Diagnosis of Creutzfeldt-Jakob disease

Editor—Collinge et al recommend that tonsil biopsy be considered in all those in whom new variant Creutzfeldt-Jakob disease is suspected.¹ Though the detection of protease resistant prion protein in tonsillar tissue from a young person with a rapidly progressive dementia may have a high specificity for this diagnosis, there are no published data on sensitivity, specificity, or safety; the procedure carries the risk of haemorrhage and infection as well as the risks associated with anaesthesia. Some patients clinically suspected of having new variant Creutzfeldt-Jakob disease, and therefore potential candidates for tonsil biopsy, have subsequently recovered.² Further information is obviously required, and we concur with the recommendation of a recent WHO consultation that this should come from postmortem studies.³

Brain biopsy has been carried out in 9 of the 27 cases of new variant Creutzfeldt-Jakob disease in the United Kingdom. This procedure has risks but, in contrast to tonsillar biopsy, enables potentially treatable neurological disorders to be identified. New variant Creutzfeldt-Jakob disease is confirmed in about 1 in 7 cases,² and routine tonsillar biopsy in the population of suspected cases would lead to a high proportion of negative results. A negative result on tonsillar biopsy does not preclude the necessity to proceed to brain biopsy in selected cases. There is clearly a need for a non-invasive diagnostic test for new variant Creutzfeldt-Jakob disease, and preliminary investigation indicates that the presence of posterior thalamic high signal on brain magnetic resonance imaging may be diagnostically useful.⁴

The accepted clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease have depended on electroencephalography, and an alternative paraclinical criterion would be useful. Cerebrospinal fluid 14-3-3 protein has proved to be a remarkably sensitive and specific marker for sporadic Creutzfeldt-Jakob disease when used appropriately. Protease resistant prion protein has not been detected in palatine tonsillar tissue obtained at necropsy from the small number of patients with sporadic Creutzfeldt-Jakob disease studied to date (unpublished data).⁵ Unless necropsy studies yield positive results, the clinical use of tonsil biopsy in sporadic Creutzfeldt-Jakob disease is not justified.