Relapse recovery in multiple sclerosis: Effect of treatment and contribution to long-term disability

Sotiropoulos, Marinos G; Lokhande, Hrishikesh; Healy, Brian C.; Polgar‐Turcsanyi, Mariann; Glanz, Bonnie I.; Bakshi, Rohit; Weiner, Howard L.; Chitnis, Tanuja

doi:10.1177/20552173211015503

Cited by 11 publications

(11 citation statements)

References 40 publications

(91 reference statements)

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“…This observational study has several important limitations. The average time from symptom onset to first visit at our centre was 8.4 years, and thus the baseline assessment for each patient was limited in terms of baseline examination and early attack history, despite being previously identified as important factors for long-term outcomes and may help further stratify patients with younger age at MS onset into higher to lower risk groups 7 9 10 39. Likewise, initial MRI was not available for every patient if scans occurred out-of-hospital.…”

Section: Discussionmentioning

confidence: 99%

Younger age at multiple sclerosis onset is associated with worse outcomes at age 50

Bose

Healy

Barro

et al. 2022

J Neurol Neurosurg Psychiatry

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ObjectiveOlder age at multiple sclerosis (MS) onset has been associated with worse 10-year outcomes. However, disease duration often exceeds 10 years and age-related comorbidities may also contribute to disability. We investigated patients with>10 years disease duration to determine how age at MS onset is associated with clinical, MRI and occupational outcomes at age 50.MethodsWe included patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women’s Hospital with disease duration>10 years. Outcomes at age 50 included the Expanded Disability Status Scale (EDSS), development of secondary-progressive multiple sclerosis (SPMS), brain T2-lesion volume (T2LV) and brain parenchymal fraction (BPF), and occupational status. We assessed how onset age was independently associated with each outcome when adjusting for the date of visit closest to age 50, sex, time to first treatment, number of treatments by age 50 and exposure to high-efficacy treatments by age 50.ResultsWe included 661 patients with median onset at 31.4 years. The outcomes at age 50 were worse the younger first symptoms developed: for every 5 years earlier, the EDSS was 0.22 points worse (95% CI: 0.04 to 0.40; p=0.015), odds of SPMS 1.33 times higher (95% CI: 1.08 to 1.64; p=0.008), T2LV 1.86 mL higher (95% CI: 1.02 to 2.70; p<0.001), BPF 0.97% worse (95% CI: 0.52 to 1.42; p<0.001) and odds of unemployment from MS 1.24 times higher (95% CI: 1.01 to 1.53; p=0.037).ConclusionsAll outcomes at age 50 were worse in patients with younger age at onset. Decisions to provide high-efficacy treatments should consider younger age at onset, equating to a longer expected disease duration, as a poor prognostic factor.

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Section: Discussionmentioning

confidence: 99%

Younger age at multiple sclerosis onset is associated with worse outcomes at age 50

Bose

Healy

Barro

et al. 2022

J Neurol Neurosurg Psychiatry

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“…Baseline assessment incorporated the EDSS, 6 individual FSS, T25FW

\geq

6 seconds, 36 presence of spinal cord or infratentorial lesions on initial MRI, 37 and baseline T2LV and BPF 10,12 . Early disease activity within 3 years of onset included annualized relapse rate (ARR); attack symptomatology of optic neuritis, motor, sensory, or brainstem/cerebellar; attacks treated with glucocorticoids; attacks while on DMT; poor attack recovery, defined as EDSS worsening of

\geq

1.0, confirmed 6 months after attack 38 ; and gadolinium‐enhancing or new or enlarging T2 brain or spinal cord lesions 7 . DMT information included time to first DMT, 39 number of DMTs, and presence of high‐efficacy DMTs, defined as fingolimod, natalizumab, ocrelizumab, rituximab, or cyclophosphamide, within 3 years of onset 23 …”

Section: Methodsmentioning

confidence: 99%

Early Predictors of Clinical andMRIOutcomes UsingLeast Absolute Shrinkage and Selection Operator (LASSO)in Multiple Sclerosis

Bose

Healy

Lokhande

et al. 2022

Annals of Neurology

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Objective: The objective of this study was to identify predictors in common between different clinical and magnetic resonance imaging (MRI) outcomes in multiple sclerosis (MS) by comparing predictive models. Methods: We analyzed 704 patients from our center seen at MS onset, measuring 37 baseline demographic, clinical, treatment, and MRI predictors, and 10-year outcomes. Our primary aim was identifying predictors in common among clinical outcomes: aggressive MS, benign MS, and secondary-progressive (SP)MS. We also investigated MRI outcomes: T2 lesion volume (T2LV) and brain parenchymal fraction (BPF). The performance of the full 37-predictor model was compared with a least absolute shrinkage and selection operator (LASSO)-selected model of predictors in common between each outcome by the area under the receiver operating characteristic curves (AUCs). Results: The full 37-predictor model was highly predictive of clinical outcomes: in-sample AUC was 0.91 for aggressive MS, 0.81 for benign MS, and 0.81 for SPMS. After variable selection, 10 LASSO-selected predictors were in common between each clinical outcome: age, Expanded Disability Status Scale, pyramidal, cerebellar, sensory and bowel/ bladder signs, timed 25-foot walk ≥6 seconds, poor attack recovery, no sensory attacks, and time-to-treatment. This reduced model had comparable cross-validation AUC as the full 37-predictor model: 0.84 versus 0.81 for aggressive MS, 0.75 versus 0.73 for benign MS, and 0.76 versus 0.75 for SPMS, respectively. In contrast, 10-year MRI outcomes were more strongly influenced by initial T2LV and BPF than clinical outcomes. Interpretation: Early prognostication of MS is possible using LASSO modeling to identify a limited set of accessible clinical features. These predictive models can be clinically usable in treatment decision making once implemented into web-based calculators.

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“…as the trajectory of recovery stays similar with subsequent demyelinating events pointing to individual specific factors responsible for a "good" vs "poor" recovery paradigm 4,8 . While younger age and lower severity of relapse are well established predictors of relapse remission, complete recovery may mask the accumulation of neuroaxonal damage below the clinical threshold creating the necessity for reliable biomarkers reflecting subclinical processes [8][9][10][11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

“…Cohort characteristicsMean retinal thinning from OCT baseline to OCT follow-up was 25.3µm (SD 22.7) in pRNFL and13.2µm (SD 7.9) in GCIPL, while from OCT acute to OCT follow-up it was 43.1µm (SD 45.2) in ∆pRNFL and 12.1µm (SD 8.2) in ∆GCIPL.Visual impairment at ON (visual FS) was weakly to moderately correlated with retinal thinning from OCT baseline to OCT follow-up in both pRNFL (Spearman rho = 0.219, p=0.046) and GCIPL (Spearman rho = 0.326, p=0.002), whereas from OCT acute to OCT follow-up only ∆GCIPL (Spearman rho = 0.302, p=0.008) but not ∆pRNFL (Spearman rho = 0.103, p=0.374) correlated with visual impairment. Similarly, complete ON recovery (visual FS post-relapse ≤ pre-relapse) was associated with lower pRNFL and GCIPL thinning from OCT baseline to OCT follow-up compared to incomplete ON recovery (∆pRNFL: 19.9µm [SD 24.3] vs. 31.1µm [SD 29.4], p=0.008; ∆GCIPL: 10.2µm [SD 10.8] vs. 16.5µm [SD 11.6], p<0.001).…”

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confidence: 99%

Retinal Layer Thinning After Optic Neuritis Is Associated With Future Relapse Remission in Relapsing Multiple Sclerosis

et al. 2022

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Introduction:Remission of relapses is an important contributor to both short- and long-term prognosis in relapsing multiple sclerosis (RMS). In MS-associated acute optic neuritis (MS-ON), retinal layer thinning measured by optical coherence tomography (OCT) is a reliable biomarker of both functional recovery and the degree of neuroaxonal damage. However, prediction of non-ON relapse remission is challenging. We aimed to investigate whether retinal thinning after ON is associated with relapse remission after subsequent non-ON relapses.Methods:For this longitudinal observational study from the Vienna MS database (VMSD), we included MS patients with 1) an episode of acute ON, 2) available spectral-domain OCT scans within 12 months before ON onset (OCTbaseline), within 1 week after ON onset (OCTacute) and 3-6 months after ON (OCTfollow-up), and 3) at least one non-ON relapse after the ON episode. Subsequent non-ON relapses were classified as displaying either complete or incomplete remission based on change in expanded disability status scale (EDSS) assessed 6 months post-relapse. Association of retinal thinning in peripapillary retinal nerve fiber layer (ΔpRNFL) and macular ganglion-cell-and-inner-plexiform-layer (ΔGCIPL) with incomplete remission was tested by multivariate logistic regression models adjusting for age, sex, disease duration, relapse severity, time to steroid treatment, and DMT status.Results:We analyzed 167 MS patients (mean age 36.5 years [SD 12.3], 71.3% female, mean disease duration 3.1 years [SD 4.5]) during a mean observation period of 3.4 years (SD 2.8) after the ON episode. In 61 patients (36.5%) at least one relapse showed incomplete remission. In the multivariable analyses, incomplete remission of non-ON relapse was associated with ΔGCIPL thinning both from OCTbaseline to OCTfollow-up and from OCTacute to OCTfollow-up (odds ratio [OR] 2.4 per 5µm, p<0.001, respectively), independently explaining 29% and 27% of variance respectively. ΔpRNFL was also associated with incomplete relapse remission when measured from OCTbaseline to OCTfollow-up (OR 1.9 per 10µm, p<0.001) independently accounting for 22% of variance, but not when measured from OCTacute to OCTfollow-up.Conclusions:Retinal layer thinning after optic neuritis may be useful as a marker of future relapse remission in RMS.

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Relapse recovery in multiple sclerosis: Effect of treatment and contribution to long-term disability

Cited by 11 publications

References 40 publications

Younger age at multiple sclerosis onset is associated with worse outcomes at age 50

Younger age at multiple sclerosis onset is associated with worse outcomes at age 50

Early Predictors of Clinical andMRIOutcomes UsingLeast Absolute Shrinkage and Selection Operator (LASSO)in Multiple Sclerosis

Retinal Layer Thinning After Optic Neuritis Is Associated With Future Relapse Remission in Relapsing Multiple Sclerosis

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