Clinical rating of cortical atrophy and cognitive correlates following traumatic brain injury

We report on the utility of using a rapid, easy-to-use, visually based semi-quantitative neuroimaging atrophy rating scale in individuals with traumatic brain injury (TBI) and normal control subjects. Magnetic resonance (MR) scans were rated using a standardized semi-quantitative MR rating method. A four-point scale was used to rate each scan for atrophy in frontal, temporal, and parietal areas. Seventy-five TBI subjects (50 males, 25 females) and 75 age- and gender-matched control subjects were compared for atrophy ratings. Clinical atrophy ratings were also compared to a quantitative measure of atrophy, the ventricle-to-brain ratio, and with the TBI subjects' scores on standard neuropsychological tests. TBI patients had significantly higher clinical atrophy ratings in frontal and temporal lobe areas compared to controls. The clinical atrophy ratings significantly correlated with the ventricle-to-brain ratio, a quantitative measure of atrophy in the same TBI subjects. Higher clinical ratings of frontal and temporal atrophy correlated with deficits in memory and executive function. These findings indicate that clinical ratings of trauma-induced atrophy can be reliably performed and are associated with neuropsychological outcome and quantitative measures of cerebral atrophy.     

Magnetic resonance imaging (MRI) findings and neuropsychological sequelae in children after severe traumatic brain injury: the role of cerebellar lesion

We studied the relationships between magnetic resonance imaging (MRI) findings and neuropsychological sequelae in children after severe traumatic brain injury. Twenty-three children ages 7-13 years underwent MRI assessment of brain lesion topography and volume and neuropsychological evaluations, more than 1 year after sustaining severe traumatic brain injury. Most children had lesions to the corpus callosum and frontal lobes. Total lesion volume and extent of cerebral atrophy did not impact on the neuropsychological evaluation. Additional relationships were observed: left frontal lesions with lower semantic verbal fluency, right occipital lesions with lower visual recognition task scores, dyscalculia with cerebellar lesions, and cerebellar damage with lower cognitive performances and lower visual recognition memory. This study demonstrates the significance of the cerebellum's role in neuropsychological outcomes after traumatic brain injury and the importance of the lesion depth classification in predicting functional results.     

Effects of traumatic brain injury on cognitive functioning and cerebral metabolites in HIV-infected individuals

We explored the possible augmenting effect of traumatic brain injury (TBI) history on HIV (human immunodeficiency virus) associated neurocognitive complications. HIV-infected participants with self-reported history of definite TBI were compared to HIV patients without TBI history. Groups were equated for relevant demographic and HIV-associated characteristics. The TBI group evidenced significantly greater deficits in executive functioning and working memory. N-acetylaspartate, a putative marker of neuronal integrity, was significantly lower in the frontal gray matter and basal ganglia brain regions of the TBI group. Together, these results suggest an additional brain impact of TBI over that from HIV alone. One clinical implication is that HIV patients with TBI history may need to be monitored more closely for increased risk of HIV-associated neurocognitive disorder signs or symptoms.     

Early nonischemic oxidative metabolic dysfunction leads to chronic brain atrophy in traumatic brain injury

Chronic brain atrophy after traumatic brain injury (TBI) is a well-known phenomenon, the causes of which are unknown. Early nonischemic reduction in oxidative metabolism is regionally associated with chronic brain atrophy after TBI. A total of 32 patients with moderate-to-severe TBI prospectively underwent positron emission tomography (PET) and volumetric magnetic resonance imaging (MRI) within the first week and at 6 months after injury. Regional lobar assessments comprised oxidative metabolism and glucose metabolism. Acute MRI showed a preponderance of hemorrhagic lesions with few irreversible ischemic lesions. Global and regional chronic brain atrophy occurred in all patients by 6 months, with the temporal and frontal lobes exhibiting the most atrophy compared with the occipital lobe. Global and regional reduction in cerebral metabolic rate of oxygen (CMRO₂), cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of glucose were observed. The extent of metabolic dysfunction was correlated with the total hemorrhage burden on initial MRI (r=0.62, P=0.01). The extent of regional brain atrophy correlated best with CMRO₂ and CBF. Lobar values of OEF were not in the ischemic range and did not correlate with chronic brain atrophy. Chronic brain atrophy is regionally specific and associated with regional reductions in oxidative brain metabolism in the absence of irreversible ischemia.     

Gambling task performance in traumatic brain injury: relationships to injury severity, atrophy, lesion location, and cognitive and psychosocial outcome.

OBJECTIVE: To determine the sensitivity of the Gambling Test (GT) to the neurocognitive effects of traumatic brain injury (TBI) and to examine the cognitive, neural, and psychosocial correlates of impaired GT performance in patients with TBI. BACKGROUND: The GT is sensitive to behavioral deficits in patients with prefrontal brain damage, especially in ventral regions. Patients with TBI and behavioral deficits often have focal ventral prefrontal damage as well as diffuse damage. Analysis of the correlates of the GT in this population has implications for interpretation of the GT in other groups. METHOD: Seventy-one TBI patients were administered the GT, neuropsychological tests, and psychosocial outcome questionnaires. Patients also had high-resolution structural magnetic resonance imaging analyzed for both lesion location and tissue compartment volumes. RESULTS: The GT was sensitive to TBI in general, but not to TBI severity or quantified chronic phase atrophy. Marked impairment was observed in (but not limited to) patients with large frontal lesions. There were modest correlations between the GT and tests of working memory and executive functioning as well as between self- and other-rated real-life memory, executive, and emotional problems. CONCLUSIONS: The GT can be a useful adjunct to assessment of patients with TBI. Interpretation of GT performance in patients with complex neuropsychological deficits such as TBI should consider the influence of domain-general resources in addition to specific ventral prefrontal function.     

Neuropsychological and information processing deficits following mild traumatic brain injury.

Neuroradiological and neuropathological investigations have found evidence of diffuse brain damage in the frontal and temporal lobes, corpus callosum, and fornices in patients who have sustained a mild traumatic brain injury (TBI). However, neuropsychological assessments of these patients do not typically target many of the subtle information processing deficits that may arise from diffuse damage involving the frontotemporal regions of the brain as well as white matter pathology, including the corpus callosum. Consequently, we have a limited understanding of the deficits that may be attributable to temporary or permanent disruptions to these functional pathways. This study assessed a group of mild TBI patients (N = 40) and a matched control group (N = 40) on a number of standard neuropsychological tests of selective and sustained attention, verbal and non-verbal fluency, and verbal memory. In addition, reaction time (RT) tasks, requiring both the inter- and intra-hemispheric processing of visual and tactile information, were used to assess the functional integrity of the tracts that are likely to be affected by diffuse damage. In the 1st month after sustaining their injury, the mild TBI group demonstrated deficits in attention, non-verbal fluency, and verbal memory. They also demonstrated slower visual and tactile RTs, with the visual RTs of mild TBI patients being more affected by increased task difficulty and the need to transfer information across the corpus callosum, than did their matched controls.     

Vulnerability of the anterior commissure in moderate to severe pediatric traumatic brain injury

In relation to the adult brain, the immature brain might be more vulnerable to damage during and following traumatic brain injury, particularly in white-matter tracts. Given well-established evidence of corpus callosum atrophy, we hypothesized that anterior commissure volume (using quantitative magnetic resonance imaging [MRI]) in this structure would be decreased in children with moderate to severe traumatic brain injury relative to typically developing children. Second, given the purported role of the anterior commissure in interhemispheric axon conveyance between temporal lobes, we hypothesized that temporal lobe white matter, temporal lesion volume, and injury severity (Glasgow Coma Scale score) would be predictive of decreased anterior commissure cross-sectional volume in patients with traumatic brain injury. Finally, we wished to establish the relationship between the anterior commissure and the temporal stem, a major white-matter tract into the temporal lobes, using diffusion tensor imaging fiber-tracking maps for each patient. We also hypothesized that children with traumatic brain injury would exhibit decreased fractional anisotropy in relation to typically developing children in a fiber system including the anterior commissure and the temporal lobes. Decreased anterior commissure cross-sectional volume was observed in patients with traumatic brain injury, and, as predicted, anterior commissure and temporal white-matter volumes were positively related to each other and to higher Glasgow Coma Scale scores. Lesion volume was not independently predictive of anterior commissure volume in the overall model. Diffusion tensor imaging fractional anisotropy values differed between the groups for the temporal stem-anterior commissure system, with the traumatic brain injury group exhibiting decreased fractional anisotropy. The anterior commissure, like the corpus callosum, appears to be highly vulnerable to white-matter degenerative changes resulting from mechanisms such as the direct impact of trauma, progressive axonal injury as tissue in other brain regions atrophies, or myelin degeneration. This is the first systematic examination of anterior commissure atrophy following traumatic brain injury using in vivo quantitative MRI and diffusion tensor imaging fiber tracking in pediatric subjects.     

Executive dysfunction following traumatic brain injury: neural substrates and treatment strategies

Executive dysfunction is among the most common and disabling aspects of cognitive impairment following traumatic brain injury (TBI), and may include deficits in reasoning, planning, concept formation, mental flexibility, aspects of attention and awareness, and purposeful behavior. These impairments are generally attributed to frontal systems dysfunction, due either to direct insult to the frontal lobes or to disruption of their connections to other brain regions. Evaluation of executive deficits typically includes neuropsychological assessment, though adjunctive interviews can be critical in detecting subtle dysexecutive symptoms that may not be apparent on standardized testing. Rehabilitation programs emphasizing cognitive-behavioral approaches to the retraining of planning and problem-solving skills can be effective in ameliorating identified executive deficits. In addition, pharmacological approaches may be useful in addressing aspects of executive dysfunction. This review summarizes the nature of executive deficits following TBI, their neuroanatomical substrates, selected assessment and treatment strategies, and recent research findings and trends.     

Profound amnesia and confabulation following traumatic brain injury

Amnesia and confabulation may persist following acute aneurysmal hemorrhage of the anterior communicating artery, chronic alcoholic Korsakoff's syndrome, and late-stage dementia of the Alzheimer type. However, there is a paucity of information regarding the persistence of these symptoms following traumatic brain injury. We present the case of JL, a 43-year-old male with persistent and severe anterograde amnesia for verbal and visual information with co-occurring provoked confabulation which persists well into the chronic phase of recovery after a severe traumatic brain injury. Neuropsychological testing at 7 weeks post-injury demonstrated severe anterograde amnesia with co-occurring confabulation. Follow-up testing at 9.5 months post-injury showed persistent and severe anterograde amnesia and provoked confabulation despite superior non-verbal intelligence and above average attentional and perceptual abilities. Late computed tomography showed chronic hypodense regions in the temporal lobes, bilaterally (L > R), and in the region of the left ventrolateral frontal lobe. This case demonstrates that anterograde amnesia and provoked confabulation may persist long after the acute phase of recovery after traumatic brain injury, and also supports previous research which asserts that medial temporal lobe damage must be accompanied by ventral frontal lobe pathology to produce the amnestic-confabulatory syndrome.     

Humans with traumatic brain injuries show place-learning deficits in computer-generated virtual space

Spatial learning and memory has been linked to the hippocampus and temporal lobes and though these areas are often damaged in traumatic brain injury (TBI), spatial learning deficits after TBI have not received much attention. In the present study, a virtual environment was used to challenge people with TBI to solve a task comparable to the Morris water maze, which in turn has been shown to be highly sensitive to hippocampal and frontal lobe dysfunction in laboratory animals. A regular computer monitor was used to present 12 participants with TBI and 12 age- and sex-matched comparison participants with a computer-generated, three-dimensional "virtual arena maze," consisting of a large round arena within a very large square room. Participants were required to learn the place of an invisible target on the floor of the room based solely on distal cues on the walls of the room. Eight of the 12 participants with moderate to severe TBI showed substantial place-learning deficits in comparison to the uninjured participants. Performance in the virtual environment correlated with self-reported frequency of wayfinding problems in everyday life and with scores on a test of episodic memory, the Rivermead Behavioural Memory Task. These data confirm that deficits in spatial learning and memory follow TBI, and suggest that the virtual arena maze may provide a new method for objectively assessing them.     

PET findings and neuropsychological deficits in a case of Fahr's disease.

In a case of Fahr's disease with frontal lobe type dementia and hyperkinetic-hypotone syndrome, functional changes were investigated using positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) as a tracer. Computed tomography showed bilateral calcifications in the putamen and globus pallidus consistent with the diagnosis of Fahr's disease and a frontally pronounced brain atrophy. In contrast, reduced glucose uptake in PET was not only confined to the areas mentioned above, but extended to the temporal and parietal cortices, bilaterally. These functional changes corresponded to the neuropsychological deficits observed, i.e. disturbed selective attention and cognitive flexibility, verbal perseverations, and declarative memory deficits. It is suggested that functional changes may precede cerebral atrophy in Fahr's disease and may reflect deficits in functional circuits, which involve both the basal ganglia and the frontal, parietal, and temporal lobes.     

Multiple fregoli delusions after traumatic brain injury.

A 61 year old man after a traumatic brain injury resulting in right frontal and left temporoparietal contusions developed florid Fregoli-type misidentifications. Extensive neuropsychological testing demonstrated significant deficits in executive and memory functions. The patient's neuropsychological profile closely resembled that seen in previously reported patients with Capgras syndrome. Our findings are consistent with the hypothesis that a combination of executive and memory deficits may account for cases of delusional misidentification associated with brain lesions. However, the form which the delusion takes may be influenced by other factors including motivation.     

Classic Pick's disease type with ubiquitin-positive and tau-negative inclusions: case report

We report on a patient presenting Pick's disease similar to the one reported by Pick in 1892, with ubiquitin-positive and tau-negative inclusions. His diagnosis was made on the basis of clinical (language disturbance and behavioural disorders), neuropsychological (progressive aphasia of the expression type and late mutism), neuroimaging with magnetic resonance (bilateral frontal and temporal lobes atrophy) and brain single photon emission computed tomography (frontal and temporal lobes hypoperfusion) studies. Macroscopic examination showed atrophy on the frontal and temporal lobes. The left hippocampus displayed a major circumscribed atrophy. The diagnostic confirmation was made by the neuropathological findings of the autopsy that showed neuronal loss with gliosis of the adjacent white matter and apearance of status spongiosus in the middle frontal and especially in the upper temporal lobes. There were also neuronal swelling (ballooned cell) and argyrophilic inclusions (Pick's bodies) in the left and right hippocampi. Anti-ubiquitin reaction tested positive and anti-tau tested negative.     

Cognitive decline in AD and mild cognitive impairment is associated with global brain damage

OBJECTIVE: To investigate the relationships between structural damage in the whole brain, the temporal lobes, and the frontal lobes and cognitive decline at old age. The authors hypothesized that widespread brain damage as quantified using magnetization transfer imaging (MTI) is related to global cognitive decline, whereas regional damage to the temporal lobes is related to memory impairment, and regional damage to the frontal lobes is related to executive dysfunctioning. METHODS: Cognitive function of 22 patients with probable AD, 13 patients with mild cognitive impairment (MCI), and 28 elderly controls was assessed using an extensive neuropsychological test battery. Structural damage in the whole brain, the temporal lobes, and the frontal lobes was estimated using volumetric MTI analysis. Associations between MTI measures and neuropsychological tests were investigated using Pearson correlation analysis. RESULTS: MTI measures of the whole brain, as well as the temporal and the frontal lobes, were strongly associated with global cognitive deterioration and impairment in memory, orientation, language, praxis, gnosis, and executive functioning. However, there were no specific cognitive correlates of regional brain damage to the temporal and frontal lobes. CONCLUSIONS: Using whole brain volumetric magnetization transfer imaging, the authors demonstrated that cognitive decline in patients with mild cognitive impairment and AD is associated with widespread structural brain damage. As there were no specific relationships between regional brain damage and impairment of specific cognitive functions, pathology in AD and mild cognitive impairment is much more generalized than was expected.     

Diffuse axonal injury due to traumatic brain injury alters inhibition of imitative response tendencies

It is well known that traumatic brain injury particularly affects the frontal lobes. Consequently, patients often suffer from executive dysfunction and behavioral disturbances. Accordingly, our study aimed at investigating patients after traumatic brain injury with two tasks involving different functional processes and structural networks supported by the frontal lobes. Two paradigms were applied: the Stroop color-word task and a task in which subjects had to inhibit imitative response tendencies. We selected a patient group solely with diffuse axonal injury, as this type of injury is homogenous and is correlated with cognitive dysfunction more than focal contusions. To evaluate long-term effects most relevant for rehabilitation, we selected a patient group whose brain injuries dated back several years. Our results show that patients with diffuse axonal injury inhibited imitative responses more successfully than control subjects, whereas executive processes examined with the Stroop task were unaltered. Interestingly, impairments were tightly correlated both with the length of the post-traumatic amnesia predicting outcome in traumatic brain injury and with behavioral disturbances. Impairments in the imitation-inhibition task may indicate alterations in an anterior frontomedian neural network even years after traumatic brain injury.     

MRI-based brain volumetry in chronic whiplash patients: no evidence for traumatic brain injury

Introduction –  Cognitive complaints, such as poor concentration and memory deficits, are frequent after whiplash injury and play an important role in disability. The origin of these complaints is discussed controversially. Some authors postulate brain lesions as a consequence of whiplash injuries. Potential diffuse axonal injury (DAI) with subsequent atrophy of the brain and ventricular expansion is of particular interest as focal brain lesions have not been documented so far in whiplash injury.
Objective –  To investigate whether traumatic brain injury can be identified using a magnetic resonance (MR)-based quantitative analysis of normalized ventricle–brain ratios (VBR) in chronic whiplash patients with subjective cognitive impairment that cannot be objectively confirmed by neuropsychological testing.
Materials and methods –  MR examination was performed in 21 patients with whiplash injury and symptom persistence for 9 months on average and in 18 matched healthy controls. Conventional MR imaging (MRI) was used to assess the volumes of grey and white matter and of ventricles. The normalized VBR was calculated.
Results –  The values of normalized VBR did not differ in whiplash patients when compared with that in healthy controls ( F  = 0.216, P  = 0.645).
Conclusions –  This study does not support loss of brain tissue following whiplash injury as measured by VBR. On this basis, traumatic brain injury with subsequent DAI does not seem to be the underlying mechanism for persistent concentration and memory deficits that are subjectively reported but not objectively verifiable as neuropsychological deficits.     

Technetium-99m-HmPAO brain SPECT in infantile Gaucher's disease

The authors report serial technetium-99m hexamethylpropylene-amine-oxime brain single photon emission computed tomography (SPECT) findings in two infants with Gaucher's disease type 2. Detailed neurologic and laboratory examinations, including bone marrow biopsies and enzymatic assays, were described. Serial brain magnetic resonance imaging studies in one patient illustrated the progressive cerebral atrophy in the frontal and temporal lobes. The SPECT in both cases demonstrated positive findings of initial scattered hypoperfusion, with extending to hypoperfusion of the entire cerebrum after 4 months of clinical deterioration. These changes in the SPECT findings may reflect progressive degeneration of the cerebrum in Gaucher's disease type 2. Brain SPECT may provide useful information on cerebral flow and metabolic distribution corresponding to the neurologic deficits of neuronopathic Gaucher's disease.     

Virtual environment navigation tasks and the assessment of cognitive deficits in individuals with brain injury

Navigation in real environments is often impaired by traumatic brain injury (TBI). These deficits in wayfinding appear to be due to disruption of cognitive processes underlying navigation and may in turn be due to damage to the hippocampus and frontal lobes. These wayfinding problems after TBI were investigated using a virtual simulation of a Morris Water Maze (MWM), a standard test of hippocampal function in laboratory animals. The virtual environment consisted of a large virtual arena in a very large virtual room whose walls provided views of a naturalistic landscape. Eleven community-dwelling TBI survivors and 12 comparison participants, matched for gender, age and education were tested to see if they could find a location in the arena marked by one of the following: (a) a visible platform, (b) a single proximal object, (c) a single proximal object among seven other distracter objects, or (d) distal features inside and outside the room. The proximal objects allowed participants to use egocentric (body-centered) navigational strategies that rely on relatively simple stimulus-response associations. The absence of proximal cues forced the participants to rely on distal features of the environment (room walls, landscape elements) and tested their ability to use allocentric (world-based) navigational strategies requiring cognitive mapping. Results indicated that the navigation of TBI survivors was not impaired when the proximal cues were present but was impaired when proximal cues were absent. These results provide more evidence that the navigational deficit after TBI is due to an inability to form, remember or use cognitive maps.     

Planning,problem-solving and organizational abilities in children following traumatic brain injury: Intervention techniques

Due to the mechanisms involved in traumatic brain injury (TBI), the frontal lobes are often impacted. As the frontal regions of the brain are believed to subsume executive functioning, then it follows that post-TBI deficits may be seen in this domain. Executive functioning broadly refers to a set of inter-related skills necessary to maintain an appropriate problem-solving set for the attainment of a future goal and may include areas such as attentional control, planning, problem-solving, cognitive flexibility, abstraction and information processing. The literature available on interventions for executive difficulties following TBI is minimal, with that focused on the paediatric population even more limited. From the few evaluation studies available, results tend to suggest that specific types of intervention lead to positive outcomes. However, as the interventions are few and often based on case studies, there is much need for more evaluation studies to be conducted.     

The usefulness of quantitative EEG (QEEG) and neurotherapy in the assessment and treatment of post-concussion syndrome.

Mild traumatic brain injury (TBI) is associated with damage to frontal, temporal and parietal lobes. Post-concussion syndrome has been used to describe a range of residual symptoms that persist 12 months or more after the injury, often despite a lack of evidence of brain abnormalities on MRI and CT scans. The core deficits of post-concussion syndrome are similar to those of ADHD and mood disorders, and sufferers often report memory, socialization problems and frequent headaches. While cognitive rehabilitation and psychological support are widely used, neither has been shown to be effective in redressing the core deficits of post-concussion syndrome. On the other hand, quantitative EEG has been shown to be highly sensitive (96%) in identifying post-concussion syndrome, and neurotherapy has been shown in a number of studies to be effective in significantly improving or redressing the symptoms of post-concussion syndrome, as well as improving similar symptoms in non-TBI patients.