unfortunately, this can lead to confusion when considering mild HT because clinical CT and MRI are typically negative for mild HT patients, especially several months after the traumatic event.9 Thus, objec- tive evidence of actual TBI subsequent to mild HT is often lacking. TBI is a potential consequence of head trauma, but it is not a necessary one. Throughout this article, special care is therefore taken to distinguish mild HT from mild-TBI, with a major goal of the study being to provide objective documentation of actual mild-TBI in cases of observed mild HT.

    Because routine clinical MRI rarely reveals gross structural abnormalities following mild HT (even in cases with significant and persistent postconcussive com- plaints), many research teams are exploring the possi- bility that functional brain imaging methods will be more sensitive to subtle TBI. Methods of particular in- terest include hemodynamic techniques such as positron emission tomography (PET) and single photon emission computed tomography (SPECT), and electrophysiolog- ical methods such as electroencephalography (EEG) and magnetoencephalography (MEG).

    In cases of moderate and severe head trauma with clear structural lesions on MRI, resting-baseline PET and SPECT data generally demonstrate concordant perfu- sion and metabolic deficits. These perfusion deficits may extend into normal appearing tissue, and in some cases, very diffuse hemodynamic abnormalities consistent with the concept of diaschisis have been reported.10,11 Some resting PET studies reveal a high sensitivity to mild HT,10,12,13 but this is not always the case.14 SPECT studies in mild trauma often show focal regions of hy- poperfusion consistent with expectations based on neu- ropsychological testing,15,16 but not all groups have re- ported a strong correlation between specific regional SPECT findings and specific cognitive test results.2,17,18

    Overall, resting PET and SPECT demonstrate abnor- malities in 25% to 80% of head trauma survivors—the likelihood of a positive finding being dependent on the

    severity of initial trauma, the presence of MRI find- ings, the severity of postconcussive compromise, and the time lag between imaging and the traumatic event.2,10–18

    When scanning is performed several months after mild trauma, most studies report resting hemodynamic ab- normalities in fewer than 50% of subjects, even when considering only patients who report persistent post- concussive problems. Another limitation of the resting hemodynamic approach to mild HT is a general lack of specificity for the methods. Although normal com- parison participants rarely show hemodynamic anoma- lies, hypoperfusions can be seen in almost all neurologic and psychiatric diseases, including stoke, epilepsy, de- pression, schizophrenia, attention-deficit disorder, and dementia.

    Most hemodynamic imaging studies in head trauma have focused on resting hemodynamic profiles, but there is a growing trend in functional brain imaging to ex- amine activity profiles during performance of specific cognitive tasks. Recently, several investigators have used PET, SPECT, and/or functional MRI (fMRI) to exam- ine hemodynamic responses in patients with mild HT performing working memory tasks.14,19,20 These studies indicate that mild HT can lead to activation deficits, but most deficits are subtle and apparent only in group data, with critical observations failing to be sufficiently robust for diagnostic use on a case-by-case basis.

    Turning toward electrophysiological methods (EEG and MEG), there are also 2 general types of studies— those that use evoked response paradigms to assess spe- cific cognitive processes and those that examine “resting” activity patterns. In general, simple sensory and motor evoked responses (potentials and fields) are within nor- mal limits following mild HT,21 although some recent pilot data indicate that somatosensory e