Different lesion types in the central nervous system of NMO patients []: a–c lesion type 3 represents areas of Wallerian degeneration; myelin sheaths (a) and axons (b) are lost in comparable degree; there is profound astrocytic gliosis (c); the astrocytes express GFAP and AQP1 and 4; (patient 499, spinal cord) ×30. d–g Lesion type 4 shows selective loss of AQP4 (e), while myelin sheaths (d), axons and neurons remain preserved; reactive astrocytes express GFAP (g) and AQP1 (f); some astrocytes also show granular intra-cytoplasmic reactivity for AQP4 (e, insert); (patient 499 spinal cord), ×250; insert: ×1,100. h–q lesion type 5 shows extensive loss of astrocytes (h) and astrocytic clasmatodendrosis (l–q), while myelin sheaths (i) and axons are preserved; there is profound macrophage infiltration (k), but no deposition of activated complement or granulocyte infiltration (j); astrocyte clasmatodendrosis is characterized by enlargement or peri-nuclear astrocyte cytoplasm and clumping and beading of cell processes (l–q), granular internalization of AQP1 (n), AQP4 (l, m) and IgG (p) and condensed nuclei (m, n, p) with DNA fragmentation (apoptosis; q); h–k (patient 216, medulla); ×50; l–q ×1,100. r–y Lesion type 6 is characterized by selective primary demyelination (r), axonal preservation (s), profound astrocytic gliosis (t) and a variable expression of AQP4 (u). AQP4 is lost in adjacent areas, which show features of complement-mediated active tissue destruction (adjacent lesion 1; Fig. a) or a destructive lesion pattern 2 (adjacent lesion 2, Fig. a); active demyelination is associated with macrophage infiltration (v); astrocytes show partial loss of AQP4 (y) and AQP1 (w) and some astrocytes with clasmatodendrosis (x, y); r–u (patient 499, spinal cord); ×20; v–y ×150