Open AccessAdult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and N asu– H akola disease: lesion staging and dynamic changes of axons and microglial subsets
Author(s) -
Oyanagi Kiyomitsu,
Kinoshita Michiaki,
SuzukiKouyama Emi,
Inoue Teruhiko,
Nakahara Asa,
Tokiwai Mika,
Arai Nobutaka,
Satoh Junichi,
Aoki Naoya,
Jinnai Kenji,
Yazawa Ikuru,
Arai Kimihito,
Ishihara Kenji,
Kawamura Mitsuru,
Ishizawa Keisuke,
Hasegawa Kazuko,
Yagisita Saburo,
Amano Naoji,
Yoshida Kunihiro,
Terada Seishi,
Yoshida Mari,
Akiyama Haruhiko,
Mitsuyama Yoshio,
Ikeda Shuichi
Publication year - 2017
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12443
Subject(s) - axon , white matter , leukoencephalopathy , pathology , atrophy , brainstem , lesion , cerebral atrophy , cerebellum , internal capsule , microglia , anatomy , medicine , biology , neuroscience , magnetic resonance imaging , disease , inflammation , radiology
Abstract The brains of 10 Japanese patients with adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) encompassing hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD) and eight Japanese patients with Nasu–Hakola disease (N‐HD) and five age‐matched Japanese controls were examined neuropathologically with special reference to lesion staging and dynamic changes of microglial subsets. In both diseases, the pathognomonic neuropathological features included spherically swollen axons (spheroids and globules), axon loss and changes of microglia in the white matter. In ALSP, four lesion stages based on the degree of axon loss were discernible: Stage I, patchy axon loss in the cerebral white matter without atrophy; Stage II, large patchy areas of axon loss with slight atrophy of the cerebral white matter and slight dilatation of the lateral ventricles; Stage III, extensive axon loss in the cerebral white matter and dilatation of the lateral and third ventricles without remarkable axon loss in the brainstem and cerebellum; Stage IV, devastated cerebral white matter with marked dilatation of the ventricles and axon loss in the brainstem and/or cerebellum. Internal capsule and pontine base were relatively well preserved in the N‐HD, even at Stage IV, and the swollen axons were larger with a higher density in the ALSP. Microglial cells immunopositive for CD68, CD163 or CD204 were far more obvious in ALSP, than in N‐HD, and the shape and density of the cells changed in each stage. With progression of the stage, clinical symptoms became worse to apathetic state, and epilepsy was frequently observed in patients at Stages III and IV in both diseases. From these findings, it is concluded that (i) shape, density and subsets of microglia change dynamically along the passage of stages and (ii) increase of IBA‐1‐, CD68‐, CD163‐ and CD204‐immunopositive cells precedes loss of axons in ALSP.