Traumatic axonal injury (TAI): definitions, pathophysiology and imaging—a narrative review

Abstract Introduction Traumatic axonal injury (TAI) is a condition defined as multiple, scattered, small hemorrhagic, and/or non-hemorrhagic lesions, alongside brain swelling, in a more confined white matter distribution on imaging studies, together with impaired axoplasmic transport, axonal swelling, and disconnection after traumatic brain injury (TBI). Ever since its description in the 1980s and the grading system by Adams et al., our understanding of the processes behind this entity has increased. Methods We performed a scoping systematic, narrative review by interrogating Ovid MEDLINE, Embase, and Google Scholar on the pathophysiology, biomarkers, and diagnostic tools of TAI patients until July 2020. Results We underline the misuse of the Adams classification on MRI without proper validation studies, and highlight the hiatus in the scientific literature and areas needing more research. In the past, the theory behind the pathophysiology relied on the inertial force exerted on the brain matter after severe TBI inducing a primary axotomy. This theory has now been partially abandoned in favor of a more refined theory involving biochemical processes such as protein cleavage and DNA breakdown, ultimately leading to an inflammation cascade and cell apoptosis, a process now described as secondary axotomy. Conclusion The difference in TAI definitions makes the comparison of studies that report outcomes, treatments, and prognostic factors a daunting task. An even more difficult task is isolating the outcomes of isolated TAI from the outcomes of severe TBI in general. Targeted bench-to-bedside studies are required in order to uncover further pathways involved in the pathophysiology of TAI and, ideally, new treatments.

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Association of cause of injury and traumatic axonal injury: a clinical MRI study of moderate and severe traumatic brain injury

Journal of Neurosurgery ◽

10.3171/2019.6.jns191040 ◽

2020 ◽

Vol 133 (5) ◽

pp. 1559-1567 ◽

Cited By ~ 1

Author(s):

Hans Kristian Moe ◽

Janne Limandvik Myhr ◽

Kent Gøran Moen ◽

Asta Kristine Håberg ◽

Toril Skandsen ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Severe Traumatic Brain Injury ◽

Axonal Injury ◽

Traumatic Axonal Injury ◽

Alpine Skiing ◽

Severe Tbi ◽

Mri Study ◽

Mass Lesions ◽

Clinical Mri

OBJECTIVEThe authors investigated the association between the cause of injury and the occurrence and grade of traumatic axonal injury (TAI) on clinical MRI in patients with moderate or severe traumatic brain injury (TBI).METHODSData for a total of 396 consecutive patients, aged 7–70 years, with moderate or severe TBI admitted to a level 1 trauma center were prospectively registered. Data were included for analysis from the 219 patients who had MRI performed within 35 days (median 8, IQR 4–17 days) and for whom cause of injury was known. Cause of injury was registered as road traffic accident (RTA) or fall (both with respective subcategories), alpine skiing or snowboarding accident, or violence. The MRI protocol consisted of T2*-weighted gradient echo, FLAIR, and diffusion-weighted imaging scans. TAI lesions were evaluated in a blinded manner and categorized into 3 grades, hemispheric/cerebellar white matter (grade 1), corpus callosum (grade 2), and brainstem (grade 3). The absence of TAI was analyzed as grade 0. Contusions and mass lesions on CT were also registered.RESULTSCause of injury did not differ between included and nonincluded patients. TAI was found in 83% of patients in the included group after RTAs and 62% after falls (p < 0.001). Observed TAI grades differed between the subcategories of both RTAs (p = 0.004) and falls (p = 0.006). Pedestrians in RTAs, car drivers/passengers in RTAs, and alpine skiers had the highest prevalence of TAI (89%–100%) and the highest TAI grades (70%–82% TAI grades 2–3). TAI was found in 76% of patients after falls from > own height (45% TAI grade 2–3), 63% after falls down the stairs (26% TAI grade 2–3), and 31% after falls from ≤ own height (12% TAI grade 2–3). Moreover, 53% of patients with TAI after RTAs and 68% with TAI after falls had cortical contusions or mass lesions on CT.CONCLUSIONSThis prospective study of moderate and severe TBI is to the authors’ knowledge the first clinical MRI study to demonstrate both the high prevalence and grade of TAI after most of the different types of RTAs, alpine skiing accidents, and falls from a height. Importantly, TAI was also common following more low-energy trauma such as falls down the stairs or from own height. Physicians managing TBI patients in the acute phase should be aware of the possibility of TAI no matter the cause of injury and also when the CT scan shows cortical contusions or mass lesions.

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Traumatic Axonal Injury in the Optic Nerve: Evidence for Axonal Swelling, Disconnection, Dieback, and Reorganization

Journal of Neurotrauma ◽

10.1089/neu.2011.1756 ◽

2011 ◽

Vol 28 (7) ◽

pp. 1185-1198 ◽

Cited By ~ 62

Author(s):

Jiaqiong Wang ◽

Robert J. Hamm ◽

John T. Povlishock

Keyword(s):

Optic Nerve ◽

Axonal Injury ◽

Traumatic Axonal Injury ◽

Axonal Swelling

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A Review of Traumatic Axonal Injury

Acta Medica ◽

10.32552/2021.actamedica.467 ◽

2021 ◽

pp. 1-7

Author(s):

Dicle Karakaya ◽

Ahmet İlkay Işıkay

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Clinical Outcome ◽

Glasgow Coma Score ◽

Brain Injuries ◽

Vegetative State ◽

Axonal Injury ◽

Traumatic Axonal Injury ◽

Axonal Swelling ◽

Blunt Head Trauma

Traumatic brain injury is a major cause of mortality and neurological disability worldwide and varies according to its cause, pathogenesis, severity and clinical outcome. This review summarizes a significant aspect of diffuse brain injuries – traumatic axonal injury – important cause of severe disability and vegetative state. Traumatic axonal injury is a type of traumatic brain injury caused by blunt head trauma. It is defined both clinically (immediate and prolonged unconsciousness, characteristically in the absence of space-occupying lesions) and pathologically (widespread and diffuse damage of axons). Following traumatic brain injury, progressive axonal degeneration starts with disruption of axonal transport, axonal swelling, secondary axonal disconnection and Wallerian degeneration, respectively. However, traumatic axonal injury is difficult to define clinically, it should be considered in patients with Glasgow coma score < 8 for more than six hours after trauma and diffuse tensor imaging and sensitivity-weighted imaging MRI sequences are highly sensitive in its diagnosis. Glasgow coma score at the time of presentation, location and severity of axonal damage are prognostic factors for clinical outcome.

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Traumatic axonal injury on clinical MRI: association with the Glasgow Coma Scale score at scene of injury or at admission and prolonged posttraumatic amnesia

Journal of Neurosurgery ◽

10.3171/2020.6.jns20112 ◽

2020 ◽

pp. 1-12

Author(s):

Hans Kristian Moe ◽

Turid Follestad ◽

Nada Andelic ◽

Asta Kristine Håberg ◽

Anne-Mari Holte Flusund ◽

...

Keyword(s):

Glasgow Coma Scale ◽

Predictive Value ◽

Alcohol Intoxication ◽

Axonal Injury ◽

Traumatic Axonal Injury ◽

Coma Scale ◽

Lesion Location ◽

Posttraumatic Amnesia ◽

Severe Tbi ◽

Gcs Score

OBJECTIVEThe aim in this study was to investigate if MRI findings of traumatic axonal injury (TAI) after traumatic brain injury (TBI) are related to the admission Glasgow Coma Scale (GCS) score and prolonged duration of posttraumatic amnesia (PTA).METHODSA total of 490 patients with mild to severe TBI underwent brain MRI within 6 weeks of injury (mild TBI: median 2 days; moderate to severe TBI: median 8 days). The location of TAI lesions and measures of total TAI lesion burden (number and volume of lesions on FLAIR and diffusion-weighted imaging and number of lesions on T2*-weighted gradient echo or susceptibility-weighted imaging) were quantified in a blinded manner for clinical information. The volume of contusions on FLAIR was likewise recorded. Associations between GCS score and the location and burden of TAI lesions were examined with multiple linear regression, adjusted for age, Marshall CT score (which includes compression of basal cisterns, midline shift, and mass lesions), and alcohol intoxication. The predictive value of TAI lesion location and burden for duration of PTA > 28 days was analyzed with multiple logistic regression, adjusted for age and Marshall CT score. Complete-case analyses of patients with TAI were used for the regression analyses of GCS scores (n = 268) and PTA (n = 252).RESULTSTAI lesions were observed in 58% of patients: in 7% of mild, 69% of moderate, and 93% of severe TBI cases. The TAI lesion location associated with the lowest GCS scores were bilateral lesions in the brainstem (mean difference in GCS score −2.5), followed by lesions bilaterally in the thalamus, unilaterally in the brainstem, and lesions in the splenium. The volume of TAI on FLAIR was the measure of total lesion burden most strongly associated with the GCS score. Bilateral TAI lesions in the thalamus had the largest predictive value for PTA > 28 days (OR 16.2, 95% CI 3.9–87.4). Of the measures of total TAI lesion burden, the FLAIR volume of TAI predicted PTA > 28 days the best.CONCLUSIONSBilateral TAI lesions in the brainstem and thalamus, as well as the total volume of TAI lesions on FLAIR, had the strongest association with the GCS score and prolonged PTA. The current study proposes a first step toward a modified classification of TAI, with grades ranked according to their relation to these two measures of clinical TBI severity.

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