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PubMed2004

Thalamic deep brain stimulation for posttraumatic action tremor.

We report a case of thalamic deep brain stimulation (DBS) for treatment of posttraumatic tremor. An 18-year-old right-handed man developed a disabling and medically refractory action tremor in the right upper extremity 9 months after sustaining diffuse axonal injury in a motor vehicle collision. DBS of the left ventral intermediate nucleus of the thalamus (Vim) suppressed the tremor without complication and should be considered as an option for the management of intractable posttraumatic tremor.

Adolescent↗
PubMed2005

Executive functions after traumatic brain injury in children.

There is growing recognition that executive function, the superordinate, managerial capacity for directing more modular abilities, is frequently impaired by traumatic brain injury in children and mediates the neurobehavioral sequelae exhibited by these patients. This review encompasses the definition of specific executive functions, age-related changes in executive functions in typically developing children, and the effects of traumatic brain injury on executive functions. The neural substrate for executive functions is described, including relevant functional brain imaging studies that have implicated mediation by prefrontal and parietal cortex and their circuitry. The vulnerability of the neural substrate for executive function to the pathophysiology of traumatic brain injury is discussed, including focal lesions and diffuse axonal injury. Domains of executive functions covered in this review include the basic processes of working memory and inhibition and more complex processes such as decision making. Other domains of executive function, including motivation, self-regulation, and social cognition are discussed in terms of research methodology, clinical assessment, and findings in children with traumatic brain injury. Proposed approaches to the rehabilitation of executive functions are presented.

Brain Injuries↗
PubMed1994

Early detection of axonal injury after human head trauma using immunocytochemistry for beta-amyloid precursor protein.

Severe non-missile head injury commonly results in a form of brain damage known as diffuse axonal injury (DAI). The histological diagnosis of DAI is made by silver staining for the presence of axonal retraction balls. This feature takes about 24 h to develop and does not allow for the early histological diagnosis of DAI. We have used immunocytochemistry for the beta-amyloid precursor protein (beta APP) as a marker for axonal injury in formalin-fixed, paraffin-embedded sections of human brain. Axonal beta APP immunoreactivity was present in all cases which had survived for 3 h or more. This was true even where the degree of head injury did not appear to be severe, supporting the theory that DAI is a severe form of a more common phenomenon of axonal injury which occurs after cerebral trauma. beta APP immunoreactivity was also found in some non-head injured cases and so cannot be considered to be a specific marker for trauma. The results show that beta APP immunocytochemistry may be useful in the detection of traumatic axonal injury in its early stages, before the formation of axonal retraction balls, provided care is taken to exclude other causes of such immunoreactivity.

Adult↗
PubMed2004

Traumatic lesions of corpus callosum: early multidetector CT findings.

Corpus callosum is one of the common sites of brain lesion, whose involvement is an indicator of a more severe prognosis, produced by traumatic shearing stresses resulting in diffuse axonal injury (DAI). Computed tomography (CT) in acute phase is considered to have a limited role for the detection of non-hemorrhagic or petechial hemorrhagic DAI lesions. New generation multidetector CT scanners allow faster acquisition of thinner-slice images and post-processing reformations. Three patients with severe closed head trauma underwent CT examinations using a multidetector scanner, a few hours and the day after injury. The review of original images with narrow window width and integration with reconstruction of thinner slices from raw-data and post-processing multiplanar reformations (MPR) helped to detect the onset of hypodense or predominantly hypodense areas of corpus callosum, not present at admission and afterwards confirmed by MRI.

Adolescent↗
PubMed1997

Axonal injury in falls.

Amyloid precursor protein (APP) immunocytochemistry was used as a marker for axonal injury (AI) in a series of 16 cases of head trauma associated with fatal falls. Nine cases were falls from not more than the person's own height (falls from < or = own height) and seven cases were falls from a distance greater than the person's own height (falls from > own height). AI was recorded on a series of line diagrams of standard brain sections divided into 116 sectors. AI around focal lesions (infarcts, hemorrhages, contusions) was distinguished from nonfocal axonal injury that was distant from any focal area of damage. The percentage of sectors showing focal AI provided the Focal Axonal Injury Score (FAIS) and the percentage showing nonfocal AI the Non-Focal Axonal Injury Score (NFAIS). The FAIS is a measure of secondary AI and the NFAIS of diffuse axonal injury (DAI). The percentage of sectors involved with AI (focal and nonfocal) provided the cumulative Axonal Injury Score (AIS). A semiquantitative grading system was also used to assess the severity of axonal injury in each sector and the sum of the grades from all sectors was expressed as a percentage to provide the Axonal Injury Severity Score (AISS). Widespread AI was present in all cases irrespective of the height of the fall. AI was present in the midbrain (94%), pons (94%), corpus callosum (100%), central grey matter (100%), and cerebral hemispheric white matter (94%). AIS ranged from 10 to 94 in falls from < or = own height (mean 73) and from 38 to 92 in falls from > own height (mean 82). AISS ranged from 6 to 95 in falls from < or = own height (mean 65) and 28 to 95 in falls from > own height (mean 72). There was no statistically significant difference in AIS or AISS between the two groups. The extent and severity of AI cannot be predicted from biomechanical data, such as the height of the fall, as the total AI in a given case is a variable mixture of Nonfocal AI (DAI) and Focal AI arising by secondary mechanisms, and APP immunostaining is unable to distinguish primary from secondary AI. However, the combination of the Hypoxic-Ischemic Score (HIS) defined as the percentage of sectors showing any hypoxic-ischemic damage ranging from neuronal "red cell change" to infarction in conjunction with the FAIS and NFAIS provided a measure of the relative contribution of primary and secondary AI in a given brain.

Accidental Falls↗
PubMedDate not supplied

Turbo-Proton Echo Planar Spectroscopic Imaging (t-PEPSI) MR technique in the detection of diffuse axonal damage in brain injury. Comparison with Gradient-Recalled Echo (GRE) sequence.

PURPOSE: Diffuse axonal injury (DAI) is a common type of primary neuronal injury in patients with severe traumatic brain injury, and is frequently accompanied by tissue tear haemorrhage. The T2*-weighted gradient-recalled echo (GRE) sequences are more sensitive than T2-weighted spin-echo images for detection of haemorrhage. This study was undertaken to determine whether turbo-PEPSI, an extremely fast multi-echo-planar-imaging sequence, can be used as an alternative to the GRE sequence for detection of DAI. MATERIALS AND METHODS: Nineteen patients (mean age 24,5 year) with severe traumatic brain injury (TBI), occurred at least 3 months earlier, underwent a brain MRI study on a 1.5-Tesla scanner. A qualitative evaluation of the turbo-PEPSI sequences was performed by identifying the optimal echo time and in-plane resolution. The number and size of DAI lesions, as well as the signal intensity contrast ratio (SI CR), were computed for each set of GRE and turbo-PEPSI images, and divided according to their anatomic location into lobar and/or deep brain. RESULTS: There was no significant difference between GRE and turbo-PEPSI sequences in the total number of DAI lesions detected (283 vs 225 lesions, respectively). The GRE sequence identified a greater number of hypointense lesions in the temporal lobe compared to the t-PEPSI sequence (72 vs 35, p<0.003), while no significant differences were found for the other brain regions. The SI CR was significantly better (i.e. lower) for the turbo-PEPSI than for the GRE sequence (p<0.00001). CONCLUSIONS: Owing to its very short scan time and high sensitivity to the haemorrhage foci, the turbo-PEPSI sequence can be used as an alternative to the GRE to assess brain DAI in severe TBI patients, especially if uncooperative and medically unstable.

Journal Article↗
PubMed2001

Intra-axonal neurofilament compaction does not evoke local axonal swelling in all traumatically injured axons.

Traumatic axonal injury (TAI) contributes to morbidity and mortality following traumatic brain injury (TBI). Single-label immunocytochemical studies employing antibodies to neurofilament compaction (NFC), RM014, and antibodies to APP, a marker of impaired axonal transport (AxT), have shown that TAI involves both NFC and disruption of AxT. Although it may be hypothesized that both events occur within the same injured axon, this has not been confirmed. To determine the relationship between NFC and impaired AxT, dual-label immunofluorescence was employed. To compare and contrast specific changes associated with these two markers of TAI, single-label electron microscopy was also used. Rats were subjected to an impact acceleration injury (30 min-6 h survival), and their brains were prepared for dual-label immunofluorescence and single-label electron microscopy. APP and RM014 were consistently found in two distinct classes of TAI. One, which showed only RM014 immunoreactivity, was thin and elongate, was sometimes vacuolated, and revealed little progressive change over time. The second was distinguished by focal axonal swellings containing APP immunoreactivity alone in small-caliber axons or in combination with RM014 immunoreactivity in large-caliber axons. These swellings were localized to either nodal or internodal loci and underwent progressive swelling over time, ultimately leading to secondary axotomy. Ultrastructural examination of these two classes of TAI revealed NFC together with mitochondrial dilation without organelle pooling in the RM014 single-labeled axons. However, the APP single-labeled small-caliber axons and APP/RM014 dual-labeled large-caliber axons revealed a progressive accumulation of organelles associated with increased axonal swelling over time. In contrast to previous thought, it now appears that NFC may occur independent of impaired AxT in TAI. This finding underscores the complexity of TAI, suggesting the need for multiple immunocytochemical approaches to fully assess the overall axonal response to TBI.

Animals↗
PubMed1996

Neurochemical mechanisms in brain injury and treatment: a review.

This article reviews cellular energy transformation processes and neurochemical events that take place at the time of brain injury and shortly thereafter emphasizing hypoxia-ischemia, cerebrovascular accident, and traumatic brain injury. New interpretations of established concepts, such as diffuse axonal injury, are discussed; specific events, such as free radical production, excess production of excitatory amino acids, and disruption of calcium homeostasis, are reviewed. Neurochemically-based interventions are also presented: calcium channel blockers, excitatory amino acid antagonists, free radical scavengers, and hypothermia treatment. Concluding remarks focus on the role of clinical neuropsychologists in validation of treatment interventions.

Animals↗
PubMed2001

Decrease and recovery of N-acetylaspartate/creatine in rat brain remote from focal injury.

Magnetic resonance spectroscopy (MRS) studies on traumatic brain injury (TBI) have shown that the neuronal metabolite N-acetylaspartate (NAA) may be reduced in regions of brain remote from sites of focal injury. Such reductions have generally been attributed to diffuse axonal injury (DAI) or neuron death. The aim of the present study was to investigate the contribution of metabolic depression, in the absence of DAI or cell death, to remote NAA reduction after TBI. The right sensorimotor cortices of adult rats were injured by weight drop. Two and six days later, tissue slices from the ipsilateral occipital cortex, or from the same region in uninjured rats, were superfused and examined by 1H-MRS. The occipital cortex has been shown to have negligible DAI or cell death but marked transient metabolic depression in this model of TBI. Two days after injury, the ratio of the NAA peak height to the total creatine peak height (NAA/TCr) was 14% lower than in control samples. Six days after injury, NAA/TCr recovered to within 7% of the control value. The time course of NAA/TCr decrease and recovery was similar to the time courses of widespread depression and recovery of 2-deoxyglucose uptake and mitochondrial alpha-glycerophosphate dehydrogenase activity measured previously in this model of TBI. Together, these results suggest that at least one component of remote NAA depression after TBI may be associated with a widespread and reversible metabolic depression that is unrelated to either DAI or cell death.

Animals↗
PubMed1992

The role of glutamate antagonists for the treatment of CNS injury.

Ischemic damage, chiefly of the focal type, and axonal disruption (diffuse axonal injury) are the major factors causing brain damage after human head injury. About one third of this damage may be delayed hours or days after the injury. Evidence from four animal models, each relevant to different aspects of human head injury, has shown that excitatory amino acid-induced changes are responsible for a proportion of the posttraumatic sequelae and that these effects can be blocked by EAA antagonists. This evidence is reviewed, and the implications for the conduct of human trials with EAA antagonists are discussed.

Animals↗
PubMed2006

Interface parameters of impact-induced mild traumatic brain injury.

Commonly considered a continuum of injuries, diffuse brain injury (DBI) ranges from mild concussion to severe diffuse axonal injury. The lower end of the spectrum is generally referred to as mild traumatic brain injury (MTBI). More severe forms of DBI have garnered extensive experimentation while these milder cases are considerably less explored. Recently, a new device was designed to generate DBI in the rodent using impact-induced angular acceleration. This device is modifiable so the entire spectrum of DBI can be investigated. Severity of DBI is critically dependent on magnitude of angular acceleration. A small animal surrogate like a rodent has a relatively small brain mass. This constraint poses a unique problem because the angular acceleration necessary for DBI is inversely related to brain mass. Prior experimentation estimated an angular acceleration of approximately 350 krad/s2 is necessary for the induction of mild traumatic brain injury (MTBI) in the rodent. To induce these magnitudes of angular acceleration in a repeatable manner, the impacting interface must be critically analyzed. This investigation uses a mathematical model based on parameters of a previously developed experimental model to assess the impacting interface such that angular accelerations are sufficient to produce MTBI in the rodent.

Acceleration↗
PubMed1992

Neuropsychiatric sequelae of head injuries.

Based on the above review several general points can be highlighted: Head injuries are extremely common, affecting probably close to 2,000,000 people in this country each year. The most common are nonmissile, closed-head injuries, the majority of which occur in association with motor vehicle accidents. Virtually all studies of head injury suggest a peak incidence in the 15 to 24 years of age group. Coarse measures of outcome suggest that the very young and the elderly have poorer outcomes. Because of improved acute care, however, a large number of young, otherwise healthy patients are surviving head injuries with a variety of profound neuropsychiatric sequelae. Because of the mechanics of brain injury in acceleration-deceleration injuries, certain brain injury profiles are common including orbitofrontal, anterior and inferior temporal contusions, and diffuse axonal injury. The latter particularly affects the corpus callosum, superior cerebellar peduncle, basal ganglia, and periventricular white matter. The neuropsychiatric sequelae follow from the above injury profiles. Cognitive impairment is often diffuse with more prominent deficits in rate of information processing, attention, memory, cognitive flexibility, and problem solving. Prominent impulsivity, affective instability, and disinhibition are seen frequently, secondary to injury to frontal, temporal, and limbic areas. In association with the typical cognitive deficits, these sequelae characterize the frequently noted "personality changes" in TBI patients. In addition, these changes can exacerbate premorbid problems with impulse control. Marked difficulties with substance use, sexual expression, and aggression often result. The constellation of symptoms, which make up the postconcussive syndrome, are seen across the whole spectrum of brain injury severity. Even in so-called mild or minor head injury, these symptoms are likely to have an underlying neuropathologic, neurochemical, or neurophysiologic cause. Higher than expected rates of certain psychopathologic disorders occur in the TBI population, including psychotic syndromes and depressive syndromes. Manic syndromes also are associated with TBI; however, the incidence has not been established. Assessment and treatment of the neuropsychiatric sequelae is a complex and challenging process. The mixture of diffuse and focal injuries, the combination of cognitive, language, somatic, and behavioral difficulties do not fit easily into current diagnostic categories.

Age Factors↗
PubMed1989

Brain damage in fatal non-missile head injury in relation to age and type of injury.

Brain damage in a series of 635 fatal non-missile head injuries has been analysed with particular reference to the age of the patient and the type of injury. The differences in the type of brain damage in relation to age were less than we had anticipated, lending further support to the contention that the aged brain has a reduced potential for recovery. The analysis confirms the relationship between road traffic accidents, diffuse axonal injury, gliding contusions and 'basal ganglia' haematomas, and the importance of diffuse brain swelling resulting from a head injury in children.

Adolescent↗
PubMed1998

Material characterization of the brainstem from oscillatory shear tests.

Traumatic damage to the brainstem occurs frequently when the brain skull complex experiences injurious loading especially during those traumatic situations that produce diffuse axonal injury (DAI). DAI has been shown to be dependent on load direction and correlated with regional tissue deformation in response to rotational inertial loads. Possible mechanisms for the selective vulnerability of the brainstem are (1) the geometry of the central nervous system is responsible for producing high tissue strains in these regions, (2) regional differences in overall material stiffness result in larger deformations at these sites, and (3) the anisotropic mechanical properties of these regions lead to a sensitivity to the rotational load direction and magnitude. This paper investigates the latter two hypotheses by performing oscillatory shear tests on adult porcine brainstem in three mutually perpendicular directions. The complex shear moduli were calculated over a range of frequencies (20-200 Hz), for three levels of peak engineering strain (2.5%, 5.0%, and 7.5%). The directional data demonstrated that the brainstem exhibits significant transversely isotropic behavior. Both components of the complex modulus in which the axonal fibers are oriented parallel to the plane of shear but transverse to the shear direction were significantly higher than those of the other two, mutually indistinguishable test cases across the range of strains tested. By comparison with similar tests on cerebral tissue, these data demonstrated that the brainstem displays a stiffer biomechanical response. These differences were present for both components of the complex shear modulus and were greater as the magnitude of the applied strain increased. The regional stiffness and anisotropic response of the brainstem coupled with its location as a narrow bridge between CNS regions interact to result in the selective vulnerability of this region in rotational loading.

Animals↗
PubMed1994

A modified fluid percussion device.

This report examines a modified fluid percussion device with specific improvements made to address deficiencies found in previously reported devices. These improvements include the use of a cylindrical saline reservoir made of stainless steel, placement of the reservoir in a 15-degree head-up position for the easy release of air bubbles, placement of the fluid flushing outlet and the pressure transducer close to the piston on the same plane, with both perpendicular to the direction of the piston, and adjustable reservoir volume to vary the waveform of the pressure pulse, and a metallic central injury screw secured to the animal's skull over the exposed dura. Using this device, midline fluid percussion (MFP) and lateral fluid percussion (LFP) injuries were performed in 70 rats. Histopathologic findings included diffuse axonal injury in the MFP model and cortical contusion in the LFP model. Survival rate was 41.4% in MFP animals and 100% in LFM animals when the device settings were 178 mm3 of the cylindrical reservoir and 50 degrees-60 degrees in height of the pendulum. Our results suggest that this modified fluid percussion device may offer significant improvements over previously reported fluid percussion models for use in experimental head injury.

Animals↗
PubMed1986

Deep intracerebral (basal ganglia) haematomas in fatal non-missile head injury in man.

Deep intracerebral (basal ganglia) haematomas were found post mortem in 63 of 635 fatal non-missile head injuries. In patients with a basal ganglia haematoma, contusions were more severe, there was a reduced incidence of a lucid interval, and there was an increased incidence of road traffic accidents, gliding contusions and diffuse axonal injury than in patients without this type of haematoma. Intracranial haematoma is usually thought to be a secondary event, that is a complication of the original injury, but these results suggest that a deep intracerebral haematoma is a primary event. If a deep intracerebral haematoma is identified on an early CT scan it is likely that the patient has sustained severe diffuse brain damage at the time of injury. In the majority of head injuries damage to blood vessels or axons predominates. In patients with a traumatic deep intracerebral haematoma, it would appear that the deceleration/acceleration forces are such that both axons and blood vessels within the brain are damaged at the time of injury.

Adolescent↗
PubMed2002

Attenuation of the electrophysiological function of the corpus callosum after fluid percussion injury in the rat.

This study describes a new method used to evaluate axonal physiological dysfunction following fluid percussion induced traumatic brain injury (TBI) that may facilitate the study of the mechanisms and novel therapeutic strategies of posttraumatic diffuse axonal injury (DAI). Stimulated compound action potentials (CAP) were recorded extracellularly in the corpus callosum of superfused brain slices at 3 h, and 1, 3, and 7 days following central fluid percussion injury and demonstrated a temporal pattern of functional deterioration. The maximal CAP amplitude (CAPA) covaried with the intensity of impact 1 day following sham, mild (1.0-1.2 atm), and moderate (1.8-2.0 atm) injury (p < 0.05; 1.11 +/- 0.10, 0.82 +/- 0.11, and 0.49 +/- 0.08 mV, respectively). The CAPA in sham animals were approximately 1.1 mV and did not vary with survival interval (3 h, and 1, 3, and 7 days); however, they were significantly decreased at each time point following moderate injury (p < 0.05; 0.51 +/- 0.11, 0.49 +/- 0.08, 0.46 +/- 0.10, and 0.75 +/- 0.13 mV, respectively). The CAPA at 7 days in the injured group were higher than at 3 h, and 1 and 3 days. H&E and amyloid precursor protein (APP) light microscopic analysis confirmed previously reported trauma-induced axonal injury in the corpus callosum seen after fluid percussion injury. Increased APP expression was confirmed using Western blotting showing significant accumulation at 1 day (IOD 913.0 +/- 252.7; n = 3; p = 0.05), 3 days (IOD 753.1 +/- 159.1; n = 3; p = 0.03), and at 7 days (IOD 1093.8 = 105.0; n = 3; p = 0.001) compared to shams (IOD 217.6 +/- 20.4; n = 3). Thus, we report the characterization of white matter axonal dysfunction in the corpus callosum following TBI. This novel method was easily applied, and the results were consistent and reproducible. The electrophysiological changes were sensitive to the early effects of impact intensity, as well as to delayed changes occurring several days following injury. They also indicated a greater degree of attenuation than predicted by APP expression changes alone.

Action Potentials↗
PubMed1997

Effects of basic fibroblast growth factor on hippocampal neurons after axonal injury.

OBJECTIVE: Axons of adult central nervous system neurons fail to regenerate after diffuse axonal injury in head trauma. Basic fibroblast growth factor (bFGF) has been reported to enhance neuritic extensions after neuronal injury in immature nerve cells. To investigate the effects of bFGF on adult neurons and axonal reoutgrowth, differentiated nerve cells were axonally transected and bFGF was applied. DESIGN: Cell culture study with primary rat hippocampal neurons. MATERIALS AND METHODS: After axotomy, hippocampal cultures were maintained untreated or in the presence of 0.5, 1, 10, or 20 ng/mL bFGF and evaluated over a 7-day period after injury. MEASUREMENTS AND MAIN RESULTS: Seven days after injury, axotomy decreased cell survival to 65%, increased [3H]arachidonic acid release 1.8-fold from prelabeled cells, and showed negligible effects on neuronal dendrites. bFGF reduced this neurodegeneration at all doses applied. bFGF at 10 ng/mL most efficiently increased live cells to 85% and decreased [3H]arachidonic acid release from prelabeled cells to control values (p < 0.01, vs. damaged cells). Furthermore, 10 ng/mL bFGF induced axonal branching and the longest axonal re-extensions from 60 +/- 8 to 377 +/- 10 microns 7 days after injury (p < 0.01, vs. damaged cells). CONCLUSIONS: bFGF increased cell survival and supported axonal re-elongations in adult hippocampal neurons in vitro when applied after axotomy. bFGF may play a role in new therapeutic concepts for the management of axonal injury after head trauma.

Animals↗