Charité - Universitätsmedizin Berlin
Department of Neurology

Author Of 2 Presentations

Prognostic Factors Poster Presentation

P0509 - Utility of NEDA-3 status as a predictor of future disease activity (ID 1643)

Speakers
Presentation Number
P0509
Presentation Topic
Prognostic Factors

Abstract

Background

No evidence of disease activity (NEDA) is viewed as an important goal in relapsing multiple sclerosis (MS) and has been advocated as a benchmark for treatment decisions. However, NEDA status is maintained only by a minority of MS patients over prolonged periods, regardless of disease-modifying treatment. The predictive value and utility of NEDA in guiding individual therapy remains unclear.

Objectives

To investigate the association of NEDA-3 status and criteria subitems in a one-year reference period with subsequent disease activity.

Methods

We included 113 patients (age 35 ± 10 years, 67 (59.3%) female) with relapsing remitting MS who had annual clinical and MRI follow-up visits. There were no restrictions on disease-modifying therapy. The first year of follow-up was considered the reference period. Patients had a median of 2.8 years follow-up time (interquartile range 1.1 - 4.0 years) after the reference period. NEDA-3 status was established based on relapse assessment, 1-point increase in the expanded disability status scale (EDSS, unrelated to relapse activity) and the appearance of new T2-weighted or contrast-enhancing lesions.

Results

Patients who failed NEDA-3 criteria during the reference period had an increased rate of subsequent NEDA-3 failure (Hazard ratio (HR) 1.84, 95% confidence interval (CI) 1.12-3.02, p=0.0165). Attacks and new lesions during the reference period were associated with a new relapse (HR 2.872, CI 1.31-6.30, p=0.00843) or a new lesion (HR 2.57, CI 1.49-4.43, p=0.000691) during subsequent follow-up, respectively. An EDSS increase in the reference period was not predictive of a future failure of NEDA-3.

Conclusions

Relapses and new lesions increase the risk of future disease activity in relapsing-remitting MS, irrespective of disease-modifying therapy. Relapse-independent disability progression appears to be less useful in predicting future disease activity.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0715 - Failure of Age-Expected Brain Growth in Children with ADEM is Independent of MOG-Antibody Status (ID 893)

Abstract

Background

Acute disseminated encephalomyelitis (ADEM) is an acquired demyelinating syndrome (ADS) presenting with polyfocal neurological symptoms, encephalopathy, and predominant white matter MRI changes that mainly occurs in children. Although ADEM is typically a monophasic disease, a negative impact on brain growth over time was previously reported. Recently, it was shown that a large proportion of ADEM patients is seropositive for autoantibodies against myelin oligodendrocyte glycoprotein (MOG-abs). Furthermore, MOG-abs were associated with an increased risk for relapsing disease. However, the effect of MOG-abs on brain volume development remains unclear.

Objectives

Analysis of whole brain and ventricular volumes in children with ADEM with and without MOG-abs at disease onset and over time.

Methods

Twenty-four ADEM patients (median age 4.5 years; range 0-15; 13 females) from 12 different centers were included. MOG-abs were detected in 16 patients. All patients had a cerebral MRI scan at disease onset before steroid treatment. A total of 58 MRI scans (including 34 follow-up MRIs from 16 patients) were analyzed using FSL SIENAX for whole brain and ventricular volume. Patient brain volumes were compared to age- and gender-matched healthy controls by longitudinal mixed-effect models and group comparison (1:5; n=290) using healthy controls from the NIH Pediatric MRI Data Repository as well as an additional matched local control cohort (n=24).

Results

ADEM patients showed significantly increased ventricular volume (median volume [IQR] 34.25cm3 [17.07] vs. 22.29cm3 [9.88]; p=1.118e-05) and a trend of reduced whole brain volume (1741.9cm3 [160.1] vs. 1788.1cm3 [113.1]; p=0.055) at baseline compared to matched healthy NIH controls. Longitudinal-mixed-effect models showed failure of age-expected brain growth in all ADEM patients. Importantly, MOG-ab status was not a significant predictor of brain volume suggesting no difference in brain volume development between MOG-ab-positive and -negative patients. Patients with relapsing disease (n=6, all MOG-ab-positive) showed increased ventricular volume compared to monophasic patients at last visit (median ventricular volume z-score [IQR] 3.72 [3.58] vs. 0.38 [IQR 0.40]; p=0.04).

Conclusions

Children with ADEM exhibit significant brain volume loss and failure of age-expected brain growth compared to healthy controls. Importantly, this affects both MOG-ab-positive and -negative patients. Relapsing disease seems to be associated with more pronounced brain volume loss.

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