446 research outputs found

    The role of microglia in human disease: therapeutic tool or target?

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    Modelling neurological diseases in large animals: criteria for model selection and clinical assessment

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    Issue: The impact of neurological disorders is recognised globally, with one in six people affected in their lifetime and few treatments to slow or halt disease progression. This is due in part to the increasing ageing population, and is confounded by the high failure rate of translation from rodent-derived therapeutics to clinically effective human neurological interventions. Improved translation is demonstrated using higher order mammals with more complex/comparable neuroanatomy. These animals effectually span this translational disparity and increase confidence in factors including routes of administration/dosing and ability to scale, such that potential therapeutics will have successful outcomes when moving to patients. Coupled with advancements in genetic engineering to produce genetically tailored models, livestock are increasingly being used to bridge this translational gap. Approach: In order to aid in standardising characterisation of such models, we provide comprehensive neurological assessment protocols designed to inform on neuroanatomical dysfunction and/or lesion(s) for large animal species. We also describe the applicability of these exams in different large animals to help provide a better understanding of the practicalities of cross species neurological disease modelling. Recommendation: We would encourage the use of these assessments as a reference framework to help standardise neurological clinical scoring of large animal models

    The comparative neuropsychology of dementia

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    PhD ThesisOn the basis of neuropathological, neurochemical, genetic, and clinical profile studies on patients, distinct forms of dementia, such as dementia with Lewy bodies (DLB), have been distinguished which were originally thought to be Alzheimer's disease (AD). Dementia with Lewy bodies is probably the second most common form of dementia in the elderly. In this thesis, a well characterised and investigated cohort of DLB and AD patients were compared to non-demented elderly controls in order to establish profiles of cognitive decline in these groups. Initially, comprehensively matched experimental groups were compared using the Cambridge Neuropsychological Test Automated Battery (CANTAB). The DLB group was less impaired than the AD group on a test of visual pattern recognition memory. However, the DLB group performed worse on a number of cognitive tests. Comparison of larger, carefully matched, experimental groups using the Cognitive Drug Research Computerised Assessment Battery (CDR) also revealed differences in the profile of cognitive impairment in DLB and AD. The DLB group showed more marked deficits in attentional abilities than the AD group. In particular, the DLB group were unable to sustain attention. Conversely, the DLB group were less impaired on a test of visual secondary recognition memory than the AD group. Further division of the DLB group into cases with and without persistent visual hallucinations revealed distinct patterns of cognitive impairment in these two groups. Generally, DLB cases with persistent visual hallucinations showed greater attentional and spatial working memory deficits than the DLB cases without persistent visual hallucinations. A final study compared decline in cognitive function over 1 year in DLB, AD and control groups. Similar rates of cognitive decline were identified in a number of cognitive domains in AD and DLB groups. In addition, disproportionate decline in the ability to sustain attention was identified in the DLB group. A comparative model relating known neuropsychological, neurochemical, and neuropathological features of DLB and AD was proposed

    MCV/Q, Medical College of Virginia Quarterly, Vol. 12 No. 3

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    Immunogenetic and viral study of alzheimer's disease

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    The principal aims of the study were: 1) To identify possible genetic and immunological factors in AD, by studying ABO and Rhesus blood groups, and HLA antigens, in patients suffering from this disorder. 2) To clarify the nosological relationship between PDAT and SDAT using these genetic markers, and by family studies. 3) To determine if any HLA antigen, found to be significantly associated with AD, influences the clinical features of the disorder. 4) To investigate the possible role of CMV in the aetiology of AD

    Pupillary Response in an Auditory Rhythm Omissions Task in Parkinson´s Disease: A Pilot Study

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    When presented with short, rhythmical, musical excerpts, containing omitted beats which vary in saliency in terms of rhythmical patterns (contextual omission), and position (salience omissions), fMRI studies have shown a small effect depending on position of omission. Furthermore, when presented with auditory stimuli, a pupillary dilation response (PDR) is evoked, resulting in a pupillary peak dilation (PPD) sometime after stimulus onset. By utilizing and adapting an auditory beat-omission fMRI paradigm, to allow measurement of PDR and PPD, we used pupillometry data to investigate the effect of contextual omission (Simple vs Complex rhythm) and salience omission (O1 vs O2). We report data from a total of 25 participants, based on 45 datasets. The data were analyzed using four separate direct t-tests. We found that the omission has an effect on PPD, in that the most metrical salient omission (O1) results in a higher activation level compared to a less salient omission (O2), i.e., PPD was significantly higher in O1 simple rhythm omissions, and in O1 complex rhythm omissions, at an uncorrected threshold level.Masteroppgave i psykologiMAPSYK360INTL-HFINTL-PSYKINTL-SVINTL-MNINTL-MEDINTL-KMDMAPS-PSYKINTL-JU

    Early detection of central nervous system involvement in hypothyroidism by electrophysiological study

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    INTRODUCTION: Hypothyroidism is one of the most common endocrine disorders, affecting over one percent of the general population and about 5 percent of individuals over age of 60 years. It is a syndrome characterised by the clinical and biochemical manifestation of thyroid hormone deficiency in the target tissue. Iodine deficiency remains the most common cause of hypothyroidism worldwide. In areas of iodine sufficiency, autoimmune disease (Hashimotos thyroiditis) and iatrogenic causes (treatment for hypothyroidism) are most common. AIM AND OBJECTIVES: 1. This study was undertaken to compare electrophysiological parameters between hypothyroid patients and control. 2. To evaluate functional changes in nervous system in hypothyroidism by different electrophysiological parameters like visual evoked potential, Brain stem auditory evoked potential, Somatosensory evoked potential. MATERIALS AND METHODS: This study was conducted in the Department of Physiology, Thanjavur Medical College & hospital, Thanjavur. Case control type of study was done. The study period extended between may 2011 to 2012. The patients were selected from medicine and surgery department. Out of 40 subjects, 7 males and 33 females with Hypothyroidism of age group (17-64 years) were selected. Diagnosis of hypothyroidism was confirmed when the total thyroxine level was below 4μg/dl and the thyrotropin level was above 4.5mU/ml. A history was taken, and a complete medical examination and neurological examination were out for every patient. Out of 40 controls, 10 males, 30 females, of age group (17-64 years) were selected. Inclusion criteria: • Patients with biochemical evidence of hypothyroidism (Serum total thyroxine 4.5mU/ml. Exclusion criteria: • Diabetes mellitus. • Neurological disorders. • Psychiatric illness. • Seizures. • Hypertension. • Eye diseases (severe myopia, cataract, glaucoma etc). • Collagen disease. • Renal impairment. • Drug abuse. RESULTS: Out of 80 subjects, 40 were hypothyroid patients forming the study group and remaining 40 were normal subjects forming control group. In this study hypothyroid patients who form the study group were in age group 17-64 years, mean 39.64 and the subjects in control groups were in the age group 17-64 years, mean 35.75. The mean values and their standard deviation for the control group and the study group of hypothyroids were tabulated. The two groups differ significantly in various electrophysiological parameters like VEP, BAEP, and SSEP. ’P’ value was derived from data analysis by using statistical package SPSS version 18 and statistical analysis was done by student ‘t’ test. The statistical significance was considered at p value < 0.05. CONCLUSION: The result of present study shows that there is involvement of Central Nervous System in hypothyroidism. The hypothyroid patients show prolongation of latency in electrophysiological studies. Electrophysiological parameters like P100 latency of VEP, latency and inter peak latencies of I-III, III-V, I-V of BAEP and peripheral and cortical latencies of SSEP of median nerve were evaluated. The observation shows prolongation of latencies suggestive of central nervous system involvement in hypothyroidism. This study suggests that periodic evaluation of hypothyroid patients to electrophysiological test will help in monitoring the progress of neuropathy and earlier detection of nervous system involvement to reduce the morbidity of hypothyroid patients. However further studies are required to evaluate the correlation between the electrophysiological parameters and thyrotropin (TSH) level and duration of disease so that preventive measures can be suggested to prevent the central nervous system involvement
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