TSS WHO'S vCJD case definition should be revised Mon Mar 13, 2006 16:56 70.110.86.250
Monday March 13 2006
The Lancet 2006; 367:874
The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram
WHO'S vCJD case definition should be revised
Case Report
In February, 2004, a 50-year-old Japanese man was referred to our Creutzfeldt-Jakob disease (CJD) surveillance committee. In the first half of 1990, the patient had spent about 24 days in the UK, 3 days in France, and 2 weeks in other European countries where variant CJD (vCJD) has not been reported. He had no history of surgery or blood transfusion, or a family history of prion disease. In June, 2001, aged 48 years, he had difficulty in writing Chinese characters. In October, 2001, he showed mental symptoms, such as irritability, personality changes, and memory impairment, followed by painful dysaesthesia in the legs, ataxia, dementia, and abnormal behaviour. Retrospective review of an MRI taken in August, 2002, showed slight hyperintensity in the thalamus. In January, 2003, he showed dementia, ataxia, and hyperreflexia. Brain MRI at that time showed symmetrical hyperintensity of the thalamus. Electroencephalogram (EEG) showed diffuse slowing, but no periodic synchronous discharges (PSD). The cerebrospinal fluid was positive for 14-3-3 protein. Analysis of the prion protein (PrP) gene showed no mutation, methionine/methionine at codon 129, and glutamic acid/glutamic acid at codon 219. He showed rapid deterioration of both motor and cognitive function. In December, 2003, he developed akinetic mutism, myoclonus, and pyramidal signs. Brain MRI showed hyperintensity in the caudate, putamen, thalamus, and cerebral cortex, with higher intensity in the caudate and putamen than the thalamus. EEG suggested the presence of PSD (figure, A). The diagnosis of probable sporadic CJD was supported by EEG and MRI findings.1 He died of pneumonia in December, 2004. Autopsy showed findings characteristic of vCJD, including florid plaques (figure, B) and the Parchi type 2B or Collinge type 4 pattern of protease-resistant PrP (not shown). This is the first Japanese case of definite vCJD. The progressive neuropsychiatric disorder was consistent with vCJD, although the illness duration was unusually long compared with most vCJD cases reported to date (median 14 months).2 The findings 19 months after onset of symptoms, showing the pulvinar sign on MRI and the absence of PSD on EEG, together with the clinical features, fulfilled the criteria of probable vCJD.3 However, 30 months after onset, PSD appeared on EEG, and the pulvinar sign on MRI disappeared following an increase in intensity of other grey matter nuclei, fulfilling the criteria of probable sCJD.1 There have been no previous reports of PSD on EEG in vCJD, although conversion of a positive to negative pulvinar sign on MRI has been described in a few vCJD patients.4 Our case shows that PSD does not exclude the possibility of vCJD. We suggest revision of the WHO vCJD case definition3 to prevent missing cases of vCJD. It is unclear when our patient was exposed to the infective agent. The BSE outbreak in the UK was still increasing when he visited the UK, and it was confirmed that he ate food containing mechanically recovered meat that may be associated with contamination with BSE agent from nervous tissue;5 however, exposure in France, other European countries, and Japan cannot be excluded. If he was exposed to the BSE agent in the UK (exposure just once would be sufficient to cause vCJD), we calculate the incubation period between such pinpoint exposure and onset of vCJD to be 11·5 years. Contributors Following the identification of this first Japanese case of vCJD by the CJD Surveillance Committee, Japan, we constituted the vCJD Working Group in the Committee. To protect the patient’s privacy, we have decided to publish this report under the name of the vCJD Working Group, CJD Surveillance Committee, Japan. The corresponding author is the chair of both the vCJD Working Group and the CJD Surveillance Committee. Acknowledgments We thank the patient’s family for permission to publish this report. The CJD Surveillance Committee is funded by the Ministry of Health, Labour and Welfare, Japan; the funding source had no involvement in the process of publication of this paper. References 1 Global surveillance, diagnosis and therapy of human transmissible spongiform encephalopathies: Report of a WHO consultation. Geneva, Switzerland, 9–11 February 1998 (http://www.who.int/csr/ resources/publications/bse/WHO_EMC_ZDI_98_9/en/) (accessed Nov 30, 2005). 2 Will RG, Ward HJ. Clinical features of variant Creutzfeldt-Jakob disease. Curr Top Microbiol Immunol 2004; 284: 121–32. 3 The revision of the surveillance case definition for variant Creutzfeldt-Jakob Disease (vCJD). Report of a WHO consultation Edinburgh, United Kingdom 17 May 2001 (http://www.who.int/ csr/resources/publications/bse/WHO_CDS_CSR_EPH_2001_5/ en/) (accessed Nov 30, 2005). 4 Collie DA, Summers DM, Sellar RJ, et al. Diagnosing variant Creutzfeldt-Jakob disease with the pulvinar sign: MR imaging findings in 86 neuropathlogically confirmed cases. Am J Neuroradiol 2003; 24: 1560–69. 5 Food Standards Agency. Agency study reports on historic use of mechanically recovered meat in food 1980–1995 (2002) (http:// www1.food.gov.uk/news/pressreleases/2002/oct/report_ mrm) (accessed Nov 30, 2005). Lancet 2006; 367: 874 Creutzfeldt-Jakob Surveillance Committee, Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, 13-1, Takara-machi, Kanazawa 920-8640, Japan Correspondence to: Prof Masahito Yamada m-yamada@med.kanazawau. ac.jp 874 www.thelancet.com Vol 367 March 11, 2006 The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram Masahito Yamada on behalf of the Variant CJD Working Group, Creutzfeldt-Jakob Disease Surveillance Committee, Japan Figure: (A) EEG in August, 2004, 39 months after onset, showing PSD typical of sporadic CJD. (B) The frontal cortex showing florid plaques, severe spongiform changes, and neuronal loss (HE, bar = 100 m). PrP immunohistochemistry showed many PrP-positive plaques and PrP deposits with a pericellular pattern (not shown). A B FP1–A1 FP2–A2 C3–A1 C4–A2 T3–A1 T4–A2 O1–A1 O2–A2 50 V 1 s
