Evaluation of CSF1R-related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia diagnostic criteria.

Abstract

BACKGROUND\nDiagnostic criteria for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) due to colony-stimulating factor 1 receptor (CSF1R) mutation have been recently proposed. Our objective was to assess their accuracy in an independent multicentre cohort.\n\n\nMETHODS\nWe evaluated the sensitivity and specificity of the diagnostic criteria for ALSP (including the probable and possible definitions) in a national cohort of 22 patients with CSF1R mutation, and 59 patients with an alternative diagnosis of adult-onset inherited leukoencephalopathy.\n\n\nRESULTS\nOverall, the sensitivity of the diagnostic criteria for ALSP was 82% including 9/22 patients diagnosed as probable and 9/22 diagnosed as possible. Twenty of the 59 CSF1R-mutation-negative leukoencephalopathies fulfilled the diagnostic criteria leading to a specificity of 66%.\n\n\nDISCUSSION & CONCLUSION\nDiagnostic criteria for ALSP have an overall limited sensitivity along with a modest specificity. We suggest that in patients suspected of genetic leukoencephalopathy, a comprehensive MRI-pattern based approach is warranted together with white matter gene panel or whole exome sequencing.