Recurrent hyperCKemia with normal muscle biopsy in a pediatric patient with neuromyelitis optica

Franciotta, Diego; Massa, Roberto; Gregorio, Maria Di; Zardini, Elisabetta; Gastaldi, Matteo; Terracciano, Chiara; Rastelli, Emanuele; Gaetani, Lorenzo; Iannone, Alessia; Menduno, Paola; Floridi, Piero; Sarchielli, Paola; Calabresi, Paolo

doi:10.1212/wnl.0b013e3182698d39

Cited by 27 publications

(25 citation statements)

References 6 publications

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“…In a retrospective study by Suzuki and colleagues, 3 patients with generalized fatigue were noted to have significant, transient, hyperCKemia preceding the onset of optic neuritis . Subsequently, other reports documented an elevation in CK preceding NMO attacks as well as in isolation . AQP4 expression has been shown to be greatly reduced in Duchenne and Becker muscular dystrophies, sarcoglycanopathies, and dysferlinopathies .…”

Section: Discussionmentioning

confidence: 98%

Transient hyperckemia in the setting of neuromyelitis optica (NMO)

et al. 2014

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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.

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Section: Discussionmentioning

confidence: 98%

Transient hyperckemia in the setting of neuromyelitis optica (NMO)

et al. 2014

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“…There are three case reports of AQP4 antibody seropositive NMO patients who developed hyperCKemia during the two weeks before the onset of CNS symptoms (i.e. hiccup, optic neuritis, or myelitis), and 2 of the three cases had interstitial pneumonia (17, 18, 34, 99, 116). The pathogenic role of AQP4 antibody outside the CNS however remains unclear.…”

Section: Nmo Pathology Outside Cnsmentioning

confidence: 99%

The Pathology of an Autoimmune Astrocytopathy: Lessons Learned from Neuromyelitis Optica

et al. 2013

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Neuromyelitis optica (NMO) is a disabling autoimmune astrocytopathy characterized by typically severe and recurrent attacks of optic neuritis and longitudinally-extensive myelitis. Until recently, NMO was considered an acute aggressive variant of multiple sclerosis (MS), despite the fact that early studies postulated that NMO and MS may be two distinct diseases with a common clinical picture. With the discovery of a highly specific serum autoantibody (NMO-IgG), Lennon and colleagues provided the first unequivocal evidence distinguishing NMO from MS and other CNS inflammatory demyelinating disorders. The target antigen of NMO-IgG was confirmed to be aquaporin-4 (AQP4), the most abundant water channel protein in the central nervous system (CNS), mainly expressed on astrocytic foot processes at the blood brain barrier, subpial and subependymal regions. Pathological studies demonstrated that astrocytes were selectively targeted in NMO as evidenced by the extensive loss of immunoreactivities for the astrocytic proteins, AQP4 and glial fibrillary acidic protein (GFAP), as well as perivascular deposition of immunoglobulins and activation of complement even within lesions with a relative preservation of myelin. In support of these pathological findings, GFAP levels in the cerebrospinal fluid (CSF) during acute NMO exacerbations were found to be remarkably elevated in contrast to MS where CSF-GFAP levels did not substantially differ from controls. Additionally, recent experimental studies showed that AQP4 antibody is pathogenic, resulting in selective astrocyte destruction and dysfunction in vitro, ex vivo, and in vivo. These findings strongly suggest that NMO is an autoimmune astrocytopathy where damage to astrocytes exceeds both myelin and neuronal damage. This chapter will review recent neuropathological studies that have provided novel insights into the pathogenic mechanisms, cellular targets, as well as the spectrum of tissue damage in NMO.

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“…Importantly, GABA A R are not only expressed in astroglial SEZ cells, but in general in adult astrocytes [25], the cell class most strongly expressing AQP4 in the CNS and the one mainly damaged by AQP4-IgG in NMO. We therefore recommend using GABA A R agonists in patients with NMO with caution, in particular during acute attacks, until an effect similar to that observed by Li et al can be excluded in the human brain (as well as in AQP4-expressing extra-CNS cells potentially targeted by AQP4-IgG [5,[26][27][28][29][30][31][32]). …”

Section: Hypothesismentioning

confidence: 90%