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Symposium on disorders of memory
013 Differential diagnosis of rapidly progressive dementia
  1. R Knight

    Author information: Richard Knight graduated from Oxford in PPE and then Medicine, undertaking postgraduate training in a variety of UK hospitals leading to a first NHS Consultant appointment in at Aberdeen Royal Infirmary in 1987. He moved to Edinburgh in 1996 where he now holds a Personal Chair of Clinical Neurology at the University of Edinburgh and is an Honorary Consultant Clinical Neurologist in the Lothian University Hospitals Trust. He is the current Director of the National CJD Surveillance Unit with specific research interests in the epidemiology, surveillance, clinical features and diagnosis of human prion disease.


Abstract: Dementia, as a clinical syndrome, has many potential causes. The majority of cases are due to neurodegenerative diseases and/or vascular disease with relatively gradual progressive clinical courses. However, dementia can be rapidly progressive with time courses measured in only weeks or a few months. These more rapidly progressive dementias often have clinical characteristics that are distinctive from the more typical slower dementias and with different aetiological considerations. There is no specific definition of “rapidly progressive dementia (RPD)”. This talk will review the differential diagnosis of RPD in adults. Infections must be considered, including HIV-associated dementia, PML, SSPE, Whipples disease and prion diseases. Malignancy enters into the differential diagnosis in a variety of ways: rapidly progressive brain primary neoplasm, cerebral secondaries, intravascular lymphoma and non-metastatic encephalopathy. There are a number of miscellaneous immunological/inflammatory disorders, including Hashimoto's Encephalopathy, Morvan's Syndrome and primary cerebral vasculitis. Some causes (such as malignancy) are relatively common and usually relatively easy to diagnose and some may be suggested by past medical history or clinical context (as with HIV) but there are also great rarities (like Whipple's disease) that may be very difficult to confirm. Many of these conditions, especially other infections, will have helpfully differentiating systemic features, general test abnormalities, a CSF pleocytosis and brain imaging abnormalities. Primary and secondary malignancies should be demonstrable on cerebral imaging. Some conditions will have specific diagnostic tests such as HIV testing. Various antibody tests will be helpful in certain situations such as Morvan's syndrome, Hashimoto's encephalopathy and paraneoplastic syndromes. There are no specific, non-invasive tests for prion diseases in general, although genetic testing is available for those associated with PRNP mutations. Clinical diagnosis depends on a combination of clinical features, EEG and cerebral MRI characteristics and CSF protein findings. In sporadic CJD, the EEG and CSF 14-3-3 testing have been the main relevant supportive tests, but certain brain MR appearances have been evaluated in recent times. In variant CJD, the brain MR Pulvinar Sign and tonsil biopsy have been most useful. Brain biopsy may be considered in a minority of cases. Autopsy may be necessary for definitive diagnosis of RPD, especially in prion diseases.

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