160 results on '"Jansen GH"'
Search Results
2. P.088 Dysautonomia and Diabetes: A Prodrome to Fatal Familial Insomnia (FFI)
- Author
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Liu, RR, primary, Bendahan, N, additional, Briggs, DE, additional, Jansen, GH, additional, Taylor, S, additional, and Lomax, LB, additional
- Published
- 2021
- Full Text
- View/download PDF
3. Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease (vol 132, pg 2659, 2009)
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Zerr, I, Kallenberg, K, Summers, DM, Romero, C, Taratuto, A, Heinemann, U, Breithaupt, M, Varges, D, Meissner, B, Ladogana, A, Schuur, Maaike, Haik, S, Collins, SJ, Jansen, GH, Stokin, GB, Pimentel, J, Hewer, E, Collie, D, Smith, P, Roberts, H, Brandel, JP, Duijn, Cornelia, Pocchiari, M, Begue, C, Cras, P, Will, RG, Sanchez-Juan, P, Neurology, and Epidemiology
- Published
- 2012
4. Growth of mycoplasma transformed tTN129 cells depends on IGF-I
- Author
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Roholl Pj, Angulo Af, Den Otter W, Prinsen Im, Giltay Jc, Rombouts Ag, Wills I, Jansen Gh, Rademakers Lh, and Van der Ven Lt
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Glial fibrillary acidic protein ,Schwann cell ,Sodium butyrate ,Cell Biology ,General Medicine ,Mycoplasma ,Biology ,medicine.disease_cause ,Molecular biology ,Cell biology ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Cell culture ,medicine ,biology.protein ,Stem cell ,Developmental biology ,Population doubling ,Developmental Biology - Published
- 1993
5. Mortalité associée à la maladie de Creutzfeldt-Jakob au Canada, de 1998 à 2013
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Coulthart, MB, primary, Jansen, GH, additional, Connolly, T, additional, D’Amour, R, additional, Kruse, J, additional, Lynch, J, additional, Sabourin, S, additional, Wang, Z, additional, Giulivi, A, additional, Ricketts, MN, additional, and Cashman, NR, additional
- Published
- 2015
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6. Creutzfeldt-Jakob disease mortality in Canada, 1998 to 2013
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Coulthart, MB, primary, Jansen, GH, additional, Connolly, T, additional, D’Amour, R, additional, Kruse, J, additional, Lynch, J, additional, Sabourin, S, additional, Wang, Z, additional, Giulivi, A, additional, Ricketts, MN, additional, and Cashman, NR, additional
- Published
- 2015
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7. Ziekte van Creutzfeld-Jakob: diagnostiek, incidentie, preventie en behandeling
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Croes, EA (Esther), Duijn, Cornelia, van Gool, WA, Jansen, GH, and Epidemiology
- Published
- 2002
8. Human Prion Diseases in The Netherlands (1998-2009): Clinical, Genetic and Molecular Aspects
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Jansen, C, Parchi, P, Capellari, S, Verbaas, Carla, Schuur, Maaike, Strammiello, R, Corrado, P, Bishop, MT, van Gool, WA, Verbeek, MM, Baas, F, van Saane, W, Spliet, WGM, Jansen, GH, Duijn, Cornelia, Rozemuller, AJM, Jansen, C, Parchi, P, Capellari, S, Verbaas, Carla, Schuur, Maaike, Strammiello, R, Corrado, P, Bishop, MT, van Gool, WA, Verbeek, MM, Baas, F, van Saane, W, Spliet, WGM, Jansen, GH, Duijn, Cornelia, and Rozemuller, AJM
- Abstract
Prion diseases are rare and fatal neurodegenerative disorders that can be sporadic, inherited or acquired by infection. Based on a national surveillance program in the Netherlands we describe here the clinical, neuropathological, genetic and molecular characteristics of 162 patients with neuropathologically confirmed prion disease over a 12-year period (1998-2009). Since 1998, there has been a relatively stable mortality of Creutzfeldt-Jakob disease (CJD) in the Netherlands, ranging from 0.63 to 1.53 per million inhabitants per annum. Genetic analysis of the codon 129 methionine/valine (M/V) polymorphism in all patients with sporadic CJD (sCJD) showed a trend for under-representation of VV cases (7.0%), compared with sCJD cohorts in other Western countries, whereas the MV genotype was relatively over-represented (22,4%). Combined PrP Sc and histopathological typing identified all sCJD subtypes known to date, except for the VV1 subtype. In particular, a "pure" phenotype was demonstrated in 60.1% of patients, whereas a mixed phenotype was detected in 39.9% of all sCJD cases. The relative excess of MV cases was largely accounted for by a relatively high incidence of the MV 2K subtype. Genetic analysis of the prion protein gene (PRNP) was performed in 161 patients and showed a mutation in 9 of them (5.6%), including one FFI and four GSS cases. Iatrogenic CJD was a rare phenomenon (3.1%), mainly associated with dura mater grafts. Three patients were diagnosed with new variant CJD (1.9%) and one with variably protease-sensitive prionopathy (VPSPr). Post-mortem examination revealed an alternative diagnosis in 156 patients, most commonly Alzheimer's disease (21.2%) or vascular causes of dementia (19.9%). The mortality rates of sCJD in the Netherlands are similar to those in other European countries, whereas iatrogenic and genetic cases are relatively rare. The unusual incidence of the VV2 sCJD subtype compared to that reported to date in other Western countries deserves fur
- Published
- 2012
9. Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease
- Author
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Zerr, I, Kallenberg, K, Summers, DM, Romero, C, Taratuto, A, Heinemann, U, Breithaupt, M, Varges, D, Meissner, B, Ladogana, A, Schuur, M, Haik, S, Collins, SJ, Jansen, GH, Stokin, GB, Pimentel, J, Hewer, E, Collie, D, Smith, P, Roberts, H, Brandel, JP, van Duijn, C, Pocchiari, M, Begue, C, Cras, P, Will, RG, Sanchez-Juan, P, Zerr, I, Kallenberg, K, Summers, DM, Romero, C, Taratuto, A, Heinemann, U, Breithaupt, M, Varges, D, Meissner, B, Ladogana, A, Schuur, M, Haik, S, Collins, SJ, Jansen, GH, Stokin, GB, Pimentel, J, Hewer, E, Collie, D, Smith, P, Roberts, H, Brandel, JP, van Duijn, C, Pocchiari, M, Begue, C, Cras, P, Will, RG, and Sanchez-Juan, P
- Abstract
Several molecular subtypes of sporadic Creutzfeldt-Jakob disease have been identified and electroencephalogram and cerebrospinal fluid biomarkers have been reported to support clinical diagnosis but with variable utility according to subtype. In recent years, a series of publications have demonstrated a potentially important role for magnetic resonance imaging in the pre-mortem diagnosis of sporadic Creutzfeldt-Jakob disease. Magnetic resonance imaging signal alterations correlate with distinct sporadic Creutzfeldt-Jakob disease molecular subtypes and thus might contribute to the earlier identification of the whole spectrum of sporadic Creutzfeldt-Jakob disease cases. This multi-centre international study aimed to provide a rationale for the amendment of the clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease. Patients with sporadic Creutzfeldt-Jakob disease and fluid attenuated inversion recovery or diffusion-weight imaging were recruited from 12 countries. Patients referred as 'suspected sporadic Creutzfeldt-Jakob disease' but with an alternative diagnosis after thorough follow up, were analysed as controls. All magnetic resonance imaging scans were assessed for signal changes according to a standard protocol encompassing seven cortical regions, basal ganglia, thalamus and cerebellum. Magnetic resonance imaging scans were evaluated in 436 sporadic Creutzfeldt-Jakob disease patients and 141 controls. The pattern of high signal intensity with the best sensitivity and specificity in the differential diagnosis of sporadic Creutzfeldt-Jakob disease was identified. The optimum diagnostic accuracy in the differential diagnosis of rapid progressive dementia was obtained when either at least two cortical regions (temporal, parietal or occipital) or both caudate nucleus and putamen displayed a high signal in fluid attenuated inversion recovery or diffusion-weight imaging magnetic resonance imaging. Based on our analyses, magnetic resonance imaging was positi
- Published
- 2009
10. Human transmissible spongiform encephalopathies in eleven countries: diagnostic pattern across time, 1993-2002
- Author
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de Pedro-Cuesta, J, Glatzel, M, Almazan, J, Stoeck, K, Mellina, V, Puopolo, M, Pocchiari, M, Zerr, I, Kretszchmar, HA, Brandel, J-P, Delasnerie-Laupretre, N, Alperovitch, A, Van Duijn, C, Sanchez-Juan, P, Collins, S, Lewis, V, Jansen, GH, Coulthart, MB, Gelpi, E, Budka, H, Mitrova, E, de Pedro-Cuesta, J, Glatzel, M, Almazan, J, Stoeck, K, Mellina, V, Puopolo, M, Pocchiari, M, Zerr, I, Kretszchmar, HA, Brandel, J-P, Delasnerie-Laupretre, N, Alperovitch, A, Van Duijn, C, Sanchez-Juan, P, Collins, S, Lewis, V, Jansen, GH, Coulthart, MB, Gelpi, E, Budka, H, and Mitrova, E
- Abstract
BACKGROUND: The objective of this study was to describe the diagnostic panorama of human transmissible spongiform encephalopathies across 11 countries. METHODS: From data collected for surveillance purposes, we describe annual proportions of deaths due to different human transmissible spongiform encephalopathies in eleven EUROCJD-consortium countries over the period 1993-2002, as well as variations in the use of diagnostic tests. Using logistic models we quantified international differences and changes across time. RESULTS: In general, pre-mortem use of diagnostic investigations increased with time. International differences in pathological confirmation of sporadic Creutzfeldt-Jakob disease, stable over time, were evident. Compared to their counterparts, some countries displayed remarkable patterns, such as: 1) the high proportion, increasing with time, of variant Creutzfeldt-Jakob disease in the United Kingdom, (OR 607.99 95% CI 84.72-4363.40), and France (OR 18.35, 95% CI 2.20-152.83); 2) high, decreasing proportions of iatrogenic Creutzfeldt-Jakob disease in France, (OR 5.81 95% CI 4.09-8.24), and the United Kingdom, (OR 1.54 95% CI 1.03-2.30); and, 3) high and stable ratios of genetic forms in Slovakia (OR 21.82 95% CI 12.42-38.33) and Italy (OR 2.12 95% CI 1.69-2.68). CONCLUSION: Considerable international variation in aetiological subtypes of human transmissible spongiform encephalopathies was evident over the observation period. With the exception of variant Creutzfeldt-Jakob disease and iatrogenic Creutzfeldt-Jakob disease in France and the United Kingdom, these differences persisted across time.
- Published
- 2006
11. Creutzfeldt-Jakob disease 38 years after diagnostic use of human growth hormone
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Croes, EA (Esther), Roks, CMAA (Gerwin), Jansen, GH, Nijssen, PC, Duijn, Cornelia, Croes, EA (Esther), Roks, CMAA (Gerwin), Jansen, GH, Nijssen, PC, and Duijn, Cornelia
- Published
- 2002
12. A novel germline mutation of PTEN associated with brain tumours of multiple lineages
- Author
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Staal, Frank, van der Luijt, RB, Baert, Miranda, van Drunen, J, van Bakel, H, Peters, E, de Valk, I, van Amstel, HKP, Taphoorn, MJR, Jansen, GH, van Veelen, CWM, Burgering, B, Staal, GEJ, Staal, Frank, van der Luijt, RB, Baert, Miranda, van Drunen, J, van Bakel, H, Peters, E, de Valk, I, van Amstel, HKP, Taphoorn, MJR, Jansen, GH, van Veelen, CWM, Burgering, B, and Staal, GEJ
- Published
- 2002
13. Zerebrale MRT-Veränderungen molekularer Subtypen der sCJK: eine Multizenterstudie
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Kallenberg, K, primary, Meissner, B, additional, Sanchez-Juan, P, additional, Summers, DM, additional, Mellina, V, additional, Collins, SJ, additional, Cras, P, additional, Jansen, GH, additional, Brandel, JP, additional, Galanaud, D, additional, Will, RG, additional, and Zerr, I, additional
- Published
- 2009
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14. Unilateral haemorrhagic parenchymal lesions in the preterm infant: shape, site and prognosis
- Author
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Rademaker, KJ, primary, Groeneadaal, F, additional, Jansen, GH, additional, Eken, P, additional, and De Vries, LS, additional
- Published
- 2008
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15. Growth of cultured human glioma tumour cells can be regulated with histamine and histamine antagonists
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Van der Ven, LTM, primary, Prinsen, IM, additional, Jansen, GH, additional, Roholl, PJM, additional, Defferrari, R, additional, Slater, R, additional, and Den Otter, W, additional
- Published
- 1993
- Full Text
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16. MRI lesion profiles in sporadic Creutzfeldt-Jakob disease.
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Meissner B, Kallenberg K, Sanchez-Juan P, Collie D, Summers DM, Almonti S, Collins SJ, Smith P, Cras P, Jansen GH, Brandel JP, Coulthart MB, Roberts H, Van Everbroeck B, Galanaud D, Mellina V, Will RG, and Zerr I
- Published
- 2009
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17. Determinants of diagnostic investigation sensitivities across the clinical spectrum of sporadic Creutzfeldt-Jakob disease.
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Collins SJ, Sanchez-Juan P, Masters CL, Klug GM, van Duijn C, Poleggi A, Pocchiari M, Almonti S, Cuadrado-Corrales N, de Pedro-Cuesta J, Budka H, Gelpi E, Glatzel M, Tolnay M, Hewer E, Zerr I, Heinemann U, Kretszchmar HA, Jansen GH, and Olsen E
- Published
- 2006
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18. Unilateral haemorrhagic parenchymal lesions in the preterm infant: shape, site and prognosis.
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Rademaker, KJ, Groeneadaal, F, Jansen, GH, Eken, P, De Vries, LS, Rademaker, K J, Groenendaal, F, Jansen, G H, and de Vries, L S
- Published
- 1994
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19. Gerstmann-Straussler-Scheinker disease due to a novel prion protein gene mutation.
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Hinnell C, Coulthart MB, Jansen GH, Cashman NR, Lauzon J, Clark A, Costello F, White C, Midha R, Wiebe S, Furtado S, Hinnell, C, Coulthart, M B, Jansen, G H, Cashman, N R, Lauzon, J, Clark, A, Costello, F, White, C, and Midha, R
- Published
- 2011
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20. Genome wide association study of clinical duration and age at onset of sporadic CJD.
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Hummerich H, Speedy H, Campbell T, Darwent L, Hill E, Collins S, Stehmann C, Kovacs GG, Geschwind MD, Frontzek K, Budka H, Gelpi E, Aguzzi A, van der Lee SJ, van Duijn CM, Liberski PP, Calero M, Sanchez-Juan P, Bouaziz-Amar E, Laplanche JL, Haïk S, Brandel JP, Mammana A, Capellari S, Poleggi A, Ladogana A, Pocchiari M, Zafar S, Booth S, Jansen GH, Areškevičiūtė A, Løbner Lund E, Glisic K, Parchi P, Hermann P, Zerr I, Appleby BS, Safar J, Gambetti P, Collinge J, and Mead S
- Subjects
- Humans, Aged, Middle Aged, Female, Male, Phenotype, Genotype, Creutzfeldt-Jakob Syndrome genetics, Creutzfeldt-Jakob Syndrome pathology, Age of Onset, Genome-Wide Association Study, Polymorphism, Single Nucleotide
- Abstract
Human prion diseases are rare, transmissible and often rapidly progressive dementias. The most common type, sporadic Creutzfeldt-Jakob disease (sCJD), is highly variable in clinical duration and age at onset. Genetic determinants of late onset or slower progression might suggest new targets for research and therapeutics. We assembled and array genotyped sCJD cases diagnosed in life or at autopsy. Clinical duration (median:4, interquartile range (IQR):2.5-9 (months)) was available in 3,773 and age at onset (median:67, IQR:61-73 (years)) in 3,767 cases. Phenotypes were successfully transformed to approximate normal distributions allowing genome-wide analysis without statistical inflation. 53 SNPs achieved genome-wide significance for the clinical duration phenotype; all of which were located at chromosome 20 (top SNP rs1799990, pvalue = 3.45x10-36, beta = 0.34 for an additive model; rs1799990, pvalue = 9.92x10-67, beta = 0.84 for a heterozygous model). Fine mapping, conditional and expression analysis suggests that the well-known non-synonymous variant at codon 129 is the obvious outstanding genome-wide determinant of clinical duration. Pathway analysis and suggestive loci are described. No genome-wide significant SNP determinants of age at onset were found, but the HS6ST3 gene was significant (pvalue = 1.93 x 10-6) in a gene-based test. We found no evidence of genome-wide genetic correlation between case-control (disease risk factors) and case-only (determinants of phenotypes) studies. Relative to other common genetic variants, PRNP codon 129 is by far the outstanding modifier of CJD survival suggesting only modest or rare variant effects at other genetic loci., Competing Interests: Stéphane Haik reports grants from Santé Publique France, during the conduct of the study; grants from LFB Biomedicaments, grants from Institut de Recherche Servier, grants from MedDay Pharmaceuticals, outside the submitted work; In addition, Stéphane Haik has a patent Method for treating prion diseases (PCT/EP2019/070457) pending. Brian Appleby has received funding from CDC, NIH, CJD Foundation, Alector, and Ionis. He has served as a consultant for Ionis, Sangamo, and Gate Biosciences. He has received royalties from Wolter Kluwers. Karl Fronztek reports grants from Ono Pharmaceuticals outside the submitted work. Simon Mead reports grants from Medical Research Council (UK) and grants from National Institute of Health Research’s Biomedical Research Centre at University College London Hospitals NHS Foundation Trust during the conduct of the study. Gabor G Kovacs reports personal fees from Biogen, outside the submitted work. John Collinge reports grants from Medical Research Council, grants from NIHR UCLH Biomedical Research Centre, during the conduct of the study; and is a Director and shareholder of D-Gen Limited, an academic spinout in the field of prion disease diagnostics, decontamination and therapeutics. Inga Zerr reports grants from the Bundesministerium für Gesundheit via Robert Koch institute, JPND and personal fees (not related to the content of the manuscript) from Ferring Pharmaceuticals and IONIS, speaking honoraria for medical lectures from Lilly, Biogen, Medfora, DGLN (German Society for cerebrospinal fluid diagnostics in Neurology). Maurizio Pocchiari reports personal fees from Ferring Pharmaceuticals, personal fees from CNCCS (Collection of National Chemical Compounds and Screening Center), non-financial support from Fondazione Cellule Staminali, outside the submitted work. Michael D Geschwind has consulted for3D Communications, Adept Field Consulting, Advanced Medical Inc., Best Doctors Inc., Second Opinion Inc., Gerson Lehrman Group Inc., Guidepoint Global LLC, InThought Consulting Inc., Market Plus, Trinity Partners LLC, Biohaven Pharmaceuticals, Quest Diagnostics and various medical-legal consulting. He has received speaking honoraria for various medical center lectures and from Oakstone publishing. He has received past research support from Alliance Biosecure, CurePSP, the Tau Consortium, and Quest Diagnostics. Michael D Geschwind serves on the board of directors for San Francisco Bay Area Physicians for Social Responsibility and on the editorial board of Dementia & Neuropsychologia., (Copyright: © 2024 Hummerich et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
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21. Development of an Automated Capillary Immunoassay to Detect Prion Glycotypes in Creutzfeldt-Jakob Disease.
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Myskiw J, Lamoureux L, Peterson A, Knox D, Jansen GH, Coulthart MB, and Booth SA
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- Humans, Brain metabolism, Prion Proteins genetics, Prion Proteins metabolism, Peptide Hydrolases metabolism, Codon metabolism, Creutzfeldt-Jakob Syndrome diagnosis, Creutzfeldt-Jakob Syndrome metabolism, Prions metabolism
- Abstract
Creutzfeldt-Jakob disease (CJD) comprises a group of transmissible neurodegenerative diseases with vast phenotypic diversity. Sporadic CJD heterogeneity is predominantly influenced by the genotype at codon 129 of the prion-encoding gene and the molecular weight of PrP
Sc fragments after protease digestion, resulting in a classification of 6 subtypes of CJD (MM1, MM2, MV1, MV2, VV1, and VV2). The majority of cases with CJD can be distinguished using this classification system. However, a number of reported CJD cases are phenotypically unique from others within their same subtype, such as variably protease-sensitive prionopathies, or exist as a mixture of subtypes within the same patient. Western blotting of brain tissue, along with the genotyping of codon 129 of the prion-encoding gene, is considered the "gold standard" for the biochemical characterization of CJD. Western blotting requires a significant amount of prion protein for detection, is labor-intensive, and is also associated with high interassay variability. In addition to these limitations, a growing body of research suggests that unique subtypes of CJD are often undetected or misdiagnosed using standard diagnostic western blotting protocols. Consequently, we successfully optimized and developed a capillary-based western assay using the JESS Simple Western (ProteinSimple) to detect and characterize prion proteins from patients with CJD. We found that this novel assay consistently differentiated CJD type 1 and type 2 cases with a limit of detection 10 to 100× higher than traditional western blotting. Cases with CJD in which type 1 and type 2 coexist within the same brain region can be detected using type 1-specific and type 2-specific antibodies, and we found that there was remarkable specificity for the detection of cases with variably protease-sensitive prionopathy. The assay presented displays outstanding sensitivity, allowing for the preservation of valuable samples and enhancing current detection methods., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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22. Diagnostic Accuracy of Centrally Restricted Diffusion Sign in Cerebral Metastatic Disease: Differentiating Radiation Necrosis from Tumor Recurrence.
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Puac-Polanco P, Zakhari N, Miller J, McComiskey D, Thornhill RE, Jansen GH, Nair VJ, and Nguyen TB
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- Humans, Retrospective Studies, Diffusion Magnetic Resonance Imaging methods, Necrosis diagnostic imaging, Sensitivity and Specificity, Diagnosis, Differential, Neoplasm Recurrence, Local diagnostic imaging, Brain Neoplasms diagnostic imaging, Brain Neoplasms radiotherapy
- Abstract
Purpose : The centrally restricted diffusion sign of diffusion-weighted imaging (DWI) is associated with radiation necrosis (RN) in treated gliomas. Our goal was to evaluate its diagnostic accuracy to distinguish RN from tumor recurrence (TR) in treated brain metastases. Methods : Retrospective study of consecutive patients with brain metastases who developed a newly centrally necrotic lesion after radiotherapy (RT). One reader placed regions of interest (ROI) in the enhancing solid lesion and the non-enhancing central necrosis on the apparent diffusion coefficient (ADC) map. Two readers qualitatively assessed the presence of the centrally restricted diffusion sign. The final diagnosis was made by histopathology (n = 39) or imaging follow-up (n = 2). Differences between groups were assessed by Fisher's exact or Mann-Whitney U tests. Diagnostic accuracy and inter-reader agreement were evaluated using receiver operating characteristic (ROC) curve analysis and kappa scores. Results : Forty-one lesions (32 predominant RN; 9 predominant TR) were analyzed. An ADC value ≤ 1220 × 10-6 mm2/s (sensitivity 74%, specificity 89%, area under the curve [AUC] .85 [95% confidence interval {CI}, .70-.94] P < .0001) from the necrosis and an ADC necrosis/enhancement ratio ≤1.37 (sensitivity 74%, specificity 89%, AUC .82 [95% CI, .67-.93] P < .0001) provided the highest performance for RN diagnosis. The qualitative centrally restricted diffusion sign had a sensitivity of 69% (95% CI, .50-.83), specificity of 77% (95% CI, .40-.96), and a moderate (k = .49) inter-reader agreement for RN diagnosis. Conclusions : Radiation necrosis is associated with lower ADC values in the central necrosis than TR. A moderate interobserver agreement might limit the qualitative assessment of the centrally restricted diffusion sign.
- Published
- 2023
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23. Case 309: Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy.
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Puac-Polanco P, Zakhari N, Jansen GH, and Torres C
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- Male, Humans, Middle Aged, Glial Fibrillary Acidic Protein, Pandemics, Brain, COVID-19, Cerebellar Ataxia
- Abstract
History: A 64-year-old man presented with a 6-month history of lightheadedness and intermittent balance and coordination difficulties. Two months before admission, symptoms became more substantial and persistent, with a worsening sense of disequilibrium and unsteady gait. He reported difficulties pronouncing words and mild word-finding difficulties. His wife noted a change in his cognition and memory over the same time. His medical history included well-controlled chronic obstructive pulmonary disease (COPD) secondary to a long history of smoking with associated unintentional 30-lb (13.6-kg) weight loss over the previous 3 years, for which chest CT scanning was performed, revealing no abnormality. On clinical examination, the patient was alert and oriented but had slurred speech. A positive Romberg sign was noted, finger-to-nose and hand rapid alternating movement tests revealed impairment on the right side, and his gait was ataxic. The motor examination revealed normal muscle tone, bulk, and power in the upper and lower extremities. Sensory testing results were normal. Initial MRI of the brain at admission revealed abnormal findings in the left supratentorial brain. Of note, this patient's presentation predated the COVID-19 pandemic. Cerebrospinal fluid (CSF) analysis revealed predominant pleocytosis (23 × 106/L; normal range, [0-5] × 106/L) (78% lymphocytes, 22% monocytes), elevated protein level (1.23 g/L; normal range, 0.19-0.64 g/L), oligoclonal bands (faint one or two), and a high immunoglobulin G (IgG) index (0.130 g/L; normal reference, ≤0.059 g/L). Despite extensive initial work-up for inflammatory, infectious, autoimmune, or neoplastic causes, a definitive diagnosis was not reached. Thus, repeat MRI of the brain was performed 2 weeks after admission.
- Published
- 2023
- Full Text
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24. Case 309.
- Author
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Puac-Polanco P, Zakhari N, Jansen GH, and Torres C
- Subjects
- Brain, Humans, Lymphocytes, Magnetic Resonance Imaging, Male, Middle Aged, COVID-19, Pandemics
- Abstract
History: A 64-year-old man presented with a 6-month history of lightheadedness, intermittent balance, and coordination difficulties. Two months before admission, symptoms became more substantial and persistent, with a worsening sense of disequilibrium and unsteady gait. He reported difficulties pronouncing words and mild word-finding difficulties. His wife noted a change in his cognition and memory over the same time. His medical history included well-controlled chronic obstructive pulmonary disease (COPD) secondary to a long history of smoking with associated unintentional 30-lb (13.6-kg) weight loss over the previous 3 years, for which chest CT scanning was performed, revealing no abnormality. On clinical examination, the patient was alert and oriented but had slurred speech. A positive Romberg sign was noted, finger-to-nose and hand rapid alternating movement tests revealed impairment on the right side, and his gait was ataxic. The motor examination revealed normal muscle tone, bulk, and power in the upper and lower extremities. Sensory testing results were normal. Initial MRI of the brain at admission revealed abnormal findings in the left supratentorial brain (Figs 1-3). Of note, this patient's presentation predated the COVID-19 pandemic. Cerebrospinal fluid analysis revealed predominant pleocytosis (23 × 10
6 /L; normal range, [0-5] × 106 /L) (78% lymphocytes, 22% monocytes), elevated protein level (1.23 g/L; normal range, 0.19-0.64 g/L), oligoclonal bands (faint one or two), and a high immunoglobulin G index (0.130 g/L; normal reference, ≤0.059 g/L). Despite extensive initial work-up for inflammatory, infectious, autoimmune, or neoplastic causes, a definitive diagnosis was not reached. Thus, repeat MRI of the brain was performed 2 weeks after admission (Fig 4).- Published
- 2022
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25. Embryonal Tumor With Multilayered Rosettes of the Parietooccipital Region: A Case Report.
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Horwitz J, Huang A, McAuley D, Jansen GH, and Johnston D
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- Autografts, Chemoradiotherapy, Adjuvant, Child, Preschool, Female, Humans, Brain Neoplasms genetics, Brain Neoplasms pathology, Brain Neoplasms therapy, Chromosomes, Human, Pair 19 genetics, Genetic Loci, Isotretinoin administration & dosage, Neoplasms, Germ Cell and Embryonal genetics, Neoplasms, Germ Cell and Embryonal pathology, Neoplasms, Germ Cell and Embryonal therapy, Stem Cell Transplantation, Vorinostat administration & dosage
- Abstract
Embryonal tumor with multilayered rosettes is a rare and highly malignant early childhood brain tumor. We report a case of embryonal tumor with multilayered rosettes in the parietooccipital region of a 2-year-old girl. Histopathology of the tumor demonstrated amplification of the 19q13.42 locus and strong positivity for LIN28A. Treatment was multimodal and included 3 surgical resections, adjuvant chemotherapy with autologous stem cell rescue, and focal radiotherapy. The use of the agents vorinostat and isotretinoin, and the addition of focal radiation have not been extensively described in this patient population, but may attribute to our patient's sustained remission at 2.5-years follow-up., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2022
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26. Creutzfeldt-Jakob disease in pregnancy: the use of modified RT-QuIC to determine infectivity in placental tissues.
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Luk CC, Mathiason CK, Orrù CD, Jansen GH, Thiele A, Caughey B, and Sim VL
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- Adult, Biological Assay, Female, Humans, Placenta, Pregnancy, Prion Proteins, Creutzfeldt-Jakob Syndrome, Prions
- Abstract
Sporadic Creutzfeldt-Jakob Disease (sCJD) rarely affects women of childbearing age. There is currently no evidence of vertical transmission. Given the biosafety implications of performing Caesarean sections (C-section) in these patients, we used sensitive real-time quaking-induced conversion (RT-QuIC) assays to test for the infectious prion protein (PrP
Sc ) in products of gestation. A 35-year-old woman with sCJD presented in her 10th gestational week with an eight month history of progressive cognitive impairment. During C-section, amniotic fluid, cord blood and placental tissue were collected and analysed using RT-QuIC protocols adapted for use with these tissues. The patient's diagnosis of sCJD, MM2 subtype, was confirmed at autopsy. There were borderline positive results in one sampled area of the placenta, but otherwise the cord blood and amniotic fluid were negative on our RT-QuIC assays. A healthy baby was delivered via C-section at 36 weeks and 3 days gestational age, with no evidence of neurological disease to date. We conclude that precautions should be taken with products of gestation, but the level of PrPSc is extremely low.- Published
- 2021
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27. Progressive multifocal leukoencephalopathy and Creutzfeldt-Jakob disease: population-wide incidences, comorbidities, costs of care, and outcomes.
- Author
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Bakal JA, Charlton CL, Hlavay B, Jansen GH, Svenson LW, and Power C
- Subjects
- Adult, Aged, Aged, 80 and over, Alberta epidemiology, Cerebrovascular Disorders diagnosis, Cerebrovascular Disorders economics, Cerebrovascular Disorders mortality, Chronic Disease, Comorbidity, Creutzfeldt-Jakob Syndrome diagnosis, Creutzfeldt-Jakob Syndrome economics, Creutzfeldt-Jakob Syndrome mortality, Female, HIV Infections diagnosis, HIV Infections economics, HIV Infections mortality, Humans, Incidence, Leukoencephalopathy, Progressive Multifocal diagnosis, Leukoencephalopathy, Progressive Multifocal economics, Leukoencephalopathy, Progressive Multifocal mortality, Male, Middle Aged, Survival Analysis, Cerebrovascular Disorders epidemiology, Cost of Illness, Creutzfeldt-Jakob Syndrome epidemiology, HIV Infections epidemiology, Leukoencephalopathy, Progressive Multifocal epidemiology
- Abstract
Neurological disorders associated with chronic infections are often progressive as well as challenging to diagnose and manage. Among 4.4 million persons from 2004 to 2019 receiving universal health, progressive multifocal leukoencephalopathy (PML, n = 58) and Creutzfeldt-Jakob disease (CJD, n = 93) cases were identified, revealing stable yearly incidence rates with divergent comorbidities: HIV/AIDS affected 37.8% of PML cases while cerebrovascular disease affected 26.9% of CJD cases. Most CJD cases died within 1 year (73%) although PML cases lived beyond 5 years (34.1%) despite higher initial costs of care. PML and CJD represent important neurological disorders with evolving risk variables and impact on health care.
- Published
- 2021
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28. Prospective Study Demonstrates Utility of EP-QuIC in Creutzfeldt-Jakob Disease Diagnoses.
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Simon SLR, Peterson A, Phillipson C, Walker JM, Richmond M, Jansen GH, and Knox JD
- Subjects
- Canada, Humans, Predictive Value of Tests, Prospective Studies, Sensitivity and Specificity, Creutzfeldt-Jakob Syndrome diagnosis
- Abstract
Prospectively acquired Canadian cerebrospinal fluid samples were used to assess the performance characteristics of three ante-mortem tests commonly used to support diagnoses of Creutzfeldt-Jakob disease. The utility of the end-point quaking-induced conversion assay as a test for Creutzfeldt-Jakob disease diagnoses was compared to that of immunoassays designed to detect increased amounts of the surrogate markers 14-3-3γ and hTau. The positive predictive values of the end-point quaking-induced conversion, 14-3-3γ, and hTau tests conducted at the Prion Diseases Section of the Public Health Agency of Canada were 96%, 68%, and 66%, respectively.
- Published
- 2021
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29. Creutzfeldt-Jakob Disease with a Five-Year Clinical Course, Multicentric Cerebellar Prion Plaques and Prior History of Biopsy-Proven Primary Angiitis of the Central Nervous System: A Case for Iatrogenic Exposure?
- Author
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Jeon K, Joseph JT, Jansen GH, Peterson A, Knox JD, and Sim VL
- Subjects
- Cerebellum diagnostic imaging, Creutzfeldt-Jakob Syndrome metabolism, Disease Progression, Disease Susceptibility, Humans, Iatrogenic Disease, Immunohistochemistry, Magnetic Resonance Imaging, Middle Aged, Cerebellum metabolism, Cerebellum pathology, Creutzfeldt-Jakob Syndrome diagnosis, Creutzfeldt-Jakob Syndrome etiology, Prions metabolism, Vasculitis, Central Nervous System diagnosis, Vasculitis, Central Nervous System etiology
- Abstract
Creutzfeldt-Jakob disease (CJD) is a rapidly progressive neurodegenerative disease that can arise spontaneously, genetically, or be acquired through iatrogenic exposure. Most patients die within a year of symptom onset. It is rare, affecting 1-2 per million per year, and the majority of cases are sporadic. Primary angiitis of the central nervous system (PACNS) is also rare, affecting 2.4 per million per year. We present a case of an unusually long clinical course of CJD, almost five years, which began with symptoms of apraxia. The patient had biopsy-proven PACNS 16 years prior to clinical presentation, and the site of biopsy was the left parietal lobe. Autopsy revealed multicentric prion plaques in the cerebellum, in the setting of normal genetic testing. The presence of plaques in the cerebellum, and prior neurosurgery, raises the possibility of iatrogenic exposure. We present the details of this case, including pathology from the original biopsy and final autopsy, as well as a review of relevant cases in the literature.
- Published
- 2020
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30. Identification of novel risk loci and causal insights for sporadic Creutzfeldt-Jakob disease: a genome-wide association study.
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Jones E, Hummerich H, Viré E, Uphill J, Dimitriadis A, Speedy H, Campbell T, Norsworthy P, Quinn L, Whitfield J, Linehan J, Jaunmuktane Z, Brandner S, Jat P, Nihat A, How Mok T, Ahmed P, Collins S, Stehmann C, Sarros S, Kovacs GG, Geschwind MD, Golubjatnikov A, Frontzek K, Budka H, Aguzzi A, Karamujić-Čomić H, van der Lee SJ, Ibrahim-Verbaas CA, van Duijn CM, Sikorska B, Golanska E, Liberski PP, Calero M, Calero O, Sanchez-Juan P, Salas A, Martinón-Torres F, Bouaziz-Amar E, Haïk S, Laplanche JL, Brandel JP, Amouyel P, Lambert JC, Parchi P, Bartoletti-Stella A, Capellari S, Poleggi A, Ladogana A, Pocchiari M, Aneli S, Matullo G, Knight R, Zafar S, Zerr I, Booth S, Coulthart MB, Jansen GH, Glisic K, Blevins J, Gambetti P, Safar J, Appleby B, Collinge J, and Mead S
- Subjects
- Creutzfeldt-Jakob Syndrome diagnosis, Creutzfeldt-Jakob Syndrome epidemiology, Genetic Predisposition to Disease epidemiology, Humans, Polymorphism, Single Nucleotide genetics, Risk Factors, Creutzfeldt-Jakob Syndrome genetics, Genetic Loci genetics, Genetic Predisposition to Disease genetics, Genome-Wide Association Study methods
- Abstract
Background: Human prion diseases are rare and usually rapidly fatal neurodegenerative disorders, the most common being sporadic Creutzfeldt-Jakob disease (sCJD). Variants in the PRNP gene that encodes prion protein are strong risk factors for sCJD but, although the condition has similar heritability to other neurodegenerative disorders, no other genetic risk loci have been confirmed. We aimed to discover new genetic risk factors for sCJD, and their causal mechanisms., Methods: We did a genome-wide association study of sCJD in European ancestry populations (patients diagnosed with probable or definite sCJD identified at national CJD referral centres) with a two-stage study design using genotyping arrays and exome sequencing. Conditional, transcriptional, and histological analyses of implicated genes and proteins in brain tissues, and tests of the effects of risk variants on clinical phenotypes, were done using deep longitudinal clinical cohort data. Control data from healthy individuals were obtained from publicly available datasets matched for country., Findings: Samples from 5208 cases were obtained between 1990 and 2014. We found 41 genome-wide significant single nucleotide polymorphisms (SNPs) and independently replicated findings at three loci associated with sCJD risk; within PRNP (rs1799990; additive model odds ratio [OR] 1·23 [95% CI 1·17-1·30], p=2·68 × 10
-15 ; heterozygous model p=1·01 × 10-135 ), STX6 (rs3747957; OR 1·16 [1·10-1·22], p=9·74 × 10-9 ), and GAL3ST1 (rs2267161; OR 1·18 [1·12-1·25], p=8·60 × 10-10 ). Follow-up analyses showed that associations at PRNP and GAL3ST1 are likely to be caused by common variants that alter the protein sequence, whereas risk variants in STX6 are associated with increased expression of the major transcripts in disease-relevant brain regions., Interpretation: We present, to our knowledge, the first evidence of statistically robust genetic associations in sporadic human prion disease that implicate intracellular trafficking and sphingolipid metabolism as molecular causal mechanisms. Risk SNPs in STX6 are shared with progressive supranuclear palsy, a neurodegenerative disease associated with misfolding of protein tau, indicating that sCJD might share the same causal mechanisms as prion-like disorders., Funding: Medical Research Council and the UK National Institute of Health Research in part through the Biomedical Research Centre at University College London Hospitals National Health Service Foundation Trust., (Copyright © 2020 Elsevier Ltd. All rights reserved.)- Published
- 2020
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31. Prospective comparative diagnostic accuracy evaluation of dynamic contrast-enhanced (DCE) vs. dynamic susceptibility contrast (DSC) MR perfusion in differentiating tumor recurrence from radiation necrosis in treated high-grade gliomas.
- Author
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Zakhari N, Taccone MS, Torres CH, Chakraborty S, Sinclair J, Woulfe J, Jansen GH, Cron GO, Thornhill RE, McInnes MDF, and Nguyen TB
- Subjects
- Brain diagnostic imaging, Diagnosis, Differential, Female, Humans, Male, Middle Aged, Necrosis diagnostic imaging, Necrosis etiology, Prospective Studies, Reproducibility of Results, Brain Neoplasms diagnostic imaging, Contrast Media, Glioma diagnostic imaging, Image Enhancement methods, Magnetic Resonance Imaging methods, Neoplasm Recurrence, Local diagnostic imaging, Radiation Injuries diagnostic imaging
- Abstract
Background: The appearance of a new enhancing lesion after surgery and chemoradiation for high-grade glioma (HGG) presents a common diagnostic dilemma. Histopathological analysis remains the reference standard in this situation., Purpose: To prospectively compare the diagnostic accuracy of dynamic contrast-enhanced (DCE) vs. dynamic susceptibility contrast (DSC) in differentiating tumor recurrence (TR) from radiation necrosis (RN)., Study Type: Prospective diagnostic accuracy study., Population: In all, 98 consecutive treated HGG patients with new enhancing lesion. We excluded 32 patients due to inadequate follow-up or technical limitation., Field Strength/sequence: 3 T DCE and DSC MR., Assessment: Histogram and hot-spot analysis of cerebral blood volume (CBV), corrected CBV, K
trans , area under the curve (AUC), and plasma volume (Vp). The reference standard of TR and/or RN was determined by histopathology in 43 surgically resected lesions or by clinical/imaging follow-up in the rest., Statistical Tests: Mann-Whitney U-tests, receiver operating characteristic (ROC) curve, and logistic regression analysis., Results: A total of 68 lesions were included. There were 37 TR, 28 RN, and three lesions with equal proportions of TR and RN. TR had significantly higher CBV, corrected CBV, CBV ratio, corrected CBV ratio, AUC ratio, and Vp ratio (P < 0.05) than RN on hot-spot analysis. CBV had the highest diagnostic accuracy (AUROC 0.71). On histogram analysis, TR had higher CBV and corrected CBV maximal value compared with RN (P = 0.006, AUROC = 0.70). Only CBV on hot-spot analysis remained significant after correction for multiple comparison, with no significant improvement in diagnostic accuracy when using a combination of parameters (AUROC 0.71 vs. 0.76, P = 0.24)., Data Conclusion: DSC-derived CBV is the most accurate perfusion parameter in differentiating TR and RN. DSC and DCE-derived parameters reflecting the blood volume in an enhancing lesion are more accurate than the DCE-derived parameter Ktrans . Clinical practice may be best guided by blood volume measurements, rather than permeability assessment for differentiation of TR from RN., Level of Evidence: 1 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2019;50:573-582., (© 2019 International Society for Magnetic Resonance in Medicine.)- Published
- 2019
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32. Sporadic Creutzfeldt-Jakob Disease in a Young Girl With Unusually Long Survival.
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D'Arcy CE, Bitnun A, Coulthart MB, D'Amour R, Friedman J, Knox JD, Rapoport A, Carter S, Widjaja E, Hazrati LN, and Jansen GH
- Subjects
- Adolescent, Autopsy, Creutzfeldt-Jakob Syndrome mortality, Fatal Outcome, Female, Humans, Brain pathology, Creutzfeldt-Jakob Syndrome pathology
- Abstract
Creutzfeldt-Jakob disease (CJD) is a rapidly progressive, fatal degenerative encephalopathy caused by a pathologically altered form of the prion protein (PrP). CJD is rare, with 1 and 2 cases per million per year reported in the general population, mostly in individuals over 50 years of age. It is almost unknown in the pediatric population. Sporadic CJD with unusually long survival (sCJD-LS), an unusual clinicopathological variant of CJD, has been described mostly in Japanese patients. We present here the first case report of pediatric CJD-LS occurring sporadically in a teenage girl of European descent, with initially rapid neurocognitive decline followed by a prolonged (∼10 years) clinical course. Neuropathological findings at autopsy included generalized cerebral and cerebellar atrophy with relative sparing of the hippocampi, cerebral and cerebellar white and gray matter involvement, minimal spongiform change, PrP deposits in the neocortex, striatum and cerebellum by immunohistochemistry, and protease-resistant PrP by Western immunoblot. With its longer disease duration and atypical manifestations of white matter loss, CJD-LS can be clinically mistaken for other neurodegenerative diseases, or in the pediatric setting for metabolic/genetic conditions. This case clearly demonstrates that with rapid-onset encephalopathy, prion disease should be carefully considered, even in younger patients with slower disease progression., (© 2019 American Association of Neuropathologists, Inc. All rights reserved.)
- Published
- 2019
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33. Intraneural Ganglion Cysts of the Fibular Nerve: A Cause of Fluctuating Painful Foot Drop.
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Bourque PR, Boyd KU, Jansen GH, Warman-Chardon J, Zwicker J, Pringle EB, Rakhra K, and Breiner A
- Subjects
- Female, Gait Disorders, Neurologic diagnostic imaging, Ganglion Cysts diagnostic imaging, Humans, Magnetic Resonance Imaging, Middle Aged, Nerve Fibers metabolism, Nerve Fibers pathology, Neurofilament Proteins metabolism, Pain diagnostic imaging, Gait Disorders, Neurologic complications, Gait Disorders, Neurologic etiology, Ganglion Cysts complications, Pain complications, Pain etiology
- Published
- 2018
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34. [ 18 F]AV-1451 binding and postmortem pathology of CBD.
- Author
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Coakeley S, Ang LC, Jansen GH, Cho SS, Lang AE, Houle S, Kalia LV, and Strafella AP
- Subjects
- Aged, Autopsy, Basal Ganglia drug effects, Cerebral Cortex drug effects, Humans, Male, Positron-Emission Tomography, Basal Ganglia diagnostic imaging, Carbolines pharmacokinetics, Cerebral Cortex diagnostic imaging, Tauopathies diagnostic imaging, Tauopathies metabolism
- Published
- 2018
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35. Diagnostic Accuracy of Centrally Restricted Diffusion in the Differentiation of Treatment-Related Necrosis from Tumor Recurrence in High-Grade Gliomas.
- Author
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Zakhari N, Taccone MS, Torres C, Chakraborty S, Sinclair J, Woulfe J, Jansen GH, and Nguyen TB
- Subjects
- Adult, Aged, Brain Neoplasms pathology, Diagnosis, Differential, Diffusion Magnetic Resonance Imaging methods, Female, Glioma pathology, Humans, Male, Middle Aged, Necrosis diagnostic imaging, Necrosis pathology, Neoplasm Recurrence, Local pathology, Prospective Studies, ROC Curve, Sensitivity and Specificity, Brain Neoplasms diagnostic imaging, Glioma diagnostic imaging, Neoplasm Recurrence, Local diagnostic imaging, Radiation Injuries diagnostic imaging
- Abstract
Background and Purpose: Centrally restricted diffusion has been demonstrated in recurrent high-grade gliomas treated with bevacizumab. Our purpose was to assess the accuracy of centrally restricted diffusion in the diagnosis of radiation necrosis in high-grade gliomas not treated with bevacizumab., Materials and Methods: In this prospective study, we enrolled patients with high-grade gliomas who developed a new ring-enhancing necrotic lesion and who underwent re-resection. The presence of a centrally restricted diffusion within the ring-enhancing lesion was assessed visually on diffusion trace images and by ADC measurements on 3T preoperative diffusion tensor examination. The percentage of tumor recurrence and radiation necrosis in each surgical specimen was defined histopathologically. The association between centrally restricted diffusion and radiation necrosis was assessed using the Fisher exact test. Differences in ADC and the ADC ratio between the groups were assessed via the Mann-Whitney U test, and receiver operating characteristic curve analysis was performed., Results: Seventeen patients had re-resected ring-enhancing lesions: 8 cases of radiation necrosis and 9 cases of tumor recurrence. There was significant association between centrally restricted diffusion by visual assessment and radiation necrosis ( P = .015) with a sensitivity of 75% and a specificity of 88.9%, a positive predictive value 85.7%, and a negative predictive value of 80% for the diagnosis of radiation necrosis. There was a statistically significant difference in the ADC and ADC ratio between radiation necrosis and tumor recurrence ( P = .027)., Conclusions: The presence of centrally restricted diffusion in a new ring-enhancing lesion might indicate radiation necrosis rather than tumor recurrence in high-grade gliomas previously treated with standard chemoradiation without bevacizumab., (© 2018 by American Journal of Neuroradiology.)
- Published
- 2018
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36. A novel Gerstmann-Sträussler-Scheinker disease mutation defines a precursor for amyloidogenic 8 kDa PrP fragments and reveals N-terminal structural changes shared by other GSS alleles.
- Author
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Mercer RCC, Daude N, Dorosh L, Fu ZL, Mays CE, Gapeshina H, Wohlgemuth SL, Acevedo-Morantes CY, Yang J, Cashman NR, Coulthart MB, Pearson DM, Joseph JT, Wille H, Safar JG, Jansen GH, Stepanova M, Sykes BD, and Westaway D
- Subjects
- Adult, Alleles, Amino Acid Sequence, Animals, Humans, Mice, Mice, Transgenic, Middle Aged, Peptide Fragments genetics, PrPSc Proteins metabolism, Protein Domains genetics, Protein Precursors chemistry, Protein Precursors genetics, Gerstmann-Straussler-Scheinker Disease genetics, Mutation, PrPSc Proteins chemistry, PrPSc Proteins genetics, Prion Diseases genetics
- Abstract
To explore pathogenesis in a young Gerstmann-Sträussler-Scheinker Disease (GSS) patient, the corresponding mutation, an eight-residue duplication in the hydrophobic region (HR), was inserted into the wild type mouse PrP gene. Transgenic (Tg) mouse lines expressing this mutation (Tg.HRdup) developed spontaneous neurologic syndromes and brain extracts hastened disease in low-expressor Tg.HRdup mice, suggesting de novo formation of prions. While Tg.HRdup mice exhibited spongiform change, PrP aggregates and the anticipated GSS hallmark of a proteinase K (PK)-resistant 8 kDa fragment deriving from the center of PrP, the LGGLGGYV insertion also imparted alterations in PrP's unstructured N-terminus, resulting in a 16 kDa species following thermolysin exposure. This species comprises a plausible precursor to the 8 kDa PK-resistant fragment and its detection in adolescent Tg.HRdup mice suggests that an early start to accumulation could account for early disease of the index case. A 16 kDa thermolysin-resistant signature was also found in GSS patients with P102L, A117V, H187R and F198S alleles and has coordinates similar to GSS stop codon mutations. Our data suggest a novel shared pathway of GSS pathogenesis that is fundamentally distinct from that producing structural alterations in the C-terminus of PrP, as observed in other prion diseases such as Creutzfeldt-Jakob Disease and scrapie.
- Published
- 2018
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37. Mononeuritis multiplex associated with minocycline in an adolescent.
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McMillan HJ, Jansen GH, Koujok K, Milman N, Duffy CM, and Watanabe Duffy K
- Subjects
- Adolescent, Humans, Knee pathology, Male, Mononeuropathies complications, Mononeuropathies diagnosis, Prednisone therapeutic use, Vasculitis complications, Vasculitis diagnosis, Minocycline adverse effects, Minocycline therapeutic use, Mononeuropathies etiology, Vasculitis etiology
- Published
- 2017
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38. Correlation of Tumor Immunohistochemistry with Dynamic Contrast-Enhanced and DSC-MRI Parameters in Patients with Gliomas.
- Author
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Nguyen TB, Cron GO, Bezzina K, Perdrizet K, Torres CH, Chakraborty S, Woulfe J, Jansen GH, Thornhill RE, Zanette B, and Cameron IG
- Subjects
- Adult, Algorithms, Blood Volume, Brain Neoplasms diagnostic imaging, Brain Neoplasms physiopathology, Contrast Media, Female, Glioma diagnostic imaging, Glioma physiopathology, Humans, Immunohistochemistry, Male, Microvessels diagnostic imaging, Microvessels pathology, Middle Aged, Prognosis, Statistics, Nonparametric, Brain Neoplasms blood supply, Glioma blood supply, Magnetic Resonance Imaging methods
- Abstract
Background and Purpose: Tumor CBV is a prognostic and predictive marker for patients with gliomas. Tumor CBV can be measured noninvasively with different MR imaging techniques; however, it is not clear which of these techniques most closely reflects histologically-measured tumor CBV. Our aim was to investigate the correlations between dynamic contrast-enhanced and DSC-MR imaging parameters and immunohistochemistry in patients with gliomas., Materials and Methods: Forty-three patients with a new diagnosis of glioma underwent a preoperative MR imaging examination with dynamic contrast-enhanced and DSC sequences. Unnormalized and normalized cerebral blood volume was obtained from DSC MR imaging. Two sets of plasma volume and volume transfer constant maps were obtained from dynamic contrast-enhanced MR imaging. Plasma volume obtained from the phase-derived vascular input function and bookend T1 mapping (Vp_Φ) and volume transfer constant obtained from phase-derived vascular input function and bookend T1 mapping (K
trans _Φ) were determined. Plasma volume obtained from magnitude-derived vascular input function (Vp_SI) and volume transfer constant obtained from magnitude-derived vascular input function (Ktrans _SI) were acquired, without T1 mapping. Using CD34 staining, we measured microvessel density and microvessel area within 3 representative areas of the resected tumor specimen. The Mann-Whitney U test was used to test for differences according to grade and degree of enhancement. The Spearman correlation was performed to determine the relationship between dynamic contrast-enhanced and DSC parameters and histopathologic measurements., Results: Microvessel area, microvessel density, dynamic contrast-enhanced, and DSC-MR imaging parameters varied according to the grade and degree of enhancement (P < .05). A strong correlation was found between microvessel area and Vp_Φ and between microvessel area and unnormalized blood volume (rs ≥ 0.61). A moderate correlation was found between microvessel area and normalized blood volume, microvessel area and Vp_SI, microvessel area and Ktrans _Φ, microvessel area and Ktrans _SI, microvessel density and Vp_Φ, microvessel density and unnormalized blood volume, and microvessel density and normalized blood volume (0.44 ≤ rs ≤ 0.57). A weaker correlation was found between microvessel density and Ktrans _Φ and between microvessel density and Ktrans _SI (rs ≤ 0.41)., Conclusions: With dynamic contrast-enhanced MR imaging, use of a phase-derived vascular input function and bookend T1 mapping improves the correlation between immunohistochemistry and plasma volume, but not between immunohistochemistry and the volume transfer constant. With DSC-MR imaging, normalization of tumor CBV could decrease the correlation with microvessel area., (© 2016 by American Journal of Neuroradiology.)- Published
- 2016
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39. A case cluster of variant Creutzfeldt-Jakob disease linked to the Kingdom of Saudi Arabia.
- Author
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Coulthart MB, Geschwind MD, Qureshi S, Phielipp N, Demarsh A, Abrams JY, Belay E, Gambetti P, Jansen GH, Lang AE, and Schonberger LB
- Subjects
- Adult, Age of Onset, Animals, Cattle, Cohort Studies, Creutzfeldt-Jakob Syndrome diagnostic imaging, Creutzfeldt-Jakob Syndrome epidemiology, Creutzfeldt-Jakob Syndrome metabolism, Encephalopathy, Bovine Spongiform epidemiology, Humans, Magnetic Resonance Imaging, Male, Prion Proteins metabolism, Risk Factors, Saudi Arabia epidemiology, United Kingdom epidemiology, Young Adult, Creutzfeldt-Jakob Syndrome etiology, Disease Outbreaks, Encephalopathy, Bovine Spongiform transmission
- Abstract
As of mid-2016, 231 cases of variant Creutzfeldt-Jakob disease-the human form of a prion disease of cattle, bovine spongiform encephalopathy-have been reported from 12 countries. With few exceptions, the affected individuals had histories of extended residence in the UK or other Western European countries during the period (1980-96) of maximum global risk for human exposure to bovine spongiform encephalopathy. However, the possibility remains that other geographic foci of human infection exist, identification of which may help to foreshadow the future of the epidemic. We report results of a quantitative analysis of country-specific relative risks of infection for three individuals diagnosed with variant Creutzfeldt-Jakob disease in the USA and Canada. All were born and raised in Saudi Arabia, but had histories of residence and travel in other countries. To calculate country-specific relative probabilities of infection, we aligned each patient's life history with published estimates of probability distributions of incubation period and age at infection parameters from a UK cohort of 171 variant Creutzfeldt-Jakob disease cases. The distributions were then partitioned into probability density fractions according to time intervals of the patient's residence and travel history, and the density fractions were combined by country. This calculation was performed for incubation period alone, age at infection alone, and jointly for incubation and age at infection. Country-specific fractions were normalized either to the total density between the individual's dates of birth and symptom onset ('lifetime'), or to that between 1980 and 1996, for a total of six combinations of parameter and interval. The country-specific relative probability of infection for Saudi Arabia clearly ranked highest under each of the six combinations of parameter × interval for Patients 1 and 2, with values ranging from 0.572 to 0.998, respectively, for Patient 2 (age at infection × lifetime) and Patient 1 (joint incubation and age at infection × 1980-96). For Patient 3, relative probabilities for Saudi Arabia were not as distinct from those for other countries using the lifetime interval: 0.394, 0.360 and 0.378, respectively, for incubation period, age at infection and jointly for incubation and age at infection. However, for this patient Saudi Arabia clearly ranked highest within the 1980-96 period: 0.859, 0.871 and 0.865, respectively, for incubation period, age at infection and jointly for incubation and age at infection. These findings support the hypothesis that human infection with bovine spongiform encephalopathy occurred in Saudi Arabia., (© Her Majesty the Queen in Right of Canada 2016. Reproduced with the permission of the Minister of Public Health.)
- Published
- 2016
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40. Evidence for transmissibility of Alzheimer disease pathology: Cause for concern?
- Author
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Coulthart MB, Jansen GH, and Cashman NR
- Subjects
- Adult, Alzheimer Disease etiology, Creutzfeldt-Jakob Syndrome complications, Humans, Middle Aged, Plaque, Amyloid pathology, Prion Proteins, Alzheimer Disease pathology, Brain pathology, Creutzfeldt-Jakob Syndrome transmission
- Published
- 2016
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41. Amyloid Neuropathy Following Domino Liver Transplantation: Response to Diflunisal.
- Author
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Bourque PR, Shafi S, Jansen GH, McCurdy A, and Warman Chardon J
- Subjects
- Aged, Amyloid Neuropathies etiology, Humans, Liver Transplantation trends, Male, Treatment Outcome, Amyloid Neuropathies diagnosis, Amyloid Neuropathies drug therapy, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Diflunisal therapeutic use, Liver Transplantation adverse effects
- Published
- 2016
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42. Creutzfeldt-Jakob Disease-Like Periodic Sharp Wave Complexes in Voltage-Gated Potassium Channel-Complex Antibodies Encephalitis: A Case Report.
- Author
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Savard M, Irani SR, Guillemette A, Gosselin-Lefebvre S, Geschwind M, Jansen GH, Gould PV, and Laforce R Jr
- Subjects
- Autoantibodies immunology, Channelopathies, Diagnosis, Differential, Electrocardiography methods, Humans, Autoimmune Diseases of the Nervous System immunology, Brain Waves immunology, Creutzfeldt-Jakob Syndrome diagnosis, Creutzfeldt-Jakob Syndrome physiopathology, Encephalitis immunology, Potassium Channels, Voltage-Gated immunology
- Abstract
Introduction: Voltage-gated potassium channel-complex antibodies (VGKC-cAbs) encephalitis, a treatable autoantibody encephalopathy, has been previously reported to clinically mimic sporadic Creutzfeldt-Jakob disease. Among available clinical clues to distinguish them, periodic sharp wave complexes, a typical finding in sporadic Creutzfeldt-Jakob disease, have never been reported in association with VGKC-cAbs encephalitis., Case Presentation: A 76-year-old man was transferred to a tertiary neurology center with a clinical history of 6-month weight loss, cognitive disturbance, and nonspecific generalized weakness. He had two seizures the month before transfer and then evolved to severe encephalopathy, requiring mechanical ventilation. Periodic sharp wave complexes every 1 to 2 seconds over slowed background were found on EEG, and MRI showed cerebellar and bifrontal cortical T2/FLAIR/DWI hypersignal without restricted diffusion on ADC mapping. Pancorporal positron emission tomography scan was negative. An immunotherapy trial did not improve the patient condition. Therefore, he died after life support withdrawal. Brain autopsy revealed mononuclear neocortex infiltrate without significant spongiosis, and the anti-VGKC test showed a seropositivity of 336 pmol/L (normal, 0-31), 3 month after the patient deceased., Conclusions: This is the first reported case of VGKC-cAbs encephalitis associated with periodic sharp wave complexes on EEG, which further confuse the differential diagnosis with sporadic Creutzfeldt-Jakob disease. However, the cortical DWI hypersignal without restriction seems to remain a way to discriminate these two entities appropriately, when present. These clues are of paramount importance because VGKC-cAbs encephalitis is a treatable disease.
- Published
- 2016
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43. Comparison of the Diagnostic Accuracy of DSC- and Dynamic Contrast-Enhanced MRI in the Preoperative Grading of Astrocytomas.
- Author
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Nguyen TB, Cron GO, Perdrizet K, Bezzina K, Torres CH, Chakraborty S, Woulfe J, Jansen GH, Sinclair J, Thornhill RE, Foottit C, Zanette B, and Cameron IG
- Subjects
- Adult, Aged, Algorithms, Contrast Media, Female, Humans, Male, Middle Aged, Organometallic Compounds, Prospective Studies, ROC Curve, Statistics, Nonparametric, Astrocytoma pathology, Brain Neoplasms pathology, Magnetic Resonance Imaging methods, Neoplasm Grading methods, Preoperative Care methods
- Abstract
Background and Purpose: Dynamic contrast-enhanced MR imaging parameters can be biased by poor measurement of the vascular input function. We have compared the diagnostic accuracy of dynamic contrast-enhanced MR imaging by using a phase-derived vascular input function and "bookend" T1 measurements with DSC MR imaging for preoperative grading of astrocytomas., Materials and Methods: This prospective study included 48 patients with a new pathologic diagnosis of an astrocytoma. Preoperative MR imaging was performed at 3T, which included 2 injections of 5-mL gadobutrol for dynamic contrast-enhanced and DSC MR imaging. During dynamic contrast-enhanced MR imaging, both magnitude and phase images were acquired to estimate plasma volume obtained from phase-derived vascular input function (Vp_Φ) and volume transfer constant obtained from phase-derived vascular input function (K(trans)_Φ) as well as plasma volume obtained from magnitude-derived vascular input function (Vp_SI) and volume transfer constant obtained from magnitude-derived vascular input function (K(trans)_SI). From DSC MR imaging, corrected relative CBV was computed. Four ROIs were placed over the solid part of the tumor, and the highest value among the ROIs was recorded. A Mann-Whitney U test was used to test for difference between grades. Diagnostic accuracy was assessed by using receiver operating characteristic analysis., Results: Vp_ Φ and K(trans)_Φ values were lower for grade II compared with grade III astrocytomas (P < .05). Vp_SI and K(trans)_SI were not significantly different between grade II and grade III astrocytomas (P = .08-0.15). Relative CBV and dynamic contrast-enhanced MR imaging parameters except for K(trans)_SI were lower for grade III compared with grade IV (P ≤ .05). In differentiating low- and high-grade astrocytomas, we found no statistically significant difference in diagnostic accuracy between relative CBV and dynamic contrast-enhanced MR imaging parameters., Conclusions: In the preoperative grading of astrocytomas, the diagnostic accuracy of dynamic contrast-enhanced MR imaging parameters is similar to that of relative CBV., (© 2015 by American Journal of Neuroradiology.)
- Published
- 2015
- Full Text
- View/download PDF
44. Radiological and pathological features associated with IDH1-R132H mutation status and early mortality in newly diagnosed anaplastic astrocytic tumours.
- Author
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Wasserman JK, Nicholas G, Yaworski R, Wasserman AM, Woulfe JM, Jansen GH, Chakraborty S, and Nguyen TB
- Subjects
- Adult, Aged, Aged, 80 and over, Astrocytoma diagnostic imaging, Astrocytoma pathology, Brain Neoplasms diagnostic imaging, Brain Neoplasms genetics, Brain Neoplasms mortality, Brain Neoplasms pathology, Female, Humans, Male, Middle Aged, Neoplasm Grading, Prognosis, Radiography, Retrospective Studies, Survival Rate, Young Adult, Astrocytoma genetics, Astrocytoma mortality, Biomarkers, Tumor genetics, Isocitrate Dehydrogenase genetics, Magnetic Resonance Imaging methods, Mutation genetics
- Abstract
Background: Glioblastoma can occur either de novo or by the transformation of a low grade tumour; the majority of which harbor a mutation in isocitrate dehydrogenase (IDH1). Anaplastic tumours are high-grade gliomas that may represent the final step in the evolution of a secondary glioblastoma or the initial presentation of an early primary glioblastoma. We sought to determine whether pathological and/or radiological variables exist that can reliably distinguish IDH1-R132H-positive from IDH1-R132H-negative tumours and to identify variables associated with early mortality., Methods: Patients diagnosed with anaplastic astrocytic tumours were included. Magnetic resonance imaging was performed and immunohistochemistry was used to identify tumours with the IDH1-R132H mutation. Survival was assessed 12 months after diagnosis. Variables associated with IDH1-R132H status were identified by univariate and ROC analysis., Results: 37 gliomas were studied; 18 were positive for the IDH1-R132H mutation. No tumours demonstrated a combined loss of chromosomes 1p/19q. Patients with IDH1-R132H-positive tumours were less likely to die within 12 months of diagnosis (17% vs. 47%; p=0.046), more likely to have tumours located in the frontal lobe (55% vs. 16%; p=0.015), and have a higher minimum apparent diffusion coefficient (1.115 x 10-3 mm2/sec vs. 0.838 x 10-3 mm2/sec; p=0.016), however, these variables demonstrated only moderate strength for predicting the IDH1-R132H mutation status (AUC=0.735 and 0.711, respectively). The Ki-67 index was significantly lower in IDH1-R132H-positive tumours (0.13 vs. 0.21; p=0.034). An increased risk of death was associated with contrast-enhancement ≥ 5 cm3 in patients with IDH1-R132H-positive tumours while edema ≥ 1 cm beyond the tumour margin and < 5 mitoses/mm2 were associated with an increased risk of death in patients with IDH1-R132H-negative tumours., Conclusions: IDH1-R132H-positive and -negative anaplastic tumours demonstrate unique features. Factors associated with early mortality are also dependent on IDH1-R132H status and can be used to identify patients at high risk for death.
- Published
- 2015
- Full Text
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45. Metastatic renal cell carcinoma mimicking a schwannoma in a dorsal root ganglion: case report.
- Author
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Wasserman JK, Tsai EC, Glikstein R, Mai KT, and Jansen GH
- Subjects
- Aged, Carcinoma, Renal Cell secondary, Female, Humans, Neurilemmoma diagnosis, Peripheral Nerves pathology, Peripheral Nervous System Neoplasms diagnosis, Carcinoma, Renal Cell diagnosis, Diagnosis, Differential, Ganglia, Spinal pathology, Kidney Neoplasms pathology, Neurilemmoma pathology, Peripheral Nervous System Neoplasms pathology
- Abstract
Peripheral nerve tumors are soft-tissue tumors that can occur in any nerve throughout the body. The majority of peripheral nerve tumors arise from elements of the nerve sheath with the two most common being neurofibromas and schwannomas. More than 90% of all peripheral nerve tumors are benign. When there is peripheral nerve involvement in metastatic carcinoma, it is often via contiguous spread from the primary mass; hematogenous seeding to a peripheral nerve is seldom seen. In this report the authors describe the even rarer case of metastatic renal cell carcinoma mimicking a schwannoma in a dorsal root ganglion. Cases from the literature show the rarity of this finding and its late clinical appearance. Given that survival in patients with metastatic carcinoma continues to increase, dorsal root ganglion metastasis may become more common over time.
- Published
- 2015
- Full Text
- View/download PDF
46. Preoperative prognostic value of dynamic contrast-enhanced MRI-derived contrast transfer coefficient and plasma volume in patients with cerebral gliomas.
- Author
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Nguyen TB, Cron GO, Mercier JF, Foottit C, Torres CH, Chakraborty S, Woulfe J, Jansen GH, Caudrelier JM, Sinclair J, Hogan MJ, Thornhill RE, and Cameron IG
- Subjects
- Adult, Aged, Contrast Media, Female, Humans, Image Interpretation, Computer-Assisted, Male, Middle Aged, Prognosis, Prospective Studies, Survival Analysis, Survival Rate, Brain Neoplasms mortality, Brain Neoplasms pathology, Glioma mortality, Glioma pathology, Magnetic Resonance Imaging methods
- Abstract
Background and Purpose: The prognostic value of dynamic contrast-enhanced MR imaging-derived plasma volume obtained in tumor and the contrast transfer coefficient has not been well-established in patients with gliomas. We determined whether plasma volume and contrast transfer coefficient in tumor correlated with survival in patients with gliomas in addition to other factors such as age, type of surgery, preoperative Karnofsky score, contrast enhancement, and histopathologic grade., Materials and Methods: This prospective study included 46 patients with a new pathologically confirmed diagnosis of glioma. The contrast transfer coefficient and plasma volume obtained in tumor maps were calculated directly from the signal-intensity curve without T1 measurements, and values were obtained from multiple small ROIs placed within tumors. Survival curve analysis was performed by dichotomizing patients into groups of high and low contrast transfer coefficient and plasma volume. Univariate analysis was performed by using dynamic contrast-enhanced parameters and clinical factors. Factors that were significant on univariate analysis were entered into multivariate analysis., Results: For all patients with gliomas, survival was worse for groups of patients with high contrast transfer coefficient and plasma volume obtained in tumor (P < .05). In subgroups of high- and low-grade gliomas, survival was worse for groups of patients with high contrast transfer coefficient and plasma volume obtained in tumor (P < .05). Univariate analysis showed that factors associated with lower survival were age older than 50 years, low Karnofsky score, biopsy-only versus resection, marked contrast enhancement versus no/mild enhancement, high contrast transfer coefficient, and high plasma volume obtained in tumor (P < .05). In multivariate analysis, a low Karnofsky score, biopsy versus resection in combination with marked contrast enhancement, and a high contrast transfer coefficient were associated with lower survival rates (P < .05)., Conclusions: In patients with glioma, those with a high contrast transfer coefficient have lower survival than those with low parameters., (© 2015 by American Journal of Neuroradiology.)
- Published
- 2015
- Full Text
- View/download PDF
47. Interpretation of cerebrospinal fluid protein tests in the diagnosis of sporadic Creutzfeldt-Jakob disease: an evidence-based approach.
- Author
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Coulthart MB, Jansen GH, and Cashman NR
- Subjects
- Creutzfeldt-Jakob Syndrome metabolism, Diagnosis, Differential, Humans, Cerebrospinal Fluid Proteins analysis, Creutzfeldt-Jakob Syndrome diagnosis, Evidence-Based Medicine methods
- Published
- 2014
- Full Text
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48. Guidelines from the Canadian Association of Pathologists for establishing a telepathology service for anatomic pathology using whole-slide imaging.
- Author
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Bernard C, Chandrakanth SA, Cornell IS, Dalton J, Evans A, Garcia BM, Godin C, Godlewski M, Jansen GH, Kabani A, Louahlia S, Manning L, Maung R, Moore L, Philley J, Slatnik J, Srigley J, Thibault A, Picard DD, Cracower H, and Tetu B
- Abstract
The use of telepathology for clinical applications in Canada has steadily become more attractive over the last 10 years, driven largely by its potential to provide rapid pathology consulting services throughout the country regardless of the location of a particular institution. Based on this trend, the president of the Canadian Association of Pathologists asked a working group consisting of pathologists, technologists, and healthcare administrators from across Canada to oversee the development of guidelines to provide Canadian pathologists with basic information on how to implement and use this technology. The guidelines were systematically developed, based on available medical literature and the clinical experience of early adopters of telepathology in Canada. While there are many different modalities and applications of telepathology, this document focuses specifically on whole-slide imaging as applied to intraoperative pathology consultation (frozen section), primary diagnosis, expert or second opinions and quality assurance activities. Applications such as hematopathology, microbiology, tumour boards, education, research and technical and/or standard-related issues are not covered.
- Published
- 2014
- Full Text
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49. Intensity of human prion disease surveillance predicts observed disease incidence.
- Author
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Klug GM, Wand H, Simpson M, Boyd A, Law M, Masters CL, Matěj R, Howley R, Farrell M, Breithaupt M, Zerr I, van Duijn C, Ibrahim-Verbaas C, Mackenzie J, Will RG, Brandel JP, Alperovitch A, Budka H, Kovacs GG, Jansen GH, Coulthard M, and Collins SJ
- Subjects
- Australia epidemiology, Canada epidemiology, Europe epidemiology, Humans, Incidence, Creutzfeldt-Jakob Syndrome epidemiology, Epidemiological Monitoring, Prion Diseases epidemiology, Public Health Surveillance methods, Registries
- Abstract
Background: Prospective national screening and surveillance programmes serve a range of public health functions. Objectively determining their adequacy and impact on disease may be problematic for rare disorders. We undertook to assess whether objective measures of disease surveillance intensity could be developed for the rare disorder sporadic Creutzfeldt-Jakob disease (CJD) and whether such measures correlate with disease incidence., Method: From 10 countries with national human prion disease surveillance centres, the annual number of suspected prion disease cases notified to each national unit (n=17,610), referrals for cerebrospinal fluid (CSF) 14-3-3 protein diagnostic testing (n=28,780) and the number of suspect cases undergoing diagnostic neuropathological examination (n=4885) from 1993 to 2006 were collected. Age and survey year adjusted incidence rate ratios with 95% CIs were estimated using Poisson regression models to assess risk factors for sporadic, non-sporadic and all prion disease cases., Results: Age and survey year adjusted analysis showed all three surveillance intensity measures (suspected human prion disease notifications, 14-3-3 protein diagnostic test referrals and neuropathological examinations of suspect cases) significantly predicted the incidence of sporadic CJD, non-sporadic CJD and all prion disease., Conclusions: Routine national surveillance methods adjusted as population rates allow objective determination of surveillance intensity, which correlates positively with reported incidence for human prion disease, especially sporadic CJD, largely independent of national context. The predictive relationship between surveillance intensity and disease incidence should facilitate more rapid delineation of aberrations in disease occurrence and assessment of the adequacy of disease monitoring by national registries.
- Published
- 2013
- Full Text
- View/download PDF
50. Neurosurgical management of intracranial metastatic mesothelioma.
- Author
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Westwick HJ, Jansen GH, and Da Silva VF
- Subjects
- Humans, Mesothelioma
- Published
- 2013
- Full Text
- View/download PDF
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