Traumatic axonal injury: is the prognostic information produced by conventional MRI and DTI complementary or supplementary?

OBJECTIVE: A traumatic axonal injury (TAI) diagnosis has traditionally been based on conventional MRI, especially on those sequences with a higher sensitivity to edema and blood degradation products. A more recent technique, diffusion tensor imaging (DTI), can infer the microstructure of white matter (WM) due to the restricted diffusion of water in organized tissues. However, there is little information regarding the correlation of the findings obtained by both methods and their use for outcome prognosis. The main objectives of this study were threefold: 1) study the correlation between DTI metrics and conventional MRI findings; 2) evaluate whether the prognostic information provided by the two techniques is supplementary or complementary; and 3) determine the incremental value of the addition of these variables compared to a traditional prognostic model. METHODS: The authors studied 185 patients with moderate to severe traumatic brain injury (TBI) who underwent MRI with DTI study during the subacute stage. The number and volume of lesions in hemispheric subcortical WM, corpus callosum (CC), basal ganglia, thalamus, and brainstem in at least four conventional MRI sequences (T1-weighted, T2-weighted, FLAIR, T2* gradient recalled echo, susceptibility-weighted imaging, and diffusion-weighted imaging) were determined. Fractional anisotropy (FA) was measured in 28 WM bundles using the region of interest method. Nonparametric tests were used to evaluate the colocalization of macroscopic lesions and FA. A multivariate logistic regression analysis was performed to assess the independent prognostic value of each neuroimaging modality after adjustment for relevant clinical covariates, and the internal validation of the model was evaluated in a contemporary cohort of 92 patients. RESULTS: Differences in the lesion load between patients according to their severity and outcome were found. Colocalization of macroscopic nonhemorrhagic TAI lesions (not microbleeds) and lower FA was limited to the internal and external capsule, corona radiata, inferior frontooccipital fasciculus, CC, and brainstem. However, a significant association between the FA value and the identification of macroscopic lesions in distant brain regions was also detected. Specifically, lower values of FA of some hemispheric WM bundles and the splenium of the CC were related to a higher number and volume of hyperintensities in the brainstem. The regression analysis revealed that age, motor score, hypoxia, FA of the genu of the CC, characterization of TAI lesions in the CC, and the presence of thalamic/basal ganglia lesions were independent prognostic factors. The performance of the proposed model was higher than that of the IMPACT (International Mission on Prognosis and Analysis of Clinical Trials in TBI) model in the validation cohort. CONCLUSIONS: Very limited colocalization of hyperintensities (none for microbleeds) with FA values was discovered. DTI and conventional MRI provide complementary prognostic information, and their combination can improve the performance of traditional prognostic models.

Diffuse axonal injury (DAI) in moderate to severe head injured patients: Pure DAI vs. non-pure DAI.

OBJECTIVE: Diffuse axonal injury (DAI) is known to be associated with poor outcome. DAI often associates with other intracranial injuries but their distinct features have not been established. In this retrospective cohort study, we compared clinical outcomes between pure and non-pure DAI patients. PATIENTS AND METHODS: Total of 1047 traumatic brain injury (TBI) patients visited our institute between 2011 and 2017. Age ranged between 15-85 years old and Glasgow coma scale (GCS) score less than 13 were included. DAI was diagnosed in 45 patients using CT and MRI and their clinical features and outcomes were compared depending on their associated cranial injury; 20 patients without evidence of associated injury (Pure DAI group) and other 25 patients with associated injury (Non-pure DAI group). DAI stage was adopted using Gentry, L.R. CLASSIFICATION: Glasgow outcome scale (GOS) was measured at least 6 months after trauma to evaluate their functional outcome. RESULTS: The mean age and follow-up period were 45.36 years and 15.09 months, respectively. There were no significant differences between pure and non-pure DAI groups regarding demographic data and clinical findings on their admission. Logistic regression model was used to examine the association between GOS and clinical factors. In this analysis, pure DAI was no significantly different to non-pure DAI (p = 0.607). However, DAI Stage, transfusion, and hypotension on admission were strongly related to poor outcome. Stage III showed sevenfold higher risk when compared to Stage I (p = 0.010). The risk was also high when Stage III was compare to Stage I and II (p = 0.002). Interestingly, no significant difference was observed between Stage I and II (p = 0.847). CONCLUSIONS: Unfavorable outcome was observed in 14 patients (31.11%) which was lower than we expected. Interestingly, non-pure DAI was no worse than pure DAI on their functional outcome. However, DAI Stage III was independently associated with poor outcome when compared to Stage I or I and II. Finally, we concluded that Stage II is clinically more related to Stage I, rather than Stage III.

Dyskalaemia following diffuse axonal injury: case report and review of the literature.

Traumatic brain injury, and its management, commonly causes derangements in potassium balance. There are a number of recognised causative factors including head trauma, hypothermia and iatrogenic factors such as pharmacological agents and permissive cooling. We describe a case of a 19-year-old man with a severe traumatic brain injury. In a 36-h period, his intracranial pressure increased despite maximal medical therapy and he developed refractory hypokalaemia. Immediately following a decompressive craniectomy, the patient was noted to be profoundly hyperkalaemic; this led to the development of ventricular tachycardia and cardiac arrest, from which the patient did not recover. The effects of brain injury on potassium balance are not well appreciated; the effect of decompressive craniectomy on potassium (K(+)) balance has not been described previously. We would like to emphasise the potential effect of diffuse axonal injury, a severe form of brain injury and decompressive craniectomy on potassium balance.

Traumatic brain injury: review of current management strategies.

Head injury is a common condition with a high morbidity and mortality. Serious intracranial haematomas require early recognition and evacuation to maximise chances of independent outcomes. Recent organisational changes have promoted the development of trauma units and major trauma centres where patients can go through triage and be managed in an appropriate environment, and the development of management pathways in intensive treatment units has resulted in improvements in the outcome of traumatic brain injuries. Evidence for the treatment of cerebral perfusion pressure, and management of hyperventilation, osmotherapy, tracheostomy, and leakage of cerebrospinal fluid (CSF) has accumulated during the last decade and is important in the management of patients in all clinical settings. Since head injury is commonly associated with maxillofacial injuries, this review will be relevant to all who deal with this aspect of trauma.

Transplanted bone marrow stromal cells improves cognitive dysfunction due to diffuse axonal injury in rats.

Diffuse axonal injury (DAI) often leads to persistent cognitive dysfunction in spite of the lack of gross lesions on MRI. Therefore, this study was aimed to evaluate whether transplanted bone marrow stromal cells (BMSC) can improve DAI-induced cognitive dysfunction or not. The rats were subjected to impact acceleration head injury, using a pneumatic high-velocity impactor. The BMSC were harvested from the mice and were cultured. The BMSC (4.0 x 10(5) cells) or vehicle were stereotactically transplanted into the right striatum at 10 days post-injury. Cognitive function analysis was repeated at 1, 2, and 4 weeks post-injury, using the Morris water maze test. Histological analysis was performed at 2, 8 and 20 weeks post-injury, using double fluorescence immunohistochemistry. Transplanted BMSC were widely distributed in the injured brain and gradually acquired the phenotypes of neurons and astrocytes over 20 weeks. In addition, they significantly improved DAI-induced cognitive dysfunction as early as 2 weeks post-injury, although their processes of neuronal differentiation were not completed at this time point. The findings suggest that the engrafted BMSC may exhibit this early beneficial effect on cognitive function by producing neuroprotective or neurotrophic factors. In conclusion, direct transplantation of BMSC may serve as a novel therapeutic strategy to enhance the recovery from DAI-induced cognitive impairment.

Value of repeat cranial computed tomography in pediatric patients sustaining moderate to severe traumatic brain injury.

BACKGROUND: Repeat head computed tomography (CT) is standard practice for traumatic brain injury (TBI) at many centers. The few studies available in children remain unclear over the value of repeat CT within 24 hours to 48 hours of lesion in such patients. The purpose of the present study was to assess the value of repeat cranial CT in children presenting moderate or severe TBI. METHODS: A retrospective study performed within a pediatric intensive care unit between January 2000 and December 2006. All patients with moderate and severe TBI who survived the first 24 hours after admission were included. Clinical data collected included age, lesion mechanism, time between first and second CTs, disease severity score at admission, and Glasgow Coma Scale (GCS) both at admission and day of repeat CT. RESULTS: A total of 63 children were assessed whose mean age was 72 months (48-112). The time between the first and the second CT scans averaged 25.78 hours +/- 13.75 hours (range, 6-48 hours). The reasons for ordering repeat CT scans were divided as follows: follow-up (78%), neurologic deterioration (20.4%), and increased intracranial pressure (1.6%). The change on the follow-up CT scan was compared with the GCS score. The GCS score was improved in 66.6% of patients, remained the same in 15.9%, and worsened in 17.5%. The appearance on the CT scans was better, the same or worse in 41.3%, 34.9%, and 23.8% of patients, respectively. There was a significant association between GCS and changes in findings on repeat CT (OR = 34.5, confidence interval [5.98-199.04], p = 0.000009). The positive and negative predictive values were 82% and 89%, respectively. One patient with a worsened GCS required surgical intervention based on the repeat CT scan. CONCLUSION: An unchanged or improving neurologic examination in children sustaining moderate or severe TBI who are appropriately monitored may be adequate to exclude the possibility of neurosurgical intervention and, hence, repeat head CT scan.

Hyper flow and intracranial hypertension in diffuse axonal injury: an update to gennarelli doctrine.

Twelve consecutive paediatric (six) and adult (six) patients harbouring a neuroradiological pattern consistent with diffuse axonal injury (DAI) along with slit ventricles underwent haemodynamic study in the Intensive Care Unit of our University. All the patients had GCS scores less than 8 after a severe brain injury. serial head computed tomography (CT) and magnetic resonance (MR) scans demonstrated a radiological pattern of DAI. Transcranial Doppler Sonography (TCD) of the middle cerebral arteries was performed through the temporal bone window in all the patients. All patients but one underwent a continuous monitoring of intracranial pressure (ICP) and cerebral extraction of 02 (CEO2). Therapy with barbiturates and hyperventilation was necessary in all the cases. In two patients (one adult and one paediatric) a bilateral decompressive craniectomy was performed in order to decrease a severe intracranial hypertension. Hyperflow along with intracranial hypertension, variably responsive to barbiturate therapy, was observed in all the patients by means of TCD and CEO2. In our patients intracranial hypertension along with hyperflow syndrome were found associated with DAI. Medical as well as surgical treatments were tailored according to the haemodynamic study.

Early predictors of unfavourable outcome in subjects with moderate head injury in the emergency department.

BACKGROUND: Subjects with moderate head injury are a particular challenge for the emergency physician. They represent a heterogeneous population of subjects with large variability in injury severity, clinical course and outcome. We aimed to determine the early predictors of outcome of subjects with moderate head injury admitted to an Emergency Department (ED) of a general hospital linked via telemedicine to the Regional Neurosurgical Centre. PATIENTS AND METHODS: We reviewed, prospectively, 12,675 subjects attending the ED of a General Hospital between 1999 and 2005 for head injury. A total of 309 cases (2.4%) with an admission Glasgow Coma Scale (GCS) 9-13 were identified as having moderate head injury. The main outcome measure was an unfavourable outcome at 6 months after injury. The predictive value of a model based on main entry variables was evaluated by logistic regression analysis. FINDINGS: 64.7% of subjects had a computed tomographic scan that was positive for intracranial injury, 16.5% needed a neurosurgical intervention, 14.6% had an unfavourable outcome at 6 months (death, permanent vegetative state, permanent severe disability). Six variables (basal skull fracture, subarachnoid haemorrhage, coagulopathy, subdural haematoma, modified Marshall category and GCS) predicted an unfavourable outcome at 6 months. This combination of variables predicts the 6-month outcome with high sensitivity (95.6%) and specificity (86.0%). INTERPRETATION: A group of selected variables proves highly accurate in the prediction of unfavourable outcome at 6 months, when applied to subjects admitted to an ED of a General Hospital with moderate head injury.

True hemicranial decompression for severe pediatric cranial trauma: a short series of 4 cases and literature review.

BACKGROUND: Traumatic acute SDH in pediatric patients is a life-threatening situation. There is a severe increase in ICP caused by acute SDH or diffuse brain swelling or secondary to ischemic brain damage. In certain situations, conventional measures may fail to control such a rapid increase in ICP. CASE DESCRIPTION: The cases of 4 pediatric patients with cranial trauma with raised ICP, in whom hemicranial decompression was performed, are described. All patients had acute SDH with diffuse brain injury; in addition, 2 of them had associated massive infarcts. Three of them survived and had a favorable outcome. CONCLUSIONS: In certain situations, pediatric patients with cranial trauma may be offered hemicranial decompression as a surgical option. These children may have a better long-term outcome despite massive infarcts.

Traumatic brain injury and subarachnoid hemorrhage: in vivo occult pathology demonstrated by magnetic resonance spectroscopy may not be "ischaemic". A primary study and review of the literature.

OBJECTIVES: To look for evidence of early ischaemic neurochemical changes in patients suffering severe traumatic brain injury (TBI) and severe subarachnoid haemorrhage (SAH). Proton metabolite concentrations were measured in normal and abnormal areas of brain on T2 MR imaging, in regions considered particularly vulnerable to ischaemic injury. METHODS: Intensive care patients underwent T2 weighted imaging in a 1.5 Tesla MR scanner and proton magnetic resonance spectroscopy (single voxel or chemical shift imaging). Metabolite values in areas that appeared 'normal' and 'abnormal' on T2 MR imaging were compared with those obtained from normal controls. RESULTS: 18 TBI and 6 SAH patients were imaged at 1 to 26 days. N-acetyl aspartate (NAA) was lower in TBI and SAH patients compared to controls in both T2 normal and T2 abnormal areas (p<0.0005). SAH, but not TBI patients also had increased choline and creatine compared to controls in the T2 normal (p<0.02, p<0.02 respectively) and T2 abnormal (p=0.0003, p=0.003) areas. No lactate was found in TBI or SAH patients. CONCLUSIONS: Significant loss of normal functioning neurones was present in TBI and SAH, but no evidence of anaerobic metabolism using lactate as a surrogate marker, questioning the role of 'ischemia' as a major mechanism of damage. Increased choline and creatine were found in SAH patients suggestive of increased cell-wall turnover. Current theories of brain injury after TBI or SAH do not explain these observed neurochemical changes and further research is required.

Diffuse axonal injury with or without an evacuated intracranial hematoma in head injured patients. Are they different lesions?

The general classification of head injury proposed by Marshall et al., based on admission CT scan findings, might mask a group of patients who have Diffuse Brain Injury (DI) in addition to intracranial haematomas. The aim of this study was to assess possible differences in outcome with respect to the level of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) between a group of patients with DI: III-IV (Marshall's classification) after the evacuation of an intracranial haematoma (group A) and another group with DI: III-IV in the absence of a mass lesion (group B). We prospectively studied 129 patients with isolated and closed severe head injury (GCS < 9). In group A (n = 61), the median percentage of hours with ICP > 20 mmHg and CPP < 70 mmHg was 42.8 and 18, respectively and 17 (28%) survived with GOS 4-5. In group B (n = 68), median values of 20 and 5.5 hours were obtained for ICP > 20 and CPP < 70 respectively, whilst 39 (57.3%) survived with favourable outcomes. When we analysed the effects of the DI: III-IV in both groups of patients, we found that the differences in percentage of time with ICP > 20 and CPP < 70 were statistically significant (p < 0.01) and patients in group A had a higher morbidity and mortality (p < 0.05). This study has demonstrated that the levels of ICP, morbidity and mortality in patients with DI: III-IV and an evacuated mass lesion were higher than in patients with DI: III-IV without a mass lesion.