Towards a histological diagnosis of childhood small vessel CNS vasculitis
Abstract Background Primary small vessel CNS vasculitis (sv-cPACNS) is a challenging inflammatory brain disease in children. Brain biopsy is mandatory to confirm the diagnosis. This study aims to develop and validate a histological scoring tool for diagnosing small vessel CNS vasculitis. Methods A s...
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BMC
2024-12-01
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| Series: | Pediatric Rheumatology Online Journal |
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| Online Access: | https://doi.org/10.1186/s12969-024-01053-4 |
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| author | Maryam Nabavi Nouri Anastasia Dropol Pascal N. Tyrrell Sheila Sheikh Marinka Twilt Jean Michaud Benjamin Ellezam Harvey B. Sarnat Christopher Dunham Peter W. Schutz Julia Keith David G. Munoz Harry V. Vinters Cynthia Hawkins Susanne M. Benseler |
| author_facet | Maryam Nabavi Nouri Anastasia Dropol Pascal N. Tyrrell Sheila Sheikh Marinka Twilt Jean Michaud Benjamin Ellezam Harvey B. Sarnat Christopher Dunham Peter W. Schutz Julia Keith David G. Munoz Harry V. Vinters Cynthia Hawkins Susanne M. Benseler |
| author_sort | Maryam Nabavi Nouri |
| collection | DOAJ |
| description | Abstract Background Primary small vessel CNS vasculitis (sv-cPACNS) is a challenging inflammatory brain disease in children. Brain biopsy is mandatory to confirm the diagnosis. This study aims to develop and validate a histological scoring tool for diagnosing small vessel CNS vasculitis. Methods A standardized brain biopsy scoring instrument was developed and applied to consecutive full-thickness brain biopsies of pediatric cases and controls at a single center. Stains included immunohistochemistry and Hematoxylin & Eosin. Nine North American neuropathologists, blinded to patients’ presentation, diagnosis, and therapy, scored de-identified biopsies independently. Results A total of 31 brain biopsy specimens from children with sv-cPACNS, 11 with epilepsy, and 11 with non-vasculitic inflammatory brain disease controls were included. Angiocentric inflammation in the cortex or white matter increases the likelihood of sv-cPACNS, with odds ratios (ORs) of 3.231 (95CI: 0.914–11.420, p = 0.067) and 3.923 (95CI: 1.13–13.6, p = 0.031). Moderate to severe inflammation in these regions is associated with a higher probability of sv-cPACNS, with ORs of 5.56 (95CI: 1.02–29.47, p = 0.046) in the cortex and 6.76 (95CI: 1.26–36.11, p = 0.025) in white matter. CD3, CD4, CD8, and CD20 cells predominated the inflammatory infiltrate. Reactive endothelium was strongly associated with sv-cPACNS, with an OR of 8.93 (p = 0.001). Features reported in adult sv-PACNS, including granulomas, necrosis, or fibrin deposits, were absent in all biopsies. The presence of leptomeningeal inflammation in isolation was non-diagnostic. Conclusion Distinct histological features were identified in sv-cPACNS biopsies, including moderate to severe angiocentric inflammatory infiltrates in the cortex or white matter, consisting of CD3, CD4, CD8, and CD20 cells, alongside reactive endothelium with specificity of 95%. In the first study of its kind proposing histological criteria for evaluating brain biopsies, we aim to precisely characterize the type and severity of the inflammatory response in patients with sv-cPACNS; this can enable consolidation of this population to assess outcomes and treatment methodologies comprehensively. |
| format | Article |
| id | doaj-art-534f33a7e4da432ea8649097fb3e0d47 |
| institution | Kabale University |
| issn | 1546-0096 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
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| series | Pediatric Rheumatology Online Journal |
| spelling | doaj-art-534f33a7e4da432ea8649097fb3e0d472025-01-05T12:11:12ZengBMCPediatric Rheumatology Online Journal1546-00962024-12-0122111110.1186/s12969-024-01053-4Towards a histological diagnosis of childhood small vessel CNS vasculitisMaryam Nabavi Nouri0Anastasia Dropol1Pascal N. Tyrrell2Sheila Sheikh3Marinka Twilt4Jean Michaud5Benjamin Ellezam6Harvey B. Sarnat7Christopher Dunham8Peter W. Schutz9Julia Keith10David G. Munoz11Harry V. Vinters12Cynthia Hawkins13Susanne M. Benseler14Division of Pediatric Neurology, Department of Paediatrics, Schulich School of Medicine and Dentistry, Western UniversityFaculty of Medicine, Digital Solutions, University of British ColumbiaDepartment of Medical Imaging, Institute of Medical Science, and Department of Statistical Sciences, University of TorontoDepartment of Paediatrics, Hospital for Sick Children, University of TorontoDepartment of Pediatrics, Division of Rheumatology, Alberta Children’s Hospital, University of CalgaryDepartment of Pathology and Laboratory Medicine, Children’s Hospital of Eastern Ontario, University of OttawaDepartment of Pathology (Neuropathology) and Clinical Neurosciences, Alberta Children’s Hospital, University of CalgaryDepartment of Pathology and Cell Biology, Université de Montréal, Sainte-Justine HospitalDepartment of Pathology and Laboratory Medicine, Children’s and Women’s Health Centre of B.C, University of British ColombiaDepartment of Pathology and Laboratory Medicine, University of British ColumbiaDepartment of Laboratory Medicine and Pathobiology, Sunnybrook Health Sciences Centre, University of TorontoDepartment of Laboratory Medicine and Pathobiology, St. Michael’s Hospital, University of TorontoDepartments of Pathology, Laboratory Medicine and Neurology, David Geffen School of Medicine at UCLA and Ronald Reagan-UCLA Medical CenterDepartment of Paediatric Laboratory Medicine, Hospital for Sick Children, University of TorontoSection of Rheumatology, Department of Pediatrics, Alberta Children’s Hospital, University of CalgaryAbstract Background Primary small vessel CNS vasculitis (sv-cPACNS) is a challenging inflammatory brain disease in children. Brain biopsy is mandatory to confirm the diagnosis. This study aims to develop and validate a histological scoring tool for diagnosing small vessel CNS vasculitis. Methods A standardized brain biopsy scoring instrument was developed and applied to consecutive full-thickness brain biopsies of pediatric cases and controls at a single center. Stains included immunohistochemistry and Hematoxylin & Eosin. Nine North American neuropathologists, blinded to patients’ presentation, diagnosis, and therapy, scored de-identified biopsies independently. Results A total of 31 brain biopsy specimens from children with sv-cPACNS, 11 with epilepsy, and 11 with non-vasculitic inflammatory brain disease controls were included. Angiocentric inflammation in the cortex or white matter increases the likelihood of sv-cPACNS, with odds ratios (ORs) of 3.231 (95CI: 0.914–11.420, p = 0.067) and 3.923 (95CI: 1.13–13.6, p = 0.031). Moderate to severe inflammation in these regions is associated with a higher probability of sv-cPACNS, with ORs of 5.56 (95CI: 1.02–29.47, p = 0.046) in the cortex and 6.76 (95CI: 1.26–36.11, p = 0.025) in white matter. CD3, CD4, CD8, and CD20 cells predominated the inflammatory infiltrate. Reactive endothelium was strongly associated with sv-cPACNS, with an OR of 8.93 (p = 0.001). Features reported in adult sv-PACNS, including granulomas, necrosis, or fibrin deposits, were absent in all biopsies. The presence of leptomeningeal inflammation in isolation was non-diagnostic. Conclusion Distinct histological features were identified in sv-cPACNS biopsies, including moderate to severe angiocentric inflammatory infiltrates in the cortex or white matter, consisting of CD3, CD4, CD8, and CD20 cells, alongside reactive endothelium with specificity of 95%. In the first study of its kind proposing histological criteria for evaluating brain biopsies, we aim to precisely characterize the type and severity of the inflammatory response in patients with sv-cPACNS; this can enable consolidation of this population to assess outcomes and treatment methodologies comprehensively.https://doi.org/10.1186/s12969-024-01053-4Sv-cPACNSPACNScPACNSBrain biopsyInflammatory brain disease |
| spellingShingle | Maryam Nabavi Nouri Anastasia Dropol Pascal N. Tyrrell Sheila Sheikh Marinka Twilt Jean Michaud Benjamin Ellezam Harvey B. Sarnat Christopher Dunham Peter W. Schutz Julia Keith David G. Munoz Harry V. Vinters Cynthia Hawkins Susanne M. Benseler Towards a histological diagnosis of childhood small vessel CNS vasculitis Pediatric Rheumatology Online Journal Sv-cPACNS PACNS cPACNS Brain biopsy Inflammatory brain disease |
| title | Towards a histological diagnosis of childhood small vessel CNS vasculitis |
| title_full | Towards a histological diagnosis of childhood small vessel CNS vasculitis |
| title_fullStr | Towards a histological diagnosis of childhood small vessel CNS vasculitis |
| title_full_unstemmed | Towards a histological diagnosis of childhood small vessel CNS vasculitis |
| title_short | Towards a histological diagnosis of childhood small vessel CNS vasculitis |
| title_sort | towards a histological diagnosis of childhood small vessel cns vasculitis |
| topic | Sv-cPACNS PACNS cPACNS Brain biopsy Inflammatory brain disease |
| url | https://doi.org/10.1186/s12969-024-01053-4 |
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