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Revisiting Grade 3 Diffuse Axonal Injury: Not All Brainstem Microbleeds are Prognostically Equal

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Abstract

Background

Recovery of functional independence is possible in patients with brainstem traumatic axonal injury (TAI), also referred to as “grade 3 diffuse axonal injury,” but acute prognostic biomarkers are lacking. We hypothesized that the extent of dorsal brainstem TAI measured by burden of traumatic microbleeds (TMBs) correlates with 1-year functional outcome more strongly than does ventral brainstem, corpus callosal, or global brain TMB burden. Further, we hypothesized that TMBs within brainstem nuclei of the ascending arousal network (AAN) correlate with 1-year outcome.

Methods

Using a prospective outcome database of patients treated for moderate-to-severe traumatic brain injury at an inpatient rehabilitation hospital, we retrospectively identified 39 patients who underwent acute gradient-recalled echo (GRE) magnetic resonance imaging (MRI). TMBs were counted on the acute GRE scans globally and in the dorsal brainstem, ventral brainstem, and corpus callosum. TMBs were also mapped onto an atlas of AAN nuclei. The primary outcome was the disability rating scale (DRS) score at 1 year post-injury. Associations between regional TMBs, AAN TMB volume, and 1-year DRS score were assessed by calculating Spearman rank correlation coefficients.

Results

Mean ± SD number of TMBs was: dorsal brainstem = 0.7 ± 1.4, ventral brainstem = 0.2 ± 0.6, corpus callosum = 1.8 ± 2.8, and global = 14.4 ± 12.5. The mean ± SD TMB volume within AAN nuclei was 6.1 ± 18.7 mm3. Increased dorsal brainstem TMBs and larger AAN TMB volume correlated with worse 1-year outcomes (R = 0.37, p = 0.02, and R = 0.36, p = 0.02, respectively). Global, callosal, and ventral brainstem TMBs did not correlate with outcomes.

Conclusions

These findings suggest that dorsal brainstem TAI, especially involving AAN nuclei, may have greater prognostic utility than the total number of lesions in the brain or brainstem.

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Acknowledgements

This study was supported by the National Institutes of Health (R25NS065743, K23NS094538), the American Academy of Neurology/American Brain Foundation, the James S. McDonnell Foundation, and the National Institute on Disability, Independent Living, and Rehabilitation Research, Administration for Community Living, US Department Health and Human Services to Spaulding Rehabilitation Hospital (H133A120085). However, the contents of this manuscript do not necessarily represent the policy of the Department of Health and Human Services and endorsement by the Federal Government should not be assumed.

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Authors and Affiliations

  1. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Saef Izzy, Sergi Martinez, Camille A. Spencer, Steven M. Greenberg & Brian L. Edlow

  2. Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA

    Saef Izzy & Joshua P. Klein

  3. Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Joshua P. Klein

  4. Department of Physical Medicine and Rehabilitation, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Nicole L. Mazwi

  5. Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Nicole L. Mazwi & Mel B. Glenn

  6. Program in Trauma, Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA

    Gunjan Parikh

  7. Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA

    Ona Wu & Brian L. Edlow

  8. Department of Neurology, Yale-New Haven Hospital, Yale School of Medicine, New Haven, CT, USA

    David M. Greer

  9. Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Ona Wu

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  1. Saef Izzy
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Correspondence to Saef Izzy.

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Izzy, S., Mazwi, N.L., Martinez, S. et al. Revisiting Grade 3 Diffuse Axonal Injury: Not All Brainstem Microbleeds are Prognostically Equal. Neurocrit Care 27, 199–207 (2017). https://doi.org/10.1007/s12028-017-0399-2

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