Elsevier

The Lancet

Volume 355, Issue 9213, 22 April 2000, Pages 1412-1418
The Lancet

Articles
The pulvinar sign on magnetic resonance imaging in variant Creutzfeldt-Jakob disease

https://doi.org/10.1016/S0140-6736(00)02140-1Get rights and content

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% CL 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.

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 criteria2 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, 4, 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 CJD6 but the characteristic periodic changes are not a feature of vCJD.3 The cerebrospinal fluid 14–3–3 test7, 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.

Section snippets

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

Results

MRI was done for 93 patients (table 1); 36 had histologically confirmed vCJD. The control group consisted of 57 individuals with a diagnosis other than vCJD. The mean age of the 36 histologically confirmed vCJD cases was 30 years (range 15–52) and of the 57 controls was 52 years (range 14–79). 27 controls were younger than 52 years. The age distribution of the 14 controls who were initially suspected to have vCJD but were later given a different diagnosis was similar to that of the

Discussion

Traditionally the main role of neuroimaging in patients with suspected CJD has been to exclude other conditions. Computed tomography and MRI in sporadic CJD might be normal15 or show atrophy, the latter particularly with protracted illness.16 MRI has been reported to show increased cortical17, 18 or white matter signal on T2-weighted images in sporadic CJD, in some cases corresponding to the clinical syndrome, such as occipital lobe high signal in patients with prominent visual symptoms.17

References (30)

  • I Zerr et al.

    Detection of 14–3–3 protein in the cerebrospinal fluid supports the diagnosis of Creutzfeldt-Jakob disease

    Ann Neurol

    (1998)
  • R de Silva et al.

    Single photon emission computed tomography in the identification of new variant Creutzfeldt-Jakob disease

    BMJ

    (1998)
  • R Howard

    Creutzfeldt-Jakob disease in a young woman

    Lancet

    (1996)
  • RJ Sellar et al.

    MR imaging of new variant Creutzfeldt-Jakob disease: the pulvinar sign

    Neuroradiology

    (1997)
  • SN Cousens et al.

    Sporadic Creutzfeldt-Jakob disease in the United Kingdom: analysis of epidemiological surveillance data for 1970–96

    BMJ

    (1997)
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