Quantitative assessments of traumatic axonal injury in human brain: concordance of microdialysis and advanced MRI.

Axonal injury is a major contributor to adverse outcomes following brain trauma. However, the extent of axonal injury cannot currently be assessed reliably in living humans. Here, we used two experimental methods with distinct noise sources and limitations in the same cohort of 15 patients with severe traumatic brain injury to assess axonal injury. One hundred kilodalton cut-off microdialysis catheters were implanted at a median time of 17 h (13-29 h) after injury in normal appearing (on computed tomography scan) frontal white matter in all patients, and samples were collected for at least 72 h. Multiple analytes, such as the metabolic markers glucose, lactate, pyruvate, glutamate and tau and amyloid-ß proteins, were measured every 1-2 h in the microdialysis samples. Diffusion tensor magnetic resonance imaging scans at 3 T were performed 2-9 weeks after injury in 11 patients. Stability of diffusion tensor imaging findings was verified by repeat scans 1-3 years later in seven patients. An additional four patients were scanned only at 1-3 years after injury. Imaging abnormalities were assessed based on comparisons with five healthy control subjects for each patient, matched by age and sex (32 controls in total). No safety concerns arose during either microdialysis or scanning. We found that acute microdialysis measurements of the axonal cytoskeletal protein tau in the brain extracellular space correlated well with diffusion tensor magnetic resonance imaging-based measurements of reduced brain white matter integrity in the 1-cm radius white matter-masked region near the microdialysis catheter insertion sites. Specifically, we found a significant inverse correlation between microdialysis measured levels of tau 13-36 h after injury and anisotropy reductions in comparison with healthy controls (Spearman's r = -0.64, P = 0.006). Anisotropy reductions near microdialysis catheter insertion sites were highly correlated with reductions in multiple additional white matter regions. We interpret this result to mean that both microdialysis and diffusion tensor magnetic resonance imaging accurately reflect the same pathophysiological process: traumatic axonal injury. This cross-validation increases confidence in both methods for the clinical assessment of axonal injury. However, neither microdialysis nor diffusion tensor magnetic resonance imaging have been validated versus post-mortem histology in humans. Furthermore, future work will be required to determine the prognostic significance of these assessments of traumatic axonal injury when combined with other clinical and radiological measures.

Experimental subarachnoid haemorrhage results in multifocal axonal injury.

The great majority of acute brain injury results from trauma or from disorders of the cerebrovasculature, i.e. ischaemic stroke or haemorrhage. These injuries are characterized by an initial insult that triggers a cascade of injurious cellular processes. The nature of these processes in spontaneous intracranial haemorrhage is poorly understood. Subarachnoid haemorrhage, a particularly deadly form of intracranial haemorrhage, shares key pathophysiological features with traumatic brain injury including exposure to a sudden pressure pulse. Here we provide evidence that axonal injury, a signature characteristic of traumatic brain injury, is also a prominent feature of experimental subarachnoid haemorrhage. Using histological markers of membrane disruption and cytoskeletal injury validated in analyses of traumatic brain injury, we show that axonal injury also occurs following subarachnoid haemorrhage in an animal model. Consistent with the higher prevalence of global as opposed to focal deficits after subarachnoid haemorrhage and traumatic brain injury in humans, axonal injury in this model is observed in a multifocal pattern not limited to the immediate vicinity of the ruptured artery. Ultrastructural analysis further reveals characteristic axonal membrane and cytoskeletal changes similar to those associated with traumatic axonal injury. Diffusion tensor imaging, a translational imaging technique previously validated in traumatic axonal injury, from these same specimens demonstrates decrements in anisotropy that correlate with histological axonal injury and functional outcomes. These radiological indicators identify a fibre orientation-dependent gradient of axonal injury consistent with a barotraumatic mechanism. Although traumatic and haemorrhagic acute brain injury are generally considered separately, these data suggest that a signature pathology of traumatic brain injury-axonal injury-is also a functionally significant feature of subarachnoid haemorrhage, raising the prospect of common diagnostic, prognostic, and therapeutic approaches to these conditions.

Cerebellar white matter abnormalities following primary blast injury in US military personnel.

Little is known about the effects of blast exposure on the human brain in the absence of head impact. Clinical reports, experimental animal studies, and computational modeling of blast exposure have suggested effects on the cerebellum and brainstem. In US military personnel with isolated, primary blast-related 'mild' traumatic brain injury and no other known insult, we found diffusion tensor MRI abnormalities consistent with cerebellar white matter injury in 3 of 4 subjects. No abnormalities in other brain regions were detected. These findings add to the evidence supporting the hypothesis that primary blast exposure contributes to brain injury in the absence of head impact and that the cerebellum may be particularly vulnerable. However, the clinical effects of these abnormalities cannot be determined with certainty; none of the subjects had ataxia or other detected evidence of cerebellar dysfunction. The details of the blast events themselves cannot be disclosed at this time, thus additional animal and computational modeling will be required to dissect the mechanisms underlying primary blast-related traumatic brain injury. Furthermore, the effects of possible subconcussive impacts and other military-related exposures cannot be determined from the data presented. Thus many aspects of topic will require further investigation.

Electroconvulsive therapy in patients with vagus nerve stimulation.

Numerous studies have demonstrated the safety and efficacy of electroconvulsive therapy (ECT) for various psychiatric conditions, and it has been approved by the Food and Drug Administration for the treatment of refractory depression. Recently, the Food and Drug Administration also approved vagus nerve stimulation as a treatment for chronic or recurrent depression. Although electrical stimulation is used for both ECT and vagus nerve stimulation, the mechanisms of their action are very different. The American Psychiatric Association task force identifies no absolute contraindications to the use of ECT. The authors present 2 interesting cases of successful ECT in combination with vagus nerve stimulator.

Electroconvulsive therapy and ocular dystonia.

Electroconvulsive therapy (ECT) has been reported to be beneficial in various movement disorders, especially tardive dystonic reactions. In this article, we report an interesting case of drug-induced blepharospasm with ocular dystonia which improved with ECT. To our knowledge, a case of ocular dystonia improving with ECT has not been previously reported in the literature.

The pleasure of dissent: a critical theory of psychotherapy as an emancipatory practice.

The intent of this paper is to examine the inherent contradictions in the practice of psychotherapy that, if left unexamined, ruin the emancipatory prospects that it holds. Critical theory and, more specifically, Jurgen Habermas' theory of communicative action is utilized as a starting point for reconceptualizing psychotherapy. This paper then establishes a phenomenological and ethical basis for solidarity despite the power differences and conflicting goals for therapists and clients. It draws heavily on a consideration of intersubjectivity and the self as fundamentally relational as conceived by theorists such as Schutz, Levinas, and Vygotsky. Through such an analysis psychotherapy will be constituted consciously as a free space for critique, dissent and action, allowing for a core experience of one's self as a source of power in the social field that will foster replication in society at large.

Sexual functioning in patients with end-stage liver disease before and after transplantation.

The effects of end-stage liver disease (ESLD) on sexual functioning are complex and often overlooked in the context of chronic illness and the transplantation evaluation. The aim of the present study is to report on the prevalence of sexual dysfunction in patients with ESLD presenting for liver transplantation evaluation, as well as to examine a cohort after transplantation. Participants included 173 consecutive adult outpatients with ESLD who presented for orthotopic liver transplantation evaluation. All transplant candidates underwent a psychiatric evaluation, and a sexual history was taken by the transplant psychiatrist. Patients who received a liver transplant were contacted by telephone for follow-up (n = 39). The following domains were explored: sexual frequency, satisfaction, ability to orgasm, sexual interest, and, for men, erectile dysfunction. Before transplantation, high levels of sexual dysfunction were found, with women showing higher levels of dysfunction than men. Increased age and more severe liver disease were related to lower sexual frequency and satisfaction. Contrary to previous work, the cause of disease (alcoholic liver disease) was not related to sexual functioning before transplantation. Those with erectile dysfunction before transplantation showed continued dysfunction after transplantation. An additional finding was an age and gender bias against taking a sexual history from older women. Overall, for both men and women, the findings point to continued and persistent sexual dysfunction after transplantation. Findings may help transplant teams routinely inquire into the sensitive domain of sexual functioning early on and thereby provide an opportunity for treatment. Liver Transpl 12:1473-1477, 2006. (c) 2006 AASLD.

Cognitive impairment in people diagnosed with end-stage liver disease evaluated for liver transplantation.

Cognitive impairments are common in patients with end-stage liver disease (ESLD). The aim of the present study was to identify and characterize the neuropsychological deficits between groups of patients with a variety of causes of ESLD and to assess the impact of heavy alcohol use on cognitive functioning. Cognitive functioning in 300 consecutive outpatients presenting for liver transplantation evaluation was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). All patients underwent a psychiatric interview and a physical and laboratory assessment. The prevalence of neuropsychological impairment was highest among patients with liver disease secondary to alcohol. Poor performance on neuropsychological testing was correlated strongly with the severity of liver disease as measured by the model for end-stage liver disease (MELD). After controlling for the linear effects of MELD in subsequent analysis, a group difference emerged in patients with cholestatic liver disease showing less cognitive impairment when compared to all other groups. After controlling for the severity of liver disease, those patients with a history of alcohol abuse or dependence were found to perform more poorly on neuropsychological testing than those patients without such a history. Furthermore, the presence of these cognitive impairments predicted disability independent of the severity of the underlying liver disease.

Aripiprazole-induced parkinsonism.

Dopamine receptor antagonism is associated not only with antipsychotic action, but also with the generation of extrapyramidal side-effects of antipsychotic medications. Positron emission tomography studies reveal that an approximate 60-70% blockade of the D2 receptors is required for typical antipsychotics to be efficacious, but a blockade of > or =75-80% results in acute extrapyramidal side-effects. The newer atypical antipsychotics have a lower propensity to produce extrapyramidal side-effects. A new class of antipsychotics with a novel pharmacological profile and improved tolerability have emerged, comprising the 'dopamine-serotonin system stabilizers' of which aripiprazole is the first agent. We present the case of a patient who developed parkinsonism during treatment with aripiprazole.

Waiting for a liver transplant.

The waiting period for liver transplantation is a difficult time fraught with uncertainty and associated with a high rate of morbidity and mortality. To understand better what it means for a transplant patient to wait, the authors explore in this phenomenological study the meaning that people with liver failure ascribe to the experience of waiting for a transplant. They conducted 9 interviews using phenomenological methods of inquiry as a guide for analysis. Eight core themes emerged from 146 significant statements and corresponding meaning units. The experience of waiting includes transformations, doctors, teams and trust, elation to despair, loss, questioning the process, searching, coping, and the paradox of time. The essence of the experience is discussed in light of the theory of chronic illness as a disruption of biographical narrative. The authors highlight implications for the transplant teams and other health care providers.

An exploratory study of constructions of masculinity, sexuality and HIV/AIDS in Namibia, Southern Africa.

The goal of the current study was to explore notions of masculinity and their linkages to HIV/AIDS among Owambo men and women in Namibia, where an estimated one-fifth of 15-49 year-olds have acquired HIV. Thirteen open-ended interviews and three focus groups were conducted with 50 male and female participants aged 19-50 in rural and urban Namibia. Qualitative analysis revealed six central themes: the evolving meanings of masculinity, power dynamics between men and women, women as active agents, the tension between formal and informal education and HIV transmission, alcohol and masculinity, and the blending of masculinity and explanations of HIV and AIDS. The findings suggest both direct and indirect linkages between notions of masculinity and AIDS, and highlight the need for prevention efforts that focus on providing alternative avenues for attaining culturally recognized markers of masculinity.