Prognostic role of proton magnetic resonance spectroscopy in acute traumatic brain injury

Proton magnetic resonance spectroscopy (MRS) is being used to evaluate individuals after acute traumatic brain injury. These studies have shown that changes in certain brain metabolites are associated with poor neurologic outcomes. The majority of MRS studies have been obtained relatively late after injury, but there have been a few reports of use early after injury to assist with outcome prediction. Altered brain metabolites may be sensitive indicators of injury and thus provide additional prognostic information when spectroscopy is done early after injury. This technology may provide a noninvasive means to evaluate early excitotoxic injury, and show changes associated with both neuronal injury and membrane disruption secondary to diffuse axonal injury. This article will review the technology of MRS, discuss its role in patient assessment after traumatic brain injury, and present a summary of our published and ongoing research.     

A longitudinal proton magnetic resonance spectroscopy study of mild traumatic brain injury

Despite the prevalence and impact of mild traumatic brain injury (mTBI), common clinical assessment methods for mTBI have insufficient sensitivity and specificity. Moreover, few researchers have attempted to document underlying changes in physiology as a function of recovery from mTBI. Proton magnetic resonance spectroscopy (1H-MRS) was used to assess neurometabolite concentrations in a supraventricular tissue slab in 30 individuals with semi-acute mTBI, and 30 sex-, age-, and education-matched controls. No significant group differences were evident on traditional measures of attention, memory, working memory, processing speed, and executive skills, though the mTBI group reported significantly more somatic, cognitive, and emotional symptoms. At a mean of 13 days post-injury, white matter concentrations of creatine (Cre) and phosphocreatine (PCre) and the combined glutamate-glutamine signal (Glx) were elevated in the mTBI group, while gray matter concentrations of Glx were reduced. Partial normalization of these three neurometabolites and N-acetyl aspartate occurred in the early days post-injury, during the semi-acute period of recovery. In addition, 17 mTBI patients (57%) returned for a follow-up evaluation (mean?=?120 days post-injury). A significant group?×?time interaction indicated recovery in the mTBI group for gray matter Glx, and trends toward recovery in white matter Cre and Glx. An estimate of premorbid intelligence predicted the magnitude of neurometabolite normalization over the follow-up interval for the mTBI group, indicating that biological factors underlying intelligence may also be associated with more rapid recovery.     

Proton MR spectroscopy detected glutamate/glutamine is increased in children with traumatic brain injury

Adults with traumatic brain injury (TBI) have been shown by invasive methods to have increased levels of the excitatory neurotransmitter glutamate. It is unclear whether glutamate release contributes to primary or secondary injury and whether its protracted elevation is predictive of a poor outcome. Preliminary studies at our institution in adults found that early increases in magnetic resonance spectroscopy (MRS)-detected glutamate/glutamine (Glx) were associated with poor outcomes. We therefore studied 38 children (mean age, 11 years; range, 1.6-17 years) who had TBI with quantitative short-echo time (STEAM, TE = 20 msec) proton MRS, a mean of 7 +/- 4 (range, 1-17) days after injury in order to determine if their occipital or parietal Glx levels correlated with the severity of injury or outcome. Occipital Glx was significantly increased in children with TBI compared to controls (13.5 +/- 2.4 vs. 10.7 +/- 1.8; p = 0.002), but there was no difference between children with good compared to poor outcomes as determined by the Pediatric Cerebral Performance Category Scale score at 6-12 months after injury. We also did not find a correlation between the amount of Glx and the initial Glasgow Coma Scale score, duration of coma, nor with changes in spectral metabolites, including N-acetyl aspartate, choline, and myoinositol. In part, this may have occurred because, in this study, most patients with poor outcomes were studied later than patients with good outcomes, potentially beyond the time frame for peak elevation of Glx after injury. Additional early and late studies of patients with varying degrees of injury are required to assess the importance to the pathophysiology of TBI of this excitatory neurotransmitter.     

Late proton magnetic resonance spectroscopy following traumatic brain injury during early childhood: relationship with neurobehavioral outcomes

We sought to extend previous research that demonstrates reduced neurometabolite concentrations during the chronic phase of pediatric traumatic brain injury (TBI) in children injured during early childhood. We hypothesized that young children with TBI in the chronic phase post-injury would have lower N-acetyl aspartate (NAA) metabolite concentrations in gray and white matter in comparison to controls. We also hypothesized that metabolite levels would be correlated with acute TBI severity and neurobehavioral skills. Ten children with a history of TBI between the ages of 3 and 6 years were compared to an age, gender, and race-matched group of 10 children with a history of an orthopedic injury (OI). Children completed neurobehavioral testing at 12 months post-injury. Proton magnetic resonance (MR) spectroscopy was completed at least 12 months post-injury when the children were 6-9 years old. Groups were compared on metabolite concentrations in the medial frontal gray matter and left frontal white matter. Metabolite levels were correlated with Glasgow Coma Scale (GCS) scores and neurobehavioral functioning. There was a trend for lower NAA concentrations in the medial frontal gray matter for the TBI group. Late NAA and Cr levels in the medial frontal gray matter and NAA levels in the left frontal white matter were strongly positively correlated with initial GCS score. Metabolite levels were correlated with some neurobehavioral measures differentially for children with TBI or OI. Some neurometabolite levels differed between the TBI and OI groups more than 1 year post-injury and were related to injury severity, as well as some neurobehavioral outcomes following TBI during early childhood.     

Assessment of mitochondrial impairment in traumatic brain injury using high-resolution proton magnetic resonance spectroscopy

OBJECTIVES: The goal of this study was to demonstrate the posttraumatic neurochemical damage in normal-appearing brain and to assess mitochondrial dysfunction by measuring N-acetylaspartate (NAA) levels in patients with severe head injuries, using proton (1H) magnetic resonance (MR) spectroscopy. METHODS: Semiquantitative analysis of NAA relative to creatine-containing compounds (Cr) and choline (Cho) was carried out from proton spectra obtained by means of chemical shift (CS) imaging and single-voxel (SV) methods in 25 patients with severe traumatic brain injuries (TBIs) (Glasgow Coma Scale scores < or = 8) using a 1.5-tesla MR unit. Proton MR spectroscopy was also performed in 5 healthy volunteers (controls). RESULTS: The SV studies in patients with diffuse TBI showed partial reduction of NAA/Cho and NAA/Cr ratios within the first 10 days after injury (means +/- standard deviations 1.59 +/- 0.46 and 1.44 +/- 0.21, respectively, in the patients compared with 2.08 +/- 0.26 and 2.04 +/- 0.31, respectively, in the controls; nonsignificant difference). The ratios gradually declined in all patients as time from injury increased (mean minimum values NAA/Cho 1.05 +/- 0.44 and NAA/Cr 1.05 +/- 0.30, p < 0.03 and p < 0.02, respectively). This reduction was greater in patients with less favorable outcomes. In patients with focal injuries, the periphery of the lesions revealed identical trends of NAA/Cho and NAA/Cr decrease. These reductions correlated with outcome at 6 months (p < 0.01). Assessment with multivoxel methods (CS imaging) demonstrated that, in diffuse injury, NAA levels declined uniformly throughout the brain. At 40 days postinjury, initially low NAA/Cho levels had recovered to near baseline in patients who had good outcomes, whereas no recovery was evident in patients with poor outcomes (p < 0.01). CONCLUSIONS: Using (1)H-MR spectroscopy, it is possible to detect the posttraumatic neurochemical damage of the injured brain when conventional neuroimaging techniques reveal no abnormality. Reduction of NAA levels is a dynamic process, evolving over time, decreasing and remaining low throughout the involved tissue in patients with poor outcomes. Recovery of NAA levels in patients with favorable outcomes suggests marginal mitochondrial impairment and possible resynthesis from vital neurons.     

Magnetic resonance spectroscopy in traumatic brain injury

Magnetic resonance spectroscopy (MRS) offers a unique non-invasive approach for assessing the metabolic status of the brain in vivo and is particularly suited to studying traumatic brain injury (TBI). In particular, MRS provides a noninvasive means for quantifying such neurochemicals as N-acetylaspartate (NAA), creatine, phosphocreatine, choline, lactate, myo-inositol, glutamine, glutamate, adenosine triphosphate (ATP), and inorganic phosphate in humans following TBI and in animal models. Many of these chemicals have been shown to be perturbed following TBI. NAA, a marker of neuronal integrity, has been shown to be reduced following TBI, reflecting diffuse axonal injury or metabolic depression, and concentrations of NAA predict cognitive outcome. Elevation of choline-containing compounds indicates membrane breakdown or inflammation or both. MRS can also detect alterations in high energy phosphates reflecting the energetic abnormalities seen after TBI. Accordingly, MRS may be useful to monitor cellular response to therapeutic interventions in TBI.     

Assessment of metabolic cerebral damage using proton magnetic resonance spectroscopy in mild traumatic brain injury

AIM: We want to appraise, through proton magnetic resonance spectroscopy (H1-MRI), the NAA's values and it's changing in cerebral tissue in consequence of cranial trauma. METHODS: Six patients with TBI undergo to H1-MRI to asses the changes occurring briefly after trauma in the spectrum's composition. RESULTS: As far as the first two cases we founded a lowering of the NAA's values. In the other four cases the NAA values were normal in all but one, which slightly brought the values of the NAA/Cr and NAA/Cho lower in comparison to the standard values. CONCLUSIONS: Existing a correlation between NAA and ATP it can be drawn that the reduction of NAA is correlated to energetic type damage. Despite the smallness of data, it remains really important that we should have a tool to monitor the cerebral metabolic picture after a mild trauma.     

Visual electrodiagnostic findings in mild traumatic brain injury

Patients with traumatic brain injury TBI frequently exhibit varied forms of visual system dysfunction including: binocular, oculomotor, accommodative, refractive error shift, visual field loss, and visual perceptual deficits. A 5-year collaborative study between optometry and ophthalmology was initiated to follow documented mild TBI patients utilizing diagnostic methods to assess the quantity and quality of visual system deficits and recovery. A group of patients with mild TBI receiving optometric rehabilitation were compared with a group of age-matched, gender-matched, and headsize-matched TBI patients not receiving such treatment. Eighteen patients diagnosed with mild TBI underwent a treatment regimen of optometric rehabilitation group I ; 32 patients diagnosed with mild TBI did not receive optometric rehabilitation group II . Pattern visually evoked cortical potential VECP testing and electroretinography ERG evaluation were utilized initially, repeated 6-12 months later and then 12-18 months after baseline. All TBI patients' VECP and ERG results were compared to agematched, headsize-matched controls. Once the ERG had been used to exclude retinal involvement, identification of visual pathway dysfunction was possible with the VECP. Full-field ERG results in all groups were not remarkable and not sensitive for patients with mild TBI. Initial testing results revealed that 72 of those TBI patients in group I demonstrated VECP waveform abnormalities and 81 of those patients in group II showed waveform dysfunction. In the testing performed 12-18 months later, 38 of group I TBI patients, after receiving a treatment regimen of optometric rehabilitation, showed VECP waveform abnormalities; 78 of group II TBI patients demonstrated waveform abnormalities. VECP evaluation in patients with mild TBI can provide a useful and reliable tool for objective assessment of visual system deficit and recovery. Significant differences in visual system recovery were shown when comparing group I and group II.     

Use of the Recognition Memory Test in traumatic brain injury: Preliminary findings

The suitability of Warrington's Recognition Memory Test (RMT) for detecting memory impairment after traumatic brain injury was investigated in a pilot study of 36 patients with moderate and severe brain injuries. The patients showed significant memory deficits on both RMT subtests, Words and Faces, with greater impairment on the Faces subtest. No significant gender differences were found. The left hemisphere lesion group obtained the lowest mean score on the Words subtest, and the right hemisphere lesion group had the lowest mean score on the Faces subtest, although these differences did not reach statistical significance. At the 90-94% specificity level the sensitivity of the Faces and Words subtests for the detection of memory impairment after traumatic brain injury was 81% and 63%, respectively. The RMT appears to be a promising instrument for measuring and describing patterns of memory impairment after brain injury.     

SPECT, MR and quantitative MR imaging: correlates with neuropsychological and psychological outcome in traumatic brain injury

This study examined the relative effectiveness of magnetic resonance (MR) imaging, single photon emission tomography (SPECT) and quantitative magnetic resonance (QMR) imaging in detecting brain abnormalities in 52 traumatically brain injured patients. The relationship between brain abnormalities and neuropsychological and psychological testing results was also investigated. Sixty-two per cent of patients had abnormal clinical MR findings, 57% had abnormal SPECT and 51% had abnormal QMR. Each neuroimaging modality detected brain abnormalities that the other two did not. Neuropsychological and psychological testing indicated significant memory impairments and subjective emotional distress even several years post-injury. Memory and intellectual impairments modestly but significantly correlated with the number of brain abnormalities indicated by all three imaging studies combined, as well as those detected individually by QMR and MR. SPECT abnormalities alone were not correlated with intellectual and memory outcome. Psychological distress was also related to the number of MR abnormalities, with most brain abnormalities being in the frontal areas.     

Psychosexual consequences of traumatic brain injury: methodology and preliminary findings

A methodology to systematically assess the psychosexual consequences of traumatic brain injury was developed and applied to a group of 21 male patients. A majority of the sample reported negative changes in sexual behaviour, including decreased sex drive, erectile function and frequency of intercourse. Common personality changes included depression, reduced self-esteem and a perceived decline in personal sex appeal. However, despite these changes in sexual behaviour, there was evidence that the quality of their marital relationships was preserved. Furthermore, there was no evidence of a relationship between the level of affect and sexual behaviour.     

CT findings in persistent vegetative state following blunt traumatic brain injury

The use of linear measurements in the analysis of CT scans of TBI patients was found to contribute to the understanding of brain damage and were correlated with outcome in severe traumatic close brain injured patients. The purpose of the present study was to analyse the data obtained by the linear measurements on CT studies of TBI patients who remained in persistent vegetative state following blunt head trauma. All 27 patients included in the study were reported to be neurologically normal prior to injury. Thirteen patients, 11 remaining in persistent vegetative state responsive but unaware and two who died, constituted the worst outcome group. Fourteen patients who regained conscious ness, underwent multidisciplinary evaluation when their recovery reached a plateau and were ranked according to severity of residual symptoms and outcome. The degree of correlation with the overall vocational outcome parameter with the various radiological indices was calculated as the Spearman rank correlation coefficient, with correction for tied scores. Fisher's z transformation was used to combine results with those of our previous analysis. Three radiological parameters showed a statistically significant correlation with clinical outcome. These were the right and left septum caudate distance and the cerebroventricular index 2; these showed Spearman rank coefficients of 0.52, 0.45 and 0.48; with two-tailed p-values under 0.01, 0.02 and 0.01 respectively. The width of the third ventricle suggested correlation with the clinical scoring. The findings of the present study point to the impor tance of loss of deep gray matter of the caudate nuclei and widening of the adjacent part of the lateral ventricles in catastrophic brain injury. This finding may highlight the role of localized ischemic changes, in addition to diffuse axonal injury. Values of over 8 mm for the width of the third ventricle and over 11 mm for septum caudate distance are suggestive of catastrophic injury and poor prognosis for recovery.     

Functional outcomes following anoxic brain injury: a comparison with traumatic brain injury

Primary objective: To compare the functional outcomes of patients with anoxic brain injury (ABI) and patients with traumatic brain injury (TBI) following inpatient rehabilitation.

Research design: Retrospective chart review.

Methods and procedures: Data on 68 patients with brain injury (34 with ABI and 34 with TBI) were collected.

Main outcomes and results: The ABI and TBI groups were demographically similar, except that patients with ABI were more likely to be married. Both groups significantly improved their function and were similar upon discharge. For the ABI group, there were trends toward a shorter length of stay, increased total FIM efficiency and decreased cost of stay when compared with the TBI group. The patients with ABI tended to be discharged to a sub-acute rehabilitation facility more than those in the TBI group.

Conclusions: This study is important because it shows that patients with ABI benefit from inpatient rehabilitation and made significant functional gains comparable to the gains of patients with TBI.     

Altered cellular metabolism following traumatic brain injury: a magnetic resonance spectroscopy study

Experimental studies have reported early reductions in pH, phosphocreatine, and free intracellular magnesium following traumatic brain injury using phosphorus magnetic resonance spectroscopy. Paradoxically, in clinical studies there is some evidence for an increase in the pH in the subacute stage following traumatic brain injury. We therefore performed phosphorus magnetic resonance spectroscopy on seven patients in the subacute stage (mean 9 days postinjury) following traumatic brain injury to assess cellular metabolism. In areas of normal-appearing white matter, the pH was significantly alkaline (patients 7.09 +/- 0.04 [mean +/- SD], controls 7.01 +/- 0.04, p = 0.008), the phosphocreatine to inorganic phosphate ratio (PCr/Pi) was significantly increased (patients 4.03 +/- 1.18, controls 2.64 +/- 0.71, p = 0.03), the inorganic phosphate to adenosine triphosphate ratio (Pi/ATP) was significantly reduced (patients 0.37 +/- 0.10, controls 0.56 +/- 0.19, p = 0.04), and the PCr/ATP ratio was nonsignificantly increased (patients 1.53 +/- 0.29, controls 1.34 +/- 0.19, p = 0.14) in patients compared to controls. Furthermore, the calculated free intracellular magnesium was significantly increased in the patients compared to the controls (patients 0.33 +/- 0.09 mM, controls 0.22 +/- 0.09 mM, p = 0.03)). Proton spectra, acquired from similar regions showed a significant reduction in N-acetylaspartate (patients 9.64 +/- 2.49 units, controls 12.84 +/- 2.35 units, p = 0.03) and a significant increase in choline compounds (patients 7.96 +/- 1.02, controls 6.67 +/- 1.01 units, p = 0.03). No lactate was visible in any patient or control spectrum. The alterations in metabolism observed in these patients could not be explained by ongoing ischemia but might be secondary to a loss of normal cellular homeostasis or a relative alteration in the cellular population, in particular an increase in the glial cell density, in these regions.     

Computed tomography findings and early cognitive outcome after traumatic brain injury

Primary objective: To examine the relationship between CT abnormalities and early neuropsychological outcome following traumatic brain injury (TBI) using quantitative CT analyses, data reduction methods for neuropsychological results and specific hypotheses based on literature review.

Research design: Observational, prospective cohort study using acute (emergency) CT data and neuropsychological test data from 89 participants with TBI who were hospitalized for rehabilitation.

Methods and procedures: Principal components analysis with varimax rotation was used to reduce data from a standard battery of eight neuropsychological tests administered after clearance of post-traumatic amnesia (1 month post-TBI on average). Bivariate correlations were used to examine relationships of three factors (verbal memory, cognitive processing speed and verbal working memory) to quantitative volumetric analysis of CT scan abnormalities (size, number and location). Specific hypotheses as to CT predictors of poor performance on each factor were tested using multivariable linear regression that included injury severity and demographic variables.

Main results: Eighty-nine per cent of participants had some pathology on initial CT. Age, education and time to follow commands (TFC), an index of overall injury severity, were significantly associated with the neuropsychological factors. However, none of the specific hypotheses about CT scan variables and cognitive outcome were strongly supported by the data. There was a trend for any CT abnormality to predict slower speed of processing and for higher number of brain lesions to predict worse memory performance.

Conclusions: Despite the precision added by quantitative CT analysis, CT findings did not improve on demographic factors and TFC in predicting early cognitive outcome of TBI. Imaging methods that are more sensitive to white matter integrity may be needed to develop pathophysiologic predictors of TBI outcome.     

Balance disorder and traumatic brain injury: preliminary findings of a multi-factorial observational study

The pathophysiology of TBI suggests that balance disorder in this population may be associated with multi-system dysfunction, but this has not been widely explored in the literature. This study was undertaken to begin to describe the nature of balance disorder across the TBI population. A clinically-based observational design was employed and data gathered by a standardized process of structured observation. Twenty-seven subjects were recruited across a range of injury severities. The sample was skewed towards mild/moderate injury with a mean summated GCS score of 9.6. Deficits were observed across a wide range of domains at both individual and group level and the overall level of balance dysfunction was high. Summary results are reported here and a more detailed analysis of individual cases is underway. Additional cross-disciplinary research is required to further develop understanding of the nature of balance disorder in this population and to develop appropriate methods of clinical assessment.