Inflammatory demyelination without astrocyte loss in MOG antibody–positive NMOSD

Abstract

We report a patient with neuromyelitis optica spectrum disorder (NMOSD) with antibodies against myelin oligodendrocyte protein (MOG) and seronegative for aquaporin-4 (AQP4) presenting with relapsingremitting longitudinally extensive transverse myelitis (LETM) and cerebral tumefactive demyelinating lesions. Neuropathology showed active inflammatory demyelination with relative preservation of astrocytes.Case report. A 67-year-old woman with a history of hypothyroidism presented with 2 distinct symptomatic episodes of LETM. At initial presentation she had a T10 dissociated sensory level, sensory ataxia, and sphincter dysfunction, from which she recovered spontaneously. One month later, she presented with burning upper limb and thoracic pain, right lower limb weakness, and sphincter dysfunction. Initial spinal MRI showed a continuous T2-hyperintense central cord lesion from T2 to T9 with mild cord expansion and patchy enhancement; MRI 1 month later showed a new central cord T2 hyperintensity from C5 to T3 (figure, A and B). CSF examination was bland, with matched CSF/serum oligoclonal bands. AQP4 antibodies were negative. She made an almost complete recovery after 3 days of IV methylprednisolone, then oral prednisone 50 mg daily tapered over 5 weeks.Five months later, the patient presented to our institution with dysarthria and left facial weakness, rapidly progressing within 24 hours to left hemiparesis, lower limb flaccid paraparesis with extensor plantar responses, and a dissociated T10 sensory level. Brain MRI revealed 3 ill-defined white matter lesions in the right cerebral hemisphere (frontal corona radiata, posterior parietal lobe, and temporal pole), sparing the cortex, associated with extensive vasogenic edema, patchy enhancement, and peripheral concentric diffusion restriction. A few small lesions in the left hemispheric white matter and the right pons were also noted. Spinal MRI showed new T2 hyperintensity from T12 to the conus (figure, C-E). Visual evoked potentials were normal. Extensive blood investigations were normal or negative, including HIV and syphilis serology, serum angiotensin converting enzyme level, and vasculitic markers. Repeat testing for AQP4 antibodies was negative.Due to concerns of a neoplastic process, biopsy of the right frontal lesion was undertaken.Histology showed a sharply demarcated lesion, with macrophage-rich active inflammatory demyelination, with prominent loss of myelin, but relative preservation of axons (figure, Q-S). Immunostaining with glial fibrillary acid protein (GFAP) confirmed reactive astrocytes within and surrounding the lesion (figure J, O, and T). In the demyelinated white matter, there were dense perivascular cuffs of small T lymphocytes and fewer B lymphocytes. Immunostaining for SV40 (surrogate marker for JC virus infection) was negative.A cell-based assay using C-terminal-truncated human MOG later identified antibodies against full/ short-length MOG, including the more specific immunoglobulin G1 (IgG1) assay.1 After treatment with IV methylprednisolone, p...

HLA association in MOG-IgG– and AQP4-IgG–related disorders of the CNS in the Dutch population

“…39 Additionally to these immunologic studies, histopathologic findings from MOG-IgGseropositive patients show activated complement at sites of ongoing demyelinating. 39,46,47 This again supports a humoral immune pathogenesis and a potential pathogenic activity of human MOG-IgG.…”

Chronic relapsing inflammatory optic neuropathy (CRION): a manifestation of myelin oligodendrocyte glycoprotein antibodies

“…Cell-based assays for MOG-IgG were rarely positive in multiple sclerosis or NMOSD-AQP4-IgG [ 11 ]. The clinical, radiological, and pathological findings of MOG-IgG-associated disorders were distinct from those with multiple sclerosis or NMOSD-AQP-IgG [ 4 , 20 , 25 ]. The MOG-IgG titers were related with disease course, which may be helpful for predicting the prognosis of disease [ 24 ].…”

Inflammatory demyelinating diseases of the central nervous system

“…Neuropathology of MOG-antibody associated demyelination has been described in a few patients with relapsing remitting MS, atypical demyelination, clinically isolated syndrome, ADEM, and NMOSD (Table 19.3) (Konig et al, 2008;Di Pauli et al, 2015;Spadaro et al, 2015;Jarius et al, 2016a;Wang et al, 2016). Irrespective of the clinical nosology, all cases showed demyelinating features of MS pattern 2, with well-demarcated…”