Advances in diagnosing Creutzfeldt-Jakob disease with MRI and CSF 14-3-3 protein analysis

When Creutzfeldt-Jakob disease (CJD) was first described in the 1920s, air encephalography was the height of neuroradiologic sophistication and CSF analysis was in its infancy. A major diagnostic breakthrough occurred in the mid-1950s with the recognition of a characteristic periodic EEG appearance.1 Unfortunately this is not observed in about one-third of cases2 (often those with other atypical clinical features) and may only become apparent late in the illness. The later arrival of CT added little, except as an aid to exclude other conditions, and MRI in its fuzzy youth was considered of no further diagnostic value.

So where are we now with paraclinical tests? Routine blood analysis is usually normal, although a transient derangement of liver function is sometimes observed—most likely an epiphenomenon, for example, due to medication. CSF characteristically lacks a pleocytosis or fall in glucose, but an elevated protein (only very rarely over 1 g/L) occurs in about 40% of cases. Various brain-specific proteins (including neuron-specific enolase, tau protein, and S100) have been studied as CSF markers, with 14-3-3 having sufficiently high diagnostic accuracy and utility to be incorporated into the WHO criteria for a probable case of sporadic CJD.3

Despite initial pessimism, brain imaging has also shown promise as a diagnostic tool.4 Basal ganglia hyperintensity on MRI was first …