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Case Report/Case Series |

Autoimmune Aquaporin-4 Myopathy in Neuromyelitis Optica Spectrum

Yong Guo, MD, PhD1; Vanda A. Lennon, MD, PhD1,2; Bogdan F. Gh. Popescu, MD, PhD1,3; Carrie Katherine Grouse, MD4; Jordan Topel, MD4; Margherita Milone, MD, PhD1; Hans Lassmann, MD5; Joseph E. Parisi, MD1,2; Sean J. Pittock, MD1,2; Dusan Stefoski, MD4; Roumen Balabanov, MD4; Claudia F. Lucchinetti, MD1
[+] Author Affiliations
1Department of Neurology, Mayo Clinic, Rochester, Minnesota
2Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
3Department Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
4Multiple Sclerosis Center, Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois
5Center for Brain Research, Medical University of Vienna, Vienna, Austria
JAMA Neurol. 2014;71(8):1025-1029. doi:10.1001/jamaneurol.2014.775.
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Importance  Documentation of muscle pathology compatible with targeting of sarcolemmal aquaporin-4 (AQP4) by complement-activating IgG implies involvement of organs beyond the central nervous system in neuromyelitis optica spectrum disorders.

Observations  We report on a 51-year-old woman who had relapsing optic neuritis, transverse myelitis, AQP4-IgG seropositivity, and recurrent myalgias with hyperCKemia. A muscle biopsy revealed scattered myofibers with internal nuclei, atrophy, and regeneration but no necrosis. Mild inflammatory exudates, in endomysial and perivascular spaces, consisted of lymphocytes, histiocytes, and scattered eosinophils. The sarcolemma exhibited loss of AQP4 and deposition of IgG and complement activation products, characteristics not seen in control biopsy samples of healthy muscle and immune-mediated myopathies.

Conclusions and Relevance  Recurrent hyperCKemia accompanying AQP4-IgG seropositivity reflects targeting of skeletal muscle AQP4 by pathogenic IgG. The entity of autoimmune AQP4 myopathy extends the neuromyelitis optica spectrum beyond the central nervous system.

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Figure 1.
Inflammatory Infiltration and AQP4 Loss in Skeletal Muscle of Case Patient With NMO

Mild endomysial and perivascular inflammation in the skeletal muscle (A-D) is evident in the case patient with neuromyelitis optica (NMO). The inflammation consists of lymphocytes (C) and eosinophils (D [arrows]), and scattered internalized nuclei can be seen as well (D [arrowheads]). Aquaporin-4 (AQP4) immunoreactivity is totally lost in the muscle lesions of the case patient with NMO (E and F), including regions of focal endomysial inflammation (E and F [arrowheads]). Dermatomyositis biopsy samples reveal perifascicular muscle atrophy with variable AQP4 immunoreactivity (G and H); AQP4 immunoreactivity is preserved in some sarcolemmal regions (G [arrowheads]), and cytoplasmic immunoreactivity is enhanced in scattered myofibers. In normal skeletal muscle, AQP4 immunoreactivity is abundant in the sarcolemma of most myofibers (I and J).

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Figure 2.
IgG and Complement Deposits in Skeletal Muscle of Case Patient With NMO

Sarcolemmal IgG (A [arrowhead]) and C9 neoantigen (B and C [arrowheads]) deposits are extensive in the skeletal muscle of the case patient with neuromyelitis optica (NMO). Dermatomyositis lesions exhibit cytoplasmic IgG (D [arrowhead]) and occasional sarcolemmal IgG in atrophic myofibers. Some atrophic myofibers in the dermatomyositis biopsy samples show cytoplasmic C9 neoantigen immunoreactivity (E and F [arrowheads]). In normal skeletal myofibers, IgG is confined to blood vessels in the endomysium and perimysium (G), and C9 neoantigen immunoreactivity is in proximity to scattered perimysial vessels (H and I).

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