• Creutzfeldt-Jakob disease
• sporadic
• PRNP genotype
• cognitive dysfunction
• neuropsychological tools

As with many diseases originally defined on purely clinicopathological phenomenological grounds, “Creutzfeldt-Jakob disease” (CJD) has been subject to various “lumping” and “splitting” processes over the years.¹ The demonstration of laboratory transmissibility and the central role of the prion protein have served to unify the concept of CJD. Sporadic CJD (sCJD) remains, of course, defined by the absence of a known cause, in contradistinction to genetic, iatrogenic, and variant CJD. Despite this background unification, there is notable clinical phenotypic variation in sCJD including age of onset, duration of illness, and presenting symptom(s) in particular. Research has attempted to correlate these variations with molecular factors such as the PRNP genotype and the prion protein structure.² If sCJD is indeed a “spontaneous” disease due to a chance protein structural change or somatic PRNP mutation, then the different presentations may simply reflect the usual function of the initially affected part of the CNS.¹ Whatever the explanation, the current view of sCJD is of an illness that may present in a variety of ways, including cerebellar ataxia, cortical blindness, dysphasia, and other deficits but which rapidly evolves into a global dementia with features of widespread brain disease. While attention has been given to the different modes of “physical” neurological presentation, there has been little comment on the pattern of cognitive dysfunction. A paper by Snowden et al (this issue pp 686–694) describes some detailed observations on five cases of sCJD (and one presumed familial case).³ The authors claim to have found a common, distinct neuropsychological profile despite different neurological presentations.

There are obvious reasons for the previous neglect of detailed cognitive assessments, as the authors indicate, including the rarity of sCJD and its rapid clinical progression (mean duration: five months). Severe neurological impairment, even mutism, may be present at first neurological assessment.¹ It is therefore particularly notable that the authors were able to assess their cases, using neuropsychological tools previously developed for other dementias. Two particular findings, namely fluctuations in ability over time and variability of responsiveness will resonate with ordinary clinical observations of cases of sCJD and accord well with comments made by many relatives.

As the authors admit, these results are derived from only a small number of slightly atypical cases. One case was relatively young, four cases had longer than average durations and at least two were of unusual PRNP genotype. Further studies are therefore needed to confirm these preliminary findings.

Although sCJD shows us different faces, perhaps there is a single facial expression. Recognising this might be helpful in diagnosis, although other diagnostic techniques (such as the established csf 14–3–3 test and the developing role of cerebral magnetic resonance imaging) will be more useful.⁴ However, understanding this may help us to manage patients and better explain unusual phenomena to distressed relatives. Understanding may also help us to explore further the mechanisms of this terrible disease. Perhaps the most intriguing suggestions made by the authors relate to the possible anatomic and pathological implications of their findings.