TY - JOUR
T1 - Cerebral Microangiopathy in Leukoencephalopathy With Cerebral Calcifications and Cysts: A Pathological Description
AU - Helman, Guy
AU - Viaene, Angela N.
AU - Takanohashi, Asako
AU - Breur, Marjolein
AU - Berger, Rebecca
AU - Woidill, Sarah
AU - Cottrell, John R.
AU - Schiffmann, Raphael
AU - Crow, Yanick J.
AU - Simons, Cas
AU - Bugiani, Marianna
AU - Vanderver, Adeline
N1 - Funding Information: We thank the individual and his family, as well as all those affected by LCC. GH and AV were supported by the Myelin Disorders Bioregistry Project. The research conducted at the Murdoch Children?s Research Institute was supported by the Victorian Government?s Operational Infrastructure Support Program. The authors thank the University of Maryland Brain and Tissue Bank for providing brain samples. We also thank Dr Ana Rubio posthumously who performed the initial neuropathologic examination. YJC acknowledges the Great Ormond Street Hospital Charity (V4017). The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: GH and ANV were supported by the Myelin Disorders Bioregistry Project. The research conducted at the Murdoch Children?s Research Institute was supported by the Victorian Government?s Operational Infrastructure Support Program. YJC acknowledges the Great Ormond Street Hospital Charity (V4017). Funding Information: We thank the individual and his family, as well as all those affected by LCC. GH and AV were supported by the Myelin Disorders Bioregistry Project. The research conducted at the Murdoch Children’s Research Institute was supported by the Victorian Government’s Operational Infrastructure Support Program. The authors thank the University of Maryland Brain and Tissue Bank for providing brain samples. We also thank Dr Ana Rubio posthumously who performed the initial neuropathologic examination. YJC acknowledges the Great Ormond Street Hospital Charity (V4017). Publisher Copyright: © The Author(s) 2020. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - Leukoencephalopathy with calcifications and cysts (LCC) is a neurological syndrome recently associated with pathogenic variants in SNORD118. We report autopsy neuropathological findings from an individual with genetically confirmed LCC. Histologic studies included staining of formalin-fixed paraffin-embedded tissue sections by hematoxylin and eosin, elastic van Gieson, and luxol fast blue. Immunohistochemistry stains against glial fibrillary acidic protein, proteolipid protein, phosphorylated neurofilament, CD31, alpha-interferon, LN3, and inflammatory markers were performed. Gross examination revealed dark tan/gray appearing white matter with widespread calcifications. Microscopy revealed a diffuse destructive process due to a vasculopathy with secondary ischemic lesions and mineralization. The vasculopathy involved clustered small vessels, resembling vascular malformations, and sporadic lymphocytic infiltration of vessel walls. The white matter was also diffusely abnormal, with concurrent loss of myelin and axons, tissue rarefaction with multifocal cystic degeneration, and the presence of foamy macrophages, secondary calcifications, and astrogliosis. The midbrain, pons, and cerebellum were diffusely involved. It is not understood why variants in SNORD118 result in a disorder that predominantly causes neurological disease and significantly disrupts the cerebral vasculature. Clinical and radiological benefit was recently reported in an LCC patient treated with Bevacizumab; it is important that these patients are rapidly diagnosed and trial of this treatment modality is considered in appropriate circumstances.
AB - Leukoencephalopathy with calcifications and cysts (LCC) is a neurological syndrome recently associated with pathogenic variants in SNORD118. We report autopsy neuropathological findings from an individual with genetically confirmed LCC. Histologic studies included staining of formalin-fixed paraffin-embedded tissue sections by hematoxylin and eosin, elastic van Gieson, and luxol fast blue. Immunohistochemistry stains against glial fibrillary acidic protein, proteolipid protein, phosphorylated neurofilament, CD31, alpha-interferon, LN3, and inflammatory markers were performed. Gross examination revealed dark tan/gray appearing white matter with widespread calcifications. Microscopy revealed a diffuse destructive process due to a vasculopathy with secondary ischemic lesions and mineralization. The vasculopathy involved clustered small vessels, resembling vascular malformations, and sporadic lymphocytic infiltration of vessel walls. The white matter was also diffusely abnormal, with concurrent loss of myelin and axons, tissue rarefaction with multifocal cystic degeneration, and the presence of foamy macrophages, secondary calcifications, and astrogliosis. The midbrain, pons, and cerebellum were diffusely involved. It is not understood why variants in SNORD118 result in a disorder that predominantly causes neurological disease and significantly disrupts the cerebral vasculature. Clinical and radiological benefit was recently reported in an LCC patient treated with Bevacizumab; it is important that these patients are rapidly diagnosed and trial of this treatment modality is considered in appropriate circumstances.
KW - SNORD118
KW - calcifications
KW - cysts
KW - leukoencephalopathy
KW - neuropathology
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85091726870&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/32988269
U2 - https://doi.org/10.1177/0883073820958330
DO - https://doi.org/10.1177/0883073820958330
M3 - Article
C2 - 32988269
SN - 0883-0738
VL - 36
SP - 133
EP - 140
JO - Journal of child neurology
JF - Journal of child neurology
IS - 2
ER -