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March 31, 2020; 94 (13) Article

Detection of subtle gait disturbance and future fall risk in early multiple sclerosis

Rachel Brandstadter, Oluwasheyi Ayeni, Stephen C. Krieger, Noam Y. Harel, Miguel X. Escalon, Ilana Katz Sand, Victoria M. Leavitt, Michelle T. Fabian, Korhan Buyukturkoglu, Sylvia Klineova, Claire S. Riley, Fred D. Lublin, Aaron E. Miller, James F. Sumowski
First published February 26, 2020, DOI: https://doi.org/10.1212/WNL.0000000000008938
Rachel Brandstadter
From the Department of Neurology (R.B.), University of Pennsylvania, Philadelphia; Department of Neurology (O.A.), Kaiser Permanente, Atlanta, GA; Department of Neurology (S.C.K., N.Y.H., M.X.E., I.K.S., M.T.F., S.K., F.D.L., A.E.M., J.F.S.), Icahn School of Medicine at Mount Sinai; James J. Peters Veterans Affairs Medical Center (N.Y.H.); and Department of Neurology (V.M.L, K.B., C.S.R..), Columbia University Medical Center, New York, NY.
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Oluwasheyi Ayeni
From the Department of Neurology (R.B.), University of Pennsylvania, Philadelphia; Department of Neurology (O.A.), Kaiser Permanente, Atlanta, GA; Department of Neurology (S.C.K., N.Y.H., M.X.E., I.K.S., M.T.F., S.K., F.D.L., A.E.M., J.F.S.), Icahn School of Medicine at Mount Sinai; James J. Peters Veterans Affairs Medical Center (N.Y.H.); and Department of Neurology (V.M.L, K.B., C.S.R..), Columbia University Medical Center, New York, NY.
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Stephen C. Krieger
From the Department of Neurology (R.B.), University of Pennsylvania, Philadelphia; Department of Neurology (O.A.), Kaiser Permanente, Atlanta, GA; Department of Neurology (S.C.K., N.Y.H., M.X.E., I.K.S., M.T.F., S.K., F.D.L., A.E.M., J.F.S.), Icahn School of Medicine at Mount Sinai; James J. Peters Veterans Affairs Medical Center (N.Y.H.); and Department of Neurology (V.M.L, K.B., C.S.R..), Columbia University Medical Center, New York, NY.
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Noam Y. Harel
From the Department of Neurology (R.B.), University of Pennsylvania, Philadelphia; Department of Neurology (O.A.), Kaiser Permanente, Atlanta, GA; Department of Neurology (S.C.K., N.Y.H., M.X.E., I.K.S., M.T.F., S.K., F.D.L., A.E.M., J.F.S.), Icahn School of Medicine at Mount Sinai; James J. Peters Veterans Affairs Medical Center (N.Y.H.); and Department of Neurology (V.M.L, K.B., C.S.R..), Columbia University Medical Center, New York, NY.
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Miguel X. Escalon
From the Department of Neurology (R.B.), University of Pennsylvania, Philadelphia; Department of Neurology (O.A.), Kaiser Permanente, Atlanta, GA; Department of Neurology (S.C.K., N.Y.H., M.X.E., I.K.S., M.T.F., S.K., F.D.L., A.E.M., J.F.S.), Icahn School of Medicine at Mount Sinai; James J. Peters Veterans Affairs Medical Center (N.Y.H.); and Department of Neurology (V.M.L, K.B., C.S.R..), Columbia University Medical Center, New York, NY.
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Ilana Katz Sand
From the Department of Neurology (R.B.), University of Pennsylvania, Philadelphia; Department of Neurology (O.A.), Kaiser Permanente, Atlanta, GA; Department of Neurology (S.C.K., N.Y.H., M.X.E., I.K.S., M.T.F., S.K., F.D.L., A.E.M., J.F.S.), Icahn School of Medicine at Mount Sinai; James J. Peters Veterans Affairs Medical Center (N.Y.H.); and Department of Neurology (V.M.L, K.B., C.S.R..), Columbia University Medical Center, New York, NY.
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Victoria M. Leavitt
From the Department of Neurology (R.B.), University of Pennsylvania, Philadelphia; Department of Neurology (O.A.), Kaiser Permanente, Atlanta, GA; Department of Neurology (S.C.K., N.Y.H., M.X.E., I.K.S., M.T.F., S.K., F.D.L., A.E.M., J.F.S.), Icahn School of Medicine at Mount Sinai; James J. Peters Veterans Affairs Medical Center (N.Y.H.); and Department of Neurology (V.M.L, K.B., C.S.R..), Columbia University Medical Center, New York, NY.
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Michelle T. Fabian
From the Department of Neurology (R.B.), University of Pennsylvania, Philadelphia; Department of Neurology (O.A.), Kaiser Permanente, Atlanta, GA; Department of Neurology (S.C.K., N.Y.H., M.X.E., I.K.S., M.T.F., S.K., F.D.L., A.E.M., J.F.S.), Icahn School of Medicine at Mount Sinai; James J. Peters Veterans Affairs Medical Center (N.Y.H.); and Department of Neurology (V.M.L, K.B., C.S.R..), Columbia University Medical Center, New York, NY.
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Korhan Buyukturkoglu
From the Department of Neurology (R.B.), University of Pennsylvania, Philadelphia; Department of Neurology (O.A.), Kaiser Permanente, Atlanta, GA; Department of Neurology (S.C.K., N.Y.H., M.X.E., I.K.S., M.T.F., S.K., F.D.L., A.E.M., J.F.S.), Icahn School of Medicine at Mount Sinai; James J. Peters Veterans Affairs Medical Center (N.Y.H.); and Department of Neurology (V.M.L, K.B., C.S.R..), Columbia University Medical Center, New York, NY.
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Sylvia Klineova
From the Department of Neurology (R.B.), University of Pennsylvania, Philadelphia; Department of Neurology (O.A.), Kaiser Permanente, Atlanta, GA; Department of Neurology (S.C.K., N.Y.H., M.X.E., I.K.S., M.T.F., S.K., F.D.L., A.E.M., J.F.S.), Icahn School of Medicine at Mount Sinai; James J. Peters Veterans Affairs Medical Center (N.Y.H.); and Department of Neurology (V.M.L, K.B., C.S.R..), Columbia University Medical Center, New York, NY.
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Claire S. Riley
From the Department of Neurology (R.B.), University of Pennsylvania, Philadelphia; Department of Neurology (O.A.), Kaiser Permanente, Atlanta, GA; Department of Neurology (S.C.K., N.Y.H., M.X.E., I.K.S., M.T.F., S.K., F.D.L., A.E.M., J.F.S.), Icahn School of Medicine at Mount Sinai; James J. Peters Veterans Affairs Medical Center (N.Y.H.); and Department of Neurology (V.M.L, K.B., C.S.R..), Columbia University Medical Center, New York, NY.
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Fred D. Lublin
From the Department of Neurology (R.B.), University of Pennsylvania, Philadelphia; Department of Neurology (O.A.), Kaiser Permanente, Atlanta, GA; Department of Neurology (S.C.K., N.Y.H., M.X.E., I.K.S., M.T.F., S.K., F.D.L., A.E.M., J.F.S.), Icahn School of Medicine at Mount Sinai; James J. Peters Veterans Affairs Medical Center (N.Y.H.); and Department of Neurology (V.M.L, K.B., C.S.R..), Columbia University Medical Center, New York, NY.
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Aaron E. Miller
From the Department of Neurology (R.B.), University of Pennsylvania, Philadelphia; Department of Neurology (O.A.), Kaiser Permanente, Atlanta, GA; Department of Neurology (S.C.K., N.Y.H., M.X.E., I.K.S., M.T.F., S.K., F.D.L., A.E.M., J.F.S.), Icahn School of Medicine at Mount Sinai; James J. Peters Veterans Affairs Medical Center (N.Y.H.); and Department of Neurology (V.M.L, K.B., C.S.R..), Columbia University Medical Center, New York, NY.
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James F. Sumowski
From the Department of Neurology (R.B.), University of Pennsylvania, Philadelphia; Department of Neurology (O.A.), Kaiser Permanente, Atlanta, GA; Department of Neurology (S.C.K., N.Y.H., M.X.E., I.K.S., M.T.F., S.K., F.D.L., A.E.M., J.F.S.), Icahn School of Medicine at Mount Sinai; James J. Peters Veterans Affairs Medical Center (N.Y.H.); and Department of Neurology (V.M.L, K.B., C.S.R..), Columbia University Medical Center, New York, NY.
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Citation
Detection of subtle gait disturbance and future fall risk in early multiple sclerosis
Rachel Brandstadter, Oluwasheyi Ayeni, Stephen C. Krieger, Noam Y. Harel, Miguel X. Escalon, Ilana Katz Sand, Victoria M. Leavitt, Michelle T. Fabian, Korhan Buyukturkoglu, Sylvia Klineova, Claire S. Riley, Fred D. Lublin, Aaron E. Miller, James F. Sumowski
Neurology Mar 2020, 94 (13) e1395-e1406; DOI: 10.1212/WNL.0000000000008938

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Abstract

Objective To test the hypothesis that higher-challenge gait and balance tasks are more sensitive than traditional metrics to subtle patient-reported gait dysfunction and future fall risk in early multiple sclerosis (MS).

Methods Persons with early MS (n = 185; ≤5 years diagnosed) reported gait function (MS Walking Scale) and underwent traditional disability metrics (Expanded Disability Status Scale [EDSS], Timed 25 Foot Walk). Patients and healthy controls (n = 50) completed clinically feasible challenge tasks of gait endurance (2-Minute Walk Test), standing balance (NIH Toolbox), and dynamic balance (balance boards; tandem walk on 2 ten-foot boards of different widths, 4.5 and 1.5 in). MRI assessed global and regional brain volumes, total T2 lesion volume (T2LV), infratentorial T2LVs and counts, and cervical cord lesion counts. Falls, near falls, and fall-related injuries were assessed after 1 year. We examined links between all tasks and patient-reported gait, MRI markers, and fall data.

Results Patients performed worse on higher challenge balance, but not gait, tasks compared with healthy controls. Worse patient-reported gait disturbance was associated with worse performance on all tasks, but only dynamic balance was sensitive to mild patient-reported gait difficulty. Balance tasks were more correlated with MRI metrics than were walking tasks or EDSS score. Thirty percent of patients reported either a fall or near fall after 1 year, with poor dynamic balance as the only task independently predicting falls.

Conclusions Balance plays a leading role in gait dysfunction early in MS. Clinically feasible higher-challenge balance tasks were most sensitive to patient-reported gait, MRI disease markers, and risk of future falls, highlighting potential to advance functional outcomes in clinical practice and trials.

Glossary

EDSS=
Expanded Disability Status Scale;
FOV=
field of view;
IQR=
interquartile range;
MS=
multiple sclerosis;
MSFC=
MS Functional Composite;
MSIS-phys=
physical component of the MS Impact Scale;
MSWS=
MS Walking Scale;
RADIEMS=
Reserve Against Disability in Early MS;
TE=
echo time;
TR=
repetition time;
T2LV=
T2 lesion volume;
T25FW=
Timed 25 Foot Walk;
2MWT=
2-Minute Walk Test

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • CME Course: NPub.org/cmelist

  • Received April 11, 2019.
  • Accepted in final form October 5, 2019.
  • © 2020 American Academy of Neurology
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