Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease: Lesion staging and dynamic changes of axons and microglial subsets

Kiyomitsu Oyanagi, Michiaki Kinoshita, Emi Suzuki-Kouyama, Teruhiko Inoue, Asa Nakahara, Mika Tokiwai, Nobutaka Arai, Jun Ichi Satoh, Naoya Aoki, Kenji Jinnai, Ikuru Yazawa, Kimihito Arai, Kenji Ishihara, Mitsuru Kawamura, Keisuke Ishizawa, Kazuko Hasegawa, Saburo Yagisita, Naoji Amano, Kunihiro Yoshida, Seishi TeradaMari Yoshida, Haruhiko Akiyama, Yoshio Mitsuyama, Shu Ichi Ikeda

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
JournalBrain Pathology
DOIs
Publication statusAccepted/In press - 2017

Fingerprint

Leukoencephalopathies
Neuroglia
Axons
Dilatation
Lateral Ventricles
Microglia
Cerebellum
Brain Stem
Atrophy
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy
Internal Capsule
Third Ventricle
Cell Shape
Epilepsy
Cell Count
White Matter

Keywords

  • ALSP
  • Hakola
  • HDLS
  • Lesion staging
  • Microglia
  • Nasu

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)
  • Clinical Neurology

Cite this

Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease : Lesion staging and dynamic changes of axons and microglial subsets. / Oyanagi, Kiyomitsu; Kinoshita, Michiaki; Suzuki-Kouyama, Emi; Inoue, Teruhiko; Nakahara, Asa; Tokiwai, Mika; Arai, Nobutaka; Satoh, Jun Ichi; 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, Shu Ichi.

In: Brain Pathology, 2017.

Research output: Contribution to journalArticle

Oyanagi, K, Kinoshita, M, Suzuki-Kouyama, E, Inoue, T, Nakahara, A, Tokiwai, M, Arai, N, Satoh, JI, Aoki, N, Jinnai, K, Yazawa, I, Arai, K, Ishihara, K, Kawamura, M, Ishizawa, K, Hasegawa, K, Yagisita, S, Amano, N, Yoshida, K, Terada, S, Yoshida, M, Akiyama, H, Mitsuyama, Y & Ikeda, SI 2017, 'Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease: Lesion staging and dynamic changes of axons and microglial subsets', Brain Pathology. https://doi.org/10.1111/bpa.12443
Oyanagi, Kiyomitsu ; Kinoshita, Michiaki ; Suzuki-Kouyama, Emi ; Inoue, Teruhiko ; Nakahara, Asa ; Tokiwai, Mika ; Arai, Nobutaka ; Satoh, Jun Ichi ; 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, Shu Ichi. / Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease : Lesion staging and dynamic changes of axons and microglial subsets. In: Brain Pathology. 2017.
@article{2adc7f797cb442c1b757095924237631,
title = "Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease: Lesion staging and dynamic changes of axons and microglial subsets",
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.",
keywords = "ALSP, Hakola, HDLS, Lesion staging, Microglia, Nasu",
author = "Kiyomitsu Oyanagi and Michiaki Kinoshita and Emi Suzuki-Kouyama and Teruhiko Inoue and Asa Nakahara and Mika Tokiwai and Nobutaka Arai and Satoh, {Jun Ichi} and Naoya Aoki and Kenji Jinnai and Ikuru Yazawa and Kimihito Arai and Kenji Ishihara and Mitsuru Kawamura and Keisuke Ishizawa and Kazuko Hasegawa and Saburo Yagisita and Naoji Amano and Kunihiro Yoshida and Seishi Terada and Mari Yoshida and Haruhiko Akiyama and Yoshio Mitsuyama and Ikeda, {Shu Ichi}",
year = "2017",
doi = "10.1111/bpa.12443",
language = "English",
journal = "Brain Pathology",
issn = "1015-6305",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease

T2 - Lesion staging and dynamic changes of axons and microglial subsets

AU - Oyanagi, Kiyomitsu

AU - Kinoshita, Michiaki

AU - Suzuki-Kouyama, Emi

AU - Inoue, Teruhiko

AU - Nakahara, Asa

AU - Tokiwai, Mika

AU - Arai, Nobutaka

AU - Satoh, Jun Ichi

AU - Aoki, Naoya

AU - Jinnai, Kenji

AU - Yazawa, Ikuru

AU - Arai, Kimihito

AU - Ishihara, Kenji

AU - Kawamura, Mitsuru

AU - Ishizawa, Keisuke

AU - Hasegawa, Kazuko

AU - Yagisita, Saburo

AU - Amano, Naoji

AU - Yoshida, Kunihiro

AU - Terada, Seishi

AU - Yoshida, Mari

AU - Akiyama, Haruhiko

AU - Mitsuyama, Yoshio

AU - Ikeda, Shu Ichi

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - ALSP

KW - Hakola

KW - HDLS

KW - Lesion staging

KW - Microglia

KW - Nasu

UR - http://www.scopus.com/inward/record.url?scp=85014249759&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85014249759&partnerID=8YFLogxK

U2 - 10.1111/bpa.12443

DO - 10.1111/bpa.12443

M3 - Article

C2 - 27608278

AN - SCOPUS:85014249759

JO - Brain Pathology

JF - Brain Pathology

SN - 1015-6305

ER -