Summary Background There is a need for an accurate non-invasive diagnostic test for variant Creutzfeldt-Jakob disease (vCJD). We investigated the sensitivity and specificity of bilateral pulvinar high signal on magnetic resonance imaging (MRI) for the diagnosis of vCJD. Methods MRI from patients with vCJD and controls (patients with suspected CJD) were analysed. Scans were reviewed on two separate occasions by two neuroradiologists and scored for the distribution of changes, and likely final diagnosis. Scans from vCJD cases were reassessed to reach a consensus on all abnormalities. Findings We analysed 36 patients and 57 controls. vCJD patients were correctly identified based on bilateral pulvinar high signal in 29 of 36 and 32 of 36 cases on the first assessment by the two radiologists, and 32 of 36 and 31 of 36 on their second assessment. Bilateral increased pulvinar signal was identified in one of 57 and one of 57 controls on the first assessment and two of 57 and three of 57 controls on the second assessment. These reported changes in controls were graded as minimal/equivocal in six of seven patients and moderate in one (<0·5% of all control assessments). 80% of the assessments in vCJD cases were graded as moderate or substantial. On consensus review, 28 of 36 cases and none of 57 controls had prominent bilateral pulvinar signal—sensitivity 78% (95% CI 60–90%) and specificity 100% (95% CI 94–100%). Other common MRI features of vCJD were medial thalamic and periaqueductal grey matter high signal, and the notable absence of cerebral atrophy. Pulvinar high signal correlated with histological gliosis. Interpretation In the appropriate clinical context the MRI identification of bilaterally increased pulvinar signal is a useful non-invasive test for the diagnosis of vCJD. Lancet 2000; 355: 1412–18 See Commentary page ??? Introduction Creutzfeldt-Jakob disease (CJD) is a rare and fatal neurodegenerative disorder that occurs in four forms: sporadic, iatrogenic, familial, and variant. 1 The diagnosis of CJD is important for clinical management, public health, and epidemiological purposes. Definitive diagnosis currently relies on neuropathological findings and therefore requires cerebral biopsy or necropsy. There is no non-invasive in vivo diagnostic test with 100% accuracy at present. Standard clinical diagnostic criteria 2 have been established for sporadic, iatrogenic, and familial CJD, allowing reasonably accurate diagnosis in most of these patients. For variant CJD (vCJD), however, there is no standard clinical diagnostic criteria, partly because there has been less accumulated clinical experience with this condition. Although cases of vCJD to date have had fairly characteristic clinical features, 3–5 none of the characteristics were specific. It would therefore be useful to have diagnostic support from routine clinical investigations. The electroencephalogram (EEG) has played an important part in the diagnosis of sporadic CJD 6 but the characteristic periodic changes are not a feature of vCJD. 3 The cerebrospinal fluid 14–3–3 test 7,8 has now been incorporated into the diagnostic criteria for sporadic CJD, 2 but this test does not seem to be as sensitive for vCJD, 3 and cannot discriminate between variant and other forms of CJD. Single photon- emission computed tomography may be helpful, but has been reported for only two vCJD cases. 9 During the course of CJD surveillance it was noted that high signal was reported in the posterior thalamus (pulvinar) bilaterally on dual echo (T2 or proton density- weighted) magnetic resonance imaging (MRI) in two histologically proven vCJD cases. 10,11 We postulate that the identification of bilateral pulvinar high signal might be a sensitive and specific test for the diagnosis of vCJD in patients with suspected disease. An earlier study provided some support for this hypothesis but was based on a small sample of cases and controls. 12 We report the findings of a larger MRI study of patients with vCJD. Methods We attempted to obtain MRI brain examinations from all patients in the UK with suspected vCJD who were referred to the National CJD Surveillance Unit. The method of CJD surveillance in the UK has been described elsewhere. 13 The surveillance study received approval from the Lothian Health Board Medical Ethics Committee. We did control MRI examinations on two groups of patients: patients suspected of having vCJD who were then diagnosed with other conditions; and patients known or suspected to have other forms of CJD. The scans were labelled with a reference number and then read by two experienced neuroradiologists (DAC and RJS) who were not aware of clinical information, including the diagnosis. When a patient had more than one set of scans available the most recent was assessed. Any earlier scans were later reviewed openly to assess any radiological change with time. The ARTICLES 1412 THE LANCET • Vol 355 • April 22, 2000 The pulvinar sign on magnetic resonance imaging in variant Creutzfeldt-Jakob disease Martin Zeidler, Robin J Sellar, Donald A Collie, Richard Knight, Gillian Stewart, Margaret-Ann Macleod, James W Ironside, Simon Cousens, Alan F C Colchester, Donald M Hadley, Robert G Will National Creutzfeldt-Jakob Disease Surveillance Unit (M Zeidler MRCP, R Knight FRCPE, G Stewart MRCP, M-A Macleod MRCP, J W Ironside FRCPath, R G Will FRCP) and Department of Neuroradiology (R J Sellar FRCR, D A Collier FRCR), Western General Hospital, Crewe Road, Edinburgh EH4 2XU; Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT (S Cousens DipMathStat); Department of Neuroradiology, Institute of Neurological Sciences, Glasgow G51 4TF (D M Hadley FRCR); and University of Kent Electronic Engineering Laboratory, Kent Institute of Medicine and Health Sciences, Canterbury, UK (Prof A F C Colchester FRCP) Correspondence to: Dr Martin Zeidler (e-mail: martinz@globalnet.co.uk)