Transient hyperckemia in the setting of neuromyelitis optica (NMO)

Abstract

Introduction: Neuromyelitis optica (NMO) is characterized by inflammatory demyelinating lesions of the spinal cord and optic nerves from an autoimmune response against water channel aquaporin-4 (AQP4). We report 2 patients with transient hyperCKemia associated with NMO suggesting possible skeletal muscle damage.

Methods: Patient 1 was a 72-year-old man who presented with muscle soreness and elevated serum creatine kinase (CK) preceding an initial attack of NMO. Patient 2 was a 25-year-old woman with an established diagnosis of NMO who presented with diffuse myalgias, proximal upper extremity weakness, and hyperCKemia. Muscle biopsies were obtained for histopathologic evaluation, protein gel electrophoresis, immunofluorescence, and complement staining.

Results: In both patients the muscle showed only mild variation in fiber diameter. There were no inflammatory changes or muscle fiber necrosis, though there was reduced AQP4 expression and deposition of activated complement.

Conclusions: Complement-mediated sarcolemmal injury may lead to hyperCKemia in NMO.

Keywords: aquaporin 4; creatine kinase; hyperCKemia; immunofluorescence; neuromyelitis optica.

FIGURE 1

Sagittal T2-weighted image of the cervical spine (patient 2) demonstrating T2 prolongation in the cord from C3 to T2. There was focal enhancement at the C5 level (not shown).

FIGURE 2

H&E stain (patient 1). There is mild variation of muscle fiber diameter. Notably, no degenerating or regenerating fibers are seen, and there is no inflammatory infiltrate.

FIGURE 3

(A) AQP4 Immunofluorescence (top row, green) showing decreased AQP4 immunoreactivity on the muscle plasma membrane. (B) Human IgG binding detected with antihuman secondary antibody (middle, red), in patient 2. (C) C5b9/membrane attack complex immunofluorescence (bottom, green) showing sarcolemmal staining in both patients.

FIGURE 4

AQP4 immunoblot following SDS-PAGE (A) showing reduced AQP4 protein expression and BN-PAGE (B) of indicated muscle homogenates demonstrating relatively greater AQP4 supramolecular aggregates in the NMO patient biopsies.