Atypical clinical presentation of variant Creutzfeldt–Jakob disease

Editor, Creutzfeldt–Jakob disease (CJD) is a rapidly progressive fatal neurodegenerative disorder caused by the accumulation in central nervous system (CNS) tissues of an abnormal form of the prion protein (PrPsc). It is diagnosed in about 1.5 people per million each year. The sporadic form (sCJD) represents 85% of cases. In remaining cases, there is an inherited mutation of the prion protein gene or transmission by contaminated human tissues (corneal graft, dura mater, human pituitary-derived growth hormone) or, before 1996, following use of contaminated medical devices. In 1996, an outbreak of CJD was reported in the United Kingdom and France. This new entity of CJD in young patients (<55 years) not only differs from sporadic CJD by its clinical presentation and slow course of the disease but also by the specific neuropathological deposits of PrPsc (florid plaques and PrP molecular type 4) and by its presence in the lymphoreticular system. Thus, this form of the disease was defined as variant CJD (vCJD) and linked to the animal form of the disease, bovine spongiform encephalopathy, strongly suggesting animal-to-human contamination. The diversity of clinical presentation, neuropathological characteristics and transmission of prion diseases is linked to the existence of different strains.1 Several cases of human-to-human transmission of vCJD were further identified after blood transfusion, raising awareness of health authorities to the transmissible lymphoid or CNS tissue or by contaminated surgical and anaesthetic instruments (laryngoscope blades, fibre optics). In various countries, to address the risk of healthcare-related transmission, authorities have implemented a number of guidelines and decontamination protocols accounting for the distinct characteristics of vCJD and sCJD, based on the specific diagnostic criteria of these two forms.2 This has practical consequences for anaesthetists, who are mainly concerned about decontamination protocols for transoesophageal probes, laryngoscope blades, bronchoscopes and supraglottic devices in contact with tonsils and other related lymphoid tissues. According to WHO guidelines, these tissues can be considered as having ‘lower infectivity’ for vCJD and ‘no detectable infectivity’ for sCJD.3 As a result, after a quarantine period of the material in contact with tonsils of symptomatic patients (suspicion or possible presence of vCJD/sCJD), the material can be reused once the diagnosis has been excluded. This approach is common to all countries (Table 1). However, as shown in Table 1, decontamination procedures could differ among countries: in countries such as Switzerland, Germany, France and Canada, the material is also reused following appropriate decontamination even if the diagnosis of sCJD is confirmed or highly suspected, whereas destruction is systematic, for example, in the United Kingdom.4 Differences in existing procedures of decontamination across European countries are available in a review released by the European Centre for Disease Prevention and Control.5Table 1: Heterogeneity of guidelines linked to the aetiological form of Creutzfeldt–Jakob diseaseMok et al.6 reported last year an atypical clinical presentation of vCJD. Disease onset, duration and clinical presentation, MRI and electroencephalogram investigations matched the sporadic form of the disease leading to the probable diagnosis of sCJD, according to worldwide diagnostic criteria of sCJD. Post-mortem examination was accepted by the family of the patient. Pathologists identified specific florid plaques in the brain associated with protease resistant PrP of type 4 (PrPres). These are the hallmarks of vCJD, leading to a shift of the diagnosis from the sporadic to the variant form of CJD. Furthermore, type 4 PrPres was also found in the spleen, suggesting a significant risk of transmission through contact with lymphoid tissues. Surprisingly, prion genotype of this vCJD case exhibited a methionine valine polymorphism at codon 129 of PrP gene (PRNP), all previous cases being methionine homozygous. Thus, genetic polymorphism of PRNP can alter the form of the disease and associated clinical signs, with variant mimicking sporadic forms of CJD. As a result, anaesthetic material decontamination protocols based on the clinical difference between the two types of CJD are becoming obsolete. Any form of sCJD exhibitng a methionine valine polymorphism at codon 129 of PrP is likely to be a misdiagnosed form of vCJD should an outbreak of atypical sCJD occur. Except in the United Kingdom, most European countries may have to reconsider the reuse of decontaminated material in patients with a likely or confirmed diagnosis of sCJD. Moreover, according to epidemiological studies in the United Kingdom, a number of healthy CJD disease carriers have been identified.7 It is unclear whether these could represent an additional source of human to human contamination. To solve this issue, we provide the following four recommendations and three suggestions. Recommendations: In case of strong suspicion or possible/probable diagnosis of sCJD, systematic PrP genotyping to identify a possible methionine valine polymorphism should be performed. Post-mortem disease confirmation for all patients (if appropriate) should be made so that reuse of quarantined material can be safely decided. Whenever possible and financially sustainable, single use rather than reusable material should be considered. Early detection of the disease, including during anaesthetic pre-operative assessment, should be performed through the implementation and the application of easy-to-use diagnostic tools or questionnaires. Suggestions: In the absence of post-mortem disease confirmation, for patients with the methionine valine genotype at PRNP codon 129 or for patients without knowledge of this genotype, material in contact with peripheral lymphoid tissues should be considered for incineration: for patients with a CJD diagnosis that could not be clearly excluded; for patients diagnosed either as not excluded sCJD or as probable/definite sCJD. Standardisation and unification of decontamination protocols for prion diseases should be encouraged whenever possible. Hospital decontamination protocols for other specialties (gastroenterology, neurosurgery, ophthalmology) should also by reconsidered in the light of the recent report of this atypical case. Acknowledgements relating to this article Assistance with the letter: none. Financial support and sponsorship: none. Conflicts of interest: none.

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