Objective
The main objective was to compare clinical features, disease course, and myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) dynamics between children and adults with MOG‐Ab–associated ...disease (MOGAD).
Methods
This retrospective multicentric, national study included 98 children and 268 adults with MOGAD between January 2014 and September 2019. Cox regression model for recurrent time‐to‐event data and Kaplan–Meier curves for time to antibody negativity were performed for the objectives.
Results
Isolated optic neuritis was the most frequent clinical presentation in both children (40.8%) and adults (55.9%, p = 0.013), and acute disseminated encephalomyelitis syndrome was more frequent in children (36.7% vs 5.6%, p < 0.001). Compared to adults, children displayed better recovery (Expanded Disability Status Scale ≥ 3.0 at last follow‐up reached only by 10 of 97 10.3% vs 66/247 26.7%, p < 0.001). In the multivariate analysis, adults were at higher risk of relapse than children (hazard ratio = 1.41, 95% confidence interval CI = 1.12–1.78, p = 0.003). At 2 years, 64.2% (95% CI = 40.9–86.5) of nonrelapsing children became MOG‐Ab negative compared to 14.1% (95% CI = 4.7–38.3) of relapsing children (log‐rank p < 0.001), with no differences observed in adults (log‐rank p = 0.280).
Interpretation
MOGAD patients differ in the clinical presentation at onset, showing an age‐related shift in the clinical features across age groups. Compared to children, adults have a higher risk of relapse and worse functional recovery. Finally, children with monophasic disease become MOG‐Ab negative earlier than relapsing children, but this is not true in adults. Considering these differences, management and treatment guidelines should be considered independently in children and adults. ANN NEUROL 2021;89:30–41
The discovery of highly specific auto-antibodies directed against the water channel aquaporin 4 was a quantum leap in the definition, classification and management of neuromyelitis optica (NMO). ...Herein, we propose an update on epidemiological, clinical and therapeutic advances in the field, underlining unmet needs.
Large-scale epidemiological studies have recently provided a more precise evaluation of NMO prevalence and a better stratification regarding ethnicity and sex. New criteria have been proposed for so-called NMO spectrum disorders (NMOSD) and their relevance is currently being assessed. The identification of a new clinical entity associated to antibodies against myelin oligodendrocyte glycoprotein questions the border of NMOSD.
The concept of NMOSD is opening a new era in clinical practice, allowing an easier and more homogeneous diagnosis and an increase in newly identified cases. This will facilitate clinical studies and support new therapeutic trial. Future researches should focus on the position of seronegative NMOSD and myelin oligodendrocyte glycoprotein-IgG disorders in the field and on promising strategies, including the immune tolerisation approaches, to eventually cure NMO.
Progression independent of relapse activity (PIRA) is the main event responsible for irreversible disability accumulation in relapsing multiple sclerosis (MS).
To investigate clinical and ...neuroimaging predictors of PIRA at the time of the first demyelinating attack and factors associated with long-term clinical outcomes of people who present with PIRA.
This cohort study, conducted from January 1, 1994, to July 31, 2021, included patients with a first demyelinating attack from multiple sclerosis; patients were recruited from 1 study center in Spain. Patients were excluded if they refused to participate, had alternative diagnoses, did not meet protocol requirements, had inconsistent demographic information, or had less than 3 clinical assessments.
Exposures included (1) clinical and neuroimaging features at the first demyelinating attack and (2) presenting PIRA, ie, confirmed disability accumulation (CDA) in a free-relapse period at any time after symptom onset, within (vs after) the first 5 years of the disease (ie, early/late PIRA), and in the presence (vs absence) of new T2 lesions in the previous 2 years (ie, active/nonactive PIRA).
Expanded Disability Status Scale (EDSS) yearly increase rates since the first attack and adjusted hazard ratios (HRs) for predictors of time to PIRA and time to EDSS 6.0.
Of the 1128 patients (mean SD age, 32.1 8.3 years; 781 female individuals 69.2%) included in the study, 277 (25%) developed 1 or more PIRA events at a median (IQR) follow-up time of 7.2 (4.6-12.4) years (for first PIRA). Of all patients with PIRA, 86 of 277 (31%) developed early PIRA, and 73 of 144 (51%) developed active PIRA. Patients with PIRA were slightly older, had more brain lesions, and were more likely to have oligoclonal bands than those without PIRA. Older age at the first attack was the only predictor of PIRA (HR, 1.43; 95% CI, 1.23-1.65; P < .001 for each older decade). Patients with PIRA had steeper EDSS yearly increase rates (0.18; 95% CI, 0.16-0.20 vs 0.04; 95% CI, 0.02-0.05; P < .001) and an 8-fold greater risk of reaching EDSS 6.0 (HR, 7.93; 95% CI, 2.25-27.96; P = .001) than those without PIRA. Early PIRA had steeper EDSS yearly increase rates than late PIRA (0.31; 95% CI, 0.26-0.35 vs 0.13; 95% CI, 0.10-0.16; P < .001) and a 26-fold greater risk of reaching EDSS 6.0 from the first attack (HR, 26.21; 95% CI, 2.26-303.95; P = .009).
Results of this cohort study suggest that for patients with multiple sclerosis, presenting with PIRA after a first demyelinating event was not uncommon and suggests an unfavorable long-term prognosis, especially if it occurs early in the disease course.
Objective:
We aimed to report the frequency and implications of antibodies to myelin oligodendrocyte glycoprotein (MOG-ab) in adults with demyelinating syndromes suspicious for neuromyelitis optica ...(NMO).
Methods:
Samples from 174 patients (48 NMO, 84 longitudinally extensive myelitis (LETM), 39 optic neuritis (ON), and three acute disseminated encephalomyelitis (ADEM) who presented initially with isolated LETM) were retrospectively examined for AQP4-ab and MOG-ab using cell-based assays.
Results:
MOG-ab were found in 17 (9.8%) patients, AQP4-ab in 59 (34%), and both antibodies in two (1.1%). Among the 17 patients with MOG-ab alone, seven (41%) had ON, five (29%) LETM, four (24%) NMO, and one (6%) ADEM. Compared with patients with AQP4-ab, those with MOG-ab were significantly younger (median: 27 vs. 40.5 years), without female predominance (53% vs. 90%), and the clinical course was more frequently monophasic (41% vs. 7%) with a benign outcome (median Expanded Disability Status Scale: 1.5 vs. 4.0). In eight patients with paired serum-cerebrospinal fluid (CSF) samples, five had MOG-ab in both samples and three only in serum. Antibody titres did not differ among clinical phenotypes or disease course. MOG-ab remained detectable in 12/14 patients (median follow-up: 23 months) without correlation between titres’ evolution and outcome.
Conclusion:
MOG-ab identify a subgroup of adult patients with NMO, LETM and ON that have better outcome than those associated with AQP4-ab. MOG-ab are more frequently detected in serum than CSF and the follow-up of titres does not correlate with outcome.
Background and purpose
Non‐(acute disseminated encephalomyelitis) (non‐ADEM) encephalitis and/or fluid attenuated inversion recovery hyperintense lesions in ...anti‐myelin‐oligodendrocyte‐glycoprotein‐associated encephalitis with seizures (FLAMES) are rarely described in patients with myelin oligodendrocyte glycoprotein (MOG) antibodies (Abs). The aim was (i) to describe the clinical features and disease course of children and adults with non‐ADEM encephalitis and/or FLAMES associated with MOG Abs and (ii) to describe their association with other central nervous system autoantibodies.
Methods
This was a systematic review following the PRISMA guidelines. Patients fulfilled criteria for non‐ADEM encephalitis and/or FLAMES, and all were MOG Ab positive.
Results
In total, 83 (79%) patients with non‐ADEM encephalitis (48 also had FLAMES) and 22 (21%) with isolated FLAMES were included. At the first episode, children (n = 45) had more infections (11/45, 24.4%; p = 0.017) and more of the phenotype consisting of non‐ADEM encephalitis (42/45, 93.3%; p = 0.014) than adults (n = 38). Children had more episodes consistent with working memory deficits (25/54, 46.3%; p = 0.014) but fewer psychiatric symptoms (16/54, 29.6%; p = 0.002). Twenty‐eight (40.6%) of 69 patients had N‐methyl‐d‐aspartate receptor (NMDAR) Abs in cerebrospinal fluid (CSF), being more frequent in adults (19/29, 65.5%; p < 0.001). Compared to negatives, positive CSF NMDAR Abs had more relapses (14/20, 70%; p = 0.050), required ventilatory support more frequently (8/34, 23.5%; p = 0.009) and had more psychiatric episodes (28/34, 82%; p < 0.001) or abnormal movements (14/34, 41.2%; p = 0.008). Apart from an older age in FLAMES, positive and negative CSF NMDAR Ab groups shared similar features.
Conclusion
Non‐ADEM encephalitis patients with MOG Abs show specific clinical and radiological features, depending on the age at first episode. The presence of MOG Abs in non‐ADEM encephalitis patients should not rule out to test other autoantibodies, especially concomitant NMDAR Abs in patients with suggestive symptoms such as behavioural or movement alterations.
In the current systematic review, patients with myelin oligodendrocyte glycoprotein (MOG) antibodies that fulfil Graus 2016 criteria for autoimmune encephalitis and Budhram 2019 criteria for fluid attenuated inversion recovery (FLAIR) hyperintense lesions in anti‐MOG‐associated encephalitis with seizures (FLAMES) were included. Patients with acute disseminated encephalomyelitis (ADEM) features or lack of clinical information were excluded. The clinical and paraclinical features of 83 patients with non‐ADEM encephalitis (48 of them also had FLAMES) and 22 patients fulfilling FLAMES criteria are reported in detail. A thorough comparison between those with and without N‐methyl‐d‐aspartate receptor antibodies is also depicted.
Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) have been reported in acute demyelinating encephalomyelitis (ADEM), optic neuritis (ON), and neuromyelitis optica spectrum disorders (NMOSD) in ...adults and pediatrics. We aimed to delineate the common features of MOG-Ab-related disorders in children and adults, and report uncommon presentations. Twenty-seven consecutive pediatric and adult patients testing positive for MOG-Ab, with a minimum follow-up of 6 months, were included. Comprehensive epidemiological, clinical, radiological, and laboratory data were retrospectively analyzed. Additionally, we compared radiological features between ADEM MOG-Ab-positive patients, and a group of ADEM MOG-Ab-negative ones, recruited during the same period. Among the whole cohort, 13 (48.1%) were pediatric, and 14 (51.9%) were female. MOG-Ab-related disorders comprised eight ADEM, eight ON, five isolated myelitis, four with NMOSD and two patients with multiple sclerosis, at last follow-up. After a median follow-up of 17.8 months, 11 (40.7%) patients presented a relapse. The most frequent clinical phenotype at onset was encephalopathy in pediatrics (53.9%) and myelitis in adults (50%) (
p
= 0.013). There were no other differences between both groups. When comparing ADEM MOG-Ab positive and negative patients, bilateral thalamic lesions were more often found in the positive group (
p
= 0.010). Unusual presentations were identified in three patients: patchy spinal cord gadolinium-enhancing lesions, an associated teratoma, and one presented with status epilepticus. MOG-Ab-related disorders shared common clinical and prognostic features, but encompass a spectrum wider than recently reported.
The clinical interest for auto-antibodies against myelin oligodendrocyte glycoprotein (MOG) has recently reemerged, with the use of more specific detection methods. Large national cohorts have ...allowed characterizing a more precise clinical spectrum delineated by the presence of human MOG-antibodies.
In adults with MOG-antibodies, optic neuritis is the most frequent clinical presentation, with features different from multiple sclerosis (MS), including bilateral involvement and predilection for the anterior part of the optic nerve. Myelitis and brainstem syndrome are also frequent, and may clinically mimic neuromyelitis optica spectrum disorders (NMOSD). Despite the frequently severe clinical presentation, most of patients recover quickly after steroids initiation. Other less typical presentations include encephalitis with seizures, cranial nerve involvement, and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids-like. Although the majority of adult patients follow a relapsing course, long-term prognosis differs from aquaporin-4-antibodies NMOSD, with only a small proportion of patients with a poor outcome.
MOG-antibodies-associated disease is a new entity in the spectrum of inflammatory demyelinating diseases, distinct from both MS and NMOSD. There is a crucial need to identify factors associated to the risk of relapse or poor outcome, to seek patient subgroups in which immunoactive treatments could be beneficial.
Objective:
We aimed to investigate the frequency and clinical significance of antibodies to myelin oligodendrocyte glycoprotein (MOG-abs) in patients who presented with a first episode of ...seronegative aquaporin 4 antibody (AQP4-ab) longitudinally extensive transverse myelitis (LETM).
Methods:
Epidemiological, clinical, and paraclinical data of 56 patients from three European centres were analysed. Patients were retrospectively tested for MOG-abs and AQP4-abs, by cell-based assays.
Findings:
Thirteen (23.2%) patients were MOG-ab positive. Among the 56 patients, six (10.7%) converted to neuromyelitis optica (NMO), one (1.8%) to multiple sclerosis (MS), nine (16.1%) had recurrent LETM, and 40 (71.4%) remained as monophasic LETM. Compared with seronegative patients, those with MOG-abs were younger (median: 32.5 vs 44 years; p=0.007), had cerebrospinal fluid pleocytosis more frequently (94% vs 45%, p=0.003) and had better outcome (median Expanded Disability Status Scale (EDSS) 2.0 vs 3.0, p=0.027). MOG-ab positive patients also showed an increase risk of optic neuritis relapse and NMO conversion (p=0.010).
Conclusion:
Patients with MOG-abs in AQP4-ab seronegative LETM have clinical distinctive features, higher risk of optic neuritis relapses, and better outcome than patients seronegative.
Aim
To describe cognitive abilities through the evaluation of academic difficulties in children with acute demyelinating syndromes (ADS) and myelin oligodendrocyte glycoprotein (MOG) antibodies.
...Method
This was an observational, retrospective study of a French paediatric cohort that included children aged 18 years and younger. Clinical, biological, and imaging data were collected and academic outcome was measured.
Results
Seventy‐six children were included in the study with a mean (SD) follow‐up of 4 years 7 months (6y 4mo). Median age at disease onset was 9 years 1 months (interquartile range=4y 7mo–13y 11mo; 36 females, 40 males). Thirty‐six children relapsed and 20 had academic difficulties at the last follow‐up. Academic difficulties, as well as deep grey matter and putaminal lesions (p=0.047 and p=0.006 respectively), were significantly more prevalent in children aged 10 years and younger (p=0.02). Using univariate binary regression analysis, we found that age at disease onset of 10 years and younger (odds ratio OR 3.72 95% confidence interval {CI} 1.19–11.64; p=0.024), acute disseminated encephalomyelitis at disease onset (OR 52.5 95% CI 5.97–461.4; p<0.001), and deep grey matter lesions (OR 17.33 95% CI 3.87–77.72; p<0.001) were associated with academic difficulties.
Interpretation
MOG antibody‐associated ADS have distinct clinical and radiological patterns that are age‐dependent. Indirect cognitive evaluation through academic difficulties was prevalent in younger children and is associated with specific clinical and magnetic resonance imaging factors that need to be considered earlier on when assessing this patient population.
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