Factors predictive of the presence of a CSF1R mutation in patients with leukoencephalopathy

Abstract

Background and purpose: The purpose was to identify statistically factors that correlate with the presence of a colony-stimulating factor 1 receptor (CSF1R) mutation and to reevaluate the accuracy of the current diagnostic criteria for CSF1R-related leukoencephalopathy.

Methods: CSF1R testing was conducted on 145 consecutive leukoencephalopathy cases who were clinically suspected of having adult-onset leukoencephalopathy with axonal spheroids and pigmented glia. From these, 135 cases whose detailed clinical information was available were enrolled. Forward logistic stepwise regression was performed to generate a probability model to predict a positive CSF1R mutation result. The current diagnostic criteria were also applied to our cohort and their sensitivity and specificity were calculated.

Results: Twenty-eight CSF1R-mutation-positive cases and 107 CSF1R-mutation-negative cases were identified. Our probability model suggested that factors raising the probability of a CSF1R-mutation-positive result were younger onset, parkinsonism, thinning of the corpus callosum and diffusion-restricted lesions. It also showed that involuntary movements and brainstem or cerebellar atrophy were negative predictors of a CSF1R-mutation-positive result. In our cohort, the sensitivity and specificity for 'probable' or 'possible' CSF1R-related leukoencephalopathy were 81% and 14%, respectively.

Conclusions: Clinical and brain imaging features predictive of the presence of a CSF1R mutation are proposed. Consideration of these factors will help prioritize patients for CSF1R testing.

Keywords: adult-onset leukoencephalopathy with axonal spheroids and pigmented glia; colony-stimulating factor 1 receptor; diagnostic criteria; leukoencephalopathy; logistic regression.

Figure 1

The variables highly related to the presence of a colony‐stimulating factor 1 receptor (CSF1R) mutation and a logistic regression plot of the odds ratio and 95% confidence interval (CI). Only age at onset was a continuous variable, and the other variables were categorical variables answered with yes or no. CC, corpus callosum; y, years. *Including rigidity, bradykinesia, parkinsonian gait (small shuffling steps, freezing of gait, and falls), postural instability, masked face, resting tremor and responsiveness to L‐dopa.

Figure 2

(a) Relationship between the probability of a colony‐stimulating factor 1 receptor (CSF1R) mutation and three factors (thinning of the corpus callosum, parkinsonism and diffusion‐restricted lesions) that increase the probability. *Including rigidity, bradykinesia, parkinsonian gait (small shuffling steps, freezing of gait, and falls), postural instability, masked face, resting tremor and responsiveness to L‐dopa. (b) Relationship between the probability of a CSF1R mutation and thinning of the corpus callosum and two factors (brainstem or cerebellar atrophy and involuntary movements) that lower the probability.