CJD mimics and chameleons

Abstract

Rapidly progressive dementia mimicking Creutzfeldt-Jakob disease (CJD) is a relatively rare presentation but a rewarding one to become familiar with, as the potential diagnoses range from the universally fatal to the completely reversible. Patients require urgent decisions about assessment and investigation and have quickly evolving needs for treatments and support, through symptom management and end-of-life care in most cases. We have based this pragmatic review on the experiences of a specialist prion referral centre in the UK, which, unsurprisingly, is strongly biased towards seeing patients with CJD. Cases eventually proven not to have prion disease might be described as 'CJD-mimics'; being referred from UK neurologists, these are the most challenging cases. CJD in its classical presentation is very rarely mimicked; however, it is highly heterogeneous, and atypical forms can mimic virtually all common neurodegenerative syndromes. Warning features of a mimic include generalised seizures, hyponatraemia, fever, a facial movement disorder, a normal neurological examination and a modestly rapid presentation. Contrast-enhancing lesions or MRI signal hyperintensity outside the striatum, thalamus or cortex and a cerebrospinal fluid pleocytosis are key investigation pointers to a CJD mimic.

Keywords: rapidly progressive dementia.

Figure 1

Creutzfeldt-Jakob disease (CJD) clinical features and progression. The boxes describe clinical variants of CJD. The width of each arrow relates to the proportion of cases with the presentation. Patients with CJD become more similar over time, and almost all enter a phase of ‘akinetic mutism’ before death.

Figure 2

Typical MRI features of Creutzfeldt-Jakob disease (CJD). (A and B) Sporadic CJD showing typical basal ganglia signal return on fluid-attenuated inversion recovery (FLAIR) (A), which is more obvious on diffusion-weighted sequences (B). (C) Diffusion-weighted imaging sequence showing striking cortical ribboning with normal basal ganglia in sporadic CJD. (D) Variant CJD showing pulvinar sign on the FLAIR sequence.

Figure 3

MR scan of brain in four patients presenting as mimics of prion disease. (A) C9orf72 mutation showing severe generalised atrophy with no parenchymal abnormal signal. Severe atrophy does occur late in some cases of Creutzfeldt-Jakob disease (CJD), but usually diffusion-weighted sequences reveal restricted diffusion. (B) B-cell lymphoma confined at the time of presentation to the brain. Note the extensive white-matter signal change with the normal cortex. Occasionally, the leukoencephalopathic form of CJD has white-matter signal alteration, but this is associated with grey matter destruction. (C) N-methyl-D-aspartate antibody encephalitis with MR imaging showing the pulvinar sign. This sign develops in most cases of variant CJD and has rarely been described with other pathologies. (D) Voltage-gated potassium channel (Casp-1) antibody encephalitis showing unilateral basal ganglia high signal on diffusion-weighted imaging but not on the apparent diffusion coefficient map (scan not shown). Note that the swelling of the caudate is a feature that does not occur in CJD.