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    ABSTRACT: Primary progressive aphasia (PPA) has been proposed to comprise 3 discrete clinical subtypes: semantic, agrammatic/nonfluent, and logopenic. Recent consensus recommendations suggest a diagnostic framework based primarily on clinical and neuropsychological findings to classify these variants. Our objective was to evaluate the extent to which patients with PPA would conform to the proposed tripartite system and whether the clustering pattern of elements of the linguistic profile suggests discrete clinical syndromes. A total of 46 patients with PPA were prospectively recruited to the Cambridge Longitudinal Study of PPA. Sufficient data were collected to assess all consensus-proposed diagnostic domains. By comparing patients' performances against those of 30 age- and education-matched healthy volunteers, z scores were calculated, and values of 1.5 SDs outside control participants' means were considered abnormal. Raw test scores were used to undertake a principal factor analysis to identify the clustering pattern of individual measures. Of the patients, 28.3%, 26.1%, and 4.3% fitted semantic, nonfluent/agrammatic, and logopenic categories respectively, and 41.3% did not fulfill the diagnostic recommendations for any of the 3 proposed variants. There was no significant between-group difference in age, education, or disease duration. Furthermore, the outcome of the factor analysis was in keeping with discrete semantic and nonfluent/agrammatic syndromes but did not support a logopenic variant. Taken together, the results of this prospective data-driven study suggest that although a substantial proportion of patients with PPA have neither the semantic nor the nonfluent variants, they do not necessarily conform to a discrete logopenic variant.
    Neurology 05/2012; 78(21):1670-7.
  • Neurology 12/2009; 73(23):2039-40.
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    ABSTRACT: To evaluate a cognitive test, the TYM ("test your memory"), in the detection of Alzheimer's disease. Cross sectional study. Outpatient departments in three hospitals, including a memory clinic. 540 control participants aged 18-95 and 139 patients attending a memory clinic with dementia/amnestic mild cognitive impairment. Cognitive test designed to use minimal operator time and to be suitable for non-specialist use. Performance of normal controls on the TYM. Performance of patients with Alzheimer's disease on the TYM compared with age matched controls. Validation of the TYM with two standard tests (the mini-mental state examination (MMSE) and the Addenbrooke's cognitive examination-revised (ACE-R)). Sensitivity and specificity of the TYM in the detection of Alzheimer's disease. Control participants completed the TYM with an average score of 47/50. Patients with Alzheimer's disease scored an average of 33/50. The TYM score shows excellent correlation with the two standard tests. A score of <or=42/50 had a sensitivity of 93% and specificity of 86% in the diagnosis of Alzheimer's disease. The TYM was more sensitive in detection of Alzheimer's disease than the mini-mental examination, detecting 93% of patients compared with 52% for the mini-mental state exxamination. The negative and positive predictive values of the TYM with the cut off of <or=42 were 99% and 42% with a prevalence of Alzheimer's disease of 10%. Thirty one patients with non-Alzheimer dementias scored an average of 39/50. The TYM can be completed quickly and accurately by normal controls. It is a powerful and valid screening test for the detection of Alzheimer's disease.
    BMJ (online) 01/2009; 338:b2030.
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    ABSTRACT: The prospect of reward changes how we think and behave. We investigated how this occurs in the brain using a novel continuous performance task in which fluctuating reward expectations biased cognitive processes between competing spatial and verbal tasks. Critically, effects of reward expectancy could be distinguished from induced changes in task-related networks. Behavioral data confirm specific bias toward a reward-relevant modality. Increased reward expectation improves reaction time and accuracy in the relevant dimension while reducing sensitivity to modulations of stimuli characteristics in the irrelevant dimension. Analysis of functional magnetic resonance imaging data shows that the proximity to reward over successive trials is associated with increased activity of the medial frontal cortex regardless of the modality. However, there are modality-specific changes in brain activity in the lateral frontal, parietal, and temporal cortex. Analysis of effective connectivity suggests that reward expectancy enhances coupling in both early visual pathways and within the prefrontal cortex. These distributed changes in task-related cortical networks arise from subjects' representations of future events and likelihood of reward.
    Journal of Cognitive Neuroscience 05/2008; 20(11):1980-92.
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    ABSTRACT: Spinal epidural empyema (SEE) represents a severe pyogenic infection of the epidural space. Clinical signs of the disease are non-specific--increased body temperature, intense neck pain, neurological signs of a transverse myelopathy--and can lead to severe and permanent neurological deficits. This report describes the diagnosis and successful surgical treatment of cervical SEE secondary to grass awn migration in a cat. Although it is uncommon, this disease should be suspected in cats with progressive myelopathy. Early diagnosis and emergency surgery combined with antibiotic therapy are required to allow a complete recovery.
    Journal of Feline Medicine & Surgery 09/2007; 9(4):340-5.
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    ABSTRACT: Recovery of function following ischaemic stroke is a fascinating clinical observation. It comprises several modes, e.g. spectacular recovery in a matter of hours or days and gradual recovery over months or even years. That a non-functioning neural system can regain its function, even partially so, is challenging because of the obvious therapeutic implications. Until the mid-70s, however, dogmas largely prevailed which underpinned the then nihilistic approach to stroke patients. Proving these dogmas wrong has been a major achievement of modern stroke research. Thanks particularly to physiological imaging, key observations from the basic neurosciences have translated into the clinical realm in ways immediately understandable to the clinician, allowing the emergence of pathophysiology-based management.
    Cerebrovascular Diseases 02/2005; 20(3):154-63.
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    Journal of Neurology Neurosurgery &amp Psychiatry 12/2004; 75(11):1606.
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    ABSTRACT: A large pedigree with autosomal dominant frontotemporal dementia has been identified. Positional cloning has linked the disease gene to the pericentromeric region of chromosome 3. Clinical, neuropsychological, imaging, pathological and molecular genetic data are presented. The genetic mutation responsible for the disease has not been identified.
    Dementia and Geriatric Cognitive Disorders 02/2004; 17(4):274-6.
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    ABSTRACT: Using indirect whole genome association screening, we have searched for multiple sclerosis susceptibility genes in the genetically isolated high risk Sardinian population. Two screens were performed; the first was based on 229 cases and 264 unrelated controls, and the second on 235 trio families. Each screen employed a dense set of microsatellite markers and DNA pooling. Data from both screens were available from 2764 markers. Nine markers showed nominally significant results in both screens independently. Five of these markers-D2S408 (2q36), D6S271 (6p21), D6S344 (6p25), D7S1818 (7p12) and D16S420 (16p12)-remained nominally significant in both studies after conservative refining analysis.
    Journal of Neuroimmunology 11/2003; 143(1-2):120-3.
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    ABSTRACT: In 1996, we reported the results of a linkage genome screen based on 129 UK multiple sclerosis multiplex families, together with follow-up typing of interesting regions in a second set of families. We have now completed screening the remainder of the genome in this second set of United Kingdom families by typing 242 microsatellite markers. These data have been analysed together with those previously published, resulting in the largest currently available whole genome linkage dataset from a single population in multiple sclerosis. Four new regions of potential linkage (chromosomes 10p, 11p, 19p, 20p) not previously described were identified. In the combined analysis of all 226 families, a total of five regions of suggestive linkage are seen (chromosomes 1p, 6p, 14q, 17q, Xq), where only one would have been expected to occur by chance alone.
    Journal of Neuroimmunology 11/2003; 143(1-2):25-30.
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