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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\u2010HD, 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\u2010HD, 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\u20101\u2010, CD68\u2010, CD163\u2010 and CD204\u2010immunopositive cells precedes loss of axons in ALSP.<\/jats:p>","DOI":"10.1111\/bpa.12443","type":"journal-article","created":{"date-parts":[[2016,9,8]],"date-time":"2016-09-08T14:47:55Z","timestamp":1473346075000},"page":"748-769","source":"Crossref","is-referenced-by-count":52,"title":["Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and <scp>N<\/scp>asu\u2013<scp>H<\/scp>akola disease: lesion staging and dynamic changes of axons and microglial subsets"],"prefix":"10.1111","volume":"27","author":[{"given":"Kiyomitsu","family":"Oyanagi","sequence":"first","affiliation":[{"name":"Division of Neuropathology, Department of Brain Disease Research Shinshu University School of Medicine Nagano Japan"},{"name":"Brain Research Laboratory Hatsuishi 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