Course of myelin oligodendrocyte glycoprotein-associated disease (MOGAD) – a cohort of patients

Overview

The aim of this paper is to provide a comprehensive overview of myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to provide our own practical experience with the diagnosis and treatment of this disease. We present a series of seven patients followed prospectively in our department from 1/2018 to 2/2023. Average age of children at the time of diagnosis was 11.4 ± 2.8 years. All patients fulfilled the MOGAD diagnostic criteria at the time. We present the individual cases and highlight the nature of the course of the disease and the pitfalls of treatment. We discuss acute and chronic therapy and point out the need for further prospective studies in children with MOGAD.

Keywords:

plasmapheresis – optic neuritis – myelitis – myelin-oligodendrocyte glycoprotein autoimmune demyelinating disorders – CNS

This is an unauthorised machine translation into English made using the DeepL Translate Pro translator. The editors do not guarantee that the content of the article corresponds fully to the original language version.

 

Introduction

In previous years, the disease associated with antibodies to myelin oligodendrocyte glycoprotein (MOGAD) was included under the umbrella term "acquired demyelinating diseases" together with MS or neuromyelitis optica and diseases of its broader spectrum. MOGAD is now considered as a distinct clinical entity with an individual course, immunopathogenesis, response to therapy and different prognosis. Its diagnosis depends on the determination of antibodies to the myelin oligodendrocyte glycoprotein (MOG) MOG-IgG [1-3].

The terminology used by different authors is not uniform [4-6]. Slightly different names are encountered in the literature (MOG-encephalomyelitis, MOG-IgG-associated diseases, MOG-related diseases and others). The European Paediatric MOG Consortium has issued a recommendation to use the term MOGAD (or MOG-ab-associated disorders) for all patients with proven MOG-IgG positivity. The next part of the diagnosis name should specify whether the disease is monophasic or recurrent and what phenotype it presents with. As an example of such nomenclature, we present "monophasic MOGAD with a phenotype of acute disseminated encephalomyelitis (ADEM) " [1]. In the following, we use the term MOGAD or MOG-encephalomyelitis.

The first references to MOG-IgG antibodies appeared in the literature in the 1990s, initially mainly in association with MS [7,8]. Previously, however, the ELISA method was used for antibody testing, which is no longer recommended due to the risk of false-positive results. These antibodies are directed against MOG, which is located on the extracellular part of the cytoplasmic membrane of the oligodendrocyte protrusion enveloping the axon in myelinated layers. Although it constitutes less than 0.05% of myelin, it is considered one of the crucial autoantigens of the CNS [9].

The formation of these autoantibodies occurs peripherally (or extrathecally). To confirm them in serum, it is recommended to use a cell-based assay, which gives fewer false-positive results compared to the ELISA method [8]. MOG-IgGs passively penetrate the blood-brain barrier into the CNS, where they initiate inflammatory changes and lead to demyelination.

Although some patients may meet the diagnostic criteria for neuromyelitis optica and neuromyelitis optica spectrum disorder (NMOSD), the pathogenesis of the two diseases is different. While MOGAD is primarily a demyelinating disease with oligodendrocyte involvement, NMOSD with positive antibodies to aquaporin 4 (NMO AQP4+) is a primary astrocytopathies and demyelination is a secondary phenomenon [10,11].

The MOG-IgG autoantibody titer is higher during relapse than in remission. In some patients, especially those with a monophasic course, MOG-IgG antibodies may completely disappear over time [12]. Persistent antibody positivity is a contributing factor to the higher risk of relapse. This finding warrants testing autoinflammatory immunoglobulins repeatedly (in 6-12 months) and especially in patients without chronic immunosuppression [13,14]. A follow-up of antibodies in a patient with initial negativity is also warranted if clinical suspicion of MOGAD persists [12]. Unfortunately, it is not yet known how to work with titer values interindividually.

The incidence of MOGAD is higher in childhood [15] and in girls [8], although Juryńczyk et al. present a balanced sex ratio [16]. This disease tends to relapse [17], but usually with a better final prognosis than that reported for AQP4+ NMO [18]. The estimated risk of relapse ranges from a relatively wide range of 17-57% [1,17,19,20].

The first diagnostic criteria were proposed in 2018. They include monophasic or recurrent clinical diseases that are correlated with demyelinating findings on MRI or demonstrated electrophysiologically. At the same time, positivity of MOG-IgG antibodies is required [6]. Recently, the diagnostic criteria postulated by a consortium of experts led by Brenda Barnwell [3], which also work with the level of MOG-IgG antibody titer, should be respected. If the titer is low (less than 1 : 100) and/or autoantibodies are present only in the lymph, supporting clinical or MR criteria must be met (Table 1).

Phenotypic expression can be varied. In children, the most common initial presentation is bilateral optic neuritis (ON) or ADEM. Other clinical presentations include transverse myelitis (TM), encephalomyelitis or trunk encephalitis [3,16,18]. Especially in younger children, the so-called leukodystrophy-like phenotype is among the adverse phenotypes [1,21].

The most common first manifestation is ON, which is accompanied by eyeball pain, deterioration of visual acuity up to complete amaurosis and impaired colour vision. Almost 90% of patients have fundoscopically confirmed optic nerve oedema. Up to half of the patients have positive findings of mononuclear cells (with a predominance of lymphocytes) and elevated total protein in the liquor. Oligoclonal bands are detected in only 10-15% [16,18]. MRI often demonstrates foci in the region of both optic nerves localized most often in the anterior segment of the nerve. They tend to be longer than in MS and, unlike diseases in the NMOSD spectrum, the chiasma opticum is usually spared. The deposits are hypersignal in T2-weighted images, fluid attenuated inversion recovery (FLAIR) and double inversion recovery (DIR) [12]. MRI of the brain may be completely normal or may show numerous demyelinating foci, but these foci differ in their features from other demyelinating diseases, as Vaněčková and Nytrová point out in their own patient series. The foci tend to be more extensive with irregular shape and inaccurate margins on T2-weighted images and FLAIR sequence compared to MS [22].

Brain MRI findings have a typical evolution over time, as described and compared by Sechi et al. In MOGAD, regression of hypersignal foci on T2-weighted images occurs more frequently (72%) than in MS (17%) and NMOSD (14%) [23].

Pathological findings of visual evoked potentials (VEP) are present in 70% of patients. The same frequency of abnormalities can be seen on optical coherence tomography (OCT) examination. Significant narrowing of the retinal nerve fiber layer (RNFL) and loss of ganglion cells peripapillary in all segments are typical. These findings are also reported without a clear clinical ON. Differences that aid in the differential diagnosis of ON are listed in Table 2 [24].

We distinguish between acute attack therapy and chronic therapy. Treatment of seizures in children involves the administration of intravenous methylprednisolone (IVMP) at a dose of 20-30 mg/kg/day, max 1 g, for 3-5 days. Essentially the same dose is recommended for adult patients. The duration of the oral corticosteroid taper is not precisely defined and depends on several factors, including the age of the patient, the course of the disease and the experience of the physician. MOGAD is often cortico-responsive and in most patients the use of corticosteroids is recommended for up to 3 months, in some patients even longer. Adverse effects of corticotherapy should always be considered, especially during periods of growth and hormonal changes [18,24]. Jarius et al. report an efficacy of IVMP of 50%. The second line of treatment is plasmapheresis (PLEX), for which the same authors report further substantial improvement in 40% of non-steroid responders [12]. Armangue et al. report an effect of up to 90% for acute treatment of seizures, but do not evaluate the effect of individual treatment modalities [19]. Last but not least, it is important to mention the administration of intravenous immunoglobulins (IVIG) and combinations of the above mentioned treatments.

Bruijstens et al. [25] recommend initiating chronic therapy when the disease relapses (Figure 1) [25,26], but prognostic factors should be considered in all patients and treatment should be individualized, especially in children with more severe deficiency after the first relapse, where there is a tendency to initiate early immunosuppression.

Chronic first-line therapies include rituximab (RTX), azathioprine (AZA), mycophenolate mofetil (MMF) or monthly IVIG. Kaneko et al [27] reported elevated interleukin 6 (IL-6) levels in patients with MOGAD. Therefore, it is not surprising that IL-6 receptor inhibitors (tocilizumab, satralizumab) are also used in the next line, whose efficacy and safety in children with MOGAD has so far been demonstrated rather by single case reports [28]. It is also important to mention the ongoing study on the efficacy of satralizumab in patients with MOGAD (ClinicalTrials.gov Identifier: NCT05271409). The portfolio of drugs in the field of CNS autoimmunity continues to expand. Monoclonal anti-CD20 (ocrelizumab), anti-CD19 (inebilizumab), or complement inhibitor (eculizumab) antibodies are increasingly encountered in the treatment of various demyelinating diseases (especially NMOSD spectrum diseases). Data demonstrating the efficacy and safety of these drugs in larger cohorts of patients under 18 years of age with MOGAD are lacking [29].

Drugs used in MS (e.g. interferon beta, glatiramer acetate or natalizumab) did not show a positive effect [26].

 

Patients

We present a cohort of six girls and one boy followed prospectively at the Department of Child Neurology, LF MU and FN Brno and at the RS Centre at the 1st Neurological Clinic, LF MU and FN St. Anna in Brno from 1/2018 to 2/2023 (Table 3). The mean age of the children at the time of diagnosis was 11.4 ± 2.8 years (min. 6, max. 16 years). All patients had proven MOG-IgG antibody positivity. Oligocytosis was present in the lysate of four patients. Oligoclonal bands only in the lymph were demonstrated in two of them (type 2 liquor reaction), while the other two girls had a picture of systemic inflammation in the lymph (or type 4 liquor reaction). In total, 16 attacks were treated acutely (9 times PLEX and 3 times IVIG were indicated).

The most serious complication of PLEX was left venae femoralis thrombosis after dialysis catheter extraction in patient 1 (Table 3). Asymptomatic hemoglobin drop of more than 20% occurred in two patients. In none of them was the value less than 95 g/l and always there was an increase during symptomatic therapy.

Chronic immunosuppression was initiated in four girls and one boy, two of whom had already been successfully discontinued (follow-up 12 and 18 months). Brain MRI showed postcontrast optic nerve saturation in three patients and five patients also had demyelinating lesions in the white matter of the brain. Although two patients would have fulfilled McDonald's criteria for MS during the course of the disease, the lesions on MRI were not typical, and thus the differential diagnosis was guided in a different direction from the outset. A more detailed description of the cohort is given in Table 3. In the next section we present selected cases.

 

Patient 1

A girl (Table 3, Patient 1) born in 2011 [30] was admitted to our clinic at the age of 6 years for investigation of a suspected acquired demyelinating disease. Her family and personal history was unremarkable.

Since April 2018, she complained of worse vision in the left eye, then also in the right eye. Fundoscopic examination confirmed bilateral optic nerve papillary atrophy with temporal maximum. There were 10 lymphocytes and normal total protein in the lymph, intact blood-brain barrier, and two identical oligoclonal bands were confirmed in the lymph and serum (reaction type 4). The results of serum autoimmune factors of systemic diseases (ANA, anti dsDNA, ANCA and others) and other laboratory markers were normal. Initial MRI of the brain (Figure 2) showed multiple asymmetric demyelinating lesions with maximum size of individual lesions up to 11 mm (largest lesion in the hypothalamus, two others paraventricularly on the right, several juxtacortically, increased optic nerve intensity bilaterally, all without postcontrast saturation). The findings were not entirely typical of MS according to the shape of the lesions. MRI of the spinal cord was normal. Initial ophthalmic examination confirmed visual acuity according to optotypes of the right eye (OD) 6/60 and left eye (OS) 80 cm. The diagnosis of bilateral ON was also supported by pathological findings of VEP. Positive MOG-IgG antibodies were found in serum. The girl was treated with IVMP (total 2.5 g for 5 days) followed by oral corticosteroid taper (initial dose of 1 mg/kg/day of prednisone with slow reduction). Due to persistent visual deficit, five cycles of PLEX were implemented and 1 g/kg IVIG was administered. Slight visual alteration persisted in the left eye during diminished vision. Complete clinical improvement and significant regression of MR findings (only one lesion persisted paraventricularly on the right) was achieved within 3 months. Due to the elevation of liver function tests, marked leukocytosis (27×10⁹), anemia, and cushingoid habitus, oral corticosteroids were reduced in a more rapid schedule than usual in MOGAD (i.e., within 6 weeks instead of 3-6 months). The second ON attack was relatively insidious. It began with the patient complaining of occipital headache and a subjective decrease in vision in the left eye. However, the visual acuity was objectively quite normal and the sector physician referred the girl for rehabilitation with headache due to vertebrogenic cause. Only after a month of overall subjective improvement was there a left-sided visual deficit with central scotoma in the left eye on perimeter examination. The relapse was supported by the finding of six cells in the liquor and an elevated serum MOG-IgG titer (1 : 320). Structural examination of the brain and spinal cord was stationary. OCT showed significant RNFL thinning bilaterally (except in the nasal quadrant OD) and ganglion cell loss in all quadrants bilaterally. The patient was treated with the same algorithm as for the first attack. The PLEX was complicated by venous thrombosis after removal of the dialysis catheter from the left vena femoralis requiring three months of anticoagulation therapy.

AZA administration was contraindicated in the chronic treatment of the patient due to low levels of thiopurine methyltransferase (TPMT) enzyme activity supported by positive genetic analysis of the heterozygous variant of the TPMT *3A/*3C gene. A follow-up MRI at 5 months on MMF treatment revealed isolated radiological activity. She was switched to rituximab after IVMP treatment. Since then, the girl has been clinically and radiologically stable and after 2 years of uncomplicated course, de-escalation of therapy was initiated (in accordance with current recommendations -⁠ Figure 1).

At the same time, the procedure was advantageous in view of the ongoing COVID-19 pandemic and concerns about the worse course of this infection when treated with anti-CD20 monoclonal antibody [31].

Currently, at the age of 11, her visual acuity is normal and her brain MRI is free of new demyelinating lesions (last follow-up was 18 months after discontinuation of therapy).

 

Patient 2

The girl (Table 3, patient 2) was born in 2007. The girl's mother was deprived of custody of the child due to an unspecified psychiatric illness; the father was healthy. The girl was transferred to our clinic at age 11 years from another institution, where she was hospitalized and treated with corticosteroids and IVIG for bilateral ON associated with MOG-IgG antibody production. AZA was introduced into chronic medication, on which she developed spinal seizures of the nature of partial spinal cord syndrome within 4 months. This was already treated not only with IVMP but also with PLEX. AZA was subsequently switched to RTX, on which there was no remission of the disease despite sufficient B cell depletion. Two further attacks on this treatment (ON right and cerebellar syndrome) required a series of PLEX in addition to 5 g IVMP treatment. At that time, a study appeared in the literature demonstrating the effect of long-term administration of IVIG at a dose of 1 g/kg/month [26], and the patient was compensated on this therapy for more than one and a half years. Upon stabilization, a slow reduction of the IVIG dose was proceeded. At that time, the COVID-19 pandemic broke out and the father decided to have the girl vaccinated. Within 2 months, she developed bilateral ON requiring IVMP and the decision was made to return to the initial IVIG dose of 1 g/kg/month. Despite this, there was no stabilization of the disease and in December 2021 an attack of right-sided ON was again demonstrated with an indication for IVMP including oral taper and five cycles of PLEX in a daily schedule. MMF was added to the doublet as part of the chronic medication regimen. At titration, there was a need to treat one more exacerbation of ON. However, after a year of adequate use, the patient had another attack of ON on the right, so the therapy was changed to subcutaneous tocilizumab, on which she has now been clinically stable for a year. The last OCT performed showed progression of optic disc atrophy bilaterally (Figure 3).

Fig. 4 summarizes the gradual evolution of demyelinating changes in brain MRI.

 

Patient 3

A 14-year-old girl (Table 3, patient 5) was hospitalized in December 2021 for right-sided ON. Her father died in cardiac arrest at age 38 years (with unspecified cardiomyopathy). The girl's sudden death and the unsuccessful attempts at cardiopulmonary resuscitation by health care professionals led to, among other things, her subsequent trypanophobia. Introducing intravenous admissions and performing necessary laboratory collections were very stressful for the girl, and this complication influenced some of our further decisions during hospitalization. No one in the family suffered from autoimmune disease. Two months prior to the development of ON, she had newly manifested headaches accompanied by increased fatigue. She self-reported significant physical and mental stress related to the competitive soccer season.

Subjectively, on admission, visual disturbance up to the character of amaurosis in the right eye was present. The objective findings included a relative afferent pupillary defect on the right. On admission, MRI was performed which showed a hyperintense right optic nerve with postcontrast enhancement. Other brain tissue and the entire spinal cord were free of demyelinating lesions. The ophthalmologist described edema of both papillary optic nerves. The liquor examination was correlated with MOGAD. IVMP therapy was started immediately at a dose of 30 mg/kg/day with minimal effect. In the next two days, it was decided to perform four cycles of PLEX under analgosedation with complete visual correction on day 5. The girl was transferred to maintenance oral corticotherapy for 3 months. At the last follow-up (1 year after the attack), her neurological findings were stationary.

 

Patient 4

In December 2022, we admitted a 16-year-old boy to Children's Hospital with severe acute myelitis (Table 3, Patient 7). The development of clinical problems was preceded by a viral respiratory infection and he was subfebrile on admission. His elder sister had suffered a stroke at the age of 18 years, and his family history was free of autoimmunity. Initial neurological findings were consistent with lateral (very severe lower limb paraparesis) and posterior spinal cord syndrome with severe sphincter dysfunction (including non-excitable anal reflex and urinary retention requiring urinary catheterization and subsequent epicystostomy). Initial MRI of the spinal cord showed findings of myelitis throughout the spinal cord and multiple demyelinating white matter foci parietally, frontally and temporally including a lesion in the pontus were present on brain MRI (Figures 5 and 6). The lymph fluid showed serous inflammation (46 monocytes, 2 polymorphonuclei, total protein 0.59 g/l), oligoclonal bands were absent. Positivity of IgG-class antiborella antibodies was noted with no intrathecal synthesis present. Despite the initial need for overlay with intravenous antibiotics, we were not inclined to make a diagnosis of neuroborreliosis (CXCL13 negative).

Examination of MOG-IgG antibodies allowed us to establish the diagnosis of monophasic MOGAD with a phenotype of acute myelitis. Because of very severe pseudorabies on admission, PLEX was started early (i.e., within 5 days of admission; within 9 days of symptom onset) after pulses of IVMP and IVIG (five cycles daily, then twice daily). We confirmed IL-6 elevation in the lysate, which allowed us to individualize therapy and administer tocilizumab i.v. at a dose of 8 mg/kg à 4 weeks. During hospitalization, the patient had to be repeatedly treated with intravenous antibiotics due to the finding of Pseudomonas aeruginosa in the urine. The patient's last follow-up was 4 months after the onset of the problems, and objectively neurologically, very mild non-restrictive central lower limb paraparesis (with maximal expression acrally) persisted. The boy is fully self-sufficient, with no sphincter dysfunction, is active in sports and walking is unrestricted in distance. Follow-up MRI of the brain and spinal cord shows significant regression of hypersignal foci in T2-weighted images and in the FLAIR sequence.

 

Discussion

In our clinic we are currently following seven children with MOGAD. In 1 patient we indicated RTX administration. This is a monoclonal antibody directed against the CD20 antigen, which is characteristic of certain developmental stages of B lymphocytes. Currently, there is no uniform globally recognized regimen for RTX administration in children with MOGAD (according to the SPC, it is still approved in the Czech Republic under autoimmunity for rheumatoid arthritis and polyangiitis). Therapy was guided by the CD19+ lymphocyte count, which is in accordance with the later published recommendations of the Union Pediatric MOG Consortium [25]. The initial regimen included RTX at a dose of 375 mg/m² a total of four times a week, and then infusion at the same dose twice every 14 days approximately every 6 months (when CD19+ lymphocytes reappeared) was indicated. This procedure proved to be successful in sufficiently depleting the B lymphocytes. The patient did not develop any major infection or other complication during treatment.

As mentioned above, in practice, RTX is more often cytoflowmetrically determined by CD19+ cells, which better reflects the current status of B cells. Patient 2 developed a third and fourth attack despite zero values of these cells. Similar experience is reported by Durozard et al. in their paper [32].

In patient 3 and patient 4, we opted for a more drastic approach in the case of acute treatment of the attack and recommended plasmapheresis as an early escalating first-line treatment. This is a highly effective method but has its side effects. Despite the relatively good prognosis of MOGAD with ON phenotype, it has been shown that axonal loss can be severe [20]. Complete recovery is expected in 56-73% of patients [33,34].

While Magaña et al. support the early implementation of PLEX given its significant effect, Savransky et al. did not demonstrate a significant association between PLEX initiation time and outcome [35,36].

Starting PLEX is not always an easy decision. It is necessary to weigh the benefits and risks of the method. The excellent improvement of patient 3's neurological deficit (two grade improvement in the Expended Disability Status Scale) between the first and fifth cycle of uncomplicated PLEX confirmed us in the correctness of the indication for escalation of acute therapy. However, we cannot prove whether this was still a waning effect of IVMP or the natural course of the disease, as already discussed by Manguinao et al. in their publication [37]. A randomized controlled clinical trial would be required to clearly conclude the above discussion.

In patient 4, we first indicated second-line TCZ treatment, knowing that it is not part of the official recommendations of the Union Pediatric MOG Consortium [25]. Nevertheless, we see its indication as justified given the high IL-6 level in the lymph. A significant effect of TCZ was demonstrated in a meta-analysis comparing the efficacy of biological therapy in MOGAD, where the percentage of relapse-free patients using AZA, MMF, RTX, IVIG and TCZ was 65%, 73%, 66%, 79% and 93%, respectively. In the group of children, 61% of patients on AZA, 69% on MMF, 53% on RTX, and 84% on IVIG were relapse-free, and the group of patients treated with TCZ was not stratified by age [38]. The efficacy and safety of TCZ was demonstrated, among others, in a study by Ringelstein et al. also including patients under 18 years of age [39].

 

Conclusion

Disease associated with antibodies to myelin oligodendrocyte glycoprotein can be considered as a separate clinical entity with a different immunopathogenesis and therapeutic approach compared to MS and NMOSD. In particular, patients with a relapsing course of the disease deserve our increased attention. Diagnostic and therapeutic recommendations are gradually being formulated, to which we must respond dynamically. The spectrum of targeted drugs is constantly expanding, but so far we do not have enough data and prospective studies in pediatric patients. We expect an updated European expert consensus on chronic treatment of MOGAD in the near future.

We will see this disease more and more often in our practices. Not only thanks to more accessible diagnostics, but also thanks to more education of medical staff.

Ethical aspects

This is a retrospective monitoring of a cohort of patients. The study is not subject to ethics committee approval. Patients and their parents consented to the diagnostic and therapeutic process and to the publication of the above data.

 

Conflict of interest

The authors declare that they have no conflict of interest in relation to the subject of the study.

 

 

Table 1. MOGAD diagnostic criteria. Loosely translated from Banwell et al. [3

MOGAD Diagnostic Criteria (A, B and C required)
A. Main clinical manifestation	Optic neuritis, myelitis, ADEM, cerebral monofocal or polyfocal deficit, trunk or cerebellar deficit, cerebral cortical encephalitis with seizures
B. Positive MOG-IgG antibody result	serum -⁠ CBA	clearly positive	no further requirements
		low positive	AQP4-IgG seronegativity  A  ≥ 1 supporting clinical or MR criterion
		positive with no titre reported
		negative S, but CSF positive
Supporting clinical or MR criteria	Optic neuritis	Bilateral  longitudinal disability ON  perineural enhancement of the optic nerve sheath  optic nerve papilla oedema
	myelitis	longitudinally extensive myelitis central spinal cord lesion or H-sign spinal cord involvement
	syndromes from the brain stem or cerebral	multiple T2-hyperintense lesions in the white matter supratentorially and often infratentorially deep grey matter involvement T2-hyperintensities affecting the pons, middle cerebellar peduncle or spinal cord cortical lesions with/without meningeal enhancement
C. Exclusion of other diagnosis

Clearly positive MOG-IgG -⁠ test result performed by a standardized method on live cells (a live CBA) evaluated as positive according to a defined cut-off or the titer value on fixed cell based assay is greater than 1 : 100; low positive result -⁠ the result of a live cell-based assay performed by a standardised method is scored as low positive according to the cut-off or the titre on fixed cells is between 1 : 10 and 1 : 100, unless clear positivity of MOG-IgG antibodies in serum is demonstrated, supporting clinical or magnetic criteria are required for the diagnosis and the absence of AQP4-IgG antibodies

ADEM -⁠ acute disseminated encephalomyelitis; AQP4 -⁠ aquaporin 4; AQP4-IgG seronegativity -⁠ AQP4-IgG antibodies in serum not demonstrated; CBA -⁠ cell-based assay used as a basic diagnostic laboratory method (= determination on cells transfected with vector carrying the relevant antigen); CSF, CSF; MOGAD, myelin oligodendrocyte glycoprotein-associated disease; ON, optic nerve; S, serum