PMID- 27919503 OWN - NLM STAT- MEDLINE DCOM- 20170228 LR - 20220408 IS - 2211-0356 (Electronic) IS - 2211-0348 (Print) IS - 2211-0348 (Linking) VI - 10 DP - 2016 Nov TI - Binocular low-contrast letter acuity and the symbol digit modalities test improve the ability of the Multiple Sclerosis Functional Composite to predict disease in pediatric multiple sclerosis. PG - 73-78 LID - S2211-0348(16)30140-7 [pii] LID - 10.1016/j.msard.2016.08.012 [doi] AB - BACKGROUND: Outcome measures to capture disability, such as the Multiple Sclerosis Functional Composite (MSFC), were developed to enhance outcome measurements for clinical trials in adults with multiple sclerosis (MS). The MSFC initially included three components: a timed 25-foot walk [T25FW], 9-hole peg test [9HPT], and the Paced Auditory Serial Addition Task [PASAT]. Modifications to the original MSFC, such as adding binocular low-contrast letter acuity (LCLA) or substituting the symbol digit modalities test (SDMT) for the PASAT, improved the capacity to capture neurologic impairment in adults. Similar outcome scales for pediatric MS have not yet been established. OBJECTIVE: To determine whether the three-component MSFC or a modified MSFC with LCLA and the SDMT better identifies neurological deficits in pediatric MS. METHODS: We evaluated 5 measures (T25FW, 9HPT, Children's PASAT [ChiPASAT], SDMT, and binocular LCLA [Sloan charts, 1.25% contrast]) in children with MS (disease onset <18 years) and healthy controls. To be able to compare measures whose scores have different scales, Z-scores were also created for each test based on the numbers of standard deviations from a control group mean, and these individual scale scores were combined to create composite scores. Logistic regression models, accounting for age, were used to determine whether the standard 3-component MSFC or modified versions (including 4 or 5 metrics) best distinguished children with MS from controls. RESULTS: Twenty pediatric-onset MS subjects, aged 6-21 years, and thirteen healthy controls, aged 6-19 years, were enrolled. MS subjects demonstrated worse scores on the 9HPT (p=0.004) and SDMT (p=0.001), but not the 25FTW (adjusted for height, p=0.63) or the ChiPASAT (p=0.10): all comparisons adjusted for age. Decreased (worse) binocular LCLA scores were associated with MS (vs. control status, p=0.03, logistic regression; p=0.08, accounting for age). The MSFC composite score for the traditional 3 components did not differ between the groups (p=0.28). Replacing the ChiPASAT with the SDMT (OR 0.72, p=0.05) better distinguished MS from controls. A modified MSFC-4 with the SDMT replacing the ChiPASAT and including binocular 1.25% LCLA had the greatest capacity to distinguish pediatric MS from controls (OR 0.89, p=0.04, logistic regression). Including all 5 metrics as a composite MSFC-5 did not improve the model (p=0.18). CONCLUSIONS: A modified MSFC (25FTW, 9HPT, SMDT, and binocular 1.25% LCLA) is more sensitive than the traditional MSFC or its components to capture the subtle impairments that characterize pediatric MS and should be validated in order to be considered for future pediatric MS trials. CI - Copyright A(c) 2016 Elsevier B.V. All rights reserved. FAU - Waldman, Amy T AU - Waldman AT AD - Division of Neurology, The Children's Hospital of Philadelphia; Departments of Neurology and Pediatrics, Perelman School of Medicine at the University of Pennsylvania, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA. Electronic address: waldman@email.chop.edu. FAU - Chahin, Salim AU - Chahin S AD - Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, 3 W. Gates, Philadelphia, PA 19104, USA. Electronic address: Salim.Chahin@uphs.upenn.edu. FAU - Lavery, Amy M AU - Lavery AM AD - Division of Neurology, The Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA. Electronic address: Laverya@email.chop.edu. FAU - Liu, Geraldine AU - Liu G AD - Division of Neurology, The Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA. Electronic address: liug@email.chop.edu. FAU - Banwell, Brenda L AU - Banwell BL AD - Division of Neurology, The Children's Hospital of Philadelphia; Departments of Neurology and Pediatrics, Perelman School of Medicine at the University of Pennsylvania, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA. Electronic address: banwellb@email.chop.edu. FAU - Liu, Grant T AU - Liu GT AD - Neuro-ophthalmology service, The Children's Hospital of Philadelphia, Departments of Neurology and Ophthalmology, Perelman School of Medicine at the University of Pennsylvania, 3 W. Gates, Philadelphia, PA 19104, USA. Electronic address: gliu@mail.med.upenn.edu. FAU - Balcer, Laura J AU - Balcer LJ AD - Department of Neurology, New York University, 240 E. 38th Street, New York, NY 10116, USA. Electronic address: Laura.Balcer@nyumc.org. LA - eng GR - K23 NS069806/NS/NINDS NIH HHS/United States GR - K24 EY018136/EY/NEI NIH HHS/United States GR - R01 EY019473/EY/NEI NIH HHS/United States PT - Evaluation Study PT - Journal Article DEP - 20160826 PL - Netherlands TA - Mult Scler Relat Disord JT - Multiple sclerosis and related disorders JID - 101580247 SB - IM MH - Adolescent MH - Age Factors MH - Child MH - Disability Evaluation MH - Female MH - Humans MH - Logistic Models MH - Male MH - Multiple Sclerosis, Relapsing-Remitting/*diagnosis/drug therapy/physiopathology MH - Outcome Assessment, Health Care/*methods MH - Sensitivity and Specificity MH - *Visual Acuity MH - Young Adult PMC - PMC5144918 MID - NIHMS817313 OTO - NOTNLM OT - Multiple sclerosis OT - Outcome measures OT - Pediatrics EDAT- 2016/12/07 06:00 MHDA- 2017/03/01 06:00 PMCR- 2017/11/01 CRDT- 2016/12/07 06:00 PHST- 2016/04/08 00:00 [received] PHST- 2016/06/24 00:00 [revised] PHST- 2016/08/25 00:00 [accepted] PHST- 2016/12/07 06:00 [entrez] PHST- 2016/12/07 06:00 [pubmed] PHST- 2017/03/01 06:00 [medline] PHST- 2017/11/01 00:00 [pmc-release] AID - S2211-0348(16)30140-7 [pii] AID - 10.1016/j.msard.2016.08.012 [doi] PST - ppublish SO - Mult Scler Relat Disord. 2016 Nov;10:73-78. doi: 10.1016/j.msard.2016.08.012. Epub 2016 Aug 26.