ORIGINAL CONTRIBUTION Cognitive Sequelae of Diffuse Axonal Injury Rainer Scheid, MD; Kathrin Walther; Thomas Guthke, PhD; Christoph Preul, MD; D. Yves von Cramon, MD, PhD Background: The results of recent studies on cognitive tor speed, executive functions, spans, learning and disability after traumatic brain injury–associated diffuse axo- memory, and intelligence 4 to 55 months (median, 9 nal injury (DAI) are inconsistent. In these studies, the di- months) after traumatic brain injury. agnosis of DAI relied on cranial computed tomography. Results: All of the patients showed impairments of 1 or Objective: To further clarify the extent and severity of more cognitive subfunctions, and no cognitive domain a possibly DAI-associated cognitive impairment by the was fundamentally spared. Memory and executive dys- use of magnetic resonance imaging (MRI) and detailed functions were most frequent, the former reaching a neuropsychological testing. moderate to severe degree in half of the patients. In com- parison, deficits of attention, executive functions, and Design and Participants: From a databank of 299 pa- short-term memory were mostly mild. Correlations tients with traumatic brain injury, 18 patients (age range, between the amount of traumatic microbleeds and spe- 17-50 years; median initial Glasgow Coma Scale score, cific or global cognitive performance were absent. 5) who showed an MRI lesion pattern compatible with pure DAI were identified. All of the patients had under- Conclusions: An MRI lesion pattern compatible with iso- gone MRI on a 3-T system. Pure DAI was defined by the findings of traumatic microbleeds on T2*-weighted gra- lated DAI is associated with persistent cognitive impair- dient-echo images in the absence of otherwise trau- ment. The traumatic microbleed load is no sufficient pa- matic or nontraumatic MRI abnormalities. rameter for the assessment of DAI severity or functional outcome. Main Outcome Measures: Neuropsychological per- formance in the categories of attention and psychomo- Arch Neurol. 2006;63:418-424 IFFUSE AXONAL INJURY In the true sense, DAI is a neuropatho- (DAI) is a distinct type of logic diagnosis. Therefore, the method that primary traumatic brain is applied for its in vivo assessment is a injury1-3 (TBI) that has critical issue. In a previous study,10 it was traditionally been associ- shown that T2*-weighted gradient-echo Dated with poor clinical outcome.4 How- magnetic resonance imaging (MRI) at high ever, the results of several studies5-8 have field strength is a useful tool for the evalu- qualified this view. Wallesch et al7 found ation of DAI in the chronic stage of TBI. that patients with mild to moderate TBI Due to the neuropathologically proven fre- and DAI mainly had transient deficits of quent hemorrhagic component,1,2 le- psychomotor speed, verbal short-term sions suspicious for DAI appear as small memory, and frontal lobe cognitive func- hypointense signal alterations (traumatic tions. Another study8 showed that slowed microbleeds [TMBs]). information processing was related to Considering the inconsistent litera- Author Affiliations: Day Clinic DAI, but subjects with predominant DAI ture, the aim of the current study was to of Cognitive Neurology, showed greater recovery over time than further examine the relevance of DAI for University of Leipzig those in whom focal lesions were the main determining outcome by means of de- (Drs Scheid, Guthke, and von abnormality. A most recent study9 on this tailed neuropsychological testing in a group Cramon and Ms Walther) and issue, however, revealed that patients with of patients with TBI whose MRIs showed Max Planck Institute for Human Cognitive and Brain probable DAI had long-lasting neuropsy- only TMBs as pathological findings. These Sciences (Drs Scheid, Preul, chological impairments that were domi- patients were therefore considered to have and von Cramon), nated by executive and memory dysfunc- had pure DAI. We hypothesized the fol- Leipzig, Germany. tions. lowing: (1) these patients show chronic cog- (REPRINTED) ARCH NEUROL / VOL 63, MAR 2006 WWW.ARCHNEUROL.COM 418 ©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 Right Left Figure. Example of magnetic resonance imaging findings for 1 patient; with comparison between fluid-attenuated inversion recovery images (upper row) and T2*-weighted gradient-echo images (lower row). Axial-view sections of exactly corresponding levels are shown. Multiple traumatic microbleeds are shown on the T2*-weighted gradient-echo images. The patient was a 25-year-old driver of a car that collided with a roadworks vehicle on September 28, 2003. nitive dysfunction; (2) owing to the diffuse character of nection to the brain surface and/or the ventricular system that the underlying brain injury, no specific cognitive domain appeared hypointense on both T1- and T2-weighted MRI and/or is predominantly affected; and (3) with respect to the re- on T2*-weighted gradient-echo MRI was defined as a trau- sults of a previous study,10 the number of TMBs does not matic microbleed (TMB) and was regarded as an MRI corre- correlate with overall cognitive performance. late of DAI (Figure). In each of the 20 patients who were se- lected for the study, MRI showed TMBs in the absence of otherwise traumatic or nontraumatic MRI abnormalities. The METHODS number of TMBs was registered for each individual. No pa- tient had symptoms or signs of preexisting or concomitant medi- PATIENTS AND MRI cal or psychiatric disorders or a history of a previous TBI. With the exception of 1 patient who had fallen from a substantial Eighteen patients (5 women, 13 men; age range, 17-50 years; height during a mountain hike, all of the patients were victims of road traffic accidents. Injury severity was assessed by the use median age, 22.5 years) with histories of TBI were included in 12 the study. Seventeen patients had closed injuries; in 1 patient, of the reported Glasgow Coma Scale (GCS) score from ini- there was suspicion of an open TBI. All of the participants had tial hospital admission (score range, 3-15; median score, 5). been inpatients of the Day Clinic of Cognitive Neurology, Uni- In cases where the GCS score was missing, specific informa- versity of Leipzig, Leipzig, Germany, and were selected from a tion from the short-term records was used to calculate GCS databank of 299 patients with TBI. Neuroradiologic and psy- scores retrospectively. Owing to insufficient information, the chometric assessment was conducted between June 8, 1996, GCS score could not be calculated for 5 patients. The duration and May 14, 2004. Magnetic resonance imaging was per- of loss of consciousness was not analyzed because of the prob- formed on a 3-T system; the imaging and evaluation protocols able interference of standard therapeutic interventions. The me- have been published previously.10 In short, the protocol com- dian interval between brain injury and neuropsychological test- prised 3 scans of the same geometry (20 slices, axial plane, slice ing was 9 months (interval range, 4-55 months). No patient thickness of 5 mm, slice gap of 2 mm): (1) 2-dimensional T1- was under continuous psychotropic medication at the time of weighted reduced power multislice modified driven equilib- the psychometric assessment. Demographic and clinical data rium Fourier transform images11 (field of view, 25.0ϫ25.0 cm; are summarized in Table 1. data matrix, 256ϫ256; repetition time, 1.3 seconds; echo time, 10 milliseconds); (2) 2-dimensional T2-weighted fast spin- NEUROPSYCHOLOGICAL ASSESSMENT echo scans (field of view, 25.0ϫ25.0 cm; data matrix, 512ϫ512; repetition time, 8.5 seconds; echo time, 21.7 milliseconds); and A variety of neuropsychological tests were used for the evaluation (3) 2-dimensional T2*-weighted gradient-echo images (field of several cognitive domains. For attention and psychomotor of view, 19.2ϫ19.2 cm; data matrix, 256ϫ256; repetition time, speed, the Test of Attentional Processes (Testbatterie zur 700 milliseconds; echo time, 15 milliseconds; flip angle, 25°). Aufmerksamkeitspru¨ fung) alertness subtest,13 which measures the In 5 patients, 2-dimensional fluid-attenuated inversion recov- simplereactiontimesforvisualpresentedstimuliandincludedmean ery imaging (repetition time, 1000 milliseconds; echo time, 94 reaction times, variation or stability of reaction, and difference in milliseconds; inversion time, 2500 milliseconds) was also per- reaction times after stimulus announcement (phasic alertness) as formed. All of the MRIs were evaluated independently by 2 of the test scores, and the Test of Attentional Processes sustained at- us (R.S. and C.P.). Any small (1- to 15-mm) focus without con- tention subtest,13 which requires a simultaneous consideration of (REPRINTED) ARCH NEUROL / VOL 63, MAR 2006 WWW.ARCHNEUROL.COM 419 ©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 less than −1.0, severe impairment. The average of all of the zrˇ Table 1. Clinical and Demographic Data scores of 1 patient represents his or her overall cognitive state. As the neuropsychological data were collected in part ret- Characteristic Value rospectively over an interval of 8 years, the applied neuropsy- Patients, No. 18 chological tests were not congruent for every patient. In 6 pa- Sex, female/male, No. 5/13 tients, missing data were replaced by the individual patient’s Age, median (range), y 22.5 (17-50) performance in tests representing comparable subfunc- 19,20 Time after injury, median (range), mo 9 (4-55) tions. For example, the Multiple Choice Vocabulary Test GCS score, median (range) (n = 13) 5 (3-15) score was replaced by the score on the Vocabulary Test (Wort- 21 TMBs, median (range), No. 15.5 (1-104) schatztest) (a revised version of the Multiple Choice Vocabu- lary Test) and educational data. One patient was not able to Abbreviations: GCS, Glasgow Coma Scale; TMB, traumatic microbleed. fulfill the demands of the Test of Attentional Processes di- vided attention subtest.