The Aleutian Enterprise sinking and posttraumatic stress disorder: Misdiagnosis in clinical and forensic settings.

This study examines the vulnerability of clinicians to overdiagnose posttraumatic stress disorder (PTSD) when survivors of a traumatic event are involved in litigation. 19 of 22 survivors of a marine disaster were seen by mental health professionals while pursuing personal injury claims and received a PTSD diagnosis that was maintained for more than 6 mo. This yielded an incidence rate for chronic PTSD of no less than 86%, a rate in excess of any previously reported in the literature for any type of trauma. The extraordinary incidence rate appeared to be explained, in part, by crew members' reports of attorney advice and symptom sharing. Clinicians are cautioned not to rely on client's self-reports and to consider postincident factors that may influence these reports when clients are involved in litigation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Head injury and the MMPI-2: Paradoxical severity effects and the influence of litigation.

Minnesota Multiphasic Personality Inventory–2 (MMPI-2) profiles of 30 consecutive patients with moderate/severe head injury were compared with those of 30 consecutive symptomatic minor/mild head injury patients. Of the severely injured, 18 had ongoing litigation and 12 did not. All 30 minor/mild patients were in litigation. The severe litigating group had significant elevations on Hypochondriasis (Hs), Hysteria (Hy), Schizophrenia (Sc), and Health Concerns relative to the severe nonlitigating group. The minor/mild group had significant elevations on Hs, Depression (D), Hy, and Psychasthenia (Pt) over both the litigating and non-litigating severe groups and additional elevations on Sc and Health Concerns over the severe nonlitigating group. Results are discussed in terms of the influence of litigation and injury severity on symptom endorsement on the MMPI-2. A model explaining persisting claims of disability after minor/mild head injury is proposed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurolaw: towards a new medical jurisprudence

Traumatic brain injuries and spinal cord injuries occur in a variety of accidents which may become the subject of civil litigation. A new field of medical jurisprudence, called neurolaw, is emerging to join health-care professionals and attorneys in a common quest to employ legal remedies to enhance the quality of life for individuals with neurological injury and their families. Presented here is a review of the underpinnings of this developing area of inquiry.     

Hippocampal and entorhinal cortex atrophy in frontotemporal dementia and Alzheimer's disease

Transient unilateral forebrain hypoxia-ischaemia (HI) in 14-day-old rats produces infarction and delayed neuronal death in the frontal cortex. Cell death can also be observed in regions distant from the primary injury, a phenomenon known as diaschisis. While apoptosis is involved in selective neuronal death, its role in infarction and diaschisis remains poorly understood. Here, we have investigated the proteolytic cleavage of poly(ADP ribose) polymerase (PARP) and the occurrence of apoptosis in the hippocampus and the cerebellum following either HI or traumatic brain injury. We demonstrate that: (i) in vitro, PARP is cleaved during apoptosis but not necrosis in cultured neuronal (N1E) cells and Swiss 3T3 fibroblasts; (ii) following HI, apoptotic cells can be detected by 4 h after injury in the hippocampus; (iii) in the ipsilateral hippocampus the appearance of cells with apoptotic morphology is preceded by a dramatic increase in PARP cleavage in the same region, starting immediately following HI and persisting for 24 h; (iv) HI also induces apoptosis in the cerebellum and, as in the hippocampus, the appearance of cells with apoptotic morphology is preceded by PARP cleavage that is greater on the side ipsilateral to forebrain injury; and (v) similarly, traumatic brain injury to the forebrain leads to PARP cleavage and apoptosis in the cerebellum. We conclude that HI injury or traumatic injury to the developing rat forebrain leads to PARP cleavage in directly affected areas and in sites distant from the primary injury that precedes the appearance of cells with apoptotic morphology. Our results are consistent with a role for apoptotic cell death in infarction and in diaschisis resulting from forebrain injury to the developing brain.     

Brain imaging and its clinical application in psychiatry

The common structural and functional brain imaging techniques are described from a practical, clinical point of view. The clinical indications for brain imaging in psychiatry are reviewed in relation to the specific limitations and advantages of each technique. The clinical applications of computerized tomography (CT), magnetic resonance imaging (MRI) and single photon emission computerized tomography (SPECT) are discussed in relation to the differential diagnosis between organic and functional psychiatric disorders. In a 55-year-old man with late onset of behavioral changes but without neurological signs the application of structural brain imaging (CT and MRI) in case management was demonstrated. The imaging findings involved the differential diagnosis between depression and focal brain lesions. In a 38-year-old man with personality changes and depression following a traumatic brain injury, time interval repeated functional brain imaging (SPECT) was used. Brain imaging reflected improvement in clinical status following treatment and was able to differentiate between reversible and permanent traumatic brain injuries. The superior yield of time interval repeated functional imaging in diagnosis and management of postconcussion syndrome is discussed.     

Attenuation of focal ischemic brain injury in mice deficient in the epsilon1 (NR2A) subunit of NMDA receptor

The role of glutamate neurotoxicity in cerebral ischemia has long been advocated but still remains controversial, because various glutamate receptor (GluR) antagonists showed inconsistent protective efficacy in brain ischemia models. To address this central issue of ischemic brain damage more directly, we used mutant mice deficient in the GluRepsilon1 (NR2A) subunit of NMDA receptor with or without additional heterozygous mutation in the GluRepsilon2 (NR2B) subunit. Those mutant mice, as well as their littermates, were subjected to focal cerebral ischemia by introducing a 6-0 nylon suture from left common carotid artery. Brain injury volumes after 2 hr of suture insertion, as evaluated by 2,3,5-triphenyltetrazolium chloride staining at 24 hr after ischemia, revealed significantly smaller injury size in GluRepsilon1 subunit knock-out mice compared with their wild-type littermates. The reduction in injury volume was not attributable to differences in body temperature or in blood flow during ischemia. Additional heterozygous GluRepsilon2 subunit disruption did not result in further reduction in injury volume. These data directly demonstrate relevance of NMDA receptor-mediated tissue injury after brain ischemia and provide evidence that GluRepsilon1 subunit is involved in these injurious mechanisms.     

Psychological assessment versus psychological testing: Validation from Binet to the school, clinic, and courtroom.

Increasingly, psychological assessment is conducted with clients and patients involved in child custody and personal injury litigation. Clinical neuropsychologists are being asked sophisticated questions by attorneys regarding the validity of practitioners' most highly respected tests. Research reviewed here bears on the validity of test-buttressed clinical opinions, including research related to the following psychometric properties of individual test scores: standard errors of measurement, test–retest stability and subtest-to-subtest intercorrelations. The highest and the lowest subtest scores used as indices, respectively, of an individual's premorbid level of cognitive functioning and the degree of current impairment from that presumed earlier level is not justified when used in isolation from the life history and current medical findings. Although many practitioners use information from the wider research, courtroom experience suggests that a number do not; contrariwise, the attempt of D. Faust and J. Ziskin (see record 1989-11643-001) to undermine the courtroom testimony of every psychologist who serves as an expert witness is also criticized. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of Case-Based Reasoning and Artificial Neural Networks

The outcome of construction litigation depends on a large number of factors. To predict the outcome of such litigation is difficult because of the complex interrelationships between these many factors. Two attempts are reported in the literature that use, respectively, case-based reasoning (CBR) and artificial neural networks (ANN) to overcome this difficulty. These studies were conducted by using the same 102 Illinois circuit court cases; an additional 12 cases were used for testing. Prediction rates of 83% in the CBR study and 67% in the ANN study were obtained. In this paper, CBR and ANN are compared, and their advantages and disadvantages are discussed in light of these two studies. It appears that CBR is more flexible when the system is updated with new cases, has better explanation facilities, and handles missing data and a large number of features better than ANN in this domain. If the use of CBR and ANN is understood better and if, as a result, the outcome of construction litigation can be predicted with reasonable accuracy and reliability, all parties involved in the construction process could save considerable money and time.     

Selective increases of extracellular brain concentrations of aromatic and branched-chain amino acids in relation to deterioration of neurological status in acute (ischemic) liver failure

Four brain-injured subjects with semantic memory impairments are described. Two had sustained traumatic head injury and two had herpes simplex virus encephalitis. The study seeks to determine (a) whether subjects with non-progressive brain injury and impaired semantic memory perform similarly to patients with progressive disorders on a semantic memory battery and (b) whether the anatomical lesions of the present group of subjects are similar to those seen in patients with progressive disorders. Results suggests that scores on the semantic memory battery are broadly similar for patients with progressive and non-progressive disorders information from magnetic resonance imaging scans supports other findings that the crucial area involved in semantic memory lies in the left temporal neocortex.     

The neuronal cytoskeleton is at risk after mild and moderate brain injury

Recent studies have described alterations in cytoskeletal proteins such as microtubule-associated protein 2 (MAP-2) and neurofilament (NF) resulting from moderate and severe experimental brain injury; however, few have investigated the consequences of mild injury, which is associated clinically and experimentally with cognitive dysfunction and neuronal damage. To contrast cytoskeletal changes within 7 days following mild injury with those following moderate injury, we subjected anesthetized, adult rats to mild (1.1-1.3 atm) or moderate (2.3-2.5 atm) lateral fluid percussion brain injury or sham injury. Rats were sacrificed at 6 h (n=4 mild; n=4 moderate; n=2 sham), 24 h (n=4 mild; n=4 moderate; n=1 sham), or 7 days (n=5 mild; n=4 moderate; n=1 sham) following injury, and immunohistochemistry was performed for MAP-2 and NF. Both mild and moderate injury produced notable cytoskeletal changes in multiple brain regions; however, mild injury generally resulted in a lesser degree of MAP-2 and NF loss over a smaller spatial extent. When compared to moderately injured animals, animals subjected to mild injury showed substantially delayed MAP-2 and NF alterations within the cortex and hippocampal dentate gyrus and no evidence of MAP-2 loss in the hippocampal CA3 region. While mild and moderate injury resulted for the most part in similar patterns of axonal injury, tissue tears in the fimbria and loss of NF immunoreactivity in regions containing injured axons were only observed following moderate injury. Elucidating the effects of modulating injury severity may yield insight into the mechanisms involved in traumatic damage to the cytoskeleton and guide future treatment strategies.     

Selective chemokine mRNA expression following brain injury

Injury in non-neuronal tissues stimulates chemokine expression leading to recruitment of inflammatory cells responsible for orchestration of repair processes. The signals involved in directing repair of damage to the brain are less well understood. We hypothesized that following brain injury, chemokines are expressed and regulate the rate and pattern of inflammatory cell accumulation. The two chemokine subfamilies are alpha(alpha)-chemokines, which primarily function as neutrophil chemoattractants, and the beta(beta)-chemokines, which function primarily as monocyte chemoattractants. We assessed alpha and beta chemokine mRNA expression patterns and leukocyte accumulation following a cerebral cortical lesion. Cortical lesions were produced with and without addition of endotoxin, Escherichia coli lipopolysaccharide (LPS), which stimulates cytokine expression. We studied the expression of the beta-chemokines: monocyte chemoattractant protein (gene product JE; MCP-1/JE), macrophage inflammatory protein-1 alpha and beta (MIP-1alpha and MIP-1beta), and the regulated upon activation normal T expressed and secreted chemokine (RANTES) as well as the alpha-chemokines: interferon-gamma-inducible protein (IP-10) and N51/KC (KC; a murine homologue of MIP-2). Changes in gene expression were analyzed by Northern analysis at different time points following injury. Leukocyte and macrophage densities were analyzed by immunohistochemistry at the same time intervals. All chemokines were elevated following cortical injury/endotoxin. MCP-1 and MIP-1alpha were elevated at 2 h and peaked 6 h, MIP-1beta peaked at 6 h, but declined more rapidly than MCP-1 or MIP-1alpha, and IP-10 peaked at 6 h and showed the most rapid decline. KC was elevated at 1 h, and peaked at 6 h following LPS. RANTES was elevated at 1 h and achieved a plateau level between 6 and 18 h, then declined. In contrast, sterile injuries produced in the absence of endotoxin only induced the mRNA of the beta-chemokine MCP-1, and its expression was delayed compared to the cortical injury/endotoxin group. The presence of chemokine message as early as 1 h indicates that expression of this class of molecules is an early response in the repair process following traumatic brain injury. Macrophage/microglia accumulation occurred more rapidly, activated microglia further from the lesion border, and more cells accumulated in cortical injury/endotoxin than in cortical lesions produced under sterile conditions. Thus, there was a positive correlation between beta-chemokine expression and the number of beta-chemokine responsive cells (i.e. microglia) accumulating in injury sites. This is the first comprehensive study using a panel of chemokine probes and specific marcophage/microglial markers to study in vivo activation of the brain following injury. Our data show that the brain is capable of expression of multiple chemokine genes upon appropriate stimulation (e.g. LPS-treatment). The gradient of microglial activation is consistent with physical damage stimulating release of chemokines that diffuse from the injury site. These data strongly suggest that chemokines are instrumental in the initiation of repair processes following brain injury.     

Managing pain in labour. Part 1: Perceptions of pain

More and more, dentists are being asked to be involved in medical-legal proceedings. The criteria for being an expert is based upon education, training, and experience, all of which every licensed practicing dentist possesses. Dental record-keeping and unbiased, thorough case analysis are the important factor involved in medical-legal litigation.     

Universal Prediction Model for Construction Litigation

Construction litigation expenditures have increased considerably over the years. An universal prediction model (UPM) was developed to predict the outcome of construction litigation and, hence, encourage settlements out of court. The study was conducted by using 151 Illinois circuit court cases filed in the period 1987–2005. UPM consists of data consolidation, attribute selection, hybrid classification, and performance assessment. A code was written to automate the entire process in the Waikato environment for knowledge analysis. UPM is versatile and scalable. The findings resulted in a higher prediction rate than those obtained in previous studies. The system proved to be quite robust and fast. If the outcome of construction litigation can be predicted with reasonable accuracy and reliability, all parties involved in the construction process could save considerable money and time.     

The role of cytokines in the neuropathology of stroke and neurotrauma

Accumulating evidence during the last decade has shown that the CNS can mount a well-defined inflammatory reaction to a variety of insults including trauma, ischemia, transplantation, viral infections as well as neurodegeneration. Many aspects of this centrally derived inflammatory response parallel to some extent the nature of such a reaction in the periphery. Through the recent application of molecular genetic techniques including PCR, utilization of cDNA probes in conjuncture with the availability of highly specific antibodies, new concepts are rapidly emerging as to the molecular mechanisms associated with the development of brain injury. In particular, the importance of cytokines, especially TNFalpha and IL-1beta, is emphasized in the propagation and maintenance of a CNS inflammatory response. This review summarizes evidence in support of a case for ischemia and trauma eliciting an inflammatory condition in the injured brain. The inflammatory condition consists of cells (neutrophils early after the onset of brain injury and subsequently monocyte infiltration) and mediators (cytokines, chemokines and adhesion molecules). It is clear that de novo up-regulation of pro-inflammatory cytokines, chemokines and endothelial-leukocyte adhesion molecules in the brain occurs soon following focal ischemia and trauma and at a time when the tissue injury is evolving. The significance of the inflammatory response and its contribution to brain injury are now becoming better understood. Evidence has emerged in support of the role of cytokines in driving the inflammatory response and that this process is causally related to the degree of brain injury. Evidence reviewed includes: (1) the capacity of specific cytokines to exacerbate brain damage; (2) the capacity of specific cytokine blockade to reduce ischemic brain damage; (3) depletion of circulating neutrophils reduces ischemic brain injury, and (4) antagonists of the endothelial-leukocyte adhesion interactions (e.g. anti-ICAM-1) reduce ischemic brain injury. Targeting the cytokines that drive the brain inflammatory response to injury provides opportunities to intervene with novel therapeutics in stroke and neurotrauma.     

CD46 (membrane cofactor protein of complement, measles virus receptor): structural and functional divergence among species (review)

OBJECT: In this retrospective study, the authors analyzed the frequency, anatomical distribution, and appearance of traumatic brain lesions in 42 patients in a posttraumatic persistent vegetative state. METHODS: Cerebral magnetic resonance (MR) imaging was used to detect the number of lesions, which ranged from as few as five to as many as 19, with a mean of 11 lesions. In all 42 cases there was evidence on MR imaging of diffuse axonal injury, and injury to the corpus callosum was detected in all patients. The second most common area of diffuse axonal injury involved the dorsolateral aspect of the rostral brainstem (74% of patients). In addition, 65% of these patients exhibited white matter injury in the corona radiata and the frontal and temporal lobes. Lesions to the basal ganglia or thalamus were seen in 52% and 40% of patients, respectively. Magnetic resonance imaging showed some evidence of cortical contusion in 48% of patients in this study; the frontal and temporal lobes were most frequently involved. Injury to the parahippocampal gyrus was detected in 45% of patients; in this subgroup there was an 80% incidence of contralateral peduncular lesions in the midbrain. The most common pattern of injury (74% in this series) was the combination of focal lesions of the corpus callosum and the dorsolateral brainstem. In patients with no evidence of diffuse axonal injury in the upper brainstem (26% in this series), callosal lesions were most often associated with basal ganglia lesions. Lesions of the corona radiata and lobar white matter were equally distributed in patients with or without dorsolateral brainstem injury. Moreover, cortical contusions and thalamic, parahippocampal, and cerebral peduncular lesions were also similarly distributed in both groups. CONCLUSIONS: The data indicate that diffuse axonal injury may be the major form of primary brain damage in the posttraumatic persistent vegetative state. In addition, the authors demonstrated in this study that MR imaging, in conjunction with a precise clinical correlation, may provide useful supportive information for the accurate diagnosis of a persistent vegetative state after traumatic brain injury.     

The effect of associated injuries, blood loss, and oxygen debt on death and disability in blunt traumatic brain injury: the need for early physiologic predictors of severity

Studies of 4590 patients with blunt trauma injuries admitted to a Level I Trauma Center, have shown that 37% had a blunt traumatic brain injury (BTBI). Of these brain injured patients 60% has an associated other injury. Examination of mortality has shown that those with an isolated brain injury had an 11% mortality compared with 21.8% in those with an associated systemic injury. Further investigation demonstrated that the cause of the increased mortality was related to the blood loss associated with the injuries and that when hypovolemic shock resulted, mortality rose from 12.8 to 62%. The severity of the associated injuries effect on the brain injured patient could be estimated by a parameter of oxygen debt, the base deficit and this allowed for a quantitative estimate of the probability of death as an index of severity. A combined linear logistic model using the admission Glasgow Coma Score (GCS) as a measure of brain injury and the base deficit as a measure of physiologic injury provides such a predictive score. The effect of associated injuries in patients with moderate brain injury (AIS 2,3) was to increase the average total cost of medical care in the first year of injury by three-fold ($12,489 to $36,177) and for severe brain injury (AIS 4,5) to increase average cost from $59,000 in isolated BTBI to $90,000 in BTBI with associated injury. The high incidence of brain injuries in motor vehicle crashes (MVC) caused by lateral impacts and their association with other side-impact injuries (lungs, spleen, kidney, and pelvic fractures) in which large blood volume losses are common, focuses attention on the need for side impact protection standards that simultaneously protect brain, thoracoabdominal viscera, and pelvis as a means of reducing the severity and cost of lateral impact MVCs.     

Fluorometric assay of nitrite and nitrate in brain tissue after traumatic brain injury and cerebral ischemia

Nitric oxide synthase (NOS) is distributed within the brain, and nitric oxide (NO) is felt to be involved in the pathophysiology of deterioration after head injury and cerebral ischemia. This study determined the levels of the stable end products of NOS (NOx=nitrite+nitrate) after traumatic brain injury (TBI) and transient cerebral ischemia. A fluorometric assay using nitrate reductase and the NADPH regenerating system was used to quantitate NOx in ultrafiltered (10-kDa cutoff) cortical and hippocampal extracts after reduction of nitrate. In TBI rats, both the plasma and tissue showed a sharp increase in NOx levels 5 min after injury. Plasma NOx returned to control levels by 2 h after injury. Ipsilateral-cortex NOx levels returned to control levels approximately 6 h after injury and remained constant from 6-24 h. Contralateral-cortex returned near to control levels after 1 h. Hippocampus also followed a similar trend. In gerbils, there was a significant elevation in tissue NOx levels immediately after 10 min transient cerebral ischemia, which gradually returned to control levels over 24 h reperfusion. This striking burst of NO synthesis immediately after injury is clearly evident whether the injury is head trauma or ischemia, or whether the measurements were performed on tissue or plasma. It is unknown whether endothelial NOS, neuronal NOS, or both caused the elevation of the NO end products seen after the CNS insults.     

Neuropsychological symptom presentation after electrical injury

OBJECTIVE: This study explored the relationship of neuropsychological complaints to accident- and injury-related characteristics, affective state, and work status in a group of electrical injury (EI) patients. METHODS: Sixty-three EI patients and 22 electricians with no history of electrical shock completed the Neuropsychological Symptom Checklist and the Beck Depression Inventory as part of an extensive neuropsychological evaluation. RESULTS: The EI group endorsed significantly more physical, cognitive, and emotional symptoms than did the controls. Symptom complaints were not related to injury parameters or litigation status. Only the time interval between injury and assessment accounted for differences in symptom presentation, with patients in the postacute stages of recovery showing the most cognitive and emotional complaints. CONCLUSION: The neuropsychological syndrome of electrical injury survival includes physical, cognitive, and emotional complaints. Considering that most electrically injured patients are treated within the acute medical setting, greater attention needs to be directed early in the course of treatment toward addressing neuropsychologic and psychiatric issues.     

Cytokines and perinatal brain injury

A rapidly expanding body of data provides support for the hypothesis that pro-inflammatory cytokines including interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) are expressed acutely in injured brain and contribute to progressive neuronal damage. Little is known about the pathogenetic role of these cytokines in perinatal brain injury. Recent experimental studies have incorporated two closely related in vivo perinatal rodent brain injury models to evaluate the role(s) of pro-inflammatory cytokines in the progression of neuronal injury: a perinatal stroke model, elicited by unilateral carotid artery ligation and subsequent timed exposure to 8% oxygen in 7-day-old rats, and a model of excitotoxic injury, elicited by stereotactic intra-cerebral injection of the selective excitatory amino acid agonist NMDA. Each of these lesioning methods results in reproducible, quantifiable focal forebrain injury at this developmental stage. Acute brain injury, evoked by cerebral hypoxia-ischemia or excitotoxin lesioning, results in transient marked increases in expression of IL-1 beta, and TNF-alpha mRNA in brain regions susceptible to irreversible injury, and there is evidence that pharmacological antagonism of IL-1 receptors can attenuate injury in both models. Recent studies also suggest that complementary strategies, based on pharmacological antagonism of platelet activating factor and on neutrophil depletion can also limit the extent of irreversible injury. In summary, current data suggest that pro-inflammatory cytokines contribute to the progression of perinatal brain injury, and that these mediators are important targets for neuroprotective interventions in the acute post-injury period.