Institute of Neurological science
Institute of Neurological science
Rossit S.,University of Western Ontario |
Malhotra P.,Imperial College London |
Muir K.,Institute of Neurological science |
Reeves I.,Southern General Hospital |
And 2 more authors.
Cerebral Cortex | Year: 2011
Recent evidence suggests the possibility that not all action modes depend on dorsal visual stream processing but that off-line nontarget-directed actions, such as antipointing, require additional and even distinct neural networks when compared with target-directed online actions. Here, we explored this potential dissociation in a group of 11 patients with left visual neglect, a syndrome characterized by a loss of awareness of the contralesional side of space. Ten healthy participants and 10 right hemisphere-damaged patients without neglect served as controls. Participants had to point either directly toward targets presented on their left or right (i.e., propointing) or to the mirror position in the opposite hemispace (i.e., antipointing). Compared with both control groups, neglect patients showed reduced accuracy when antipointing but not propointing. Lesion-behavior mapping revealed that the areas critically associated with these deficits were located in the middle and superior temporal and parahippocampal gyri. We argue that neglect patients present specific deficits only when the visuomotor task taps into more perceptual representations thought to rely on ventral visual stream processing and that our results indicate that right temporal brain regions are implicated in these off-line actions. © 2011 The Author.
Ito S.,Institute of Neurological science |
Nakaso K.,Institute of Neurological science |
Imamura K.,Institute of Neurological science |
Takeshima T.,Institute of Neurological science |
Nakashima K.,Institute of Neurological science
Neuroscience Research | Year: 2010
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the selective loss of dopaminergic neurons and the presence of Lewy bodies. α-Synuclein is a major component of Lewy bodies. Recently, many studies have focused on the interaction between α-synuclein and catecholamine in the pathogenesis of PD. However, no detailed relationship between cathecholamine and α-synuclein cytotoxicity has been elucidated. Therefore, this study established PC12 cell lines which overexpress human α-synuclein in a tetracycline-inducible manner. The overexpression of human α-synuclein increased the number of apoptotic cells in a long-term culture. Moreover, human α-synuclein expressing PC12 cells demonstrated an increased vulnerability to several stressors in a short culture period. Thapsigargin increased the SDS soluble oligomers of α-synuclein associated with catecholamine-quinone. The unfolded protein response (UPR) study showed that thapsigargin increased eIF2α phosphorylation and nuclear GADD153/CHOP induction under α-synuclein overexpressed conditions. The activities of the ATF6α and IRE1α pathways decreased. These findings suggest that an overexpression of α-synuclein partly inactivates the UPR. α-Methyltyrosine inhibited the dysfunction of the UPR caused by an overexpression of human α-synuclein. Therefore, these findings suggest that the coexistence of human α-synuclein with catecholamine enhances the endoplasmic reticulum stress-related toxicity in PD pathogenesis. © 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society.
Pezzino S.,Institute of Neurological science |
Paratore S.,Institute of Neurological science |
Cavallaro S.,Institute of Neurological science
Current Pharmaceutical Design | Year: 2011
The advent of "systems biology" has highlighted that any function of a biological system is rarely attributable to a single molecule or a single process. Hence, complex processes, such as apoptosis and survival, depend on the activity of an integrated network of genes and their encoded proteins, which almost never work alone but interact with each other in highly structured and incredibly complex ways. With the completion of genome sequencing in humans and model organisms, and the advent of DNA microarray technology, the transcriptional cascades and gene networks regulating neuronal apoptosis and survival are being elucidated providing new potential pharmacological targets. The emerging challenge is the effective selection of the myriad of targets to identify those with the most therapeutic utility. The present review will illustrate how the identification, prioritization and validation of preclinical therapeutics can be achieved through genomic analysis of critical pathways and networks in neuronal apoptosis and survival. © 2011 Bentham Science Publishers Ltd.
Gabreyes A.A.,Royal Infirmary |
Abbasi H.N.,Institute of Neurological science |
Forbes K.P.,Institute of Neurological science |
Mcquaker G.,Royal Infirmary |
And 2 more authors.
European Journal of Haematology | Year: 2013
Copper is an essential trace element that is involved in a number of important enzymatic processes throughout the body. Recent single case reports and small studies have shown that deficiency of copper can cause reversible haematological changes and irreversible neurological injury. We chose to undertake a national study, looking at all cases of copper deficiency in Scotland over a 5-yr period using information from a national reference laboratory. From 16 identified patients, we determined that 86% had both haematological and neurological features of copper deficiency, while 18% had haematological features only at presentation. Twelve of the sixteen patients had high serum zinc concentrations (>18 μm/L) nine patients were using zinc-containing dental fixatives at time of diagnosis. 94% of patients had haematological features as an initial manifestation of copper deficiency, which included anaemia, thrombocytopenia and neutropenia. Patients who underwent later bone marrow testing had appearances in keeping with refractory cytopenia with multilineage dysplasia, refractory anaemia with excess of blasts, unclassified marrow dysplasia or probable myelodysplasia (MDS). 75% of patients had neurological symptoms or signs, including progressive walking difficulties and paraesthesia, or gait difficulties without sensory signs. Clinical examination was in keeping with spastic paraparesis (either with or without sensory neuropathy). Magnetic resonance imaging (MRI) showed multifocal T2 hyper intense foci in the subcortical white matter, and atrophy of the cerebrum and cerebellum was also seen on computerised tomography (CT). MRI of the spinal cord showed signal change in the dorsal columns in either the cervical or thoracic cord. 93% of cytopenias responded to copper replacement and addressing the original cause of the copper deficiency, but only 25% of patients had improvement in their neurological function, while 33% deteriorated and 42% remained unchanged. Our study demonstrates that copper deficiency is an under-recognised cause of several types of cytopenia, which are reversible but can progress to significant neurological injury if left untreated. We illustrate the importance of identifying these patients early to prevent irreversible neurological injury. © 2012 John Wiley & Sons A/S.
Hunter M.A.,Royal Alexandra Hospital |
Santosh C.,Institute of Neurological science |
Teasdale E.,Institute of Neurological science |
Forbes K.P.,Institute of Neurological science
American Journal of Neuroradiology | Year: 2012
We performed high-resolution DIR-BBI of the cervical arteries at 3T in 19 subjects with cervical dissection. It offered excellent visualization of both the lumen and arterial wall, allowing detection of the primary and secondary features of dissection. We suggest that this is a highly useful technique for diagnosis of cervical dissection, either routinely or in equivocal cases of suspected dissection. It also offers further insight into the pathogenesis of this disorder.
Condon B.,Institute of Neurological science
EPMA Journal | Year: 2011
MRI/MRS can produce information on over 40 physico-chemical parameters regarded as biomarkers of structural, functional or metabolic significance. Though of undisputed worth in the detection of macroscopic lesions or of metabolic derangements, MRI's use in prognosis and prediction has not been so extensively studied. Serial studies can be performed to show early pre-clinical changes in biomarkers caused by disease progression or therapy, such as the adverse effect on heart function of certain cancer therapies. It can utilise various haemodynamic measures to predict the evolution of stroke and so help justify certain interventions. Changes in cerebral metabolite concentrations or the volumes of brain sub-structures can be used as objective measures of drug response in psychiatric conditions. However care must be exercised as MR can sometimes be considered 'too sensitive' as it often detects real abnormalities even in asymptomatic volunteers, the actual predictive significance of which have yet to be fully assessed. © 2011 European Association for Predictive, Preventive and Personalised Medicine.
Shaw M.,Institute of Neurological science
Acta neurochirurgica. Supplement | Year: 2012
Cerebral pressure autoregulation (AR) is a process by which blood flow is kept constant over a specific cerebral perfusion pressure (CPP) range. There have been a number of advances in recent years in the monitoring and modelling of this physiological variable; however, there has been very little work done on the comparison or optimisation of some of the existing models in clinical use today: pressure reactivity index, highest modal frequency techniques and compartmental modelling. Presented here is a methodology for the comparison and optimisation results for these main AR models. By simple mathematical manipulation of the original modelling end points each model can be converted into a form that is directly comparable to the others. Using a standardised data set with known gold standard AR status indications, the models can then be readily assessed. As a consequence each of the models can then be optimised to maximise specificity and sensitivity.
Grosset D.,Institute of Neurological science
Journal of the Neurological Sciences | Year: 2010
The response to dopamine replacement therapy in patients with degenerative parkinsonism is variable. Reasons for a poor therapy response include the type of parkinsonism, comorbidities, and differential effects on clinical features. An additional explanation, which has received much less attention, is sub-optimal therapy compliance. Single and multicentre studies of therapy compliance report significant under- and overuse of dopamine replacement therapy resulting in poor symptomatic control, or features of the dopamine dysregulation syndrome or other signs of dopaminergic excess (dyskinesia, confusion, visual hallucinations). In this article, the evidence for sub-optical adherence in Parkinson's disease (PD) is reviewed, and factors associated with sub-optimal compliance were examined, with two case vignettes to illustrate clinical consequences of deviation from the prescribed therapy regimen. © 2009.
Vijayaraghavan L.,Institute of Neurological science |
Natarajan S.,Institute of Neurological science |
Krishnamoorthy E.S.,Institute of Neurological science
Behavioural Neurology | Year: 2011
Disturbances in cognitive function, particularly memory, are a common complaint of patients with epilepsy. Factors contributing to cognitive dysfunction are the type of epilepsy, type and frequency of seizures, anti-epileptic drugs and the location of underlying brain lesions. Whilst a great deal of attention has been paid to permanent cognitive impairment, the nature and underlying mechanisms of ictal and peri-ictal cognitive changes are poorly understood. In-depth investigation of seizure related cognitive dysfunction is of great clinical relevance, as these changes are potentially reversible and treatable, thus reducing the cumulative effect of frequent seizures Greater knowledge of peri-ictal and ictal cognitive dysfunction would improve seizure prediction, localization of seizure focus and assessment of treatment effectiveness, greatly reducing distress and disability. This paper will review current understanding of peri-ictal and ictal cognitive dysfunction and discuss future directions for research.
Handique S.K.,Institute of Neurological science
Neuroimaging Clinics of North America | Year: 2011
Viral infections of the central nervous system in the tropical countries of Asia and the Indian subcontinent are different from those of the Western and developed world. Many of the endemic and epidemic encephalitides that are prevalent in these regions, such as Japanese encephalitis, have characteristic findings on imaging, especially on magnetic resonance imaging, allowing a rapid diagnosis and differentiation from clinically similar syndromes. Other emerging viral infections in the region in recent years have posed new challenges. The contribution of neuroimaging to the management of these emerging infections is also discussed. © 2011 Elsevier Inc.