Pathologic basis of the preferential thinning of thecorpus callosum in adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP)

Michiaki Kinoshita; Kiyomitsu Oyanagi; Yasufumi Kondo; Keisuke Ishizawa; Kenji Ishihara; Mari Yoshida; Teruhiko Inoue; Yoshio Mitsuyama; Kunihiro Yoshida; Mitsunori Yamada; Yoshiki Sekijima; Shu-Ichi Ikeda

doi:10.1016/j.ensci.2021.100310

Pathologic basis of the preferential thinning of thecorpus callosum in adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP)

eNeurologicalSci. 2021 Jan 22:22:100310. doi: 10.1016/j.ensci.2021.100310. eCollection 2021 Mar.

Authors

Affiliations

¹ Department of Neurology, Suwa Red Cross Hospital, 5-11-50 Kogandori, Suwa 392-8510, Japan.
² Division of Neuropathology, Department of Brain Disease Research, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
³ Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
⁴ Departments of Neurology and Pathology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan.
⁵ Department of Internal Medicine, Ushioda General Hospital, 1-6-20 Yako, Tsurumi-ku, Yokohama 230-0001, Japan.
⁶ Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, 480-1195, Japan.
⁷ Psychogeriatric Center, Daigo Hospital, 1270 Nagata, Mimata-chou, Kitamorokata-gun, Miyazaki 889-1911, Japan.
⁸ Division of Neurogenetics, Department of Brain Disease Research, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
⁹ Intractable Disease Care Center, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto 390-8621, Japan.

Abstract

Background: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is an early onset dementia characterized by axonal loss in the cerebral white matter with swollen axons (spheroids). It had been reported that the preferential thinning and "focal lesions" of the corpus callosum were observed on T2-weighted MRI in ALSP patients. The present study aimed to reveal the pathologic basis of them in relation to brain lesion staging (I ~ IV: Oyanagi et al. 2017).

Methods: Seven autopsied brains of ALSP and five controls were neuropathologically examined.

Results: Even at Stage I, corpus callosum body showed evident atrophy, and the atrophy advanced with stage progression. Spheroid size and density were maximal at Stage II in both centrum semiovale and corpus callosum body, but spheroids were larger in corpus callosum body than in centrum semiovale. Microglia in the body at Stage II had a larger cytoplasm than those in centrum semiovale. But spheroids and microglia in the "focal lesions" were identical with those of centrum semiovale.

Conclusion: Preferential thinning of corpus callosum was considered to be formed in relation to peculiar morphological alteration of microglia there in ALSP. Instead, "focal lesions" were formed in connection with the lesions in centrum semiovale.

Keywords: ALSP; CSF1R; Corpus callosum; HDLS; Lesion staging; Microglia.