Creutzfeldt-Jakob Disease Associated with Cadaveric Dura Mater Grafts – Japan, 1979-2008 : UPDATE
Posted Apr 09 2009 7:13pm
Update: Creutzfeldt-Jakob Disease Associated with Cadaveric Dura Mater Grafts – Japan, 1979-2008 PRESS CONTACT: CDC Division of Media Relations (404) 639-3286
Because of the long incubation period, possibly exceeding 24.8 years, between the receipt of a dural graft (a cadaver-derived product used by neurosurgeons to patch defects in the substance covering a patient's brain) and symptom onset, Creutzfeldt-Jakob disease cases associated with dural grafts continue to be identified in Japan, despite preventive measures taken decades earlier. This MMWR submission updates the current status of an ongoing outbreak of dural graft-associated Creutzfeldt-Jakob disease in Japan. CDC played a key role in eliminating the source of the worldwide outbreak in 1987 when the first US case was reported. Despite the manufacturer of the implicated product revising its collection and production procedures at that time as a result of CDC's investigation, cases continue to be identified due to a long incubation period that may exceed 24.8 years. To date, 132 cases have been reported in Japan, with exposures having occurred during the period 1978-1993. In contrast, only 4 dural graft-associated Creutzfeldt-Jakob disease cases have been reported in the United States.
Risk factors for sporadic Creutzfeldt-Jakob disease
Dura mater grafts
The transmission of CJD from patient to patient by cadaveric dura mater grafts was first recognised in 1987 and there have now been at least 136 cases world-wide, including 88 cases identified in Japan7. Almost all of these cases have involved the insertion of Lyodura grafts produced by B. Braun Melsungen AG and processed before May 1987. Exceptions to the use of Lyodura grafts include one case in which the source was unknown, one case in which locally produced dura was implanted and one case associated with Tutoplast dura. The risk of transmission of CJD through dura mater grafts had been thought to be low because only a small number of recipients would receive contaminated material from any individual infected donor. The large number of Lyodura-associated cases of CJD suggests that there may have been cross-contamination during the production process.
For dura mater-associated cases of CJD in Japan, the mean latency period from receipt of the graft to the onset of CJD was 8.2 years (range, 1.3–16.1 years)8 and for the 114 reported cases world-wide by the millennium, the interval from the implantation of the graft to the development of clinical disease ranged from 1.5–18 years with a mean of about 6 years9. The risk of developing CJD after exposure to a dura mater graft is difficult to estimate because of limited information on the number of recipients. The major risk, however, appears to be in those individuals who received grafts between 1981 and 1987 (Fig. 1) and in Japan the minimum risk has been estimated at approximately one case of CJD per 3000 Lyodura graft recipients.
The majority of patients with dura mater-related CJD present with symptoms and signs consistent with sporadic CJD, but in some cases the presentation is less typical. A cerebellar syndrome has been described occasionally, but this does not necessarily correlate with the anatomical site of the original graft.