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James W. Ironside - One of the best experts on this subject based on the ideXlab platform.
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sporadic creutzfeldt jakob Disease presenting as progressive nonfluent aphasia with speech apraxia
Alzheimer Disease & Associated Disorders, 2013Co-Authors: Christopher Kobylecki, James W. Ironside, Jennifer C Thompson, Matthew Jones, Samantha J Mills, Sandip Shaunak, Julie S Snowden, Anna RichardsonAbstract:Progressive non-fluent aphasia (PNFA) is typically associated with pathological changes consistent with frontotemporal lobar degeneration. A 65-year-old male presented with effortful speech, markedly impaired naming and features of speech apraxia, consistent with PNFA. Perceptuospatial function, calculation and executive function were intact. Brain SPECT showed left perisylvian hypoperfusion. He deteriorated profoundly over the subsequent eight months, with appearances on diffusion-weighted magnetic resonance imaging typical of sporadic Creutzfeldt-Jakob Disease, which was confirmed pathologically at postmortem examination. While the presence of PNFA with speech apraxia is thought to predict underlying tauopathy, sporadic Creutzfeldt-Jakob Disease may mimic this presentation and present in a highly circumscribed form not previously described.
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prion infectivity in the spleen of a prnp heterozygous individual with subclinical variant creutzfeldt jakob Disease
Brain, 2013Co-Authors: Matthew Bishop, James W. Ironside, R G Will, Abigail B Diack, Diane L Ritchie, Jean MansonAbstract:Blood transfusion has been identified as a source of human-to-human transmission of variant Creutzfeldt–Jakob Disease. Three cases of variant Creutzfeldt–Jakob Disease have been identified following red cell transfusions from donors who subsequently developed variant Creutzfeldt–Jakob Disease and an asymptomatic red cell transfusion recipient, who did not die of variant Creutzfeldt–Jakob Disease, has been identified with prion protein deposition in the spleen and a lymph node, but not the brain. This individual was heterozygous (MV) at codon 129 of the prion protein gene (PRNP), whereas all previous definite and probable cases of variant Creutzfeldt–Jakob Disease have been methionine homozygotes (MM). A critical question for public health is whether the prion protein deposition reported in peripheral tissues from this MV individual correlates with infectivity. Additionally it is important to establish whether the PRNP codon 129 genotype has influenced the transmission characteristics of the infectious agent. Brain and spleen from the MV blood recipient were inoculated into murine strains that have consistently demonstrated transmission of the variant Creutzfeldt–Jakob Disease agent. Mice were assessed for clinical and pathological signs of Disease and transmission data were compared with other transmission studies in variant Creutzfeldt–Jakob Disease, including those on the spleen and brain of the donor to the index case. Transmission of variant Creutzfeldt–Jakob Disease was observed from the MV blood recipient spleen, but not from the brain, whereas there was transmission from both spleen and brain tissues from the red blood cell donor. Longer incubation times were observed for the blood donor spleen inoculum compared with the blood donor brain inoculum, suggesting lower titres of infectivity in the spleen. The distribution of vacuolar pathology and abnormal prion protein in infected mice were similar following inoculation with both donor and recipient spleen homogenates, providing initial evidence of similar transmission properties after propagation in PRNP codon 129 MV and MM individuals. These studies demonstrate that spleen tissue from a PRNP MV genotype individual can propagate the variant Creutzfeldt–Jakob Disease agent and that the infectious agent can be present in the spleen without CNS involvement.
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ultrastructural study of florid plaques in variant creutzfeldt jakob Disease a comparison with amyloid plaques in kuru sporadic creutzfeldt jakob Disease and gerstmann straussler scheinker Disease
Neuropathology and Applied Neurobiology, 2009Co-Authors: Beata Sikorska, Herbert Budka, Pawel P Liberski, Tomasz Sobow, James W. IronsideAbstract:Background: Although the histological features of the amyloid plaques in variant Creutzfeldt–Jakob Disease (vCJD) are distinct from those in other forms of prion Disease [kuru, sporadic Creutzfeldt–Jakob Disease (sCJD) and Gerstmann–Straussler–Scheinker Disease (GSS)], their ultrastructural features have only been described in a single case report. Aims: To study vCJD plaques systematically and compare them with plaques in kuru, sCJD, GSS and Alzheimer Disease (AD). Methods: Amyloid plaques were studied by transmission electron microscopy and image analysis in five cases of vCJD, three cases of GSS, two cases of sCJD, one case of kuru and five cases of AD. Immunohistochemistry was performed on paraffin sections from one case of vCJD, two cases of GSS, one case of kuru and two cases of sCJD. Results: The florid plaques in vCJD were either compact or more diffuse; in both forms, the radiating fibrils were organized into thick ‘tongues’, in contrast to kuru plaques. Dystrophic neurites (DNs) containing lysosomal electron-dense bodies or vesicles surrounded florid plaques. Microglial cells were found within florid plaques; occasional amyloid fibrils were identified in membrane-bound pockets of microglial cells. In vCJD, there was significant tau immunoreactivity in DNs around florid plaques while, in sCJD, GSS and kuru, minimal tau immunoreactivity was observed around plaques. Conclusions: The ultrastructure of the florid plaques and DNs in vCJD is more reminiscent of neuritic plaques in AD than kuru or multicentric plaques. These findings may reflect differences both in the strains of the transmissible agents responsible for these disorders and in host factors.
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dura mater associated creutzfeldt jakob Disease experience from surveillance in the uk
Journal of Neurology Neurosurgery and Psychiatry, 2006Co-Authors: C A Heath, Mark Head, T F G Esmonde, Roge A Arke, P Harvey, Richard C Roberts, P Trend, Coli Smith, Jeanne E Ell, James W. IronsideAbstract: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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detection of type 1 prion protein in variant creutzfeldt jakob Disease
American Journal of Pathology, 2006Co-Authors: Helen Yull, James W. Ironside, Moira E Bruce, Diane Ritchie, Jan P M Langeveld, Fred G Van Zijderveld, Mark HeadAbstract:Molecular typing of the abnormal form of the prion protein (PrPSc) has come to be regarded as a powerful tool in the investigation of the prion Diseases. All evidence thus far presented indicates a single PrPSc molecular type in variant Creutzfeldt-Jakob Disease (termed type 2B), presumably resulting from infection with a single strain of the agent (bovine spongiform encephalopathy). Here we show for the first time that the PrPSc that accumulates in the brain in variant Creutzfeldt-Jakob Disease also contains a minority type 1 component. This minority type 1 PrPSc was found in all 21 cases of variant Creutzfeldt-Jakob Disease tested, irrespective of brain region examined, and was also present in the variant Creutzfeldt-Jakob Disease tonsil. The quantitative balance between PrPSc types was maintained when variant Creutzfeldt-Jakob Disease was transmitted to wild-type mice and was also found in bovine spongiform encephalopathy cattle brain, indicating that the agent rather than the host specifies their relative representation. These results indicate that PrPSc molecular typing is based on quantitative rather than qualitative phenomena and point to a complex relationship between prion protein biochemistry, Disease phenotype and agent strain.
R G Will - One of the best experts on this subject based on the ideXlab platform.
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variant creutzfeldt jakob Disease strain is identical in individuals of two prnp codon 129 genotypes
Brain, 2019Co-Authors: Abigail B Diack, R G Will, Aileen Boyle, Christopher Plinston, Emma Hunt, Matthew Bishop, Jean MansonAbstract:In 2004, a subclinical case of variant Creutzfeldt-Jakob Disease in a PRNP 129 methionine/valine heterozygous individual infected via blood transfusion was reported, and we established that the spleen from this individual was infectious. Since host genetics is an important factor in strain modification, the identification of variant Creutzfeldt-Jakob Disease infection in a PRNP 129 methionine/valine heterozygous individual has raised the possibility that the properties of the variant Creutzfeldt-Jakob Disease agent could change after transmission to this different genetic background and concerns that this could lead to a more virulent strain of variant Creutzfeldt-Jakob Disease. The variant Creutzfeldt-Jakob Disease strain has to date been characterized only in methionine homozygous individuals, therefore to establish whether the strain characteristics of variant Creutzfeldt-Jakob Disease had been modified by the host genotype, spleen material with prion protein deposition from a PRNP 129 methionine/valine individual was inoculated into a panel of wild-type mice. Three passages in mice were undertaken to allow stabilization of the strain characteristics following its passage into mice. In each passage, a combination of clinical signs, neuropathology (transmissible spongiform encephalopathy vacuolation and prion protein deposition) were analysed and biochemical analysis carried out. While some differences were observed at primary and first subpassage, following the second subpassage, strain characteristics in the methionine/valine individual were totally consistent with those of variant Creutzfeldt-Jakob Disease transmitted to 129 methionine/methionine individuals thus demonstrated no alteration in strain properties were imposed by passage through the different host genotype. Thus we have demonstrated variant Creutzfeldt-Jakob Disease strain properties are not affected by transmission through an individual with the PRNP methionine/valine codon 129 genotype and thus no alteration in virulence should be associated with the different host genotype.
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prion infectivity in the spleen of a prnp heterozygous individual with subclinical variant creutzfeldt jakob Disease
Brain, 2013Co-Authors: Matthew Bishop, James W. Ironside, R G Will, Abigail B Diack, Diane L Ritchie, Jean MansonAbstract:Blood transfusion has been identified as a source of human-to-human transmission of variant Creutzfeldt–Jakob Disease. Three cases of variant Creutzfeldt–Jakob Disease have been identified following red cell transfusions from donors who subsequently developed variant Creutzfeldt–Jakob Disease and an asymptomatic red cell transfusion recipient, who did not die of variant Creutzfeldt–Jakob Disease, has been identified with prion protein deposition in the spleen and a lymph node, but not the brain. This individual was heterozygous (MV) at codon 129 of the prion protein gene (PRNP), whereas all previous definite and probable cases of variant Creutzfeldt–Jakob Disease have been methionine homozygotes (MM). A critical question for public health is whether the prion protein deposition reported in peripheral tissues from this MV individual correlates with infectivity. Additionally it is important to establish whether the PRNP codon 129 genotype has influenced the transmission characteristics of the infectious agent. Brain and spleen from the MV blood recipient were inoculated into murine strains that have consistently demonstrated transmission of the variant Creutzfeldt–Jakob Disease agent. Mice were assessed for clinical and pathological signs of Disease and transmission data were compared with other transmission studies in variant Creutzfeldt–Jakob Disease, including those on the spleen and brain of the donor to the index case. Transmission of variant Creutzfeldt–Jakob Disease was observed from the MV blood recipient spleen, but not from the brain, whereas there was transmission from both spleen and brain tissues from the red blood cell donor. Longer incubation times were observed for the blood donor spleen inoculum compared with the blood donor brain inoculum, suggesting lower titres of infectivity in the spleen. The distribution of vacuolar pathology and abnormal prion protein in infected mice were similar following inoculation with both donor and recipient spleen homogenates, providing initial evidence of similar transmission properties after propagation in PRNP codon 129 MV and MM individuals. These studies demonstrate that spleen tissue from a PRNP MV genotype individual can propagate the variant Creutzfeldt–Jakob Disease agent and that the infectious agent can be present in the spleen without CNS involvement.
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real time quaking induced conversion analysis of cerebrospinal fluid in sporadic creutzfeldt jakob Disease
Annals of Neurology, 2012Co-Authors: Lynne Mcguire, Christina D. Orrú, Byron Caughey, Mark Head, Alexander Peden, Jason M Wilham, Nigel E J Appleford, Gary Mallinson, Mary Andrews, R G WillAbstract:Objective Current cerebrospinal fluid (CSF) tests for sporadic Creutzfeldt-Jakob Disease (sCJD) are based on the detection of surrogate markers of neuronal damage such as CSF 14-3-3 which are not specific for sCJD. A number of prion protein conversion assays have been developed, including real-time quaking induced conversion (RT-QuIC). The objective of this study is to investigate whether CSF RT-QuIC analysis could be used as a diagnostic test in sCJD.
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iatrogenic creutzfeldt jakob Disease final assessment
Emerging Infectious Diseases, 2012Co-Authors: Paul Brown, R G Will, J. Mackenzie, Maurizio Pocchiari, Jean Philippe Brandel, Takeshi Sato, Yosikazu Nakamura, Anna Ladogana, Ellen W Leschek, Lawrence B SchonbergerAbstract:The era of iatrogenic Creutzfeldt-Jakob Disease (CJD) has nearly closed; only occasional cases with exceptionally long incubation periods are still appearing. The principal sources of these outbreaks are contaminated growth hormone (226 cases) and dura mater grafts (228 cases) derived from human cadavers with undiagnosed CJD infections; a small number of additional cases are caused by neurosurgical instrument contamination, corneal grafts, gonadotrophic hormone, and secondary infection with variant CJD transmitted by transfusion of blood products. No new sources of Disease have been identified, and current practices, which combine improved recognition of potentially infected persons with new disinfection methods for fragile surgical instruments and biological products, should continue to minimize the risk for iatrogenic Disease until a blood screening test for the detection of preclinical infection is validated for human use.
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first hundred cases of variant creutzfeldt jakob Disease retrospective case note review of early psychiatric and neurological features
BMJ, 2002Co-Authors: Michael D Spencer, Richard Knight, R G WillAbstract:Abstract Objective: To describe the early psychiatric and neurological features of variant Creutzfeldt-Jakob Disease. Design: Cohort study. Setting: National surveillance system for Creutzfeldt-Jakob Disease in the United Kingdom. Participants: The first 100 cases of variant Creutzfeldt-Jakob Disease identified in the United Kingdom. Main outcome measures: The timing and nature of early psychiatric and neurological symptoms in variant Creutzfeldt-Jakob Disease. Results: The early stages of variant Creutzfeldt-Jakob Disease are dominated by psychiatric symptoms, but neurological symptoms precede psychiatric symptoms in 15% of cases and are present in combination with psychiatric symptoms in 22% of cases from the onset of Disease. Common early psychiatric features include dysphoria, withdrawal, anxiety, insomnia, and loss of interest. No common early neurological features exist, but a significant proportion of patients do exhibit neurological symptoms within 4 months of clinical onset, including poor memory, pain, sensory symptoms, unsteadiness of gait, and dysarthria. Conclusions: Although the diagnosis of variant Creutzfeldt-Jakob Disease may be impossible in the early stages of the illness, particular combinations of psychiatric and neurological features may allow early diagnosis in an appreciable proportion of patients.
Tetsuyuki Kitamoto - One of the best experts on this subject based on the ideXlab platform.
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clinical features and diagnosis of dura mater graft associated creutzfeldt jakob Disease
Neurology, 2007Co-Authors: Moeko Noguchishinohara, Tetsuyuki Kitamoto, Tsuyoshi Hamaguchi, Takeshi Sato, Yosikazu Nakamura, Hidehiro Mizusawa, M YamadaAbstract:Background: A subset of patients with dura mater graft–associated Creutzfeldt–Jakob Disease (dCJD) demonstrates atypical clinical features and plaque formation in the brain (plaque type). Objective: To elucidate the frequency and clinical features of plaque type dCJD in comparison with the non-plaque type. Methods: We analyzed clinicopathologic findings of 66 patients who had been registered as having dCJD by the Creutzfeldt–Jakob Disease Surveillance Committee, Japan, between April 1999 and February 2006. Results: 1) Analysis of pathologically confirmed dCJD patients (n = 23) demonstrated plaque type dCJD in 11 patients (48%). In contrast to the non-plaque type with classic CJD features, the plaque type commonly presented with ataxic gait as an initial manifestation, relatively slow progression of neurologic symptoms, and no or late occurrence of periodic sharp-wave complexes (PSWCs) on EEG. MRI, especially diffusion-weighted images, and CSF 14-3-3 protein and neuron specific enolase (NSE) showed high diagnostic sensitivities for plaque as well as non-plaque types. 2) Analysis of clinically diagnosed dCJD patients (n = 34) demonstrated that 7 patients (21%) had atypical clinical features without PSWCs, probably corresponding to plaque type dCJD. Conclusion: The frequency of the plaque type in dura mater graft–associated Creutzfeldt–Jakob Disease is apparently higher than previously recognized. For the clinical diagnosis of the plaque type dura mater graft–associated Creutzfeldt–Jakob Disease, MRI and CSF markers would be useful, in addition to the core features, i.e., onset with ataxic gait disturbance, relatively slow progression, and no or late occurrence of periodic sharp-wave complexes on EEG.
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clinical diagnosis of mm2 type sporadic creutzfeldt jakob Disease
Neurology, 2005Co-Authors: Tsuyoshi Hamaguchi, Tetsuyuki Kitamoto, Takeshi Sato, Yosikazu Nakamura, Hidehiro Mizusawa, M Noguchi, Yutaka Furukawa, Chiho Ishida, Ichiei Kuji, K MitaniAbstract:Background: No method for the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob Disease (sCJD) has been established except for pathologic examination. Objective: To identify a reliable marker for the clinical diagnosis of MM2-type sCJD. Methods: CSF, EEG, and neuroimaging studies were performed in eight patients with MM2-type sCJD confirmed by neuropathologic, genetic, and western blot analyses. Results: The eight cases were pathologically classified into the cortical (n = 2), thalamic (n = 5), and combined (corticothalamic) (n = 1) forms. The cortical form was characterized by late-onset, slowly progressive dementia, cortical hyperintensity signals on diffusion-weighted imaging (DWI) of brain, and elevated levels of CSF 14-3-3 protein. The thalamic form showed various neurologic manifestations including dementia, ataxia, and pyramidal and extrapyramidal signs with onset at various ages and relatively long Disease duration. Characteristic EEG and MRI abnormalities were almost absent. However, all four patients examined with cerebral blood flow (CBF) study using SPECT showed reduction of the CBF in the thalamus as well as the cerebral cortex. The combined form had features of both the cortical and the thalamic forms, showing cortical hyperintensity signals on DWI and hypometabolism of the thalamus on [18F]2-fluoro-2-deoxy-d-glucose PET. Conclusion: For the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob Disease, cortical hyperintensity signals on diffusion-weighted MRI are useful for the cortical form and thalamic hypoperfusion or hypometabolism on cerebral blood flow SPECT or [18F]2-fluoro-2-deoxy-d-glucose PET for the thalamic form.
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clinical features of creutzfeldt jakob Disease with v180i mutation
Neurology, 2004Co-Authors: Kazutaka Jin, Tetsuyuki Kitamoto, Katsumi Dohura, Yusei Shiga, Satoshi Shibuya, Keiji Chida, Yasufumi Sato, Hidehiko Konno, Y ItoyamaAbstract:The authors describe the clinical features of Creutzfeldt-Jakob Disease (CJD) with the causative point mutation at codon 180. The symptoms never started with visual or cerebellar involvement. The patients showed slower progression of the Disease compared with sporadic CJD. They never showed periodic sharp and wave complexes in EEG. MRI demonstrated remarkable high-intensity areas with swelling in the cerebral cortex except for the medial occipital and cerebellar cortices. These characteristic MRI findings are an important clue for an accurate premortem diagnosis.
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Creutzfeldt-Jakob Disease transmitted by a cadaveric dura mater graft
Neurosurgery, 1994Co-Authors: Shozo Yamada, Yuzo Endo, Mitsuru Hara, Tadashi Aiba, Tetsuyuki Kitamoto, Jun TateishiAbstract:We report a case of Creutzfeldt-Jakob Disease developing in a 31-year-old woman 56 months after she received a cadaveric dura mater graft after the removal of a giant pituitary adenoma. Creutzfeldt-Jakob Disease was confirmed by a brain autopsy and the existence of an abnormal isoform of prion protein, verified by both immunohistochemical and Western blot analysis. Moreover, prion protein gene analysis was shown in this case to possess a wild-type genotype. The characteristics of Creutzfeldt-Jakob Disease after a cadaveric dura mater graft are reviewed and discussed.
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abnormal isoform of prion proteins accumulates in the synaptic structures of the central nervous system in patients with creutzfeldt jakob Disease
American Journal of Pathology, 1992Co-Authors: Tetsuyuki Kitamoto, Tamaki Muramoto, Katsumi Dohura, Ryong Wong Shin, Naoyuki Tomokane, Masayuki Miyazono, Jun TateishiAbstract:A new method, which enabled the first immunohistochemical documentation of abnormal prion protein (PrP) in all patients with Creutzfeldt-Jakob Disease (CJD), was established. This method designated as "hydrolytic autoclaving" revealed punctate PrPCJD stainings around the neuronal cell bodies and dendrites in CJD brains. These punctate stainings were almost identical with that of synaptophysin, suggesting PrPCJD accumulations in the synaptic structures. Subcellular fractionation revealed that prion protein in Creutzfeldt-Jakob Disease (PrPCJD) was most concentrated in the synaptosomal fraction. In CJD patients with a long clinical course, synaptophysin immunoreactivity decreased, and synaptic PrPCJD accumulated with a wider distribution. These results suggest that synaptic PrPCJD accumulations might be responsible for the neuronal dysfunction and degeneration in CJD.
Takeshi Sato - One of the best experts on this subject based on the ideXlab platform.
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iatrogenic creutzfeldt jakob Disease final assessment
Emerging Infectious Diseases, 2012Co-Authors: Paul Brown, R G Will, J. Mackenzie, Maurizio Pocchiari, Jean Philippe Brandel, Takeshi Sato, Yosikazu Nakamura, Anna Ladogana, Ellen W Leschek, Lawrence B SchonbergerAbstract:The era of iatrogenic Creutzfeldt-Jakob Disease (CJD) has nearly closed; only occasional cases with exceptionally long incubation periods are still appearing. The principal sources of these outbreaks are contaminated growth hormone (226 cases) and dura mater grafts (228 cases) derived from human cadavers with undiagnosed CJD infections; a small number of additional cases are caused by neurosurgical instrument contamination, corneal grafts, gonadotrophic hormone, and secondary infection with variant CJD transmitted by transfusion of blood products. No new sources of Disease have been identified, and current practices, which combine improved recognition of potentially infected persons with new disinfection methods for fragile surgical instruments and biological products, should continue to minimize the risk for iatrogenic Disease until a blood screening test for the detection of preclinical infection is validated for human use.
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clinical features and diagnosis of dura mater graft associated creutzfeldt jakob Disease
Neurology, 2007Co-Authors: Moeko Noguchishinohara, Tetsuyuki Kitamoto, Tsuyoshi Hamaguchi, Takeshi Sato, Yosikazu Nakamura, Hidehiro Mizusawa, M YamadaAbstract:Background: A subset of patients with dura mater graft–associated Creutzfeldt–Jakob Disease (dCJD) demonstrates atypical clinical features and plaque formation in the brain (plaque type). Objective: To elucidate the frequency and clinical features of plaque type dCJD in comparison with the non-plaque type. Methods: We analyzed clinicopathologic findings of 66 patients who had been registered as having dCJD by the Creutzfeldt–Jakob Disease Surveillance Committee, Japan, between April 1999 and February 2006. Results: 1) Analysis of pathologically confirmed dCJD patients (n = 23) demonstrated plaque type dCJD in 11 patients (48%). In contrast to the non-plaque type with classic CJD features, the plaque type commonly presented with ataxic gait as an initial manifestation, relatively slow progression of neurologic symptoms, and no or late occurrence of periodic sharp-wave complexes (PSWCs) on EEG. MRI, especially diffusion-weighted images, and CSF 14-3-3 protein and neuron specific enolase (NSE) showed high diagnostic sensitivities for plaque as well as non-plaque types. 2) Analysis of clinically diagnosed dCJD patients (n = 34) demonstrated that 7 patients (21%) had atypical clinical features without PSWCs, probably corresponding to plaque type dCJD. Conclusion: The frequency of the plaque type in dura mater graft–associated Creutzfeldt–Jakob Disease is apparently higher than previously recognized. For the clinical diagnosis of the plaque type dura mater graft–associated Creutzfeldt–Jakob Disease, MRI and CSF markers would be useful, in addition to the core features, i.e., onset with ataxic gait disturbance, relatively slow progression, and no or late occurrence of periodic sharp-wave complexes on EEG.
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clinical diagnosis of mm2 type sporadic creutzfeldt jakob Disease
Neurology, 2005Co-Authors: Tsuyoshi Hamaguchi, Tetsuyuki Kitamoto, Takeshi Sato, Yosikazu Nakamura, Hidehiro Mizusawa, M Noguchi, Yutaka Furukawa, Chiho Ishida, Ichiei Kuji, K MitaniAbstract:Background: No method for the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob Disease (sCJD) has been established except for pathologic examination. Objective: To identify a reliable marker for the clinical diagnosis of MM2-type sCJD. Methods: CSF, EEG, and neuroimaging studies were performed in eight patients with MM2-type sCJD confirmed by neuropathologic, genetic, and western blot analyses. Results: The eight cases were pathologically classified into the cortical (n = 2), thalamic (n = 5), and combined (corticothalamic) (n = 1) forms. The cortical form was characterized by late-onset, slowly progressive dementia, cortical hyperintensity signals on diffusion-weighted imaging (DWI) of brain, and elevated levels of CSF 14-3-3 protein. The thalamic form showed various neurologic manifestations including dementia, ataxia, and pyramidal and extrapyramidal signs with onset at various ages and relatively long Disease duration. Characteristic EEG and MRI abnormalities were almost absent. However, all four patients examined with cerebral blood flow (CBF) study using SPECT showed reduction of the CBF in the thalamus as well as the cerebral cortex. The combined form had features of both the cortical and the thalamic forms, showing cortical hyperintensity signals on DWI and hypometabolism of the thalamus on [18F]2-fluoro-2-deoxy-d-glucose PET. Conclusion: For the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob Disease, cortical hyperintensity signals on diffusion-weighted MRI are useful for the cortical form and thalamic hypoperfusion or hypometabolism on cerebral blood flow SPECT or [18F]2-fluoro-2-deoxy-d-glucose PET for the thalamic form.
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iatrogenic creutzfeldt jakob Disease at the millennium
Neurology, 2000Co-Authors: P Brown, Inga Zerr, R G Will, Maurizio Pocchiari, Jean Philippe Brandel, Ashley Fletcher, Takeshi Sato, M Preece, Lisa M Mcshane, Neil R. CashmanAbstract: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.
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creutzfeldt jakob Disease associated with cadaveric dura mater grafts in japan
Neurology, 2000Co-Authors: K Hoshi, Yosikazu Nakamura, H Yoshino, J Urata, Hiroshi Yanagawa, Takeshi SatoAbstract:Article abstract 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
Mark Head - One of the best experts on this subject based on the ideXlab platform.
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real time quaking induced conversion analysis of cerebrospinal fluid in sporadic creutzfeldt jakob Disease
Annals of Neurology, 2012Co-Authors: Lynne Mcguire, Christina D. Orrú, Byron Caughey, Mark Head, Alexander Peden, Jason M Wilham, Nigel E J Appleford, Gary Mallinson, Mary Andrews, R G WillAbstract:Objective Current cerebrospinal fluid (CSF) tests for sporadic Creutzfeldt-Jakob Disease (sCJD) are based on the detection of surrogate markers of neuronal damage such as CSF 14-3-3 which are not specific for sCJD. A number of prion protein conversion assays have been developed, including real-time quaking induced conversion (RT-QuIC). The objective of this study is to investigate whether CSF RT-QuIC analysis could be used as a diagnostic test in sCJD.
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dura mater associated creutzfeldt jakob Disease experience from surveillance in the uk
Journal of Neurology Neurosurgery and Psychiatry, 2006Co-Authors: C A Heath, Mark Head, T F G Esmonde, Roge A Arke, P Harvey, Richard C Roberts, P Trend, Coli Smith, Jeanne E Ell, James W. IronsideAbstract: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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detection of type 1 prion protein in variant creutzfeldt jakob Disease
American Journal of Pathology, 2006Co-Authors: Helen Yull, James W. Ironside, Moira E Bruce, Diane Ritchie, Jan P M Langeveld, Fred G Van Zijderveld, Mark HeadAbstract:Molecular typing of the abnormal form of the prion protein (PrPSc) has come to be regarded as a powerful tool in the investigation of the prion Diseases. All evidence thus far presented indicates a single PrPSc molecular type in variant Creutzfeldt-Jakob Disease (termed type 2B), presumably resulting from infection with a single strain of the agent (bovine spongiform encephalopathy). Here we show for the first time that the PrPSc that accumulates in the brain in variant Creutzfeldt-Jakob Disease also contains a minority type 1 component. This minority type 1 PrPSc was found in all 21 cases of variant Creutzfeldt-Jakob Disease tested, irrespective of brain region examined, and was also present in the variant Creutzfeldt-Jakob Disease tonsil. The quantitative balance between PrPSc types was maintained when variant Creutzfeldt-Jakob Disease was transmitted to wild-type mice and was also found in bovine spongiform encephalopathy cattle brain, indicating that the agent rather than the host specifies their relative representation. These results indicate that PrPSc molecular typing is based on quantitative rather than qualitative phenomena and point to a complex relationship between prion protein biochemistry, Disease phenotype and agent strain.
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prion protein heterogeneity in sporadic but not variant creutzfeldt jakob Disease u k cases 1991 2002
Annals of Neurology, 2004Co-Authors: Mark Head, L. Mccardle, J. Mackenzie, Matthew Bishop, Tristan J R Bunn, Victoria Mcloughlin, Suzanne Lowrie, Clive S Mckimmie, Michelle C Williams, Richard KnightAbstract:Human prion Diseases can occur as an idiopathic disorder (sporadic Creutzfeldt–Jakob Disease) or can be acquired, as is the case for variant Creutzfeldt–Jakob Disease. These disorders are characterized by the accumulation of a protease-resistant form of the host-encoded prion protein termed PrPSc in the brains of affected individuals. PrPSc has been proposed to be the principal, if not sole, component of the infectious agent, with its accumulation in the central nervous system the primary event leading to neurodegeneration. A major question remains as to whether self-propagating structural differences in PrPSc might account for the clinicopathological diversity evident in Creutzfeldt–Jakob Disease and whether different prion protein types underlie the existence of different strains of causative agent. Here, we describe the results of a large-scale biochemical study of PrPSc from autopsy-proved cases of variant Creutzfeldt–Jakob Disease (n = 59) and compare these with cases of sporadic Creutzfeldt–Jakob Disease (n = 170) in the United Kingdom over the period 1991 to 2002. The results show PrPSc in variant Creutzfeldt–Jakob Disease to be remarkably stereotyped. In contrast, considerable heterogeneity in PrPSc exists both between and within cases of sporadic Creutzfeldt–Jakob Disease. Ann Neurol 2004;55:851–859
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peripheral tissue involvement in sporadic iatrogenic and variant creutzfeldt jakob Disease an immunohistochemical quantitative and biochemical study
American Journal of Pathology, 2004Co-Authors: Mark Head, L. Mccardle, Matthew Bishop, Diane L Ritchie, Victoria Mcloughlin, Nadine Smith, William H Nailon, Sazia Samad, Stephen Masson, James W. IronsideAbstract:Human prion Diseases are rare fatal neurodegenerative conditions that occur as acquired, familial, or idiopathic disorders. A key event in their pathogenesis is the accumulation of an altered form of the prion protein, termed PrP Sc , in the central nervous system. A novel acquired human prion Disease, variant Creutzfeldt-Jakob Disease, is thought to result from oral exposure to the bovine spongiform encephalopathy agent. This Disease differs from other human prion Diseases in its neurological, neuropathological, and biochemical phenotype. We have used immunohistochemistry and Western blot techniques to analyze the tissue distribution and biochemical properties of PrP Sc in peripheral tissues in a unique series of nine cases of variant Creutzfeldt-Jakob Disease. We have compared this with the distribution and biochemical forms found in all of the major subtypes of sporadic Creutzfeldt-Jakob Disease and in a case of iatrogenic Creutzfeldt-Jakob Disease associated with growth hormone therapy. The results show that involvement of the lymphoreticular system is a defining feature of variant Creutzfeldt-Jakob Disease, but that the biochemical isoform of PrP Sc found is influenced by the cell type in which it accumulates.