Do Early Relapses Predict the Risk of Long-Term Relapsing Disease in an Adult and Paediatric Cohort with MOGAD?

OBJECTIVE: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can be monophasic or relapsing, with early relapse being a feature. However, the relevance of early relapse on longer-term relapse risk is unknown. Here, we investigate whether early relapses increase longer-term relapse risk in patients with MOGAD. METHODS: A retrospective analysis of 289 adult- and pediatric-onset patients with MOGAD followed for at least 2 years in 6 specialized referral centers. "Early relapses" were defined as attacks within the first 12 months from onset, with "very early relapses" defined within 30 to 90 days from onset and "delayed early relapses" defined within 90 to 365 days. "Long-term relapses" were defined as relapses beyond 12 months. Cox regression modeling and Kaplan-Meier survival analysis were used to estimate the long-term relapse risk and rate. RESULTS: Sixty-seven patients (23.2%) had early relapses with a median number of 1 event. Univariate analysis revealed an elevated risk for long-term relapses if any "early relapses" were present (hazard ratio [HR] = 2.11, p < 0.001), whether occurring during the first 3 months (HR = 2.70, p < 0.001) or the remaining 9 months (HR = 1.88, p = 0.001), with similar results yielded in the multivariate analysis. In children with onset below aged 12 years, only delayed early relapses were associated with an increased risk of long-term relapses (HR = 2.64, p = 0.026). INTERPRETATION: The presence of very early relapses and delayed early relapses within 12 months of onset in patients with MOGAD increases the risk of long-term relapsing disease, whereas a relapse within 90 days appears not to indicate a chronic inflammatory process in young pediatric-onset disease. ANN NEUROL 2023;94:508-517.

Factors Associated With Relapse and Treatment of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease in the United Kingdom.

Importance: Longer-term outcomes and risk factors associated with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are not well established. Objective: To investigate longer-term risk of relapse and factors associated with this risk among patients with MOGAD. Design, Setting, and Participants: This large, single-nation, prospective cohort study was conducted among 276 patients with MOGAD at 5 health care centers in the UK. Data from January 1973 to March 2020 were collected from 146 patients at Oxford and its outreach sites, 65 patients at Liverpool, 32 patients at a children's hospital in Birmingham, 22 patients at a children's hospital in London, and 11 patients at Cardiff, Wales. Data were analyzed from April through July 2020. Main Outcomes and Measures: Risk of relapse and annualized relapse rate were evaluated according to different baseline features, including onset age, onset phenotype, and incident vs nonincident group, with the incident group defined as patients diagnosed with antibodies against myelin oligodendrocyte glycoprotein before a second attack. Time to next relapse among patients experiencing relapse was measured and compared between the maintenance therapy subgroup and each first-line treatment group. The no-treatment group was defined as the off-treatment phase among patients who were relapsing, which could occur between any attack or between the last attack and last follow-up. Results: Among 276 patients with MOGAD, 183 patients were identified as being part of the incident group. There were no differences in mean (SD) onset age between total and incident groups (26.4 [17.6] years vs 28.2 [18.1] years), and female patients were predominant in both groups (166 [60.1%] female patients vs 106 [57.9%] female patients). The most common presentation overall was optic neuritis (ON) (119 patients among 275 patients with presentation data [43.3%]), while acute disseminated encephalomyelitis (ADEM), brain, or brainstem onset was predominant among 69 patients aged younger than 12 years (47 patients [68.1%]), including 41 patients with ADEM (59.4%). In the incident group, the 8-year risk of relapse was 36.3% (95% CI, 27.1%-47.5%). ON at onset was associated with increased risk of relapse compared with transverse myelitis at onset (hazard ratio [HR], 2.66; 95% CI, 1.01-6.98; P = .047), but there was no statistically significant difference with adjustment for a follow-on course of corticosteroids. Any TM at onset (ie, alone or in combination with other presentations [ie, ON or ADEM, brain, or brain stem]) was associated with decreased risk of relapse compared with no TM (HR, 0.41; 95% CI, 0.20-0.88; P = .01). Young adult age (ie, ages >18-40 years) was associated with increased risk of relapse compared with older adult age (ie, ages >40 years) (HR, 2.71; 95% CI, 1.18-6.19; P = .02). First-line maintenance therapy was associated with decreased risk of relapse when adjusted for covariates (prednisolone: HR, 0.33; 95% CI, 0.12-0.92; P = .03; prednisolone, nonsteroidal immunosuppressant, or combined: HR, 0.51; 95% CI, 0.28-0.92; P = .03) compared with the no-treatment group. Conclusions and Relevance: The findings of this cohort study suggest that onset age and onset phenotype should be considered when assessing subsequent relapse risk and that among patients experiencing relapse, prednisolone, first-line immunosuppression, or a combination of those treatments may be associated with decreased risk of future relapse by approximately 2-fold. These results may contribute to individualized treatment decisions.

A clinico-neurophysiological study of urogenital dysfunction in MOG-antibody transverse myelitis.

OBJECTIVE: To assess the clinical, urodynamic, and neurophysiologic features of patients with persisting bladder, bowel, and sexual dysfunction after transverse myelitis in myelin oligodendrocyte glycoprotein antibody (MOG-Ab) disease. METHODS: Patients with a history of MOG-Ab disease-related transverse myelitis seen prospectively in a tertiary center uro-neurology service between 2017 and 2019 were included. They received cross-sectional clinical assessment; completed standardized questionnaires on bladder, bowel, and sexual symptoms; and underwent urodynamic and pelvic neurophysiologic investigations. RESULTS: Twelve patients (9 male) were included with a total of 17 episodes of transverse myelitis. Mean age at first attack was 26 (SD 9) years, and median follow-up duration was 50 (interquartile range 32-87) months. Acute urinary retention requiring bladder catheterization occurred in 14 episodes and was the first symptom in 10 episodes. Patients with lesions affecting the conus medullaris required catheterization for significantly longer durations than those without a conus lesion (median difference 15.5 days, p = 0.007). At follow-up, all patients had recovered full ambulatory function, but persisting bladder and bowel dysfunction moderately or severely affected quality of life in 55% and 36%, respectively, and 82% had sexual dysfunction. Pelvic neurophysiology demonstrated abnormal residual conus function in 6 patients. Urodynamic findings predominantly showed detrusor overactivity and/or detrusor-sphincter dyssynergia, indicative of a supraconal pattern of lower urinary tract dysfunction. CONCLUSIONS: Persisting urogenital and bowel dysfunction is common despite motor recovery. Although a proportion of patients had neurophysiologic evidence of residual conus abnormalities at follow-up, predominant urodyamic findings suggest that ongoing lower urinary tract dysfunction results from supraconal injury.

Optical coherence tomography in central nervous system demyelinating diseases related optic neuritis.

AIM: To compare the thickness of the peripapillary retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) among patients with various forms of optic neuritis (ON) and to identify whether any particular parameters or their thinning pattern can be used to distinguish the type of ON. METHODS: This prospective study was conducted at the Department of Ophthalmology, Faculty of Medicine, Siriraj Hospital, Thailand, between January, 2015 and December, 2016. We enlisted patients over 18 years of age with history of ON and categorized patients into 4 groups: 1) aquaporin 4 antibodies (AQP4-IgG) positive; 2) multiple sclerosis (MS); 3) myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) positive; 4) idiopathic-ON patients. Healthy controls were also included during the same study period. All patients underwent complete ophthalmological examination and spectral domain optical coherence tomography (OCT) imaging to analyze RNFL and GCIPL thickness after at least 3mo since the last episode of acute ON. The generalized estimating equation (GEE) models were used to compare the data amongst ON groups. RESULTS: Among 87 previous ON eyes from 57 patients (43 AQP4-IgG+ON, 17 MS-ON, 8 MOG-IgG+ON, and 19 idiopathic-ON), mean logMAR visual acuity of AQP4-IgG+ON, MS-ON, MOG-IgG+ON, and idiopathic-ON groups was 0.76±0.88, 0.12±0.25, 0.39±0.31, and 0.75±1.08, respectively. Average, superior, and inferior RNFL were significantly reduced in AQP4-IgG+ON, MOG-IgG+ON and idiopathic-ON eyes, relative to those of MS-ON. Differences were not statistically significant for RNFL or GCIPL between the AQP4-IgG+ON and MOG-IgG+ON groups, whereas visual acuity in MOG-IgG+ON was slightly, but not significantly, better (0.39 vs 0.76). Although RNFL thickness in MOG-IgG+ON was significantly reduced as compared to MS-ON, mean visual acuity and GCIPL were not different. CONCLUSION: Thinning of superior and inferior quadrants of RNFL are more commonly seen in MOG-IgG+ON and AQP4-IgG+ON. Long term visual acuity in MOG-IgG+ON is often better than AQP4-IgG+ON, whereas the structural change from OCT is comparable.

Visual function and inner retinal structure correlations in aquaporin-4 antibody-positive optic neuritis.

PURPOSE: To investigate the correlation between visual function and thinning of the retinal nerve fiber layer (RNFL) and the macular ganglion cell-inner plexiform layer (GCIPL) as measured by optical coherence tomography (OCT) in eyes with aquaporin-4 IgG-positive optic neuritis (AQP4-IgG-positive ON). STUDY DESIGN: Prospective study. METHODS: Patients with a history of ON were categorized into 2 groups: the AQP4-IgG-positive group and the AQP4-IgG-negative group. Patients with multiple sclerosis were excluded. All patients underwent ophthalmologic examination and OCT imaging at least 6 months after the last episode of acute ON. Visual function and inner retinal structure correlations were analyzed using Pearson correlation and regression analyses. RESULTS: Thirty-one previous ON eyes of 17 AQP4-IgG-positive patients and 21 previous ON eyes of 15 AQP4-IgG-negative patients were registered. Visual function, especially the visual field, was better correlated with RNFL than with macular GCIPL. The best correlation between visual function and RNFL was the linear model, whereas the best correlation between visual function and GCIPL was the nonlinear model (inverse regression). Regression models revealed worse visual function in AQP4-IgG-positive ON than in AQP4-IgG-negative ON, whereas no differences in RNFL and GCIPL were found between the 2 groups. CONCLUSIONS: RNFL measured by OCT can be a useful retinal structure for estimating and monitoring visual field loss in AQP4-IgG-positive ON patients, particularly in patients whose visual field cannot be quantitated. The correlation between visual function and the inner retinal structure of eyes with AQP4-IgG is unique and differs from that of eyes without AQP4-IgG.

The characteristics of spinal imaging in different types of demyelinating diseases.

BACKGROUND: Transverse myelitis is the common presentation in demyelinating conditions. OBJECTIVE: To determine the characteristics of spinal lesions among each type of demyelinating diseases. METHODS: Medical records and spinal imaging of patients who were [1] older than 18years, [2] had at least one attack of TM, [3] had available spinal MRI data and [4] were tested for aquaporin-4 antibody were included. RESULTS: One hundred and fifty-eight patients were eligible (27 clinically isolated syndrome [CIS], 38 MS, 55 seropositive neuromyelitis optica spectrum disorders [NMOSD], 9 seronegative NMOSD, and 29 idiopathic transverse myelitis [IDD-TM]). All groups showed female preponderance and no difference of age at onset. In each patient group, no significant difference in the mean number of spinal lesions was found. The most common levels of involvement were thoracic in IDD-TM, cervical in CIS and MS, as well as cervico-thoracic in both NMOSD groups. Long extensive TM was the most common finding in both the seropositive and seronegative NMOSD groups compared to the other groups. Peripheral location and <30% of spinal cord area involvement were the characteristic findings in CIS and MS. Central location and intermediately involved of the cross-sectional cord area were the determinants for the seropositive and seronegative NMOSD groups, respectively. CONCLUSION: Spinal MRI findings can help to differentiate among demyelinating diseases in who presented with TM.

Clock drawing test (CDT) and activities of daily living (ADL) questionnaire as a short screening test for dementia in Thai population.

OBJECTIVE: This paper was to develop a short bedside cognitive behavioral test for screening dementia in Thai population. MATERIAL AND METHOD: The 182 elderly subjects were gathered from a community near the vicinity of Siriraj Hospital. Family interview, CDT ADL assessment were assessed by trained nurse. Neurology residents conducted TMSE and Physical examination. The diagnosis of dementia was using the DSM IV criteria. RESULTS: 67 subjects were diagnosed with dementia by DSM IV criteria. The CDT at cut off score of 7 had sensitivity 83.8% and specificity 65.2% with area under ROC being 0.825. For ADL assessment at the cut off score of 5 had sensitivity 74.6% and specificity 79.1% with the area under ROC being 0.849. Using CDT and ADL questionnaires together increased the area under the curve from 0.825 to 0.905. CONCLUSION: The combination of CDT and ADL questionnaire help increase sensitivity and specificity for screening dementia.