Cadaveric Dura Mater Graft Research Articles

Spontaneous intracerebral haemorrhage associated with early-onset cerebral amyloid angiopathy and Alzheimer’s disease neuropathological changes five decades after cadaveric dura mater graft

Cerebral amyloid angiopathy (CAA) is a small vessel disease, causing spontaneous intracerebral hemorrhage (ICH) in the elderly. It is strongly associated with Alzheimer disease (AD), as most CAA patients show deposition of Aβ—i.e. the basic component of parenchymal Alzheimer amyloid deposits—in the cerebral vessels. Iatrogenic early-onset CAA has been recently identified in patients with a history of traumatic brain injury or other cerebral as well as extra-cerebral lesions that led to neurosurgery or other medical procedures as intravascular embolization by cadaveric dura mater extracts many years before the first ICH event. In those patients, a transmission of Aβ seeds from neurosurgical instruments or from cadaveric dura mater exposure was suggested. We report a 51-year-old woman with unremarkable family history who presented abruptly with aphasia and right hemiparesis. A cerebral left lobar haemorrhagic stroke was documented by neuroimaging. Accurate anamnesis revealed a neurosurgical procedure with cadaveric dura mater graft at the age of 2 years for an arachnoid cyst. The neuropathological examination of the cerebral parietal biopsy showed severe amyloid angiopathy in many leptomeningeal and cortical vessels, as well as abundant parenchymal Aβ deposits, neurofibrillary tangles and neuropil threads. The mechanism involved in the human-to-human transmission of the Aβ proteinopathy remains to be clarified. In our patient the cadaver derived dura used for grafting is a very strong candidate as the source of the transmission. A systematic monitoring of individuals who have had neurosurgical procedures in early life, especially those involving cadaveric dural grafts, is required to determine the ratio of those affected by CAA many years later and unaffected. Moreover, our report confirms that in addition to vascular and parenchymal Aβ pathology, neurofibrillary changes indistinguishable from AD may develop in specific conditions with long latency period from the neurosurgical or embolization procedure.

Transmission of Cerebral β-Amyloidosis Among Individuals.

Deposition of amyloid β protein (Aβ) in the brain (cerebral β-amyloidosis) is a hallmark of Alzheimer's disease (AD). So far, there have been increasing number of experimental studies using AD mouse model that cerebral β-amyloidosis could be transmitted among individuals as prion-like mechanism. Furthermore, several pathological studies using autopsied patients with iatrogenic Creutzfeldt-Jakob disease (CJD) showed that cerebral β-amyloidosis in addition to the CJD pathology could be transmitted among humans via medical procedures, such as human growth hormone derived from cadaver injection and cadaveric dura mater graft. In addition, although cerebral amyloid angiopathy (CAA), which is Aβ deposition in the cerebral vessels, related cerebral hemorrhage rarely develops in young people, several patients with CAA-related cerebral hemorrhage under the age of 55 with histories of neurosurgeries with and without dura mater graft in early childhood have been reported. These patients might show that Aβ pathology is often recognized as Aβ-CAA rather than parenchymal Aβ deposition in the transmission of cerebral β-amyloidosis in humans, and we proposed an emerging concept, "acquired CAA". Considering that there have been several patients with acquired CAA with an incubation period from neurosurgery and the onset of CAA related cerebral hemorrhage of longer than 40years, the number of cases is likely to increase in the future, and detailed epidemiological investigation is required. It is necessary to continue to elucidate the pathomechanisms of acquired CAA and urgently establish a method for preventing the transmission of cerebral β-amyloidosis among individuals.

Acquired cerebral amyloid angiopathy: An emerging concept.

Cerebral amyloid angiopathy (CAA) is commonly found in older people and in patients with Alzheimer's disease (AD) accompanying cerebrovascular disorders and dementia. Early-onset CAA cases generally have been found only in rare genetic forms of CAA. Interestingly, however, CAA-related hemorrhages have been recently reported in younger people who had histories of neurosurgery with or without evidence of cadaveric dura mater grafts in childhood. It has been established in experimental settings that amyloid β-protein (Aβ) pathology can be transmitted inter-individually with Aβ seeds. Incidental Aβ pathology, predominantly Aβ-CAA, has been recognized in recipients of cadaveric dura mater grafts or cadaveric human growth hormone. These findings suggest that transmission of Aβ seeds through dura mater grafts and other contaminated materials could lead to development of CAA. In addition, neurosurgery or brain injury may contribute to cerebrovascular Aβ deposition through the disturbance of vascular Aβ drainage pathways. Thus, a novel concept, "acquired CAA," has emerged.

Estimation of the size of the iatrogenic Creutzfeldt-Jakob disease outbreak associated with cadaveric dura mater grafts in Korea.

This study estimated the overall incidence of iatrogenic Creutzfeldt-Jakob disease (iCJD) based on dura graft cases in Korea using a mathematical model. We estimated the number of annual dura grafts performed between 1980 and 1995 by applying the proportion of dura grafts recorded by the Health Insurance Review Agency claim dataset in Korea to the number of nationwide neurosurgery cases. The distribution of the incubation period was assumed to fall under a Weibull distribution with density function or a log-logistic distribution with density function. The total number of neurosurgery procedures performed from 1980 to 1995 was estimated to be 263,945, and among those operations, 37% used dura graft products. Between the years of 1980 and 2020, our model predicted that the total number of iCJD cases would be between 14.9 and 33.2 (95% confidence interval [CI], 13.4 to 50.9). Notably, we estimated that the cumulative number of iCJD cases caused by dura grafts between 1980 and 2011 was approximately 13.3 to 27.3 (95% CI, 12.2 to 40.6). Based on our model, we postulate that the incidence of iCJD will sharply decline from 2012 to 2020. However, additional new cases are still expected, which necessitates a strong national surveillance system.

O1-04-03: Creutzfeldt-Jakob Disease (CJD) surveillance in Japan: Two distinct subtypes of CJD associated with cadaveric dura mater graft and the first Japanese case of variant CJD

O1-04-03: Creutzfeldt-Jakob Disease (CJD) surveillance in Japan: Two distinct subtypes of CJD associated with cadaveric dura mater graft and the first Japanese case of variant CJD

Increased asymmetric pulvinar magnetic resonance imaging signals in Creutzfeldt–Jakob disease with florid plaques following a cadaveric dura mater graft

A 9-year-old Japanese girl received a cadaveric dura mater graft during surgery following a head injury with brain contusion. She continued to do well, but when she became 19-years-old, she gradually showed a violent character and was treated in a psychiatric hospital. Another 6 years later, 200 months after the procedure, she developed a progressive gait ataxia, which subsequently led to her death within 10 months of onset. An autopsy showed she had CJD. This patient represents an atypical case of dura-associated CJD (dCJD) with unusual clinicopathological features including the late occurrence of myoclonus, an absence of periodic synchronous discharges in the electroencephalogram, and the presence of widespread florid plaques. However, our detection of an asymmetrical increase in the MRI-derived images of pulvinar nuclei has not been previously observed in other atypical cases of dCJD. Because atypical dCJD cases share several clinicopathological features with those of vCJD, and because asymmetrical hyperintense signals in the pulvinar have been observed in some neuropathologically confirmed vCJD cases, we had some difficulty in a differential diagnosis between atypical dCJD and vCJD. This is the first atypical dCJD case showing a pulvinar high signal compared with all other basal ganglia on MRI.

Creutzfeldt-Jakob Disease and Cadaveric Dura Mater Grafts in Japan: An Updated Analysis of Incubation Time

The incubation time for 76 patients with cadaveric dura mater-transmitted Creutzfeldt-Jakob disease reported in Japan by November 2001 was analyzed to clarify its distributional feature and the risk factors which affect the earlier onset of the disease. Cluster analysis indicated that cases could be divided into 3 clusters with respect to the incubation time, i.e., short (1.4–6.2 years), medium (7.0–11.9 years) and long (12.9–17.6 years). The incubation time in females was significantly shorter than those in males. Patients who were transplanted dura mater for facial spasms had a significantly shorter incubation time than those who received transplantation for other diseases including meningioma, aneurysm, or acoustic schwannoma. These results suggest that some host factors may have an influence on the incubation time of the disease.

Update: Creutzfeldt-Jakob Disease Associated With Cadaveric Dura Mater Grafts—Japan, 1979-2003

In 1997, a nongovernment surveillance group for Creutzfeldt-Jakob disease (CJD) in Japan supported financially by the Ministry of Health and Welfare (MHW) reported 43 cases of CJD associated with receipt of cadaveric dura mater grafts. In all but one case, the most probable vehicle of transmission was a single brand of dural graft (LYODURA [B. Braun Melsungen AG, Melsungen, Germany]) produced before May 1987. As of March 2003, ongoing surveillance in Japan had identified an additional 54 dura mater graft--associated cases. This report summarizes the investigation of the 97 cases, which indicated that during 1983-1987, the estimated minimum risk for CJD within 17 years of receipt of the implicated product in Japan was approximately one case per 1,250 grafts. No cases have been reported among patients who received their first dural graft after 1991; however, because of the long latency period between graft placement and symptom onset, additional cases of graft-associated CJD are likely to be reported.

Association of an 11-12 kDa protease-resistant prion protein fragment with subtypes of dura graft-associated Creutzfeldt-Jakob disease and other prion diseases.

Creutzfeldt-Jakob disease can develop in subjects given a cadaveric dura mater graft (dCJD). This disease has a phenotypic heterogeneity despite the lack of genetic variation. Numerous plaque-type prion protein (PrP) deposits are found in the brain of some but not all subjects; hence, there may be two subtypes of this clinical entity. To validate dCJD subtypes further, we carried out a larger-scale clinicopathological analysis and typing of protease-resistant PrP (PrP(Sc)) in dCJD cases. Cases with plaque-type PrP deposits (p-dCJD) were shown to be distinct from those without PrP plaques (np-dCJD), from several clinicopathological aspects. Analysis of PrP(Sc) revealed that, while the major PrP(Sc) species from both subtypes was of 21 kDa after deglycosylation (type 1 PrP(Sc)), a C-terminal PrP fragment of 11-12 kDa (fPrP11-12) was associated with np-dCJD but not with p-dCJD. The disease type-specific association of fPrP11-12 was also observed in subjects with other prion diseases. An fPrP11-12-like C-terminal PrP fragment was detected in brain lysates from patients associated with fPrP11-12, but not from patients or normal subjects unassociated with fPrP11-12. Results indicated that fPrP was produced by CJD-associated processes in vivo. The present data provide several lines of evidence that support the need for subtyping of dCJD and contribute to the understanding of the processing of disease-specific PrP species. The unique relationship of fPrP11-12 with CJD phenotype supports the view that the phenotypic heterogeneity of CJD is related to the formation of different types of disease-specific PrP and fragments thereof.

Iatrogenic Creutzfeldt–Jakob disease at the millennium

The causes and geographic distribution of 267 cases of iatrogenic Creutzfeldt-Jakob disease (CJD) are here updated at the millennium. Small numbers of still-occurring cases result from disease onsets after longer and longer incubation periods following infection by cadaveric human growth hormone or dura mater grafts manufactured and distributed before the mid-1980s. The proportion of recipients acquiring CJD from growth hormone varies from 0.3 to 4.4% in different countries, and acquisition from dura mater varies between 0.02 and 0.05% in Japan (where most cases occurred). Incubation periods can extend up to 30 years, and cerebellar onsets predominate in both hormone and graft recipients (in whom the site of graft placement had no effect on the clinical presentation). Homozygosity at codon 129 of the PRNP gene is over-represented in both forms of disease; it has no effect on the incubation period of graft recipients, but may promote shorter incubation periods in hormone cases. Knowledge about potential high-risk sources of contamination gained during the last quarter century, and the implementation of methods to circumvent them, should minimize the potential for iatrogenic contributions to the current spectrum of CJD.

Iatrogenic Creutzfeldt-Jakob disease at the millennium.

The causes and geographic distribution of 267 cases of iatrogenic Creutzfeldt-Jakob disease (CJD) are here updated at the millennium. Small numbers of still-occurring cases result from disease onsets after longer and longer incubation periods following infection by cadaveric human growth hormone or dura mater grafts manufactured and distributed before the mid-1980s. The proportion of recipients acquiring CJD from growth hormone varies from 0.3 to 4.4% in different countries, and acquisition from dura mater varies between 0.02 and 0.05% in Japan (where most cases occurred). Incubation periods can extend up to 30 years, and cerebellar onsets predominate in both hormone and graft recipients (in whom the site of graft placement had no effect on the clinical presentation). Homozygosity at codon 129 of the PRNP gene is over-represented in both forms of disease; it has no effect on the incubation period of graft recipients, but may promote shorter incubation periods in hormone cases. Knowledge about potential high-risk sources of contamination gained during the last quarter century, and the implementation of methods to circumvent them, should minimize the potential for iatrogenic contributions to the current spectrum of CJD.

Creutzfeldt–Jakob disease associated with cadaveric dura mater grafts in Japan

A nationwide survey and recent information documented 57 patients with Creutzfeldt-Jakob disease (CJD) who had received dura mater grafts during the period between January 1979 and September 1999. At least 54 of these 57 patients received the same brand of dura mater graft from the same processor. Mean age at disease onset in the 57 patients with dural grafts was younger (51.9 years) than that in patients with sporadic CJD (63 years) (p < 0. 0001). Initial symptoms were cerebellar ataxia, disorientation, and visual or oculomotor disturbance.

Epidemiologic features of 65 Creutzfeldt-Jakob disease patients with a history of cadaveric dura mater transplantation in Japan.

A total of 65 cases of Creutzfeldt-Jakob disease with a history of cadaveric dura transplantation in Japan were analysed to clarify the epidemiologic features of such patients and to explore whether other such patients will appear in the future. The age at transplantation averaged 44.4 years with a standard deviation of 14.4 years. The age at onset had an average of 53.0 years with a standard deviation of 14.1 years. The shortest latent period was 14 months, and the longest was 218 months with an average of 103.1 months and a standard deviation of 49.9 months. From the relationship between the calendar year at transplantation and the latent period, other such patients will appear in the near future. The current data suggested that several patients with Creutzfeldt-Jakob disease will occur from those receiving cadaveric dura mater grafts in the near future.

A case-control study of Creutzfeldt-Jakob disease in Japan: transplantation of cadaveric dura mater was a risk factor.

A case-control study was conducted to reveal the relative risk of cadaveric dura mater graft transplantation for Creutzfeldt-Jakob disease. Fifty-two cases with Creutzfeldt-Jakob disease that were reported to the surveillance of the disease, and 102 age- and sex-matched hospital controls were selected. Information on family history, occupations, and medical history was collected. Eight cases and no control had a history of cadaveric dura mater graft transplantation. Surgical operations without the dura mater graft, blood transfusion, and acupuncture did not elevate the risk.

Clinical application of new bioabsorbable artificial dura mater: A preliminary report

Synthetic dural substitutes composed of bioabsorbable polymers were used in 20 patients during neurosurgical operation. Clinical manifestations such as operative wound features, white blood cell counts, C-reactive protein, and computed tomography were evaluated after neurosurgical operations. Transient subcutaneous collection of cerebrospinal fluid was observed in three patients. No other significant complication was observed. This preliminary report indicates the effectveness of the bioabsorbable artifical dura mater without risking virally transmitted infection when compared with a cadaveric dura mater graft.

Creutzfeldt-Jakob Disease Associated With Cadaveric Dura Mater Grafts--Japan, January 1979-May 1996

In 1997, a nongovernmental surveillance group for Creutzfeldt-Jakob disease (CJD) in Japan reported to the Ministry of Health and Welfare its analysis of a 1996 mail questionnaire survey of neurologic, psychiatric, and neuropathologic institutions throughout Japan. This analysis identified 829 patients with CJD diagnosed by physicians during January 1979-May 1996, including a large number (43 patients) who had received a cadaveric dura mater graft during a neurosurgical (42) or orthopedic (one) procedure during 1979-1991. This report presents a summary of features of these 43 cases, which indicated that at least 41 of these patients had received dura mater grafts from the same processor, and describes CJD in the most recent recipient of a dura mater graft. The findings indicate that an international outbreak of CJD associated with a single brand of dura mater grafts is larger than previously recognized and that recipients of contaminated grafts may remain at risk for CJD at least 16 years following receipt of grafts.

Creutzfeldt-Jakob disease and lyophilised dura mater grafts: report of two cases.

Two further cases of Creutzfeldt-Jakob disease (CJD) in association with cadaveric dura mater grafts are described. The clinical features of all such reported cases resemble more closely those of sporadic CJD, in contrast with kuru and the cases of CJD which have arisen after therapy with human pituitary-derived growth hormone. This observation may reflect the route of inoculation of the agent.

Creutzfeldt-Jacob disease following cadaveric dura mater graft.

Creutzfeldt-Jacob disease following cadaveric dura mater graft.

Major trends in nosocomial viral infections

Viruses have recently become appreciated as nosocomial pathogens. There is insufficient data to characterize trends in rates of viral nosocomial infections, but there have been major trends in methodologies and concepts. New groups of patients, such as infants and the elderly, are becoming appreciated as being at risk for serious nosocomial viral infections, whereas other groups, such as immunodeficient patients are expanding because of the epidemic of human immunodeficiency virus (HIV) infection and expanded use of immunosuppressive treatment. The continued addition of new viruses, such as HIV, human parvovirus B19, and rabies virus, to the list of potential nosocomial pathogens suggest that most human viruses can probably be serious nosocomial pathogens under the right circumstances. Advances in medical treatments and procedures, such as cadaveric dura mater grafts and laser treatment of warts, have provided new avenues for nosocomial transmission of viruses. Improved and wider availability of diagnostics promises to be a major force in improving our understanding and ability to prevent viral nosocomial infections. With these advances, viral diagnostic laboratories should become an important member of the infection control team. In parallel with trends in methodologies and concepts, there have been major advances in our understanding of ways to prevent some nosocomial viral infections. Application of these prevention measures is an important challenge to the infection control practitioner.

Leads from the MMWR. Creutzfeldt-Jakob disease in a second patient who received a cadaveric dura mater graft

Leads from the MMWR. Creutzfeldt-Jakob disease in a second patient who received a cadaveric dura mater graft