921ArticlesA new variant of Creutzfeldt-Jakob disease in the UKR G Will, J W Ironside, M Zeidler, S N Cousens, K Estibeiro, A Alperovitch, S Poser, M Pocchiari, A Hofman,P G SmithSummaryBackground Epidemiological surveillance of Creutzfeldt-Jakob disease (CJD) was reinstituted in the UK in 1990 toidentify any changes in the occurrence of this disease afterthe epidemic of bovine spongiform encephalopathy (BSE) incattle.Methods Case ascertainment of CJD was mostly by directreferral from neurologists and neuropathologists. Deathcertificates on which CJD was mentioned were alsoobtained. Clinical details were obtained for all referredcases, and information on potential risk factors for CJDwas obtained by a standard questionnaire administered topatients’ relatives. Neuropathological examination wascarried out on approximately 70% of suspect cases.Epidemiological studies of CJD using similar methodologyto the UK study have been carried out in France, Germany,Italy, and the Netherlands between 1993 and 1995.Findings Ten cases of CJD have been identified in the UK inrecent months with a new neuropathological profile. Otherconsistent features that are unusual include the young ageof the cases, clinical findings, and the absence of theelectroencephalogram features typical for CJD. Similarcases have not been identified in other countries in theEuropean surveillance system.Interpretation These cases appear to represent a newvariant of CJD, which may be unique to the UK. This raisesthe possibility that they are causally linked to BSE.Although this may be the most plausible explanation forthis cluster of cases, a link with BSE cannot be confirmedon the basis of this evidence alone. It is essential to obtainfurther information on the current and past clinical andneuropathological profiles of CJD in the UK and elsewhere.National CJD Surveillance Unit, Western General Hospital,Edinburgh EH4 2XU, UK (R G Will FRCP, J W Ironside MRCPath,M Zeidler MRCP, K Estibeiro BSc); Department of Epidemiology andPopulation Science, London School of Hygiene and TropicalMedicine, London, UK (S N Cousens Dip Math Stat, Prof P G SmithDSc); INSERM, Hopital de la Salpetriere, Paris, France(A Alperovitch MD); Klinik und Poliklinik für Neurologie, Georg-August-Universitat, Gottingen, Germany (S Poser MD); Laboratoriodi Virologia, Istituto Superiore di Sanità, Rome, Italy (M PocchiariMD); Erasmus University, Rotterdam, The Netherlands (Prof AHofman MD)Correspondence to: Dr R G WillIntroductionBecause of the epidemic of bovine spongiformencephalopathy (BSE) in cattle, surveillance ofCreutzfeldt-Jakob disease (CJD) in the UK wasreinstituted in May, 1990. The purpose of thesurveillance is to identify changes in the pattern of CJDwhich might indicate an association with BSE. We reportten cases of CJD in the UK with clinical onset of diseasein 1994 and 1995. These cases all have neuropathologicalchanges which, to our knowledge, have not beenpreviously reported. They are also unusual in that theyoccurred in relatively young people, and the clinicalcourse was not typical of cases of sporadic CJD in theUK.MethodsSince May, 1990, cases of CJD have been identified to the CJDSurveillance Unit, usually by direct referral from professionalgroups, which include neurologists and neuropathologists. Alldeath certificates in the UK on which CJD is mentioned areobtained and some cases are identified retrospectively in this way;some are identified from other sources. Clinical details areobtained for all cases, and information on potential risk factorsfor CJD is obtained with a standard questionnaire, usuallyadministered to a close relative of the case. After obtaininginformed consent from the relatives or patients, blood is obtainedfor DNA analysis in most patients. Information on all knowncases of CJD in England and Wales since 1970 and in Scotlandand Northern Ireland since 1985 is also available from previoussurveys of CJD.’ Parallel studies of CJD have been carried out inFrance, Italy, Germany, and the Netherlands between 1993 and1995 with similar methods.2Whenever possible, neuropathological examination is carriedout on cases and suspect cases notified to the CJD SurveillanceUnit. Such examinations have been done on about 70% of casesnotified since May, 1990, either by referral for necropsy inEdinburgh or in cooperation with neuropathologists in othercentres who refer cases after diagnosis. Blocks from the frontal,temporal, parietal, and occipital cortex; basal ganglia; thalamus;hypothalamus; cerebellum midbrain; pons; and medulla are fixedin formalin. Blocks are immersed in 96% formic acid for 1 hourbefore routine processing into paraffin wax. Sections are cut at5m and stained by conventional histological techniques andimmunocytochemistry for prion protein (PrP). Pretreatments forimmunocytochemistry with two monoclonal PrP antibodies(KG9 and 3F4)3 include incubation in 96% formic acid for 5min, then 4 mol/L guanidine thiocyanate for 2 hours, andhydrated autoclaving at 121°C for 10 min.ResultsPatientsOf the 207 cases of CJD examined neuropathologicallysince May, 1990, ten have neuropathological findings thatclearly distinguish them from other cases examined by theCJD Surveillance Unit (two have been reportedpreviously4,5) .These ten cases (four male) had disease onset from922*Excludes known iatrogenic and inherited cases. tEngland and Wales only for theperiod 1970-84. *Numbers in brackets indicate patients alive. Died before May1990.Table 1: Known cases of sporadic CJD* in the UK,t 1970-96,dying aged less than 45 yearsFebruary, 1994, to October, 1995. One came to theattention of the CJD Surveillance Unit in March, 1995,and the other nine between October, 1995, and January,1996. The ages at death of the eight patients who havedied range from 19 to 41 years (median 29). Two patientsremain alive at ages 18 and 31 years. Intervals betweendisease onsets and death range from 7-5 to 22-5 months(median 12). Surviving patients in March, 1996, havedisease durations of 6 and 22 months. These patients arerelatively young compared with most patients with CJDand their disease duration is relatively long. Among 185cases of sporadic CJD identified since May, 1990, averageage at onset was 65 years and median duration of diseasefour months; for half of these patients, duration was 2-21 to62’ months. Since May, 1990, only two other sporadiccases of CJD with age less than 45 years have beenidentified, both aged 44 years. These cases