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 Aß-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 Aß 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 Aß deposits, neurofibrillary tangles and neuropil threads. The mechanism involved in the human-to-human transmission of the Aß 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 Aß pathology, neurofibrillary changes indistinguishable from AD may develop in specific conditions with long latency period from the neurosurgical or embolization procedure.

Dural augmentation approaches and complication rates after posterior fossa decompression for Chiari I malformation and syringomyelia: a Park-Reeves Syringomyelia Research Consortium study.

OBJECTIVE: Posterior fossa decompression with duraplasty (PFDD) is commonly performed for Chiari I malformation (CM-I) with syringomyelia (SM). However, complication rates associated with various dural graft types are not well established. The objective of this study was to elucidate complication rates within 6 months of surgery among autograft and commonly used nonautologous grafts for pediatric patients who underwent PFDD for CM-I/SM. METHODS: The Park-Reeves Syringomyelia Research Consortium database was queried for pediatric patients who had undergone PFDD for CM-I with SM. All patients had tonsillar ectopia ≥ 5 mm, syrinx diameter ≥ 3 mm, and ≥ 6 months of postoperative follow-up after PFDD. Complications (e.g., pseudomeningocele, CSF leak, meningitis, and hydrocephalus) and postoperative changes in syrinx size, headaches, and neck pain were compared for autograft versus nonautologous graft. RESULTS: A total of 781 PFDD cases were analyzed (359 autograft, 422 nonautologous graft). Nonautologous grafts included bovine pericardium (n = 63), bovine collagen (n = 225), synthetic (n = 99), and human cadaveric allograft (n = 35). Autograft (103/359, 28.7%) had a similar overall complication rate compared to nonautologous graft (143/422, 33.9%) (p = 0.12). However, nonautologous graft was associated with significantly higher rates of pseudomeningocele (p = 0.04) and meningitis (p < 0.001). The higher rate of meningitis was influenced particularly by the higher rate of chemical meningitis (p = 0.002) versus infectious meningitis (p = 0.132). Among 4 types of nonautologous grafts, there were differences in complication rates (p = 0.02), including chemical meningitis (p = 0.01) and postoperative nausea/vomiting (p = 0.03). Allograft demonstrated the lowest complication rates overall (14.3%) and yielded significantly fewer complications compared to bovine collagen (p = 0.02) and synthetic (p = 0.003) grafts. Synthetic graft yielded higher complication rates than autograft (p = 0.01). Autograft and nonautologous graft resulted in equal improvements in syrinx size (p < 0.0001). No differences were found for postoperative changes in headaches or neck pain. CONCLUSIONS: In the largest multicenter cohort to date, complication rates for dural autograft and nonautologous graft are similar after PFDD for CM-I/SM, although nonautologous graft results in higher rates of pseudomeningocele and meningitis. Rates of meningitis differ among nonautologous graft types. Autograft and nonautologous graft are equivalent for reducing syrinx size, headaches, and neck pain.

Diagnostic Accuracy of Prion Disease Biomarkers in Iatrogenic Creutzfeldt-Jakob Disease.

Human prion diseases are classified into sporadic, genetic, and acquired forms. Within this last group, iatrogenic Creutzfeldt-Jakob disease (iCJD) is caused by human-to-human transmission through surgical and medical procedures. After reaching an incidence peak in the 1990s, it is believed that the iCJD historical period is probably coming to an end, thanks to lessons learnt from past infection sources that promoted new prion prevention and decontamination protocols. At this point, we sought to characterise the biomarker profile of iCJD and compare it to that of sporadic CJD (sCJD) for determining the value of available diagnostic tools in promptly recognising iCJD cases. To that end, we collected 23 iCJD samples from seven national CJD surveillance centres and analysed the electroencephalogram and neuroimaging data together with a panel of seven CSF biomarkers: 14-3-3, total tau, phosphorylated/total tau ratio, alpha-synuclein, neurofilament light, YKL-40, and real-time quaking induced conversion of prion protein. Using the cut-off values established for sCJD, we found the sensitivities of these biomarkers for iCJD to be similar to those described for sCJD. Given the limited relevant information on this issue to date, the present study validates the use of current sCJD biomarkers for the diagnosis of future iCJD cases.

Comparing the results of duraplasty using amniotic membrane versus pericranium as dural graft; concerning CSF leakage and pseudomeningocele.

Purpose: In many brain surgeries, dura cannot be primarily repaired and it is necessary to use a graft. Appropriate repair of dura plays a major role in preventing CSF leakage and meningitis. In the cases where sufficient Pericranium is not available for recovery, we need to use graft from other resources. The present study compares the results of amniotic membrane dural graft and pericranium dural graft in terms of CSF leakage and Pseudomeningocele. Materials and methods: This is a semi-empirical research. Thirty cases underwent dural graft with amnion membrane because of inadequate local pericranium for repair. There were 30 other historical cases that had undergone auto-graft dural graft with Pericranium in the same center.Results: The average age of the participants in Pericranium graft group (P, n = 30) and those in amniotic graft group (A, n = 30) was 39.1 ± 15 and 43.9 ± 19 years old, respectively. As for the P and A groups, there were 14 and 17 males, respectively. Two cases of CSF leakage (7%) were observed in P group, while none was reported in A group. There were 3 cases (10%) of meningitis in Pericranium group and 2 cases (7%) were reported in amnion group. Out of 2 cases of meningitis in group P, 2 cases were associated with CSF leak. 5 cases of Hydrocephalus (17%) were observed in group P and 9 cases (30%) were reported in group A. No significant difference was observed between the two groups in any complication. The frequency of hydrocephalus was significantly higher in posterior fossa craniotomy.Conclusion: Amniotic membrane may provide a good source for cases with a large dural defect and can be utilized for all ages. Of course, its application in cases of posterior fossa craniotomy needs to be carefully studied so that the best results may be obtained.

Early onset cerebral amyloid angiopathy following childhood exposure to cadaveric dura.

Amyloid-ß transmission has been described in patients both with and without iatrogenic Creutzfeldt-Jakob disease; however, there is little information regarding the clinical impact of this acquired amyloid-ß pathology during life. Here, for the first time, we describe in detail the clinical and neuroimaging findings in 3 patients with early onset symptomatic amyloid-ß cerebral amyloid angiopathy following childhood exposure to cadaveric dura (by neurosurgical grafting in 2 patients and tumor embolization in a third). Our observations provide further in vivo evidence that cerebral amyloid angiopathy might be caused by transmission of amyloid-ß seeds (prions) present in cadaveric dura and have diagnostic relevance for younger patients presenting with suspected cerebral amyloid angiopathy. Ann Neurol 2019; 1-7 ANN NEUROL 2019;85:284-290.

Autopsied case of non-plaque-type dura mater graft-associated Creutzfeldt-Jakob disease presenting with extensive amyloid-ß deposition.

We present an autopsied case of non-plaque-type dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) with extensive amyloid-ß (Aß) deposition in the brain. A 39-year-old Japanese woman presented with memory disturbance and abnormal behavior. The patient had a history of craniotomy with dura matter-graft transplant for a head injury which occurred when she was 19 years old. Magnetic resonance imaging (MRI) showed hyperintensities in the cerebral cortex and striatum on diffusion-weighted images, particularly on the dura mater-grafted right side. Her clinical symptoms, including rapidly progressing cognitive impairment, myoclonus, and periodic sharp wave complexes on electroencephalogram, could not be distinguished from typical sporadic CJD cases. The patient died 11 months after symptom onset, and pathological investigations showed extensive spongiform degeneration with prion protein (PrP) deposition without Kuru plaques; these observations were essentially the same as those of typical sporadic CJD cases. Furthermore, Aß immunohistochemistry showed extensive diffuse staining in the cerebral neocortex, plaque-type deposition, positive staining in the pia mater, and cerebral amyloid angiopathy. Although the MRI findings suggested that the pathological involvement originated from the dura mater-grafted right side, the PrP and Aß depositions showed no apparent regionalization and laterality. Tau-pathology including neurofibrillary tangles was hardly identified. The proteins phosphorylated α-synuclein and phosphorylated transactivation response DNA-binding protein 43 kDa were not detected on immunostaining. Although this report describes only one case, various speculations were made based on detailed clinical and pathological observations in conjunction with previous reports of dCJD. In particular, this report provides significant insight into the characteristics and progression of dCJD pathology and its relationship with Aß pathology.

Update: Dura Mater Graft-Associated Creutzfeldt-Jakob Disease - Japan, 1975-2017.

Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disorder that, according to the most well accepted hypothesis (1), is caused by replicating, transmissible, abnormal forms of a host-encoded prion protein (prions). Most CJD cases occur spontaneously (sporadic CJD) or are inherited (genetic CJD). Iatrogenic CJD can occur after exposure to prion-contaminated instruments or products in medical/surgical settings. Cadaveric dura mater graft-associated CJD (dCJD) accounts for a common form of iatrogenic CJD. This report summarizes the epidemiologic features of 154 cases of dCJD identified in Japan during 1975-2017; these cases account for >60% of dCJD cases reported worldwide (1,2). The unusually high prevalence of dCJD in Japan was first reported in 1997 (3). In 2008, a single brand of graft (Lyodura [B. Braun Melsungen AG, Melsungen, Germany]), frequently used as a patch in neurosurgical procedures, was identified as the probable vehicle of transmission (4). No international recall of the implicated Lyodura occurred, the product had a relatively long shelf life, and the grafts were used frequently in Japanese patients with non-life-threatening conditions (4,5). Since 2008, additional cases have been ascertained, reflecting the identification of previously missed cases and the occurrence of new cases with longer latency periods (interval from exposure to symptom onset) for dCJD (up to 30 years), underscoring the importance of maintaining surveillance for dCJD.

Closing the dura: dural hitching versus surgicel and tisseel overlay graft in craniocervicaldecompression for Chiari 1 malformation.

BACKGROUND: This study compares dural hitching to surgicel and tisseel overlay graft following craniocervical decompression and C1 laminectomy with simple durotomy for Chiari I malformation. Outcome measures were syrinx decompression, headache resolution and complication rates. METHODS: A retrospective analysis of case notes was conducted. Patients who had undergone craniocervical decompression (CCD) were grouped by method of dural closure. Outcomes compared were rates of syrinx decompression, headache resolution, and post-operative complications. Statistical analysis was conducted using SPSS v20. RESULTS: We identified 32 adult patients for inclusion in this study. 53.1% (n = 17) had asyrinx, and 78.1% (n = 25) had a pre-operative headache. All were treated with suboccipital craniectomy, C1 laminectomy (with or without C2 laminectomy), and durotomy. The dura was either left open by dural hitching (n = 23) or closed with surgicel and tisseel overlay graft (n = 9). We found a statistically significant association between the method of dural closure and the rate of syrinx resolution. Resolution occurred in 91.7% (n = 11) of the hitching group, compared to 20.0% (n = 1) of the overlay graft group: Χ2(1) = 5.6, p = .018. There were no statistically significant differences between the two groups in the rates of headache resolution or other complications. CONCLUSIONS: In patients with symptomatic Chiari I malformation and associated syringomyelia, syrinx resolution is more likely if the dura is hitched open rather than closed bysurgicel and tisseel overlay graft after durotomy.

Dura mater graft-associated Creutzfeldt-Jakob disease with 30-year incubation period.

Over 60% of all patients with dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) have been diagnosed in Japan. The incubation period has ranged from 1 to 30 years and the age at onset from 15 to 80 years. Here, we report a 77-year-old male Japanese autopsied dCJD case with the longest incubation period so far in Japan. He received a cadaveric dural graft at the right cranial convexity following a craniotomy for meningioma at the age of 46. At 30 years post-dural graft placement, disorientation was observed as an initial symptom of dCJD. He rapidly began to present with inconsistent speech, cognitive impairment and tremor of the left upper extremity. Occasional myoclonic jerks were predominantly observed on the left side. Brain MRI presented hyperintense signals on diffusion-weighted and T2-weighted images, at the right cerebral cortex. The most hyperintense lesion was located at the right parietal lobe, where the dura mater graft had been transplanted. Single-photon emission CT scan showed markedly decreased cerebral blood flow at the right parietal lobe. EEG revealed diffuse and slow activities with periodic sharp-wave complex discharges seen in the right parietal, temporal and occipital lobes. He died of pneumonia 9 months after onset. Brain pathology revealed non-plaque-type dCJD. Laterality of neuropathological changes, including spongiform change, neuronal loss, gliosis or PrP deposits, was not evident. Western blot analysis showed type 1 PrPCJD . Alzheimer-type pathology and PSP-like pathology were also observed.

Characterization and morphological comparison of human dura mater, temporalis fascia, and pericranium for the correct selection of an autograft in duraplasty procedures.

PURPOSE: The objective of this study was to characterize and compare the morphological characteristics of the dura mater, the pericranium, and the temporal fascia to ascertain the most adequate tissue to use as a dura graft. METHODS: 20 dura mater, 20 pericranium and 20 temporalis fascia samples were analyzed. Each of the samples was stained with hematoxylin and eosin, orcein, Van Gieson, Masson's trichrome and Verhoeff-Van Gieson (600 slides in total) for a general morphological evaluation, as well as a quantitative, morphometric and densitometric analysis of elastic fibers present in each of the tissues. RESULTS: The micro-densitometric analysis of the tissues indicated that the area occupied by the elastic fibers showed values of 1.766 ± 1.376, 4.580 ± 3.041, and 8.253 ± 4.467 % for the dura mater, the temporalis fascia and the pericranium, respectively (p < 0.05, all pairs). The values observed in the analysis of the density intensity were 3.42E+06 ± 2.57E+06, 1.41E+07 ± 1.28E+07, and 1.63E+07 ± 9.19E+06 for the dura mater, the temporalis fascia and the pericranium, respectively (p < 0.05), dura mater vs. temporalis fascia and dura mater vs. pericranium). CONCLUSIONS: This is the first study to compare the dura mater with tissues for dural autograft and to quantify the elastic component present in these tissues. The results indicate that the temporalis fascia is a better dural graft because of its intrinsic tissue properties.

A novel autologous duraplasty in situ technique for the treatment of Chiari malformation Type I.

OBJECTIVE The purpose of this study was to introduce a novel autologous duraplasty procedure for the treatment of Chiari malformation Type I (CM-I). METHODS The authors retrospectively reviewed data from patients who had been diagnosed with CM-I and had undergone suboccipital decompression and autologous duraplasty in situ or synthetic dural graft duraplasty; patients were treated in the authors' department between 2011 and 2014. All procedures were performed by the same surgeon. The 2 duraplasty methods were compared in terms of surgical factors and complications. The authors assessed the neurological outcome and MRI-documented syrinx size at the 6-month follow-up visit. RESULTS Twenty-seven patients were enrolled in this study, 13 in the duraplasty in situ group and 14 in the synthetic dural graft duraplasty group. The results showed no significant differences between the duraplasty in situ and synthetic dural graft duraplasty groups in overall operative time (4.9 hours vs 4.1 hours; p = 0.070), estimated blood loss (229 ml vs 254 ml; p = 0.159), and duration of hospital stay after the operation (13.5 days vs 12.8 days; p = 0.808). In the duraplasty in situ group, 1 case of meningitis occurred (7.7%). In the synthetic dural graft duraplasty group, the complications included 1 case of meningitis (7.1%) and 1 CSF leak (7.1%). The mean cost of hospitalization in the duraplasty in situ group (CNY 23,354) was significantly lower than that in the synthetic dural graft duraplasty group (CNY 29,385; p = 0.036). CONCLUSIONS Compared with synthetic dural graft duraplasty, autologous duraplasty in situ is a safe, effective, and cost-effective procedure for the treatment of CM-I. The long-term outcome of this procedure requires investigation.

Distinctive properties of plaque-type dura mater graft-associated Creutzfeldt-Jakob disease in cell-protein misfolding cyclic amplification.

There are two distinct subtypes of dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) with methionine homozygosity at codon 129 of the PRNP gene. The majority of cases is represented by a non-plaque-type (np-dCJD) resembling sporadic CJD (sCJD)-MM1 or -MV1, while the minority by a plaque-type (p-dCJD). p-dCJD shows distinctive phenotypic features, namely numerous kuru plaques and an abnormal isoform of prion protein (PrP(Sc)) intermediate in size between types 1 and 2. Transmission studies have shown that the unusual phenotypic features of p-dCJD are linked to the V2 prion strain that is associated with sCJD subtypes VV2 or -MV2. In this study, we applied protein misfolding cyclic amplification (PMCA) using recombinant human prion protein as a substrate and demonstrated that p-dCJD prions show amplification features that are distinct from those of np-dCJD. Although no amplification of np-dCJD prions was observed with either 129 M or 129 V substrate, p-dCJD prions were drastically amplified with the 129 V substrates, despite the PRNP codon 129 incompatibility between seed and substrate. Moreover, by using a type 2 PrP(Sc)-specific antibody not recognizing PrP(Sc) in p-dCJD, we found that type 2 products are generated de novo from p-dCJD prions during PMCA with the 129 V substrates. These findings suggest that our cell-PMCA is a useful tool for easily and rapidly identifying acquired CJD associated with the transmission of the V2 CJD strain to codon 129 methionine homozygotes, based on the preference for the 129 V substrate and the type of the amplified products.

Amyloid-ß pathology and cerebral amyloid angiopathy are frequent in iatrogenic Creutzfeldt-Jakob disease after dural grafting.

QUESTIONS UNDER STUDY: Alzheimer-type amyloid-ß (Aß) pathology was reported in brains of individuals developing iatrogenic Creutzfeldt-Jakob disease (iCJD) after treatment with human cadaveric growth hormone, and interpreted as evidence of human transmission of Aß by the treatment. Here we investigated the prevalence of Aß pathology in other instances of iCJD related to dura mater grafts. METHODS: By use of immunohistochemistry for Aß, we investigated seven brains of patients (age range 28-63) who succumbed to iCJD after dural grafting, which had been applied by means of neurosurgery between 11 and 25 years before death. For control, we examined a series of 21 brains of age-matched (40-63 years) patients with sporadic CJD (sCJD) and an additional series of 81 sCJD cases (55-85 years) with the same methods. RESULTS: In five of seven iCJD brains, Aß was deposited in meningeal vessels as congophilic amyloid angiopathy and brain parenchymal plaques. This was significantly (p <0.001) more frequent than in the age-matched sCJD controls and in the usual sCJD series. CONCLUSIONS: We conclude that congophilic amyloid angiopathy and brain parenchymal Aß plaques are frequent in iCJD after dural grafting. The presence of Aß pathology in young individuals is highly unusual and suggests a causal relationship to the dural grafts. Further studies will be needed to elucidate whether such pathology resulted from the seeding of Aß aggregates from the grafts to host tissues.

Long-Term Outcomes After Small-Bone-Window Posterior Fossa Decompression and Duraplasty in Adults with Chiari Malformation Type I.

BACKGROUND: Small-bone-window posterior fossa decompression with duraplasty is one of the popular surgical options for Chiari malformation type I, but its efficacy is controversial and the risk factors of clinical outcome remain unclear. METHODS: The study cohort included 152 patients with Chiari malformation type I who received small-bone-window posterior fossa decompression at Beijing Tiantan hospital from January 2008 to September 2009. All patients underwent combined surgical procedures: a small-bone-window suboccipital decompression (diameter, 2.5-3 cm) and a C1 laminectomy (1.5- to 2-cm wide) followed by a duraplasty with an autologous graft. Clinical manifestations, radiologic features, and follow-up data during a 6-year span were analyzed. Risk factors associated with outcome were investigated by the use of χ(2) analysis and logistic regression analysis. RESULTS: The average follow-up duration was 74 months. Symptoms were improved in 126 patients (82.9%), remained stable in 21 patients (13.8%), and deteriorated in 5 patients (3.3%). There was no mortality. Postoperative magnetic resonance imaging scans were available for all patients. Preoperatively, 112 patients were associated with syringomyelia, and the follow-up magnetic resonance images showed obvious reduction of syringomyelia in 73 patients (65.2%) and no significant change in 39 patients (34.8%). In addition, enlargement of the cistern magna was observed in 92 patients (85.2%). Regression analysis indicates preoperative motor dysfunction, brainstem herniation and basilar invagination may influence the clinical outcome (P < 0.05). CONCLUSIONS: Small-bone-window posterior fossa decompression with duraplasty is an effective and safe treatment option with a low complication rate. Motor dysfunction, brainstem herniation, and basilar invagination are predictors of poor clinical prognosis.