1 Clinical Lewy Body Syndromes I.G. MCKEITH a Department of Old Age Psychiatry, Institute for the Health of the Elderly, Wolfson Research Centre, Newcastle General Hospital, Newcastle upon Tyne, United Kingdom ABSTRACT: Lewy bodies are spherical, intracytoplasmic, eosinophilic, neuronal inclusions comprising abnormally truncated and phosphorylated intermediate neurofilament proteins, -synuclein, ubiquitin, and associated enzymes. The clinical presentation of LB disease varies according to the site of LB formation and associated neuronal loss. Three main clinicopathological syndromes have been described—movement disorder, autonomic failure, and dementia. Par- kinsonism is the most common presentation of LB disease developing in middle life. In older patients, a mixture of cognitive, autonomic, and motor dysfunc- tion is more common. Dementia with LB (DLB) is a relatively recently de- scribed clinicopathological syndrome that accounts for up to 20% of all cases of dementia in old age. Patients, typically in their seventh and eighth decades, have LB pathology in cortical neurons as well as in the brain stem. LB disease should be considered in the differential diagnosis of a wide range of clinical presentations including episodic disturbances of consciousness, syncope, sleep disorders, and unexplained delirium. THE SPECTRUM OF LEWY BODY DISEASE Despite early reports, Lewy bodies (LB) probably do not occur in normal ag- ing. 1,2 Their presence indicates neurological disease, the clinical presentation vary- ing according to the site of LB formation and associated neuronal loss. Three main clinicopathological syndromes have been described. 3 • Parkinson’s disease (PD), an extrapyramidal movement disorder, associated with degeneration of subcortical neurons, particularly in substantia nigra. • Dementia with Lewy bodies (DLB), a dementing disorder with prominent neu- ropsychiatric features, associated with degeneration of cortical neurons, par- ticularly in entorhinal anterior cingulate, insular, temporal, and frontal regions. • Primary autonomic failure with syncope and orthostatic hypotension, associ- ated with degeneration of sympathetic neurons in spinal cord and autonomic ganglia. In clinical practice, patients often have heterogenous combinations of parkin- sonism, dementia, and autonomic failure, reflecting pathological involvement at a Address for correspondence: I.G. McKeith, Department of Old Age Psychiatry, Institute for the Health of the Elderly, Wolfson Research Centre, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, UK. Tel.: 00 44 191 256 3018; fax: 00 44 191 219 5071. e-mail: i.g.mckeith@ncl.ac.uk