Update in autoimmune and paraneoplastic myelopathies: Newly described antigen targets and antibody testing

Abstract

Myelopathy is an increasingly recognized presentation of many antibody-mediated neuroinflammatory disorders. While specific features of certain autoimmune myelopathies such as aquaporin-4 antibody associated neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein associated disorder (MOGAD) are well-characterized, other less commonly seen antibody-associated myelopathies are not as well-defined. These include but are not limited to, Hu/ANNA1, anti-glial fibrillary acidic protein (GFAP), anti-CV2/collapsin response mediator protein (CRMP5), and amphiphysin. Here, we review the mentioned more common antibody mediated myelopathies as well those that as less common, followed by a review of differentials that may mimic these disorders.

Keywords: MOG antibody associated diseases; NMO spectrum disorder (NMOSD); autoimmune manifestations; myelitis; myelopathy; paraneoplastic syndrome (PNS).

Figure 1

All images collected from cases seen at the Autoimmune and Neuroimmunology clinics at the University of Colorado. (a–d) AQP4-IgG positive 52-year-old woman with progressive limb weakness and sensory loss with MRI showing (a) sagittal confluent T2 hyperintensity with cord edema from C2 to T1, (b) axial central predominant T2 hyperintense lesion, (c) sagittal ring-enhancement pattern from C3 to C5, and (d) Axial ring enhancement pattern with central and lateral involvement. (e–h) MOG IgG positive 12-year-old-girl with gait abnormality and mild lower extremity weakness with MRI showing (e) sagittal T2 hyperintensity with mild cord edema from C4 to C7, (f) axial gray matter T2 hyperintensity with appearance of an “H” sign, (g) sagittal T2 hyperintensity of the conus medullaris, and (h) Axial subtle symmetric central T2 hyperintensity. (i–n) CRMP5 IgG positive 54-year-old woman with paraplegia, found to have a neuroendocrine carcinoma suggestive of thymus or small cell lung origin and MRI with (i) sagittal T2 hyperintensity with cord swelling from C2 to T1, (j) axial posterior and lateral T2 hyperintensity, (k) sagittal dorsal subpial contrast enhancement from C2 through T1, (l) axial anterior, lateral, and dorsal subpial contrast enhancement, (m) sagittal T2 hyperintensity from T1 to T11, and (n) axial central predominant T2 hyperintensity. (o–t) GFAP IgG positive 63 year old woman with subacute progressive encephalomyelitis with no underlying malignancy and MRI findings of (o) sagittal patchy, extensive ventral T2 hyperintense lesions from the craniocervical junction to C7, (p) Axial ventral T2 hyperintensity, (q) sagittal dorsal and central enhancement at the margin of the craniocervical junction as well as ventral enhancement at the margin of the cord at C3 and C6, (r) axial dorsal and ventral subpial enhancement, (s) sagittal diffuse enhancement of the ventral and dorsal margins of the distal thoracic cord from T8 to T11, and (t) axial ventral subpial enhancement.