MRI comparison between hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and primary progressive multiple sclerosis (PPMS)

Abstract

Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is an autosomal dominant inherited leukoencephalopathy characterized by numerous cerebral neuroaxonal spheroids. To date, detection of colony stimulating factor 1 receptor (CSF-1R) gene mutation in HDLS gave us hint to think its pathophysiology as a microglial dysfunction, so called "primary microgliopathy". Clinical features of HDLS are variable. Typically, psychiatric symptoms and cognitive decline are initial features of HDLS. However, in some cases, when motor symptoms precede cognitive decline, HDLS may mimic primary progressive multiple sclerosis (PPMS). Herein we tried to clarify MRI features of HDLS (2 women, age 22-28 years, average 25.0 years, EDSS 7.00) in comparison with PPMS (6 men and 10 women, age 29-64 years, average 33.7 years, EDSS 6.03). In consequence, our MRI findings suggesting HDLS rather than PPMS are as follows: restricted diffusivity, severe corpus callosum atrophy, and preferential involvement of deep white matter lesion compared with periventricular white matter. In contrast, characteristic features suggesting PPMS are as follows: prevailing periventricular white matter lesion, cerebellar lesions, optic neuritis, and cervical spinal cord lesion. Sagittal fluidattenuated inversion recovery (FLAIR) images of brain and cervical cord are highly useful to discriminate these two diseases.