Cerebral Microangiopathy in Leukoencephalopathy With Cerebral Calcifications and Cysts: A Pathological Description.
Guy HelmanAngela N ViaeneAsako TakanohashiMarjolein BreurRebecca BergerSarah WoidillJohn R CottrellRaphael SchiffmannYanick J CrowCas SimonsMarianna BugianiAdeline VanderverPublished in: Journal of child neurology (2020)
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.
Keyphrases
- white matter
- cerebral ischemia
- subarachnoid hemorrhage
- end stage renal disease
- multiple sclerosis
- newly diagnosed
- copy number
- chronic kidney disease
- ejection fraction
- case report
- single cell
- protein protein
- peritoneal dialysis
- clinical trial
- high resolution
- prognostic factors
- dendritic cells
- amino acid
- single molecule
- squamous cell carcinoma
- patient reported outcomes
- blood brain barrier
- late onset
- dna methylation
- high speed
- low grade
- ischemia reperfusion injury
- amyotrophic lateral sclerosis