MOG-Ab seropositivity is much more common in the pediatric population and it predicts a better prognosis than MS or AQP4+NMOSD, except in the subset that exhibit a recurrent phenotype.
MOG-abs can be found in acute disseminated encephalomyelitis (ADEM), transverse myelitis, isolated optic neuritis (ON), or recurrent demyelinating diseases, such as multiphasic neuromyelitis optica spectrum disorders (NMOSD) without aquaporin-4 (AQP4) abs or multiphasic ADEM (MDEM), but rarely in children who subsequently develop multiple sclerosis (MS).
MOG-IgG was absent in 221 further controls, including 83 patients with AQP4-IgG-seropositive neuromyelitis optica spectrum disorders and 85 with multiple sclerosis (MS).
Most multiple sclerosis disease-modifying agents are ineffective for AQP4-IgG-positive neuromyelitis optica spectrum disorder and MOG-IgG-associated disorder.
Most experts now consider MOG-IgG-associated encephalomyelitis (MOG-EM) a disease entity in its own right, immunopathogenetically distinct from both classic multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorders (NMOSD).
Myelin-specific MS antibodies cause oligodendrocyte loss and demyelination in organotypic cerebellar slices, which are distinct from AQP4-targeted pathology, and display seminal features of active MS lesions.
Of the 65 patients with PLICL, 46 patients had NMOSD (70.8%) and were positive for anti-aquaporin (AQP4-IgG), four had NMOSD (6.2%) and were AQP4-IgG negative, 10 patients had multiple sclerosis (MS), three patients had NMDAR encephalitis, and two had autoimmune meningoencephalitis.
Our findings suggest that astrocytic impairment associated with humoral immunity against AQP4 may be primarily involved in the lesion formation of NMO, and that the pathomechanisms of NMO are different from those of MS in which demyelination is the primary pathology.
Our present and previous findings suggest that antibody-independent AQP4 loss can occur in heterogeneous demyelinating conditions, including NMO, Baló's disease and MS.
Some diseases, now recognized as conditions distinct from multiple sclerosis, may satisfy the MRI criteria for multiple sclerosis (e.g. neuromyelitis optica spectrum disorders, Susac syndrome), thus making the diagnosis of multiple sclerosis more challenging, especially if biomarker testing (such as serum anti-AQP4 antibodies) is not informative.
The aim of this study was to investigate whether patients with pattern I MS differ from patients with pattern II or III MS with regard to cerebrospinal fluid (CSF) findings, especially with reference to intrathecal IgG synthesis, which is found in most patients with MS but is frequently missing in MS mimics such as aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein-IgG-positive encephalomyelitis.
The CS-SCA at C2/C3, C3/C4, T8/T9 and T9/T10 vertebral disc levels was measured in 140 MS patients (111 with relapsing-remitting MS and 29 with progressive MS) and 42 NMOSD patients with anti-aquaporin-4 immunoglobulin G. Disability was evaluated by Expanded Disability Status Scale (EDSS) scores.
The CSF cytokine profile in the acute phase of MOG-IgG+ disease is characterised by coordinated upregulation of T helper 17 (Th17) and other cytokines including some Th1-related and regulatory T cells-related ones in adults and children, which is similar to AQP4-IgG+ NMOSD but clearly different from MS.
The detection of IgG aquaporin-4 antibodies in the serum of patients with Neuromyelitis optica (NMO) has dramatically improved the diagnosis of this disease and its distinction from multiple sclerosis.
The discovery of IgG-NMO, a specific pathogenic antibody directed against the astrocytic water channel aquaporin-4 (AQP4), has improved the differential diagnoses between MS and NMOSD.
The identification of activated T-lymphocytes restricted to myelin-derived immunogenic peptides in multiple sclerosis (MS) and aquaporin-4 water channel in neuromyelitis optica (NMO) in the blood of patients opened the possibility for developing highly selective and disease-specific therapeutic approaches.