Between 1970 and 2003, seven cases of human dura mater‐associated Creutzfeldt–Jakob disease (CJD) were identified in the UK. Furthermore, we identified a case of CJD in a porcine dura graft recipient. The mean incubation period of the human dura mater cases was 93 (range 45–177) months. The clinico‐pathological features of the cases are described and compared with cases previously reported in the world literature

Barker, R A

Bell, J E

Esmonde, T F G

Harvey, P

Head, M W

Heath, C A

Ironside, J W

Knight, R S G

Roberts, R

Smith, C

Trend, P

Will, R G

PubMed

Between 1970 and 2003, seven cases of human dura mater-associated Creutzfeldt-Jakob disease (CJD) were identified in the UK. Furthermore, we identified a case of CJD in a porcine dura graft recipient. The mean incubation period of the human dura mater cases was 93 (range 45-177) months. The clinico-pathological features of the cases are described and compared with cases previously reported in the world literature

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     Edinburgh Research Explorer                                      Dura mater-associated Creutzfeldt-Jakob diseaseCitation for published version:Heath, CA, Barker, RA, Esmonde, TFG, Harvey, P, Roberts, R, Trend, P, Head, MW, Smith, C, Bell, JE,Ironside, JW, Will, RG & Knight, RSG 2006, 'Dura mater-associated Creutzfeldt-Jakob disease: experiencefrom surveillance in the UK' Journal of Neurology, Neurosurgery & Psychiatry, vol 77, no. 7, pp. 880-2. DOI:10.1136/jnnp.2005.073395Digital Object Identifier (DOI):10.1136/jnnp.2005.073395Link:Link to publication record in Edinburgh Research ExplorerDocument Version:Publisher's PDF, also known as Version of recordPublished In:Journal of Neurology, Neurosurgery & PsychiatryPublisher Rights Statement:available via europepmc open access  linkGeneral rightsCopyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s)and / or other copyright owners and it is a condition of accessing these publications that users recognise andabide by the legal requirements associated with these rights.Take down policyThe University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorercontent complies with UK legislation. If you believe that the public display of this file breaches copyright pleasecontact openaccess@ed.ac.uk providing details, and we will remove access to the work immediately andinvestigate your claim.Download date: 28. Apr. 2017SHORT REPORTDura mater-associated Creutzfeldt–Jakob disease:experience from surveillance in the UKC A Heath, R A Barker, T F G Esmonde, P Harvey, R Roberts, P Trend, M W Head,C Smith, J E Bell, J W Ironside, R G Will, R S G Knight. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .J Neurol Neurosurg Psychiatry 2006;77:880–882. doi: 10.1136/jnnp.2005.073395Between 1970 and 2003, seven cases of human dura mater-associated Creutzfeldt–Jakob disease (CJD) were identified inthe UK. Furthermore, we identified a case of CJD in a porcinedura graft recipient. The mean incubation period of thehuman dura mater cases was 93 (range 45–177) months.The clinico-pathological features of the cases are describedand compared with cases previously reported in the worldliterature.Creutzfeldt–Jakob disease (CJD) exists in four clinicalforms: sporadic, genetic, iatrogenic and variant. Thecause of sporadic CJD, the most common form world-wide, is unknown and case–control studies have failed toidentify any consistent risk factor, although two studies haveimplicated previous surgical interventions.1 2 Genetic forms ofthe disease are associated with underlying mutations of theprion protein gene (PRNP), which are generally considered tobe directly causative. Mutations, however, possibly increaseliability to some, as of yet unrecognised, source of infection.The two remaining forms of CJD are acquired. Variant CJD isconsidered to be caused by bovine spongiform encephalo-pathy through contaminated food products3–5; iatrogenic CJDresults from the inadvertent transmission of CJD during thecourse of medical or surgical treatment. The two mostnumerically significant instances of iatrogenic CJD resultedfrom treatment with cadaveric human growth hormone andthe use of dura mater grafts in surgery. Corneal grafts, depthelectrodes and neurosurgical instruments have also rarelybeen implicated.6 7The first report of dura mater-associated CJD waspublished in 1987,8 with a more detailed report appearingthe following year;9 to date, 164 cases have been recognisedworldwide (P Brown, personal communication, 2006). Thispaper reports and describes the seven cases of human duramater graft-associated CJD identified during surveillance inthe UK and, for the first time, reports a case of CJD in aporcine dura graft recipient.METHODSCJD surveillance in the UK has been undertaken in fourphases.N A retrospective review in England and Wales from 1970 to1979.N A prospective study in England and Wales from 1980 to1984.N A retrospective review in the UK to cover the period from1985 to 1990.N A prospective surveillance was instituted in the UK in 1990and continues.The methodology of the National CJD Surveillance Unithas been described in previous publications.10 11RESULTSHuman dura materDuring the period 1970 and 2003, seven cases of human duramater-associated CJD were identified in the UK (table 1). Thelatent period between surgery and the onset of CJD rangedfrom 45 to 177 months* (mean 93). The mean age at surgerywas 33 years, with a mean age at onset of 41 years.Lyodura (B Braun Melsungen, Germany), a particularbrand of human dura mater, was implicated in six of theseven cases (the manufacturer of the dura graft implicated incase I is unknown).The six cases associated with Lyodura were exposed to thepresumed source of ‘‘infection’’ between 1983 and 1987, withthe first recognised case in the UK exposed to human duramater in 1969.A detailed account of both clinical and investigativefeatures is available at http://jnnp.bmjjournals.com/supplemental. In four cases, the clinical phenotype at onsetappears to correlate with the site of graft placement orunderlying parenchymal damage (cases II, III, V and VI). Forexample—in case II, the presenting clinical features includeda right visual field defect in an individual with a tumourlocalised to the left hemisphere. The subsequent CJD beganwith a right visual field disturbance and progressed withsigns indicating the involvement of the left hemisphere.Some of the cases were investigated before the widespreadavailability of MRI; therefore MRI was available in only fourof the seven cases. None of the cases showed the character-istic radiological features of human prion disease14 with post-surgical change being the most commonly recognisedabnormality. Despite all seven cases having at least oneelectroencephalogram during the course of investigation,only three of the seven cases showed the ‘‘typical’’ features.Autopsy was carried out in five of the seven cases. Ingeneral, the neuropathology was characterised by widespreadspongiform change accompanied by variable neuronal lossand gliosis. Western blot analysis for PrPres was carried out inthree cases (II, VI and VII). The mobility and glycoform ratioof the PrPres is indistinguishable from those of type 1 PrPresidentified in cases of sporadic CJD, and is distinct from type2B PrPres identified in variant CJD.Porcine dura materWe believe the identification of CJD in a porcine graftrecipient to be the first such report worldwide (table 1,case VIII). The recipient underwent excision of a rightfronto-parietal meningioma in 1988 and a zenoderm graftwas used to repair the dura. The recipient presented with*Case V received two dura grafts, it is assumed that the first graft wasresponsible for transmission.880www.jnnp.comheadaches, ataxia and cognitive decline 134 months later.Investigative features, including an electroencephalogram,were supportive of the clinical diagnosis, and pathologicalconfirmation was obtained. Autopsy showed spongiformchange in the frontal and temporal cortex, with similarfeatures identified in the basal ganglia, thalamus andcerebellum. Immunocytochemistry for PrP showed wide-spread accumulation and western blot analysis showed thetype 1 isoform.DISCUSSIONHuman dura mater is a rare, but important source oftransmission of human prion disease, with only seven casesrecognised in a 33-year period. Surveillance systems world-wide have identified 164 cases of CJD in people previouslyexposed to human dura mater. Prevalence is particularly highin Japan and probably reflects neurosurgical practice, with anestimated 20 000 grafts used each year.15 The overall risk ofCJD associated with human dura grafts in the UK isunknown because an accurate estimation of human duragraft use and thus a denominator for calculation of risk is notavailable. The estimated risk after exposure in Japan hasbeen estimated to be approximately 1 per 2000 patientstreated between 1979 and 2000 and approximately 1 per 1000between 1983 and 1987.16 Neurosurgical practice in Japan,with widespread use of dura mater, may be different fromother countries throughout the industrialised world andtherefore it is unreasonable to extrapolate any estimated riskfrom these data. If neurosurgical practices in the UK weremore akin to those in Australia, then a subsequent study byBrooke and co-workers would help provide additionalinformation pertaining to estimated risk. By using informa-tion from the Australian CJD Surveillance system, Brookeand co-workers estimated the risk associated with exposureto human dura mater to be approximately 1 per 500 patientstreated between 1978 and 2003.17 Clearly, the risk ofdeveloping CJD in this patient population is considerablyhigher than we would expect by chance.The human dura mater implicated in the transmission ofCJD was processed, almost exclusively, by B BraunMelsungen in Germany and traded under the nameLyodura. Over 100 Japanese cases, and all but one of theUK cases (the source of the first case identified in the UK isunknown), have been associated with this particular productand only rarely has dura processed by other manufacturersbeen associated with transmission.18 19 Although the first casein the UK was exposed to potentially infectious dura in 1969,a disproportionately large number of cases were exposedbetween 1983 and 1987 (80% of those identified worldwideand six of the seven cases in the UK). Interestingly, theapparent reduction in the number of cases post-1987coincided with the introduction of stringent donor selectioncriteria and the introduction of sodium hydroxide immersiontechniques in the manufacturing process.We found no temporal or geographical association betweenany of the dura-associated cases, or any other case of CJDidentified in the UK, despite potential contamination ofneurosurgical instruments.It has been proposed that clinical features at onset aredependent on the site of graft placement or underlyingparenchymal damage20–22 and our findings may support sucha proposition. The explanation for this observation is unclear.We, could, speculate that the pathological process startswithin a region adjacent to the graft and that this is reflectedin the early clinical features. This proposition may also besupported by findings obtained at autopsy, with severepathological changes identified adjacent to graft placementin three cases. Overall, the pathology is consistent for thatpreviously described in dura mater-associated CJD.9 18 We didnot identify either ‘‘kuru-type’’ or florid PrP plaques. Theflorid PrP plaques were previously noted in limited distribu-tion in a small number of dural graft-associated iatrogenicCJD cases in Japan.21 23 24We believe case VIII represents the first reported case ofCJD in a person previously exposed to a graft from a non-human source. The age at onset, duration of illness, clinicaland investigative features were similar to a typical case ofsporadic CJD. Furthermore, the pathological features werealso considered characteristic of sporadic CJD, with type 1PrPres identified. Neither finding can definitively exclude thepossibility of transmission of a yet unidentified pathogen. Asnatural transmissible spongiform encephalopathies are,however, as yet unrecognised in pigs, despite experimentaltransmission in animal models,25 a chance association seemsthe most plausible explanation.ACKNOWLEDGEMENTSWe thank Jan MacKenzie for all her help in producing thismanuscript. We also thank our colleagues within the Europeansurveillance programme for updated information, particularlyPascual Sanchez Jaun, and neurological colleagues throughout theTable 1 UK case details—human dura materCase Surgical procedure DuraYear ofsurgeryYear ofdeathIncubationperiod (Months)Duration ofillness (Months)I, Esmonde et al12 Suboccipital craniotomy and C1/2laminectomy for cerebellar ectopia andsyringomyelia? 1969 1979 104* 6II, Esmonde et al12 Excision of a left temporal cortexmeningiomaL 1983 1991 93* 5*III Repair surgical leak after acousticneuroma excisionL 1985 1989 51 2IV, Willison et al13 Posterior fossa decompression andcervical laminectomy for cerebellarectopia or syringomyeliaL 1985 1989 45* 4V Excision of a left parietal cortexmeningioma1:L 1985 1993 1:86 112:L 1986 2:79VI Excision of a cerebellar astrocytoma L 1986 1997 103 33VII Excision of an eosinophilicgranuloma right frontal region skullL 1987 2003 177 5Porcine dura graft:VIII Excision of a right frontoparietalmeningiomaP 1988 2000 134 3*Revised from previously published figures.L, Lyodura; P, Porcine dura.Dura mater-associated CJD 881www.jnnp.comUK, particularly Dr Graham Lennox, for assistance with thismanuscript. Finally, we thank our colleagues at the NCJDSU,particularly Alison Green, for carrying out CSF analysis, DavidSummers for advice on neuroimaging, and also Hester Ward andKaty Murray for comments on the manuscript.Additional data on the cases in this report areavailable at http://jnnp.bmjjournals.com/supplementalAuthors’ affiliations. . . . . . . . . . . . . . . . . . . . .C A Heath, M W Head, C Smith, J E Bell, J W Ironside, R G Will,R S G Knight, National CJD Surveillance Unit, University of Edinburgh,Edinburgh, UKR A Barker, Cambridge Centre for Brain Repair, University ofCambridge, Cambridge, UKT F G Esmonde, Royal Victoria Hospital, Belfast, UKP Harvey, Harley Street, London, UKR Roberts, Ninewells Hospital, Dundee, UKP Trend, The Royal Surrey County Hospital, Surrey, UKCompeting interests: None.Correspondence to: Dr R S G Knight, National CJD Surveillance Unit,Bryan Matthews Building, Western General Hospital, Edinburgh EH42XU, UK; r.knight@ed.ac.ukReceived 7 June 2005Revised version received 23 August 2005Accepted for publication 24 August 2005Published Online First 20 April 2006REFERENCES1 Collins S, Law MG, Fletcher A, et al. Surgical treatment and risk of sporadicCreutzfeldt-Jakob disease: a case-control study. Lancet 1999;353:693–7.2 Ward HJT, Everington D, Croes EA, et al. Sporadic Creutzfeldt-Jakob diseaseand surgery: a case-control study using community controls. Neurology2002;59:543–8.3 Will RG, Ironside JW, Zeidler M, et al. A new variant of Creutzfeldt-Jakobdisease in the UK. Lancet 1996;347:921–5.4 Collinge J, Sidle KCL, Meads J, et al. Molecular analysis of prion strainvariation and the aetiology of ‘new variant’ CJD. Nature 1996;383:685–90.5 Bruce ME, Will RG, Ironside JW, et al. Transmissions to mice indicate that‘new variant’ CJD is caused by the BSE agent. Nature 1997;389:498–501.6 Duffy P, Wolf J, Collins G, et al. Possible person-to-person transmission ofCreutzfeldt-Jakob disease. N Engl J Med 1974;290:692–3.7 Foncin JF, Gaches J, Cathala F, et al. Transmission iatrogene interhumainepossible de maladie de Creutzfeldt-Jakob avec atteinte des grains de cervelet.Rev Neurol 1980;136:280.8 Prichard JW, Thadani V, Kalb R, et al. Rapidly progressive dementia in apatient who received a cadaveric dura mater graft. Morb Mortal Wkly Report1987;34:49–55.9 Thadani V, Penar PL, Partington J, et al. Creutzfeldt-Jakob disease probablyacquired from a cadaveric dura mater graft. J Neurosurg 1988;69:766–9.10 Will RG. A new variant of Creutzfeldt-Jakob disease in the UK. Proceedings ofthe Society for Veterinary Epidemiology and Preventative Medicine1997:9–11 April 1997, University College, Chester, UK.11 Will RG, Zeidler M, Stewart GE, et al. Diagnosis of new variant Creutzfeldt-Jakob disease. Ann Neurol 2000;47:575–82.12 Esmonde T, Leuck CJS, Duchen LW, et al. CJD and lyophilised dura matergarfts: a report of two cases. J Neurol Neurosurg Psychiatry1991;56:999–1000.13 Willison HJ, Gale AN, McLaughlin JE. Creutzfeldt-Jakob disease followingcadaveric dura mater graft. J Neurol Neurosurg Psychiatry 1991;54:940.14 Collie DA, Sellar RJ, Zeidler M, et al. MRI of Creutzfeldt-Jakob disease:imaging features and recommended MRI protocol. Clin Radiol2001;56:726–39.15 Tateishi J. CJD transmitted through cadaveric dura grafts. J Clin Exp Med1997:992–3.16 Nakamura Y, Watanabe M, Nagoshi K. CJD associated with cadaveric duramater grafts-Japan 1979–2003. Morb Mortal Wkly Report2005;52:1179–81.17 Brooke FJ, Boyd A, Klug GM, et al. Lyodura use and the risk of iatrogenicCreutzfeldt-Jakob disease in Australia. Med J Aus 2004;180:1–5.18 Pocchiari M, Masullo C, Salvatore M, et al. Creutfeldt-Jakob disease afternon-commercial dura mater graft. Lancet 1992;340:614–5.19 Hannah EL, Belay ED, Gambetti P, et al. Creutzfeldt-Jakob disease afterreceipt of a previously unimplicated brand of dura mater graft. Neurology2001;56:1080–3.20 Sato T. CJD with dura mater transplantation. Clin Neurol 2003;43:870–2.21 Fushimi M, Sato K, Shimizu T, et al. PLEDS in Creutzfeldt Jakob diseasefollowing a cadaveric dura graft. Clin Neurophysiol 2002;113:1030–5.22 Nishida y, Yamane M, Hara k, et al. Creutzfeldt-Jakob disease afterJannetta’s operation with cadaveric dura mater. J Neurol 2002;249:480–3.23 Takashima S, Tateishi J, Taguchi Y, et al. Creutzfeldt-Jakob disease with floridplaques after cadaveric dural graft in a Japanese woman. Lancet1997;350:865–6.24 Kimura K, Nonaka A, Tashiro H, et al. Atypical form of dural graft associatedCreutzfeldt-Jakob disease: report of a postmortem case with review of theliterature. J Neurol Neurosurg Psychiatry 2001;70:696–9.25 Castilla J, Gutierrez-Adan A, Brun A, et al. Subclinical BSE infection intransgenic mice expressing porcine prion protein. J Neurosci2004;24:5063–9.882 Heath, Barker, Esmonde, et alwww.jnnp.com

Dura mater-associated Creutzfeldt-Jakob disease:experience from surveillance in the UK

C A Heath

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Dura mater-associated Creutzfeldt-Jakob disease: experience from surveillance in the UK

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Dura mater-associated Creutzfeldt-Jakob disease:experience from surveillance in the UK

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