RESEARCH PAPER A longitudinal MRI study of traumatic axonal injury in patients with moderate and severe traumatic brain injury Kent Gøran Moen, 1,2 Toril Skandsen, 1,3 Mari Folvik, 4 Veronika Brezova, 5 Kjell Arne Kvistad, 4,5 Jana Rydland, 4 Geoffrey T Manley, 6 Anne Vik 1,2 ABSTRACT Objective To study the evolution of traumatic axonal injury (TAI) detected by structural MRI in patients with moderate and severe traumatic brain injury (TBI) during the first year and relate findings to outcome. Methods 58 patients with TBI (Glasgow Coma Scale score 3e13) were examined with MRI at a median of 7 days, 3 months and 12 months post injury. TAI lesions were evaluated blinded and categorised into three stages based on location: hemispheres, corpus callosum and brainstem. Lesions in T2* weighted gradient echo (GRE), fluid attenuated inversion recovery (FLAIR) and diffusion weighted imaging (DWI) were counted and FLAIR lesion volumes were estimated. Inter-rater reliability score was calculated. Outcome was assessed 12 months post injury using the Glasgow Outcome Scale Extended. Results In the initial MRI, 31% had brainstem lesions compared with 17% at 3 months (p¼0.008). In the FLAIR sequences, number and volumes of lesions were reduced from early to 3 months (p<0.001). In T2*GRE sequences, the number of lesions persisted at 3 months but was reduced at 12 months (p¼0.007). The number of lesions in DWI and volume of FLAIR lesions on early MRI predicted worse clinical outcome in adjusted analyses (p<0.05). Conclusion This is the first study to demonstrate and quantify attenuation of non-haemorrhagic TAI lesions on structural MRI during the first 3 months after TBI; most importantly, the disappearance of brainstem lesions. Haemorrhagic TAI lesions attenuate first after 3 months. Only early MRI findings predicted clinical outcome after adjustment for other prognostic factors. Hence valuable clinical information may be missed if MRI is performed too late after TBI. INTRODUCTION Traumatic axonal injury (TAI) or diffuse axonal injury is histopathologically characterised by axonal swelling and, depending on the severity, by subsequent secondary axotomy. 1 In autopsy studies, TAI has been shown to be present in all cases of fatal traumatic brain injury (TBI). 2 However, using more sensitive MRI techniques, TAI has been shown to be an important part of the brain injury in surviving patients with moderate and severe TBI, 3 and even in mild cases. 4 As TAI is grossly underestimated by CT, 5 MRI has become the image modality of choice in the subacute and chronic phase of TBI. 6 Recent advanced techniques, such as the diffusion tensor imaging, have consistently demonstrated loss of axonal integrity in TBI patients compared with controls, 7 but normative data for diagnostic use in individual patients are not yet sufficiently devel- oped. Therefore, conventional MRI sequences is still considered to be the standard imaging method in the routine clinical evaluation of TBI patients, 8 in addition to the initial CT examinations. T2*gradient echo (T2*GRE) sequences are sensitive to iron in blood breakdown products and depict haemorrhagic TAI lesions, while fluid attenuated inversion recovery (FLAIR) also depicts non- haemorrhagic lesions due to oedema. Early MRI findings after injury have been asso- ciated with clinical outcome. 9e11 It may, however, be challenging to perform MRI during the first weeks post injury in patients who are unstable or do not cooperate. One study has demonstrated that haemorrhagic TAI lesions appear less conspicuous with time, 12 while no longitudinal conventional MRI studies have assessed how non-haemorrhagic TAI lesions evolve in number and volume from the acute to the chronic stage. Such studies have been requested, and may clarify whether it is important to perform MRI early after TBI. 13 14 Hence the aim of this study was to examine the evolution of TAI lesions during the first year post injury using conventional MRI in the early phase and at 3 and 12 months. Furthermore, we aimed to relate the findings to 12 month clinical outcome. MATERIAL AND METHODS Subjects From October 2004 to July 2007, 125 individuals aged 11e65 years were admitted with moderate or severe head injury, according to the Head Injury Severity Scale, 15 to the Neurosurgical Department, Trondheim University Hospital, Norway. Of these 125 consecutive patients, 18 patients (14%) died (13 from intracranial hypertension, three from sequelae of the head injury and two from factors not associated with the injury). Nine patients (7%) refused to participate or were not able to cooperate. Patients with a premorbid condition, such as severe cerebrovascular diseases, severe psychiatric conditions or substance abuse, were excluded (n¼14, 11%). Twenty-three patients (18%) could not complete all three repeated exam- inations because of logistic, geographical or other reasons. In three patients their early MRI scan was < Additional materials are published online only. To view these files please visit the journal online (http://dx.doi.org/ 10.1136/jnnp-2012-302644). 1 Department of Neuroscience, Norwegian University of Science and Technology (NTNU), Trondheim, Norway 2 Department of Neurosurgery, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway 3 Department of Physical Medicine and Rehabilitation, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway 4 Department of Diagnostic Imaging, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway 5 Department of Circulation and Diagnostic Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway 6 Department of Neurosurgery, Brain and Spinal injury Center, University of California, San Francisco, USA Correspondence to Dr K G Moen, Department of Neuroscience, Norwegian University of Science and Technology (NTNU), Trondheim N-7489, Norway; kent.g.moen@ntnu.no Received 16 March 2012 Revised 23 July 2012 Accepted 1 August 2012 Moen KG, Skandsen T, Folvik M, et al. J Neurol Neurosurg Psychiatry (2012). doi:10.1136/jnnp-2012-302644 1 of 8 Neurosurgery JNNP Online First, published on August 29, 2012 as 10.1136/jnnp-2012-302644 Copyright Article author (or their employer) 2012. Produced by BMJ Publishing Group Ltd under licence. group.bmj.com on August 30, 2012 - Published by jnnp.bmj.com Downloaded from