2 research outputs found
Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin
Background Antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) have
been suggested to play a role in a subset of patients with neuromyelitis
optica and related disorders. Objective To assess (i) the frequency of MOG-IgG
in a large and predominantly Caucasian cohort of patients with optic neuritis
(ON) and/or myelitis; (ii) the frequency of MOG-IgG among AQP4-IgG-positive
patients and vice versa; (iii) the origin and frequency of MOG-IgG in the
cerebrospinal fluid (CSF); (iv) the presence of MOG-IgG at disease onset; and
(v) the influence of disease activity and treatment status on MOG-IgG titers.
Methods 614 serum samples from patients with ON and/or myelitis and from
controls, including 92 follow-up samples from 55 subjects, and 18 CSF samples
were tested for MOG-IgG using a live cell-based assay (CBA) employing full-
length human MOG-transfected HEK293A cells. Results MOG-IgG was detected in 95
sera from 50 patients with ON and/or myelitis, including 22/54 (40.7%)
patients with a history of both ON and myelitis, 22/103 (21.4%) with a history
of ON but no myelitis and 6/45 (13.3%) with a history of longitudinally
extensive transverse myelitis but no ON, and in 1 control patient with
encephalitis and a connective tissue disorder, all of whom were negative for
AQP4-IgG. 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). MOG-IgG was found in 12/18 (67%) CSF samples from
MOG-IgG-seropositive patients; the MOG-IgG-specific antibody index was
negative in all cases, indicating a predominantly peripheral origin of CSF
MOG-IgG. Serum and CSF MOG-IgG belonged to the complement-activating IgG1
subclass. MOG-IgG was present already at disease onset. The antibodies
remained detectable in 40/45 (89%) follow-up samples obtained over a median
period of 16.5 months (range 0–123). Serum titers were higher during attacks
than during remission (p < 0.0001), highest during attacks of simultaneous
myelitis and ON, lowest during acute isolated ON, and declined following
treatment. Conclusions To date, this is the largest cohort studied for IgG to
human full-length MOG by means of an up-to-date CBA. MOG-IgG is present in a
substantial subset of patients with ON and/or myelitis, but not in classical
MS. Co-existence of MOG-IgG and AQP4-IgG is highly uncommon. CSF MOG-IgG is of
extrathecal origin. Serum MOG-IgG is present already at disease onset and
remains detectable in the long-term course. Serum titers depend on disease
activity and treatment status
Epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome
Background A subset of patients with neuromyelitis optica spectrum disorders
(NMOSD) has been shown to be seropositive for myelin oligodendrocyte
glycoprotein antibodies (MOG-IgG). Objective To describe the epidemiological,
clinical, radiological, cerebrospinal fluid (CSF), and electrophysiological
features of a large cohort of MOG-IgG-positive patients with optic neuritis
(ON) and/or myelitis (n = 50) as well as attack and long-term treatment
outcomes. Methods Retrospective multicenter study. Results The sex ratio was
1:2.8 (m:f). Median age at onset was 31 years (range 6-70). The disease
followed a multiphasic course in 80% (median time-to-first-relapse 5 months;
annualized relapse rate 0.92) and resulted in significant disability in 40%
(mean follow-up 75 ± 46.5 months), with severe visual impairment or functional
blindness (36%) and markedly impaired ambulation due to paresis or ataxia
(25%) as the most common long-term sequelae. Functional blindness in one or
both eyes was noted during at least one ON attack in around 70%. Perioptic
enhancement was present in several patients. Besides acute tetra-/paraparesis,
dysesthesia and pain were common in acute myelitis (70%). Longitudinally
extensive spinal cord lesions were frequent, but short lesions occurred at
least once in 44%. Fourty-one percent had a history of simultaneous ON and
myelitis. Clinical or radiological involvement of the brain, brainstem, or
cerebellum was present in 50%; extra-opticospinal symptoms included
intractable nausea and vomiting and respiratory insufficiency (fatal in one).
CSF pleocytosis (partly neutrophilic) was present in 70%, oligoclonal bands in
only 13%, and blood-CSF-barrier dysfunction in 32%. Intravenous
methylprednisolone (IVMP) and long-term immunosuppression were often
effective; however, treatment failure leading to rapid accumulation of
disability was noted in many patients as well as flare-ups after steroid
withdrawal. Full recovery was achieved by plasma exchange in some cases,
including after IVMP failure. Breakthrough attacks under azathioprine were
linked to the drug-specific latency period and a lack of cotreatment with oral
steroids. Methotrexate was effective in 5/6 patients. Interferon-beta was
associated with ongoing or increasing disease activity. Rituximab and
ofatumumab were effective in some patients. However, treatment with rituximab
was followed by early relapses in several cases; end-of-dose relapses occurred
9-12 months after the first infusion. Coexisting autoimmunity was rare (9%).
Wingerchuk’s 2006 and 2015 criteria for NMO(SD) and Barkhof and McDonald
criteria for multiple sclerosis (MS) were met by 28%, 32%, 15%, 33%,
respectively; MS had been suspected in 36%. Disease onset or relapses were
preceded by infection, vaccination, or pregnancy/delivery in several cases.
Conclusion Our findings from a predominantly Caucasian cohort strongly argue
against the concept of MOG-IgG denoting a mild and usually monophasic variant
of NMOSD. The predominantly relapsing and often severe disease course and the
short median time to second attack support the use of prophylactic long-term
treatments in patients with MOG-IgG-positive ON and/or myelitis