Review

Neuropathology and Applied Neurobiology - Tập 24 Số 2 - Trang 104-117 - 1998
Paul G. Ince1, James Lowe2, Pamela J. Shaw3
1Department of Neuropathology, Newcastle General Hospital, ,
2Department of Clinical Neurology, University of Newcastle upon Tyne ,
3Department of Clinical Laboratory Sciences, Queens Medical Centre, Nottingham, UK

Tóm tắt

P. G. Ince, J. Lowe and P. J. Shaw (1998) Neuropathology and Applied Neurobiology24, 104–117Amyotrophic lateral sclerosis: current issues in classification, pathogenesis and molecular pathologyThe classification of amyotrophic lateral sclerosis (ALS) is reconsidered in the light of developments in the molecular pathogenesis and histopathology of the condition. A current view is encapsulated in the El Escorial World Federation of Neurology criteria for the diagnosis of ALS. While intended for research purposes, use of these criteria for entry into clinical trials may result in the exclusion of some patient groups with related disorders that are likely to share aetiological mechanisms but which are not classified as ‘definite ALS’ or ‘probable ALS’. The relationship between ALS and the more restricted motor disorders of progressive lateral sclerosis and progressive muscular atrophy, together with cerebral degenerations including ALS‐dementia and ALS‐related frontal lobe dementia, are reviewed. The possibility is raised that they all represent syndromic manifestations of a similar pathogenetic cascade whose clinical phenotype depends upon the anatomical selectivity of involvement in each individual. The new evidence regarding the central role of oxidative stress and abnormal glutamatergic neurotransmission in familial and sporadic ALS seem applicable across these disorders. New evidence regarding the molecular pathology of inclusion bodies in these various syndromes, including ubiquitinated inclusions and hyaline conglomerate inclusions, shows striking similarities between them. Marked differences in the anatomical distribution of lesions determine the predominance and type of motor and cognitive features in each syndrome. This concept of a clinicopathological spectrum is potentially of equal relevance to other late onset neurodegenerative disorders including multisystem atrophies, the Lewy body disorders and various manifestations of Alzheimer's disease. It will gain increasing importance as therapies evolve from the symptomatic to those directed at underlying pathogenetic events.

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Neuropathology and Applied Neurobiology

Tập 24 Số 2

104-117

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