MRI characteristics and scoring in HDLS due to CSF1R gene mutations

Abstract

Objective: To describe the brain MRI characteristics of hereditary diffuse leukoencephalopathy with spheroids (HDLS) with known mutations in the colony-stimulating factor 1 receptor gene (CSF1R) on chromosome 5. Methods:We reviewed 20 brain MRI scans of 15 patients with autopsy-or biopsy-verified HDLS and CSF1R mutations. We assessed sagittal T1-, axial T1-, T2-, proton density-weighted and axial fluid-attenuated inversion recovery images for distribution of white matter lesions (WMLs), gray matter involvement, and atrophy. We calculated a severity score based on a point system (0Ϫ57) for each MRI scan. Results:Of the patients, 93% (14 of 15) demonstrated localized WMLs with deep and subcortical involvement, whereas one patient revealed generalized WMLs. All WMLs were bilateral but asymmetric and predominantly frontal. Fourteen patients had a rapidly progressive clinical course with an initial MRI mean total severity score of 16.7 points (range 10Ϫ33.5). Gray matter pathology and brainstem atrophy were absent, and the corticospinal tracts were involved late in the disease course. There was no enhancement, and there was minimal cerebellar pathology. Conclusion:Recognition of the typical MRI patterns of HDLS and the use of an MRI severity score might help during the diagnostic evaluation to characterize the natural history and to monitor potential future treatments. Indicators of rapid disease progression were symptomatic disease onset before 45 years, female sex, WMLs extending beyond the frontal regions, a MRI severity score greater than 15 points, and mutation type of deletion. Neurology ® 2012;79:566-574 GLOSSARY CI ϭ confidence interval; CSF1R ϭ colony-stimulating factor 1 receptor; FLAIR ϭ fluid-attenuated inversion recovery; HDLS ϭ hereditary diffuse leukoencephalopathy with spheroids; MLD ϭ metachromatic leukodystrophy; MS ϭ multiple sclerosis; SI ϭ signal intensity; WM ϭ white matter; WNL ϭ white matter lesion; X-ALD ϭ X-linked adrenoleukodystrophy.

Hereditary Diffuse Leukoencephalopathy with Spheroids Characterized by Spastic Hemiplegia Preceding Mental Impairment

“…Bifrontoparietal areas of T2/FLAIR hyperintensity are often asymmetric, especially in the early stage of the disease. The presence of lesions in deep, subcortical and periventricular areas is typical, with occasional involvement of the corticospinal tract and corpus callosum (12). Most of the MRI abnormalities observed in our case, including the presence of T2/FLAIR abnormalities in periventricular lesions, the corticospinal tract and the corpus callosum without contrast enhancement, are compatible with the well-documented radiological characteristics of this disease.…”

“…Generally, the brain MRI findings of HDLS patients show white matter lesions that are hyperintense on T2-weighted and FLAIR images and hypointense on T1-weighted images unaccompanied by contrast uptake (12). Bifrontoparietal areas of T2/FLAIR hyperintensity are often asymmetric, especially in the early stage of the disease.…”

Corpus Callosum Atrophy in Patients with Hereditary Diffuse Leukoencephalopathy with Neuroaxonal Spheroids: An MRI-based Study

“…The CC involvement included atrophy (eight patients), T2 and FLAIR high signal intensity (11 patients) and both atrophy and signal changes in the CC (five patients) (3). These data appear to indicate that hyperintense signals and atrophy in the CC are not correlated with each other.…”

Diagnostic criteria for adult‐onset leukoencephalopathy with axonal spheroids and pigmented glia due to CSF1R mutation

“…Thinning of the corpus callosum is characteristic of ALSP [9] and, thus, we included it in a parameter of 'probable.' Of the 29 cases from the literature that fulfilled the 'possible' criteria, information about the corpus callosum was not obtained in 17 cases.…”

“…Frontal and parietal lobe predominance is observed with involvement of the periventricular deep white matter and dilation of the lateral ventricles. Thinning of the corpus callosum with signal abnormalities is observed even in the early stages of the disease [9,11]. Fluid-attenuated inversion recovery sagittal imaging is recommended to evaluate changes in the corpus callosum.…”