Showing papers by "David Neary published in 2004"

Knowledge of famous faces and names in semantic dementia.

Abstract: Semantic dementia is a focal clinical syndrome, resulting from degeneration of the temporal lobes and characterized by progressive loss of conceptual knowledge about the world. Because of the highly circumscribed nature of the disorder it is a natural model for improving understanding of how semantic information is cerebrally represented. There is currently a lack of consensus. One view proposes the existence of modality specific meaning systems, in which visual and verbal information are stored separately. An opposing view assumes that information is represented by a unitary, amodal semantic system. The present study explores these alternatives in an examination of famous face and name knowledge in 15 patients with semantic dementia. The study of face recognition in patients with an established semantic disorder also permits an examination of the relationship between semantic dementia and the focal clinical syndrome of progressive prosopagnosia. The semantic dementia patients were profoundly impaired on both face and name identification and familiarity judgement tasks compared with amnesic patients with Alzheimer's disease and healthy controls. However, whereas the two reference groups performed better for names than faces, the semantic group showed the opposite pattern. This overall profile masked individual differences: semantic dementia patients with predominant left temporal lobe atrophy showed better recognition of names than faces, whereas patients with right temporal predominance showed the reverse pattern. Relative superiority for names or faces was mirrored by corresponding superiority for words or pictures on a standard semantic test. We interpret the findings as inconsistent with a unitary, amodal model of semantic memory. However, the data are not wholly compatible with a strict multiple system account. The data favour a model of semantic memory comprising a single interconnected network, with dedicated brain regions representing modality specific information. The data emphasize the importance of the anterior, inferolateral parts of the left temporal lobe for the representation of names and the corresponding parts of the right temporal lobe for faces. Dissociations between face and name knowledge provide a challenge for existing models of face processing. Moreover, they lead us to argue that the focal syndrome of progressive prosopagnosia is one of the clinical presentations of semantic dementia and not a separate clinical entity.

Autopsy proven sporadic frontotemporal dementia due to microvacuolar-type histology, with onset at 21 years of age.

Abstract: We describe the clinical, neuropsychological, and neuropathological features of a 21 year old woman with frontotemporal dementia (FTD). The early presentation was of florid behavioural change involving hyperactivity and disinhibition. Magnetic resonance imaging and single photon emission computed tomography of the brain revealed atrophy and severe functional abnormalities of the frontal and temporal lobes, respectively. Electroencephalogram was normal. At autopsy, there was gross frontotemporal brain atrophy and the underlying histology was of a microvacuolar-type degeneration; no tau or ubiquitin immunoreactive, intraneuronal inclusions were seen. There was no family history of dementia and no mutation in the tau gene. We believe this patient represents the youngest (so far) recorded case of FTD associated with this particular histological form of the disorder.

Evidence of a founder effect in families with frontotemporal dementia that Harbor the tau+16 splice mutation

Abstract: The +16 exon 10 splice mutation of the tau gene (microtubule-associated protein tau, MAPT) has been reported in numerous families with frontotemporal dementia (FTD). To date, the majority of these families are from England and Wales in the UK, although families with this mutation have been reported from Australia and the USA. Our own analysis has identified eight families with the +16 MAPT splice mutation from around the Manchester and North Wales areas of the UK. Given the proximity of the UK families to one another it is likely that they are related and represent a single extended pedigree. In order to investigate this possibility, and the possibility that the families with this mutation from London, the USA, and Australia are related, we genotyped 11 microsatellite markers around the tau locus. In most cases (20/25, 80%), a common haplotype, approximately 3 cM in size, was identified. In the remaining cases, this haplotype appears to have been varyingly reduced in size by recombination. We demonstrate that the +16 mutation is on the H1 tau haplotype and that H1 specific polymorphisms are also shared by these families. These data provide evidence that the MAPT +16 splice mutation cases from around the world analyzed in this study are indeed related and represent a single pedigree that probably originated in the North Wales area of the UK. Furthermore, this single large pedigree may be of use in the identification of disease modifying loci in FTD.

Coexistence of systemic sclerosis and multiple sclerosis.

Abstract: Sirs: A previous letter in this journal describing the rare combination of multiple sclerosis (MS) and systemic sclerosis (SSc) raised questions regarding a possible common pathogenic link [1]. We report a further two patients with both MS and SSc and discuss whether there might be an association between the diseases. Case 1: This patient originally presented in 1985 aged 28 years. She had increased tone in both legs with a spastic gait and bilateral dysdiadochokinesia. Lhermitte’s sign was positive. Three months later she developed diplopia, nystagmus, and an ataxic gait. In 1989 cerebrospinal fluid analysis was normal, but a magnetic resonance scan showed high signal intensity abnormalities in the periventricular white matter and corona radiata, in keeping with the diagnosis of MS. However, visual evoked potentials performed in 2000 were normal. In 1995 she developed Raynaud’s phenomenon and dysphagia. Examination showed mild sclerodactyly. She was anticentromere antibody positive. Nail fold microscopy showed a few slightly dilated capillary loops. A barium swallow confirmed a motility problem and a diagnosis of limited cutaneous SSc was made. Case 2: This woman first developed neurological symptoms in 1987 aged 37 years when she complained of numbness in her legs. She then presented in 1991 with deteriorating vision in her right eye. On examination she had decreased acuity with a large central scotoma and optic atrophy. The cerebrospinal fluid contained oligoclonal bands. Visual evoked potentials in the right eye showed small and moderately delayed responses and a diagnosis of MS was made. She had previously presented to the rheumatology service in 1983 with a fingertip pulp infarct, having developed Raynaud’s phenomenon around 1976. In 1987 calcinosis was noted on a hand radiograph. In 1997 she was noted to have sclerodactyly, telangiectases, and perioral sclerosis. An autoimmune screen was negative, but nail fold microscopy showed avascular areas and a barium swallow revealed abnormal motility, consistent with a diagnosis of limited cutaneous SSc. There have been only five reported cases of SSc occurring in conjunction with multiple sclerosis [1–5]. Of the 259 patients with SSc seen in our department over the past five years, no others have had MS. A prevalence of 2 out of 259 patients (0.77 %) contrasts with a prevalence for MS of 116–122 per 100,000 (~0.12 %) in the population of Northwest England [6]. While these numbers do not allow any firm conclusions, nonetheless it is interesting to speculate whether the coexistence of these two diseases is not purely coincidental, especially as both diseases have an autoimmune basis [7]. Central nervous system involvement has only rarely been described in systemic sclerosis and, when it does occur, may not be integral to the disease process, but secondary to renal or cardiovascular damage [8]. Both MS and SSc are diseases in which it has been LETTER TO THE EDITORS