• Assessing neuronal networks: understanding Alzheimer's disease.

      Bokde, Arun L W; Ewers, Michael; Hampel, Harald; Discipline of Psychiatry, School of Medicine and Trinity College Institute of, Neuroscience (TCIN), Laboratory of Neuroimaging & Biomarker Research, Trinity, College Dublin, The Adelaide and Meath Hospital incorporating the National, Children's Hospital (AMiNCH), Dublin 24, Ireland. (2012-02-01)
      Findings derived from neuroimaging of the structural and functional organization of the human brain have led to the widely supported hypothesis that neuronal networks of temporally coordinated brain activity across different regional brain structures underpin cognitive function. Failure of integration within a network leads to cognitive dysfunction. The current discussion on Alzheimer's disease (AD) argues that it presents in part a disconnection syndrome. Studies using functional magnetic resonance imaging, positron emission tomography and electroencephalography demonstrate that synchronicity of brain activity is altered in AD and correlates with cognitive deficits. Moreover, recent advances in diffusion tensor imaging have made it possible to track axonal projections across the brain, revealing substantial regional impairment in fiber-tract integrity in AD. Accumulating evidence points towards a network breakdown reflecting disconnection at both the structural and functional system level. The exact relationship among these multiple mechanistic variables and their contribution to cognitive alterations and ultimately decline is yet unknown. Focused research efforts aimed at the integration of both function and structure hold great promise not only in improving our understanding of cognition but also of its characteristic progressive metamorphosis in complex chronic neurodegenerative disorders such as AD.
    • Brain activation predicts treatment improvement in patients with major depressive disorder.

      Samson, Andrea C; Meisenzahl, Eva; Scheuerecker, Johanna; Rose, Emma; Schoepf, Veronika; Wiesmann, Martin; Frodl, Thomas; Department of Psychiatry, School of Medicine & Trinity College Institute of, Neuroscience, Integrated Neuroimaging, The Adelaide and Meath Hospital, incorporating the National Children's Hospital (AMNCH), & St. James's Hospital,, Trinity College, Dublin, Ireland. andrea.samson@stanford.edu (2012-02-01)
      Major depressive disorder (MDD) is associated with alterations in brain function that might be useful for therapy evaluation. The current study aimed to identify predictors for therapy improvement and to track functional brain changes during therapy. Twenty-one drug-free patients with MDD underwent functional MRI twice during performance of an emotional perception task: once before and once after 4 weeks of antidepressant treatment (mirtazapine or venlafaxine). Twelve healthy controls were investigated once with the same methods. A significant difference between groups was a relative greater activation of the right dorsolateral prefrontal cortex (dlPFC) in the patients vs. controls. Before treatment, patients responding better to pharmacological treatment showed greater activation in the dorsomedial PFC (dmPFC), posterior cingulate cortex (pCC) and superior frontal gyrus (SFG) when viewing of negative emotional pictures was compared with the resting condition. Activations in the caudate nucleus and insula contrasted for emotional compared to neutral stimuli were also associated with successful treatment. Responders had also significantly higher levels of activation, compared to non-responders, in a range of other brain regions. Brain activation related to treatment success might be related to altered self-referential processes and a differential response to external emotional stimuli, suggesting differences in the processing of emotionally salient stimuli between those who are likely to respond to pharmacological treatment and those who will not. The present investigation suggests the pCC, dmPFC, SFG, caudate nucleus and insula may have a key role as a biological marker for treatment response and predictor for therapeutic success.
    • Enrichment of MCI and early Alzheimer's disease treatment trials using neurochemical and imaging candidate biomarkers.

      Hampel, H; Broich, K; Discipline of Psychiatry, School of Medicine, Trinity College, University of, Dublin, Trinity Center for Health Sciences, The Adelaide and Meath Hospital, incorporating the National Children's Hospital (AMiNCH), Tallaght, Dublin 24,, Ireland. harald.hampel@tcd.ie (2012-02-01)
      In the earliest clinical stages of Alzheimer's Disease (AD), when symptoms are mild, clinical diagnosis will still be difficult. AD related molecular mechanisms precede symptoms. Biological markers can serve as early diagnostic indicators, as markers of preclinical pathological change, e.g. underlying mechanisms of action (MoA). Hypothesis based candidates are derived from structural and functional neuroimaging as well as from cerebrospinal fluid (CSF) and plasma. Unbiased exploratory approaches e.g. proteome analysis or rater independent fully automated imaging post-processing methods yield novel candidates. Recent progress in the validation of core feasible imaging and neurochemical biomarkers for functions such as early detection, classification, progression and prediction of AD is summarized. Single core feasible biomarkers can already be used to enrich populations at risk for AD and may be further enhanced using distinct combinations. Some biomarkers are currently in the process of implementation as primary or secondary outcome variables into regulatory guideline documents, e.g. regarding phase II in drug development programs as outcome measures in proof of concept or dose finding studies. There are specific biomarkers available depending on the hypothesized mechanism of action of a medicinal product, e.g. impact on the amyloidogenic cascade or on tauhyperphosphorylation. Ongoing large-scale international controlled multi-center trials will provide further validation of selected core feasible imaging and CSF biomarker candidates as outcome measures in early AD for use in phase III clinical efficacy trials. There is a need of rigorous co-development of biological trait- and statemarker candidates facilitated through planned synergistic collaboration between academic, industrial and regulatory partners.
    • European obesity and the radiology department. What can we do to help?

      Buckley, O; Ward, E; Ryan, A; Colin, Walsh; Snow, A; Torreggiani, W C; Department of Radiology, Adelaide and Meath Hospital, Dublin, Ireland. (2012-02-01)
      Obesity is a chronic disease that is now a global epidemic. The numbers of obese people are exponentially rising in Europe, and it is projected that in Europe by 2010 there will be 150 million obese people. The obesity-related health crisis does not only affect adults, with one in four European children now overweight. Radiologists, both adult and paediatric, need to be aware of the magnitude of the problem, and obese patients cannot be denied radiologic evaluation due to their size. Missed diagnosis, appointment cancellation and embarrassing situations for patients when they are referred for a radiological examination for which they are not suitable are all issues that can be avoided if careful provision is made to accommodate the needs of the obese patient requiring radiologic evaluation. This paper will discuss the epidemiology of obesity and the role of radiology in the assessment of obesity and disorders of fat metabolism. The limitations obesity poses to current radiological equipment and how the radiologist can optimise imaging in the obese patient will be described. Dose reference levels and dose control are discussed. Examples of how obesity both hinders and helps the radiologist will be illustrated. Techniques and pre-procedural preparation to help the obese patient in the interventional suite are discussed.
    • Isolated trochlear infarction: an uncommon cause of acquired diplopia.

      Walsh, Richard A; Murphy, Raymond P; Moore, David P; McCabe, Dominick J H; Department of Neurology, The Adelaide and Meath Hospital, Dublin, Ireland. (2012-02-01)
    • Unusual long-term complications of a splenic cyst.

      Ward, E V M; O'brien, J; Conlon, K; Torreggiani, W C; Department of Radiology, The Adelaide and Meath Hospital, Dublin, Ireland. (2012-02-01)
      Splenic cysts are relatively uncommon, and are usually asymptomatic. They are benign, typically treated conservatively and followed up with ultrasound examination, with few reported complications. We report a case of a simple splenic cyst that was followed up on imaging over a seven-year period. During that time, the cyst gradually enlarged from 5 cm to 12 cm in diameter, however the patient remained asymptomatic. After seven years, the patient was admitted with abdominal pain and a pelvic mass. The spleen was located within the pelvis, which was felt to be due to the weight of the cyst which caused the spleen to migrate out of its normal position. This case illustrates an extremely unusual complication, and suggests that while most splenic cysts may be managed conservatively, enlarging cysts may be prone to gravitational effects and prophylactic treatment should be considered.