Letter to the Editor. Traumatic axonal injury: causes and effects

View More View Less
  • 1 Center of Biomedical Research (CIB), Faculty of Medicine, University of Cartagena, Colombia;
  • | 2 Medical-Surgical Research Center, University of Cartagena, Colombia;
  • | 3 Latinamerican Council of Neurocritical Care (CLaNi), Cartagena, Colombia;
  • | 4 Colombian Clinical Research Group in Neurocritical Care, University of Cartagena, Colombia; and
  • | 5 Strong Memorial Hospital, University of Rochester, MN
Free access

TO THE EDITOR: We read with great interest the article published by Moe et al.1 (Moe HK, Limandvik Myhr J, Moen KG, et al. Association of cause of injury and traumatic axonal injury: a clinical MRI study of moderate and severe traumatic brain injury. J Neurosurg. 2020;133[5]:1559–1567). The authors reported their investigation of causal mechanistic effects on the incidence of traumatic axonal injury (TAI). Moe et al. accurately analyzed the role of each known cause of TAI and the underlying pathophysiology; however, some concerns need to be highlighted. It is well known that TAI is one of the main causes of impairment during the posttraumatic phase in patients who have no detectable intracranial lesions on CT,2 even patients with mild traumatic brain injury. Several phenomena explain how the strong acceleration-deceleration and rotational-angular acceleration forces in high-impact trauma lead to progressive changes in the axons, resulting in deformation of the brain tissue.2

An external injury involves shearing forces that stimulate the formation of axon retraction balls, which result from a swelling phenomenon at the end of the axonal axis due to external shear force and tension that lead to the final breakage of the axon. During this process the permeability of the axon membrane changes and large amounts of Ca+ enter the cells, reversing the flux of plasma transport and activating the cysteine protein signal pathway and caspase-3. These events lead to the degradation of the axonal cytoskeleton network. During this progressive phenomenon, axons usually maintain their morphology several hours after injury, and for that reason it is crucial to perform MRI in patients days after trauma.3

Although we understand the complex nature of reporting hundreds of neuroimaging results and thank the authors for their investigation of this important topic, we have to note the highly heterogeneous rating of the samples reported by Moe et al.1 and the possible consequences. The fact that there is substantial agreement between raters (linear Cohen's kappa 0.74) should be interpreted with caution given that some of the pitfalls in this study may have decreased the interrater reliability to an unknown degree. Having more than two raters may have masked valuable ratings in the analysis, and thus the generalized kappa may not have captured the range of potential agreement or disagreement between assessments by multiple raters.4

Disclosures

The authors report no conflict of interest.

References

  • 1

    Moe HK , Limandvik Myhr J , Moen KG , et al. Association of cause of injury and traumatic axonal injury: a clinical MRI study of moderate and severe traumatic brain injury . J Neurosurg . 2020 ;133 (5 ):1559 1567 .

    • Search Google Scholar
    • Export Citation
  • 2

    Kim M , Ahn JS , Park W , et al. Diffuse axonal injury (DAI) in moderate to severe head injured patients: Pure DAI vs. non-pure DAI. Clin Neurol Neurosurg . 2018 ;171 :116 123 .

    • Search Google Scholar
    • Export Citation
  • 3

    Ma J , Zhang K , Wang Z , Chen G . Progress of research on diffuse axonal injury after traumatic brain injury . Neural Plast . 2016 ;2016 :9746313 .

    • Search Google Scholar
    • Export Citation
  • 4

    O’Leary S , Lund M , Ytre-Hauge TJ , et al. Pitfalls in the use of kappa when interpreting agreement between multiple raters in reliability studies . Physiotherapy . 2014 ;100 (1 ):27 35 .

    • Search Google Scholar
    • Export Citation
View More View Less
  • 1 Norwegian University of Science and Technology (NTNU), Trondheim, Norway;
  • | 2 St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; and
  • | 3 Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway

Response

We thank authors Herrera-Martinez et al. for their interest in our paper on the association of cause of injury with traumatic axonal injury (TAI). The authors elaborate more thoroughly on the underlying cellular mechanisms behind TAI than what was within the scope of our study. While TAI detectability on histopathological examination has been reported to peak at 24 hours,1 little is known about how the indirect signs of TAI visualized on clinical MRI develop over the first few hours and days after injury. One recent study indicated that traumatic microbleeds detected on susceptibility-weighted imaging (SWI) were more visible 1 week after injury.2 We also know from previous studies that almost all non-hemorrhagic TAI lesions (detected on FLAIR or diffusion-weighted imaging [DWI]) have disappeared at 3 months after injury.3 We want to emphasize that in the present study we performed MRI at a median of 8 days (IQR 4–17 days) post-injury, so it is unlikely that the MRIs were performed too early and thus could have affected the results in our study.

Herrera-Martinez et al. also argue that the “substantial agreement between raters … should be interpreted with caution,” and that “having more than two raters may have masked valuable ratings in the analysis.” We acknowledge the possibility that a misunderstanding might have occurred. The linearly weighted Cohen's kappa (not the generalized kappa) was calculated between two raters in a previous paper,3 namely K.G.M. (who was able to consult with neuroradiologists K.A.K. and J.R. when needed) and M.F. Both K.G.M. and M.F. were blinded to the scores of the other rater. Interrater analyses were not performed for J.R. (n = 66) since all of his scores were also evaluated by K.A.K. or M.F. The two latter neuroradiologists had been part of the abovementioned interrater analyses.3 Moreover, in a recent larger study including the Trondheim cohort of patients with moderate and severe traumatic brain injury, interrater analyses were performed for multiple raters.4 In this more recent study, the positive and negative agreement5,6 for the presence or absence of TAI were 0.90 (95% CI 0.77–0.95) and 0.69 (95% CI 0.42–0.84), respectively, and the intraclass correlation coefficient was 0.78 for the classification of TAI grade. More details can be found in the Methods and Results sections of that paper.4 Hence, we hope our response has clarified some of the concerns raised by Herrera-Martinez et al.

References

  • 1

    Johnson VE , Stewart W , Smith DH . Axonal pathology in traumatic brain injury . Exp Neurol . 2013 ;246 :35 43 .

  • 2

    Toth A , Kovacs N , Tamas V , et al. Microbleeds may expand acutely after traumatic brain injury . Neurosci Lett . 2016 ;617 :207 212 .

    • Search Google Scholar
    • Export Citation
  • 3

    Moen KG , Skandsen T , Folvik M , et al. A longitudinal MRI study of traumatic axonal injury in patients with moderate and severe traumatic brain injury . J Neurol Neurosurg Psychiatry . 2012 ;83 (12 ):1193 1200 .

    • Search Google Scholar
    • Export Citation
  • 4

    Moe HK , Follestad T , Andelic N , et al. Traumatic axonal injury on clinical MRI: association with the Glasgow Coma Scale score at scene of injury or at admission and prolonged posttraumatic amnesia . J Neurosurg . Published online October 23, 2020. doi:10.3171/2020.6.JNS20112

    • Search Google Scholar
    • Export Citation
  • 5

    de Vet HCW , Mokkink LB , Terwee CB , et al. Clinicians are right not to like Cohen's κ . BMJ . 2013 ;346 :f2125 .

  • 6

    de Vet HCW , Dikmans RE , Eekhout I . Specific agreement on dichotomous outcomes can be calculated for more than two raters . J Clin Epidemiol . 2017 ;83 :85 89 .

    • Search Google Scholar
    • Export Citation

Artist’s illustration of the classic mulberry appearance of a cavernoma. This illustration represents the Seven Cavernomas series by Dr. Michael Lawton, a collection of articles defining the tenets and techniques for the treatment of cavernous malformations, a taxonomy for classifying these lesions, and the nuances of their surgical approaches. Artist: Peter M. Lawrence. Used with permission from Barrow Neurological Institute, Phoenix, Arizona. See the article by Garcia et al. (pp 671–682).

Contributor Notes

Correspondence Ivan David Lozada-Martínez: ivandavidloma@gmail.com.

INCLUDE WHEN CITING Published online May 7, 2021; DOI: 10.3171/2021.1.JNS204452.

Disclosures The authors report no conflict of interest.

  • 1

    Moe HK , Limandvik Myhr J , Moen KG , et al. Association of cause of injury and traumatic axonal injury: a clinical MRI study of moderate and severe traumatic brain injury . J Neurosurg . 2020 ;133 (5 ):1559 1567 .

    • Search Google Scholar
    • Export Citation
  • 2

    Kim M , Ahn JS , Park W , et al. Diffuse axonal injury (DAI) in moderate to severe head injured patients: Pure DAI vs. non-pure DAI. Clin Neurol Neurosurg . 2018 ;171 :116 123 .

    • Search Google Scholar
    • Export Citation
  • 3

    Ma J , Zhang K , Wang Z , Chen G . Progress of research on diffuse axonal injury after traumatic brain injury . Neural Plast . 2016 ;2016 :9746313 .

    • Search Google Scholar
    • Export Citation
  • 4

    O’Leary S , Lund M , Ytre-Hauge TJ , et al. Pitfalls in the use of kappa when interpreting agreement between multiple raters in reliability studies . Physiotherapy . 2014 ;100 (1 ):27 35 .

    • Search Google Scholar
    • Export Citation
  • 1

    Johnson VE , Stewart W , Smith DH . Axonal pathology in traumatic brain injury . Exp Neurol . 2013 ;246 :35 43 .

  • 2

    Toth A , Kovacs N , Tamas V , et al. Microbleeds may expand acutely after traumatic brain injury . Neurosci Lett . 2016 ;617 :207 212 .

    • Search Google Scholar
    • Export Citation
  • 3

    Moen KG , Skandsen T , Folvik M , et al. A longitudinal MRI study of traumatic axonal injury in patients with moderate and severe traumatic brain injury . J Neurol Neurosurg Psychiatry . 2012 ;83 (12 ):1193 1200 .

    • Search Google Scholar
    • Export Citation
  • 4

    Moe HK , Follestad T , Andelic N , et al. Traumatic axonal injury on clinical MRI: association with the Glasgow Coma Scale score at scene of injury or at admission and prolonged posttraumatic amnesia . J Neurosurg . Published online October 23, 2020. doi:10.3171/2020.6.JNS20112

    • Search Google Scholar
    • Export Citation
  • 5

    de Vet HCW , Mokkink LB , Terwee CB , et al. Clinicians are right not to like Cohen's κ . BMJ . 2013 ;346 :f2125 .

  • 6

    de Vet HCW , Dikmans RE , Eekhout I . Specific agreement on dichotomous outcomes can be calculated for more than two raters . J Clin Epidemiol . 2017 ;83 :85 89 .

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 67 67 67
PDF Downloads 75 75 75
EPUB Downloads 0 0 0