FormalPara Key Summary Points

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is increasingly recognised as a disease distinct from other inflammatory central nervous system demyelinating diseases, including multiple sclerosis and aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder.

Despite antibody testing, MOGAD diagnosis can remain challenging due to its heterogeneous disease course and low awareness of MOGAD among healthcare professionals.

We conducted an online survey of people living with MOGAD and their caregivers to explore the challenges faced in the pathway to final MOGAD diagnosis.

This survey revealed that many patients faced a protracted and multi-step pathway towards MOGAD diagnosis, although it is likely that some of these patients sought diagnoses before MOG antibody testing was available.

This survey provides important insights into the patient and caregiver perspectives of the challenges associated with the diagnosis of MOGAD to help facilitate improvement of the diagnostic pathway.

Introduction

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare, inflammatory, demyelinating condition of the central nervous system (CNS), caused by pathogenic serum antibodies that target MOG expressed on the surface of the myelin sheath [1,2,3]. The prevalence of MOGAD is estimated to be 1–4 cases per 100,000 people [3], and the disease is equally likely to affect males and females [4]. The disease course can be relapsing (reported for 44− 83% of patients) or monophasic, the latter subtype being more common in MOGAD than in other neurological demyelinating disorders, such as neuromyelitis optica spectrum disorder (NMOSD) or multiple sclerosis (MS) [3, 5]. The clinical phenotypes of MOGAD are variable and include transverse myelitis (TM), optic neuritis (ON), acute disseminated encephalomyelitis (ADEM), NMOSD and cerebral cortical encephalitis, making diagnosis challenging [5,6,7,8,9,10,11,12,13].

Despite the introduction of MOG antibody (MOG-Ig) diagnostic testing in some regions and countries, MOGAD diagnosis can remain challenging due to its heterogeneous disease course, its overlapping clinical presentations with other CNS demyelinating diseases and low awareness of MOGAD among healthcare professionals. In patients with clinical features consistent with MOGAD, evidence supports the use of a cell-based assay (preferably live cells) using a target antigen of full-length human MOG to detect MOG immunoglobulin G (IgG) in serum [5, 14,15,16]. In addition to MOG-Ig and aquaporin 4 (AQP4)-IgG testing, neurological examination, magnetic resonance imaging and spinal fluid analysis can also facilitate the differentiation of MOGAD, AQP4 + NMOSD and MS [5, 17,18,19,20,21]. The International Classification of Diseases (ICD) 11th Revision (updated February 2022) implies that MOGAD is a subtype of neuromyelitis optica [22]. Distinct ICD coding for MOGAD that recognises MOGAD as a distinct rare disease in global classification systems could help the patient diagnostic pathway. An international survey of neurologists conducted in 2019 reported highly varied treatment strategies for MOGAD [23]. Disease management strategies for MS and NMOSD have been applied to MOGAD, with some treatments showing high effectiveness [15, 24]; however, treatments for MOGAD adopted from MS and NMOSD may be ineffective or even harmful in some cases [15, 25,26,27]. Earlier and correct diagnosis of MOGAD may mitigate the risks associated with potentially inappropriate treatments. New expert consensus recommendations for MOGAD disease definition and diagnostic criteria [28], and refined diagnostic criteria for MS to help exclude patients with MOGAD, will help to reduce diagnostic delay and raise awareness of MOGAD.

Published data on MOGAD and the challenges of timely diagnosis are in general presented through the lens of the physician and the medical system. The patient perspective in rare disease can be informative, providing additional insights into disease-specific needs. To assess gaps in clinical care, we conducted a survey of people living with MOGAD and their caregivers covering the time from initial symptom onset and the pathway to diagnosis.

Methods

Patient Population

The MOG Project (Olney, MD, USA) is a patient advocacy group that provides resources for doctors, people living with MOGAD and caregivers, while also providing support for the community, raising awareness of MOGAD and advocating for research into a cure [29]. The MOG Project is an important global resource for people living with MOGAD. The only inclusion criterion for this survey was to be a person living with MOGAD or the caregiver of a person living with MOGAD; there were no exclusion criteria. Confirmation of diagnosis of MOGAD was not required for feasibility reasons.

Survey Development

The survey was designed by UCB Pharma (ZP) in collaboration with The MOG Project (authors JG and JL) and a paediatric neuro-immunologist (author JDS). The survey comprised 23 multiple-choice and free-text questions (Table 1) covering patient and caregiver perspectives on patient disease history and healthcare interactions up to MOGAD diagnosis. Free-text questions were included to elicit patient and caregiver perspectives that could potentially highlight any unmet educational needs of healthcare professionals, adding value to the multiple-choice questions. Some questions only required a response if the response to the preceding question was affirmative. Although the survey was presented only in English, non-English responses were permitted and were translated into English prior to analysis.

Table 1 Survey questions
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The survey received ethics approval from the University of Southern California Institutional Review Board (ID:21-0082). As the study did not involve clinical data or involve data collection from other institutions, only one centre was used to approve study material and perform ethics review. Ethics approval was waived after expedited review as there was no clinical or identifying information collected. Survey participants were informed of the intention to publish the anonymised results before they began the survey. All survey respondents provided informed consent to participate in the study on the survey landing page prior to being able to start the survey. An option to opt out of the survey was available on all displayed pages. As the study was an anonymous patient and caregiver survey to report perspectives on the pathway to MOGAD diagnosis, no verification of individual patient data was required. This study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments.

Survey Administration

The survey was distributed by The MOG Project to people living with MOGAD who had already signed up to The MOG Project email distribution list (n = 225). The survey was also shared on three social media platforms: Facebook (n = 1800 members in The MOG Project group), Instagram (approximately 150 views of the post), and Twitter (approximately 850 views of the post). Instagram and Twitter post views may not represent unique users of these social media platforms. Caregivers could complete the survey on behalf of individuals, if required (e.g. person living with MOGAD had visual impairment). Here, ‘respondents’ refers to people living with MOGAD, whether responses were self- or proxy-reported. Anonymised survey responses, collected from 18 January to 1 March 2022, were collated using QuestionPro [30]. Any identifying free-text information was removed by The MOG Project organisation before being shared with UCB Pharma for analysis. Respondents consented to publication of the resulting data through active acknowledgement on the survey landing page. Results were reviewed and analysed by UCB Pharma; only completed surveys were used in the analysis.

Statistical Analysis

All statistical analyses were performed using SAS v.9.4 for data cleaning, data manipulation and analysis; R v.4.0.2 was used for data visualisations. Given the nature of the raw data, some data cleaning was required before analysis could proceed. This included translation of some survey responses from Dutch and Spanish into English, removal of invalid responses (for example, where each question had the same response or responses had no relation to the survey), and removal of responses outside the scope of the question.

Quantitative data [survey question (Q)1–6, Q8–13, Q15, Q18–20] were summarised with number of responses, mean, standard deviation, median, minimum and maximum values; categorical variables were summarised using number and percentage of responses. Qualitative data (Q7, Q14, Q16, Q17, Q21–23) were categorised by two independent reviewers and adjudicated by a third independent reviewer in the case of differences. These data were then summarised in a manner similar to that used for the categorical variables, presenting summary statistics for the number of respondents that fell within each category. Categories for the analysis of free-text responses are listed in Supplemental Table 1.

Results

Respondents

A total of 204 respondents from 21 countries completed the survey. Most respondents (73.5%, 150/204) were from North America (Canada and USA), followed by 15.2% (31/204) from Europe (Belgium, Croatia, France, Germany, Norway, Switzerland, Spain and the UK), 6.4% (13/204) from Australia and New Zealand, 2.0% (4/204) from Asia (India, Japan and Turkey), 1.5% (3/204) from Africa (South Africa) and the Middle East (Egypt and Lebanon) and 1.5% (3/204) from South America (Brazil, Chile and Mexico). Free-text responses were reviewed by a physician author and a MOG Project representative author prior to arbitration by a clinician author. Responses were consistent with a diagnosis of MOGAD, and there was no evidence that fraudulent responses (i.e. from people who did not receive a diagnosis of MOGAD) were received.

Experience from Time of Initial Symptoms

The age of onset of initial symptoms associated with MOGAD (Survey Q1, 105 respondents) ranged from 1 to 66 years, with a mean (median) of 27.4 (28.0) years. Age at MOGAD diagnosis (Survey Q2) was most often reported in children at < 10 years of age (19.1%, 39/204) or between 30 and 49 years of age (40.2%, 82/204) (Fig. 1). Approximately 30% of respondents (62/204) were aged ≤ 18 years when they received a diagnosis of MOGAD.

Fig. 1
figure 1

Age at time of MOGAD diagnosis*. *Survey Question 2; data from 204 respondents. MOGAD myelin oligodendrocyte glycoprotein antibody-associated disease

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The most common initial health problems experienced (Survey Q3) included headache (21.0%, 41/195), followed by eye pain (13.3%, 26/195) and cold/flu-like symptoms (12.3%, 24/195) (Fig. 2). After the initial health problems (Survey Q4), headache and eye pain continued to be experienced by 56.2% (113/201) and 60.7% (122/201) of respondents, respectively (Table 2). Patients experienced other health problems including blurred vision/loss of vision (68.7%, 138/201), tiredness/fatigue (57.7%, 116/201) and leg/arm tingling/loss of sensation (47.3%, 95/201) among a wide range of other symptoms (Table 2). The MOGAD-related health problems that led respondents to seek medical care (Survey Q5) included blurred vision/loss of vision (58.2%, 117/201), eye pain (35.8%, 72/201) and difficulty walking (25.4%, 51/201) (Fig. 3).

Fig. 2
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Initial health problems experienced by patients*. *Survey Question 3; data from 195 respondents

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Table 2 Health problems that patients experienced after initial health problems
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Fig. 3
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Health problems that led respondents to seek medical care*. *Survey Question 5; data from 201 respondents

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From Initial Symptoms to MOGAD Diagnosis

Most respondents (81.3%, 165/203) sought medical care within 2 months of first experiencing MOGAD-associated symptoms (Survey Q6); almost 4% (8/203) and 8% (16/203) of patients sought medical care between 6–12 months and > 1 year, respectively. Free-text responses that elaborated on the > 1-year delay to seeking medical care (Survey Q7) revealed that 46.7% of respondents (7/15) had sought medical care but faced problems receiving a diagnosis or received an alternative primary diagnosis. One-third of respondents (33.3%, 5/15) felt that their symptoms were not severe or long-term enough to seek medical support, while 13.3% of patients (2/15) did not or could not prioritise seeking medical advice.

“I immediately sought out advice when the urinary issues began. My provider just told me it’s normal; I’ll get over it. Urinary tract infection is a normal problem for any sexually active female. I was not sexually active, and I would get one urinary tract infection a month.”—Survey Respondent (Survey Q7).

“I could explain away symptoms, I didn’t eat right, etc.…”—Survey Respondent (Survey Q7).

“Scared and felt my symptoms would go away.”—Survey Respondent (Survey Q7).

In the global patient population, most individuals first sought medical care (Survey Q8) from emergency care doctors (38.7%, 79/204) or primary care doctors (general practitioner, family medicine doctor/internist; 26.0%, 53/204). Ophthalmologists and paediatricians were the first healthcare point of contact for 15.2% (31/204) and 6.9% (14/204) of patients, respectively. In contrast, specialist doctors, such as general neurologists, neuro-ophthalmologists, and neuro-immunologists, were consulted by comparatively few patients (Supplemental Table 2). After the initial consultation with the first doctor, the next type of doctor that patients were referred to (Survey Q9) demonstrated a shift towards more specialist involvement (Supplemental Table 2): 28.0% of patients (56/200) saw general neurologists, while ophthalmologists and neuro-ophthalmologists were each consulted by 14.5% (29/200) of patients. The type of doctor who eventually made the MOGAD diagnosis (Survey Q11) was in most cases a specialist: general neurologists and neuro-immunologists for 40.4% (82/203) and 30.0% (61/203) of patients, respectively, in addition to other specialists. Only 3.0% of MOGAD diagnoses were made by emergency care doctors (Supplemental Table 2).

Subgroup analyses of the diagnostic pathway were performed for: (1) the USA and (2) Europe, Australia and New Zealand (Australia, Belgium, Croatia, France, Germany, New Zealand, Norway, Spain, Switzerland and the UK). For respondents in the USA (n = 136), emergency care doctors were typically the first point of contact, with general neurologists being the doctors to whom patients were most frequently referred next and the ones to make the diagnosis (Fig. 4). In the Europe, Australia, and New Zealand subgroup (n = 42), the first point of contact was most often a primary care doctor, with the next most common referral being to an ophthalmologist; however, most diagnoses were made by a general neurologist (Fig. 5). In both the USA and the Europe, Australia and New Zealand subgroups, a prominent shift of patient referrals toward specialist involvement was observed from the ‘next doctor’ to the ‘diagnosing doctor’ stages of the diagnostic pathway.

Fig. 4
figure 4

Diagnostic pathway from initial consultation to MOGAD diagnosis in the USA*. *Survey Questions 8, 9 and 11; data from 136 respondents†Patients were not referred to another doctor. MOGAD myelin oligodendrocyte glycoprotein antibody-associated disease

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Fig. 5
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Diagnostic pathway from initial consultation to MOGAD diagnosis in Europe, Australia and New Zealand*‡. *Survey Questions 8, 9 and 11; data from 42 respondents†Patients were not referred to another doctor‡Europe, Australia and New Zealand subgroup included Australia, Belgium, Croatia, France, Germany, New Zealand, Norway, Spain, Switzerland and the UK. MOGAD myelin oligodendrocyte glycoprotein antibody-associated disease

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The time from referral to consultation with a doctor (Survey Q10) was 1 week and 4–6 weeks for 68.5% (126/184) and 10.9% (20/184) of patients, respectively. The wait from referral to consultation was only 1 week for 68.4% (13/19) and 65.6% (80/122) of patients in the UK and USA, respectively. Only 2.7% (5/184) of respondents waited ≥ 6 months for a referral (Supplemental Table 3). The mean number of doctors seen prior to MOGAD diagnosis (Survey Q12) was 5.3 (median: 4.0; 181 respondents). Most patients (73.5%, 133/181) saw ≤ 5 doctors, but almost a quarter (26.5%, 48/181) saw ≥ 6 doctors before receiving a diagnosis of MOGAD. The time from the initial MOGAD-related health problems experienced to time of MOGAD diagnosis (Survey Q13) was < 6 months for 60% of patients (60.6%, 123/203), but ≥ 5 years for almost one-fifth of patients (17.7%, 36/203) (Table 3). Free-text responses that elaborated on the delay of ≥ 7 years from first symptoms to diagnosis (Survey Q14) highlighted unmet medical needs or lack of awareness of MOGAD in the medical community (24.1%, 7/29), unavailability of the MOG-Ig test (6.9%, 2/29), or that doctors did not believe patients about their symptoms (6.9%, 2/29) (Supplemental Table 4). The time to diagnosis from the first consultation with a doctor (Survey Q15) was < 6 months for most patients (61.3%, 125/204), but ≥ 7 years for 15.2% (31/204) of patients (Table 3).

“They simply had no clue what was going on and were unable to put the symptoms together.”—Survey Respondent (Survey Q16).

“Doctors didn’t know what I had, lack of knowledge. Some tests were not available at that time.”—Survey Respondent (Survey Q16).

“For 25 years was told symptoms were all in my head.”—Survey Respondent (Survey Q16).

Table 3 Time to MOGAD diagnosis
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Before MOGAD diagnosis, > 55% of patients (113/204) reported that they received an alternative primary diagnosis (Survey Q17; Fig. 6). The most common diagnosis received was MS (32.7%, 37/113), followed by neuromyelitis optica (11.5%, 13/113) and ADEM (8.8%, 10/113). Other primary alternative diagnoses received included meningitis (5.3%, 6/113), migraines (4.4%, 5/113), encephalitis (3.5%, 4/113), TM, chronic fatigue, chronic relapsing inflammatory optic neuropathy (each 2.7%, 3/113), psychiatric depression (1.8%, 2/113), common virus (0.9%, 1/113) and others.

Fig. 6
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Proportion of patients who received an alternative primary diagnosis before receiving a MOGAD diagnosis*. *Survey Question 17; data from 204 respondents. MOGAD myelin oligodendrocyte glycoprotein antibody-associated disease

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MOGAD Diagnosis and Disease Management

Most respondents (60.6%, 123/203) felt they were not given sufficient information and/or resources at the time of MOGAD diagnosis (Survey Q18). At that time, respondents would have liked to receive (Survey Q19) information about support groups (79.5%, 159/200), advocacy website information (68.0%, 136/200), online video resources (62.0%, 124/200), pamphlets (55.0%, 110/200) and other resources.

After receiving a MOGAD diagnosis, patients often had more than one doctor managing the disease (Survey Q20), including general neurologists (53.9%, 110/204), neuro-ophthalmologists (46.6%, 95/204), neuro-immunologists (46.1%, 94/204), primary care doctors (24.5%, 50/204), ophthalmologists (20.1%, 41/204), paediatricians (6.9%, 14/204) and other specialist doctors (13.7%, 28/204).

Disease Burden Prior to, and After, MOGAD Diagnosis

Prior to MOGAD diagnosis, patients experienced a substantial MOGAD-related health burden (Survey Q22a). Over half of respondents (57.3%, 79/138) reported that overall health and well-being were negatively affected by the disease. In addition, impairment of patients’ vision and mobility (including balance) were reported by 21.0% (29/138) and 13.0% (18/138) of respondents, respectively. Receiving a final MOGAD diagnosis (Survey Q22b) led to improvement in emotional responses, including reduced feelings of distress, depression, anxiety or fear, for more than half of respondents (61.1%, 11/18), whereas more than one-fifth of respondents reported that the final MOGAD diagnosis worsened emotional responses (22.2%, 4/18). Respondents perceived that the delay to MOGAD diagnosis led to long-term adverse health consequences (Survey Q23) including vision impairment (55.6%, 50/90), neurological disorders not including mental health (27.8%, 25/90) and bladder issues (20.0%, 18/90). Additionally, they reported other health problems, adverse impacts on the ability to perform daily living and social activities and on attendance and performance at work or school. Free-text responses describing the pathway to MOGAD diagnosis (Survey Q21) included frequently used words such as ‘diagnosis’, ‘doctor(s)’, ‘hospital’, ‘time’ and ‘vision’.

“Honestly, I wish doctors knew back then what was wrong with me and took my symptoms seriously. I’m so thankful now for my doctors, who are amazing and are knowledgeable about MOGAD […]. It was a long and stressful journey and was not taken seriously by doctors.”—Survey Respondent (Survey Q21).

“My […] daughter was misdiagnosed […]. It wasn’t until she was completely blind that we returned to the hospital and demanded that they screen for other possibilities. Had we received a correct diagnosis from the beginning, […] she could have received treatment more quickly. She has permanent damage to her optic nerves and we often wonder if she could have avoided the permanent damage had she been diagnosed and treated more quickly.”—Survey Respondent (Survey Q21).

“I felt like I was able to get a diagnosis very quick because all of the information was more prevalent at the time in 2018.”—Survey Respondent (Survey Q21).

“I feel that lack of knowledge about MOGAD caused initial ophthalmologists to not explore this disease as a possibility of my symptoms and delayed effective treatment.”—Survey Respondent (Survey Q21).

“When I was diagnosed, doctors didn’t know much about MOGAD. It was very scary and frustrating.”—Survey Respondent (Survey Q21).

Discussion

Our understanding of rare neurological diseases such as MOGAD is expanding, but challenges remain. Indeed, one of the goals of the International Rare Disease Research Consortium is that, by 2027, patients with a suspected rare disease will receive an accurate diagnosis within 1 year of seeking medical care if the disease is established within the medical literature [31]. Patients with rare diseases commonly face a difficult and protracted diagnostic pathway [32], compounded in cases where the required diagnostic expertise may be limited to specialised medical centres [33]. Despite the fact that MOGAD is now recognised as a distinct demyelinating CNS disease, and that more sensitive/specific diagnostic testing is available, there remains a need to increase awareness of MOGAD in the medical community to help better address the needs of people living with MOGAD and their caregivers. Our findings from a multinational survey of 204 people living with MOGAD and their caregivers reveal that many individuals experienced a protracted and multi-step pathway from initial symptoms to final MOGAD diagnosis, which can potentially result in adverse long-term physical and/or psychological health outcomes. Understanding the multi-factorial variables that influenced the diagnostic pathway is important to achieve earlier diagnosis.

It is likely that the variety of different phenotypes encountered in people living with MOGAD complicates diagnosis. Blurred vision/loss of vision was the MOGAD-related health problem that catalysed > 58% of respondents to seek medical care, although ON may not have been present in all of these cases. Most respondents (81.3%) sought medical care within 2 months of symptom onset. The first point of contact with a healthcare professional was most commonly with emergency care and primary care doctors, respectively, for patients in the USA subgroup and the Europe, Australia and New Zealand subgroup. Globally, MOGAD diagnosis was most frequently made by specialist doctors such as general neurologists (40.4%) or neuro-immunologists (30.0%).

Over one-quarter of patients (48/181) consulted with ≥ 6 doctors before receiving a MOGAD diagnosis. Although our survey did not capture the year a MOGAD diagnosis was received, the authors feel it is reasonable to assume that some patients with protracted delays to MOGAD diagnosis represent cases that predate the recognition of MOGAD as a distinct disease. Varied access to MOG-Ig testing may also have negatively affected the time to diagnosis. However, the correlation between serum presence of MOG antibodies and MOGAD is not absolute; MOG antibody levels may disappear over time, according to disease status and treatment [4, 7, 9]. Standardisation of MOG-Ig tests is recommended to improve clinical care for patients with MOGAD and future research of the disease [15, 34].

Some patients delayed seeking medical help within the first year of symptom onset. For several patients, the symptoms were not considered severe enough and/or were experienced intermittently. Survey responses also revealed a subset of patients who sought medical care, but their symptoms were dismissed by doctors as ‘an isolated event’ or ‘all in your head’. This finding may be related to the fact that, even when untreated, acute demyelinating events can often improve after the symptom onset causing less noticeable symptoms if evaluation is delayed. A study of misdiagnosis of MS found that women were more likely to be misdiagnosed with a mental health condition than men; the latter were also offered more investigative tests [35]. Increased education and training related to MOGAD diagnosis, targeted at both specialist and non-specialist healthcare professionals, are needed to increase awareness of this disease so that symptoms are investigated thoroughly, rather than dismissed or misinterpreted. While it may not be practical to provide bespoke education to healthcare professionals for all rare neurological conditions, general education about treatment approaches for neurological conditions may be more feasible. Healthcare professionals should be educated about the importance of early referral to neurologists and ophthalmologists for patients with suspected rare neurological conditions such as MOGAD.

Of 113 patients who received an alternative primary diagnosis, 32.7% received a diagnosis of MS. Relapsing MOG-encephalomyelitis has been misdiagnosed as MS due to a significant overlap in clinical and radiological presentation [16]. Although the survey did not record the year that these patients received a diagnosis of MS, one may assume that these diagnoses did not incorporate MOG-Ig testing and/or other recommendations to differentiate MOGAD from other inflammatory CNS demyelinating diseases [16, 28].

MOGAD can have a significant detrimental impact on patients’ health and may result in potentially irreversible consequences such as blindness, paralysis, cognitive decline or behavioural issues [5, 15, 27, 36]. MOGAD relapses are associated with disability [27]. In a cohort study (n  = 252, adult and paediatric), 41% of patients did not have any disability at last follow-up, but approximately one-quarter had moderate-to-severe disability [11]. However, other studies in children with overlapping phenotypes, such as ADEM, have reported significant neurocognitive and structural changes longitudinally, highlighting the possibility of hidden disability in individuals with MOGAD [37,38,39,40]. Early diagnosis and appropriate treatment may prevent future relapses and lead to more urgent relapse treatment with reduced permanent disability.

Once patients received a MOGAD diagnosis, disease management included doctors of differing specialities, but many patients remained dissatisfied with their care. Over half of respondents (60.3%) reported that insufficient information and/or resources were provided at the time of diagnosis; the initial management of MOGAD at diagnosis may be compromised by a lack of longitudinal data and general experience. Although high levels of dissatisfaction were recorded in this study, it is hoped that, as MOGAD is more routinely reported in the literature and identified in clinical practice, medical professional knowledge and comfort treating this condition will improve.

This study is not without limitations. In our study, two-thirds of respondents were from the USA, which has an extraordinarily complex healthcare system different from the majority of the rest of the world. Compounding this is that insurance status was not collected in this study, which could have skewed coverage and been related to some delays in diagnosis and access to care. Availability of the survey in several languages and inclusion of higher numbers of patients in different countries may have allowed assessment of the relative success of different healthcare systems in identifying and treating MOGAD. Although no association between ethnicity and MOGAD is known [4], ethnicity and race are important factors that should be explored in the diagnosis and treatment of MOGAD; exclusion of these data in the survey design is a limitation of our study. As with any survey, recall bias is likely to have been present in this study, especially for patients who have been symptomatic for long periods of time. An additional limitation is that survey responses were not stratified as self- or proxy-reported, or paediatric versus adult, and the sex of patients was not recorded. Selection bias was likely to be present as people with relapsing MOGAD were more likely to be involved with The MOG Project than patients with monophasic MOGAD. However, the strength is that this is the only study to report the impact of MOGAD and the diagnostic pathway from the patients’ perspective; even if there are biases towards overemphasis, we highlight areas that require improvement. There is precedent for patient direct surveys in neurology [41, 42], which we considered the most feasible approach for patients with a rare disease such as MOGAD. As MOGAD is poorly understood and under-recognized as a distinct disease, we believe the potential for false-positive or false-negative data to be low, and there was no evidence of fraudulent responses. Given the rarity of MOGAD and the dependence on the presence of MOG antibodies for diagnosis, it would be anticipated that false identification would be rare, although not impossible. Of particular concern would be the interpretation of low-titre MOG antibodies as causative of neurological or quasi-neurological disease. A final limitation is that the diagnostic pathway, particularly in MOGAD, which only had commercial testing available in the past half-decade, is likely to be different depending on the age of symptom onset. The year that patients experienced initial symptoms or the year that a MOGAD diagnosis was received was not asked; these questions should be included in future surveys. Re-evaluation of the diagnostic pathway and clinical experience of patients would be beneficial as MOGAD testing and diagnosis improve in the future.

Conclusions

This study highlights several challenges in the often protracted and multi-step patient pathway towards MOGAD diagnosis. Receiving an alternative primary diagnosis and delay to final MOGAD diagnosis were associated with increased frustration, physical impairment and reduced health-related quality of life. The data from this survey highlight the need for improved awareness of MOGAD in the medical community and the importance of early MOGAD diagnosis. New expert consensus recommendations for MOGAD disease definition and diagnostic criteria [28] will help in this respect. Further research is needed to assess the impact of earlier MOGAD diagnosis on long-term disease burden and health-related quality of life from patient and caregiver perspectives.