Creutzfeldt-Jakob Disease in Patients Who Received a Cadaveric Dura Mater Graft -- Spain, 1985-1992

In 1987, CDC and the Food and Drug Administration (FDA) investigated a case of Creutzfeldt-Jakob disease (CJD) in a 28-year-old woman in the United States; the patient had onset of CJD 19 months after an operation in which she received an imported, commercially prepared, cadaveric dura mater graft (LYODURA (registered), processed by B. Braun Melsungen AG of the Federal Republic of Germany) (1,2). The report of this investigation alerted medical personnel and the public about a possible increased risk for CJD in recipients of these human tissue grafts. Recently, CDC was notified of four patients with CJD who had undergone dura mater repair with the aid of LYODURA (registered). All four patients had neurosurgery at a regional hospital in Spain during April 1983-January 1984 (3,4). This report describes these four cases.

Case 1. In 1985, a 19-year-old man was hospitalized for gait ataxia, blurred vision, dysarthria, and dysmetria 16 months after surgical resection of a cystic cerebellar astrocytoma that included closure of the dura mater using LYODURA (registered). During the 2 weeks following hospitalization, he became progressively demented, developed myoclonic jerks, and had an electroencephalogram (EEG) that revealed diffuse slow activity with periodic paroxysms of bilateral spike waves. A right frontal cerebral biopsy showed spongiform changes consistent with CJD. He died in 1986, 21 months after clinical onset.

Case 2. In 1987, a 57-year-old woman was hospitalized for gait ataxia, dysarthria, dizziness, and bilateral hypertonus 43 months following a posterior fossa decompression and cervical vertebrae level 1 laminectomy, which included placement of a LYODURA (registered) graft to correct an Arnold-Chiari malformation and syringomyelia. Two weeks after hospitalization, she became demented and showed facial and limb myoclonic movements. A right frontal cerebral biopsy was consistent with CJD. She died in 1989, 25 months after clinical onset.

Case 3. In 1991, an 18-year-old man was hospitalized for ataxia, dysmetria, dysarthria, and generalized hyperreflexia 79 months after undergoing a posterior fossa craniectomy for removal of a cerebellar astrocytoma; a LYODURA (registered) graft was used to close the dura mater. During the 2 weeks following hospitalization, he was mute with decorticate posture and myoclonic movements of all four limbs. An EEG showed the characteristic triphasic waves of CJD; a cerebral biopsy was consistent with CJD. He died in 1992, 3 months after clinical onset.

Case 4. In 1992, a 34-year-old man reported dizziness and slurred speech 105 months after undergoing a posterior fossa decompression in which a LYODURA (registered) graft was used to repair an Arnold-Chiari malformation and syringomyelia. He also had ataxia, nystagmus, mild hyperreflexia, and bilateral pale optic discs. He rapidly progressed to mutism, and decorticate posturing with myoclonic movements in all four limbs. An EEG revealed periodic activity; a brain biopsy was consistent with CJD. As of June 1993, the patient was still hospitalized.

General characteristics. None of these patients had received growth or other hormones derived from cadaveric sources, had undergone prior surgical procedures, or had a familial history of CJD. From January 1983 through December 1984, of 1052 persons who underwent neurosurgical procedures at this hospital, 37 (including case-patients 1-4) had placement of a LYODURA (registered) graft. No other episodes of CJD have been noted among these 1052 patients. Although records of LYODURA (registered) lot numbers were not available at the hospital, the manufacturer indicated that the grafts were not from lot number 2105, which was implicated in the initially investigated LYODURA-associated CJD patient in the United States.

Reported by: JF Martinez-Lage, MD, M Poza, MD, JG Tortosa, MD, Regional Neurosurgery Svc, Virgin of Arrixaca Univ Hospital, Murcia, Spain. Epidemiology Activity, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: CJD is a rapidly fatal, dementing neurologic illness. It is characterized by cerebral spongiform changes and transmissibility when central nervous system tissue from a patient is inoculated into susceptible animal hosts. The infectivity of CJD has been hypothesized to be related to a novel self-replicating protein (5). In the United States and Europe, the estimated crude annual incidence is one case per million persons (6). For persons aged less than 30 years, however, the estimated incidence is less than one case per 200 million (7). Iatrogenic transmission has been reported following use of infective cadaveric materials (e.g., corneal transplant), neurosurgical procedures, contaminated EEG depth electrodes, or administration of growth and other hormones derived from cadaveric pituitaries (8).

The first report of LYODURA (registered)-associated CJD included a description of differences between the processing of LYODURA and similar products and suggested that, in the United States, the risk for transmission of CJD using LYODURA (registered) was higher than that from other dura mater products (1,2). Following the first report, the FDA issued a safety alert recommending disposal of specified packages of LYODURA (9). Subsequently, representatives of B. Braun Melsungen AG reported that their procedures for collection and processing of dura after May 1, 1987, were revised to reduce the risk for CJD transmission (6,7).

Consistent with a subsequently reduced risk for CJD transmission, there have been no reports of CJD in patients who received LYODURA (registered) processed after May 1987. However, CJD has been reported in eight patients from outside the United States, including the four described in this report, who received LYODURA (registered) products processed before May 1987 (6,10). A probable 10th case of LYODURA (registered)-associated CJD recently has been reported in a 29-year-old patient in the United States who had placement of a dural graft during the correction of an Arnold-Chiari malformation in 1985 and died in 1992 (CDC, unpublished data, 1993). CJD also has been reported in two persons from Italy who received dura allografts from other manufacturers (6).

The most stringent donor screening cannot assure the exclusion of donors with prepatent CJD. Therefore, surgeons should confirm that allogenic dura mater they use is handled according to strict guidelines such as those established by the American Association of Tissue Banks and the Southeastern Organ Procurement Foundation (11); surgeons may want to consider the alternative use of autologous fascia lata, temporalis fascia, or of synthetic substitutes.

The cases described in this report indicate that recipients of contaminated grafts may remain at risk for CJD at least 8 years following receipt of grafts. Patients who have rapidly progressive dementing illnesses consistent with CJD and who have received an allograft should be reported through their respective local or state health departments to CDC's Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, telephone (404) 639-3091.

References

1. CDC. Rapidly progressive dementia in a patient who received a cadaveric dura mater graft. MMWR 1987;36:49-50,55.

2. CDC. Update: Creutzfeldt-Jakob disease in a patient receiving a cadaveric dura mater graft. MMWR 1987;36:324-5.

3. Martinez-Lage JF, Poza M, Sola J, et al. Accidental transmission of Creutzfeldt-Jakob disease by dural cadaveric grafts. Neurosurgery (in press).

4. Martinez-Lage JF, Sola J, Poza M, Esteban JA. Pediatric Creutzfeldt-Jakob disease: probable transmission by a dural graft. Childs Nerv Syst (in press).

5. Prusiner SB, Scott M, Foster D, et al. Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication. Cell 1990;63:673-86.

6. Brown P, Preece MA, Will RG. "Friendly fire" in medicine: hormones, homografts, and Creutzfeldt-Jakob disease. Lancet 1992;340:24-7.

7. Janssen RS, Schonberger LB. Creutzfeldt-Jakob disease from allogeneic dura: a review of risks and safety. J Oral Maxillofac Surg 1991;49:274-5.

8. Fradkin JE, Schonberger LB, Mills JL, et al. Creutzfeldt-Jakob disease in pituitary growth hormone recipients in the United States. JAMA 1991;265:880-4.

9. Food and Drug Administration. FDA safety alert: possibly contaminated dura mater transplant material. Rockville, Maryland: US Department of Health and Human Services, Public Health Service, April 28, 1987.

10. Willison HJ, Gale A, McLaughlin JE. Creutzfeldt-Jakob disease following cadaveric dura mater graft. J Neurol Neurosurg Psychiatry 1991;54:940.

11. American Association of Tissue Banks. Technical manual for tissue banking, section II -- Musculoskeletal Council. Arlington, Virginia: American Association of Tissue Banks, 1987:M-1-M-25.

    
    
    

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