Traumatic axonal injury has been associated with concussions (also referred to as mild traumatic brain injury), yet the pathological course that leads from injury to recovery or to long-term sequelae is still not known.
It occurs in about half of all cases of severe traumatic brain injury, making it one of the most common traumatic brain injuries. It can also occur in moderate and mild brain injury.
Diffuse axonal injury isn’t the result of a blow to the head. Instead, it results from the brain moving back and forth in the skull as a result of acceleration or deceleration. Automobile accidents, sports-related accidents, violence, falls, and child abuse such as Shaken Baby Syndrome are common causes of diffuse axonal injury. When acceleration or deceleration causes the brain to move within the skull, axons, the parts of the nerve cells that allow neurons to send messages between them, are disrupted. As tissue slides over tissue, a shearing injury occurs. This causes the lesions that are responsible for unconsciousness, as well as the vegetative state that occurs after a severe head injury.
A diffuse axonal injury also causes brain cells to die, which cause swelling in the brain. This increased pressure in the brain can cause decreased blood flow to the brain, as well as additional injury. The shearing can also release chemicals which can contribute to additional brain injury.
The main symptom of diffuse axonal injury is lack of consciousness, which can last up to six hours or more. A person with a mild or moderate diffuse axonal injury who is conscious may also show other signs of brain damage, depending upon which area of the brain is most affected.
Magnetic Resonance Imaging (MRI) - This test is the preferred test for diagnosing diffuse axonal injury.
CT Scan - may result in false negatives, so can’t be relied on to give definitive results when it comes to diffuse axonal injury.
The classification was first proposed by Adams in 1989 5) and divides diffuse axonal injury (DAI) into three grades:
grade I : involves grey-white matter interfaces most commonly : parasagittal regions of frontal lobes, periventricular temporal lobes less commonly : parietal and occipital lobes, internal and external capsules, and cerebellum often inapparent on conventional imaging may have changes on MRS 3
grade II : involves corpus callosum in addition to stage I locations observed in approximately 20% of patients most commonly : posterior body and splenium but does advance anteriorly with increasing severity of injury most frequently unilateral may be seen on SWI 3
grade III : involves brainstem in addition to stage I and II locations most commonly : rostral midbrain, superior cerebellar peduncles, medial lemnisci and corticospinal tracts.
DTI with 3-D fiber tractography can visualize acute axonal shearing injury, which may have prognostic value for the cognitive and neurological sequelae of traumatic brain injury 6).
Twenty-four patients from Sao Paulo Brazil.with moderate or severe DAI were evaluated at 2, 6 and 12 months post-injury. Microhaemorrhage load (MHL) was evaluated at 3 months, and brain volumetry was evaluated at 3, 6 and 12 months. The trail making test (TMT) was used to evaluate executive function (EF), and the Hopkins verbal learning test (HVLT) was used to evaluate verbal episodic memory (EVM) at 6 and 12 months.
There were significant white matter volume (WMV), subcortical grey matter volume and total brain volume (TBV) reductions during the study period (p < 0.05). MHL was correlated only with WMV reduction. EF and EVM were not correlated with MHL but were, in part, correlated with WMV and TBV reductions.
The findings suggest that MHL may be a predictor of WMV reduction but cannot predict EF or EVM in DAI. Brain atrophy progresses over time, but patients showed better EF and EVM in some of the tests, which could be due to neuroplasticity 7).
Cicuendez et al. retrospectively analyzed 264 Traumatic brain injury (TBI) patients to whom a MR had been performed in the first 60 days after trauma. All clinical variables related to prognosis were registered, as well as the data from the initial computed tomography. The MR imaging protocol consisted of a 3-plane localizer sequence T1-weighted and T2-weighted fast spin-echo, FLAIR and gradient-echo images (GRET2*). Traumatic axonal injury (TAI) lesions were classified according to Gentry and Firsching classifications. They calculated weighted kappa coefficients and the area under the ROC curve for each MR sequence. A multivariable analyses was performed to correlate MR findings in each sequence with the final outcome of the patients.
TAI lesions were adequately visualized on T2, FLAIR and GRET2* sequences in more than 80% of the studies. Subcortical TAI lesions were well on FLAIR and GRET2* sequences visualized hemorrhagic TAI lesions. We saw that these MR sequences had a high inter-rater agreement for TAI diagnosis (0.8). T2 sequence presented the highest value on ROC curve in Gentry (0.68, 95%CI: 0.61-0.76, p<0.001, Nagerlkerke-R2 0.26) and Firsching classifications (0.64, 95%CI 0.57-0.72, p<0.001, Nagerlkerke-R2 0.19), followed by FLAIR and GRET2* sequences. Both classifications determined by each of these sequences were associated with poor outcome after performing a multivariable analyses adjusted for prognostic factors (p<0.02).
They recommend to perform conventional MR study in subacute phase including T2, FLAIR and GRET2* sequences for visualize TAI lesions. These MR findings added prognostic information in TBI patients 8).
Cell therapy in neurological disability after traumatic brain injury (TBI) is in its initial clinical stage.
Vaquero et al., describe the preliminary clinical experience with three patients with diffuse axonal injury (DAI) who were treated with intrathecal administration of autologous mesenchymal stem cells (MSCs).
Three patients with established neurological sequelae due to DAI received intrathecally autologous MSCs. The total number of MSCs administered was 60 × 106 (one patient), 100 × 106 (one patient) and 300 × 106 (one patient).
All three patients showed improvement after cell therapy, and subsequent studies with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) showed a diffuse and progressive increase in brain glucose metabolism.
The present results suggest benefit of intrathecal administration of MSCs in patients with DAI, as well as a relationship between this type of treatment and increase in brain glucose metabolism. These preliminary findings raise the question of convenience of assessing the potential benefit of intrathecal administration of MSCs for brain diseases in which a decrease in glucose metabolism represents a crucial pathophysiological finding, such as Alzheimer's disease (AD) and other dementias 9).
Data were collected retrospectively from a prospectively created database registry in the section of Trauma Surgery at Hamad General Hospital between January 2008 and July 2012. All patients presented with head trauma and TSAH were included. Patient data included age, gender, nationality, mechanism of injury, injury severity score (ISS), types of head injuries, and associated injuries. Ventilator days, intensive care unit length of stay, pneumonia, and mortality were also studied.
A total of 1665 patients with TBI were identified, of them 403 had TSAH with a mean age of 35 ± 15 years. Of them 93% were male patients and 86% were expatriates. MVC (53%) and FFH (35%) were the major mechanisms of injury. The overall mean ISS and head abbreviated injury score were 19 ± 10.6 and 3.4 ± 0.96, respectively. Patients in MVC group sustained severe TSAH, had significantly greater head abbreviated injury score (3.5 ± 0.9 vs. 3.2 ± 0.9; P = 0.009) and ISS (21.6 ± 10.6 vs. 15.9 ± 9.5; P = 0.001), and lower scene Glasgow coma scale (10.8 ± 4.8 vs. 13.2 ± 3.4; P = 0.001) compared with the FFH group. In addition, the MVC group sustained more intraventricular hemorrhage (4.7 vs. 0.7; P = 0.001) and diffuse axonal injury (4.2 vs. 2.9; P = 0.001). In contrast, extradural hemorrhage (14.3% vs. 11.6%; P = 0.008) was higher in the FFH group. Lower extremities (14% vs. 4.3%; P = 0.004) injury was mainly associated with the MVC group. The overall mortality was 19 % among patients with TSAH. The mortality rate was higher in the MVC group when compared with the FFH group (24% vs. 10%; P = 0.001). In both groups, ISS and Glasgow coma scale at the scene were independent predictors of mortality.
Patients with TSAH have a higher mortality rate. In this population, MVCs are associated with a 3-fold increased risk of mortality. Therefore, prevention of MVC and fall can reduce the incidence and severity of TBI in Qatar 10).
A retrospective study over a 4-year period (2004-2007) of 124 patients admitted for head trauma. Demographic, clinical, biological, and radiologic findings were recorded at admission and during intensive care unit stay.
Mean age (±standard deviation) was 28 years±15.8 years. Cranial computed tomography scan was sufficient enough to diagnose DAI in 31 patients. Magnetic resonance imaging was performed in 105 patients with a delay of 7.7 days±8.6 days. Most patients were classified as stage II (49.5%) or stage III (44.8%) according to Gentry's classification. In a multivariate analysis, factors associated with higher mortality were dysautonomia (p=0.018; odds ratio [OR]=4.17), hyperglycemia≥8 mmol/L (p=0.001; OR=3.84) on intensive care unit admission, and subdural hematoma (p=0.031; OR=3.99), whereas factors associated to poor outcome according to Glasgow Outcome Scale score were Glasgow Coma Scale score<8 (p=0.032, OR=3.55), secondary systemic injuries score≥3 (p=0.034, OR=2.83), hyperglycemia≥8 mmol/L (p=0.002, OR=5.55), and DAI count≥6 (p=0.035, OR=3.33). In patients with pure DAI, the absence of consciousness recovery was the unique independent factor of mortality (p<0.001, OR=116.4), whereas only transfusion need was an independent factor of poor outcome (p=0.017, OR=4.44).
Dysautonomia, hyperglycemia, and subdural hematoma are the main factors associated to higher mortality when DAIs are diagnosed, whereas a DAI count≥6 is associated to poor outcome. Magnetic resonance imaging classification did not have a prognosis value even in patients with pure DAI 11).