Background: Gait impairment is one of the most disabling symptoms in people with multiple sclerosis (PwMS). Fampridine, has demonstrated a positive effect on gait speed in PwMS after 14 days of treatment but the long-term effects have not yet been demonstrated. This study reviews the long-term effects of fampridine on gait in PwMS. Summary: This systematic review was conducted according to the PRISMA statement. Studies were considered long term if treatment exceeded 28 days. From the 498 studies identified, 18 (2,200 patients) fulfilled all eligibility criteria. Only 3 studies followed-up patients for >1 year and one of these showed a non-significant improvement in the gait speed. Key Messages: Fampridine seems to be beneficial at improving gait speed in PwMS in the long term. Further long-term studies are needed on related gait and functional parameters.

1.
Larocca NG: Impact of walking impairment in multiple sclerosis: perspectives of patients and care partners. Patient 2011; 4: 189–201.
2.
Yildiz M: The impact of slower walking speed on activities of daily living in patients with multiple sclerosis. Int J Clin Pract 2012; 66: 1088–1094.
3.
Hobart JC, Riazi A, Lamping DL, Fitzpatrick R, Thompson AJ: Measuring the impact of MS on walking ability: the 12-Item MS Walking Scale (MSWS-12). Neurology 2003; 60: 31–36.
4.
Créange A, Serre I, Levasseur M, Audry D, Nineb A, Boërio D, et al: Walking capacities in multiple sclerosis measured by global positioning system odometer. Mult Scler 2007; 13: 220–223.
5.
Pike J, Jones E, Rajagopalan K, Piercy J, Anderson P: Social and economic burden of walking and mobility problems in multiple sclerosis. BMC Neurol 2012; 12: 94.
6.
FAMPYRA-Product-Monograph-19Dec2012-Fr.pdf.
7.
Hayes KC: Fampridine-SR for multiple sclerosis and spinal cord injury. Expert Rev Neurother 2007; 7: 453–461.
8.
Goodman AD, Brown TR, Krupp LB, Schapiro RT, Schwid SR, Cohen R, et al: Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. Lancet 2009; 373: 732–738.
9.
Goodman AD, Brown TR, Edwards KR, Krupp LB, Schapiro RT, Cohen R, et al: A phase 3 trial of extended release oral dalfampridine in multiple sclerosis. Ann Neurol 2010; 68: 494–502.
10.
Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, et al: Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 2015; 349:g7647.
11.
Moher D, Stewart L, Shekelle P: Implementing PRISMA-P: recommendations for prospective authors. Syst Rev 2016; 5: 15.
12.
Lublin FD, Reingold SC, Cohen JA, Cutter GR, Sørensen PS, Thompson AJ, et al: Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology 2014; 83: 278–286.
13.
Goodman AD, Brown TR, Cohen JA, Krupp LB, Schapiro R, Schwid SR, et al: Dose comparison trial of sustained-release fampridine in multiple sclerosis. Neurology 2008; 71: 1134–1141.
14.
Goodman AD, Bethoux F, Brown TR, Schapiro RT, Cohen R, Marinucci LN, et al: Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials. Mult Scler 2015; 21: 1322–1331.
15.
Coleman CI, Sobieraj DM, Marinucci LN: Minimally important clinical difference of the timed 25-foot walk test: results from a randomized controlled trial in patients with multiple sclerosis. Curr Med Res Opin 2012; 28: 49–56.
16.
Applebee A, Goodman AD, Mayadev AS, Bethoux F, Goldman MD, Klingler M, et al: Effects of dalfampridine extended-release tablets on 6-minute walk distance in patients with multiple sclerosis: a post hoc analysis of a double-blind, placebo-controlled trial. Clin Ther 2015; 37: 2780–2787.
17.
Jensen H, Ravnborg M, Mamoei S, Dalgas U, Stenager E: Changes in cognition, arm function and lower body function after slow-release Fampridine treatment. Mult Scler 2014; 20: 1872–1880.
18.
Jensen HB, Mamoei S, Ravnborg M, Dalgas U, Stenager E: Distribution-based estimates of minimum clinically important difference in cognition, arm function and lower body function after slow release-fampridine treatment of patients with multiple sclerosis. Mult Scler Relat Disord 2016; 7: 58–60.
19.
Allart E, Benoit A, Blanchard-Dauphin A, Tiffreau V, Thevenon A, Zephir H, et al: Sustained-released fampridine in multiple sclerosis: effects on gait parameters, arm function, fatigue, and quality of life. J Neurol 2015; 262: 1936–1945.
20.
Keune PM, Cocks AJ, Young WR, Burschka JM, Hansen S, Hofstadt-van Oy U, et al: Dynamic walking features and improved walking performance in multiple sclerosis patients treated with fampridine (4-aminopyridine). BMC Neurol 2015; 15: 171.
21.
Costa-Arpín E, Pato A, Rodríguez-Regal A, Midaglia L, Yáñez R, Muñoz D, et al: Clinical response and tolerability of fampridine in clinical practice. Neurodegener Dis Manag 2016; 6: 99–105.
22.
Ruck T, Bittner S, Simon OJ, Göbel K, Wiendl H, Schilling M, et al: Long-term effects of dalfampridine in patients with multiple sclerosis. J Neurol Sci 2014; 337: 18–24.
23.
Pavsic K, Pelicon K, Ledinek AH, Sega S: Short-term impact of fampridine on motor and cognitive functions, mood and quality of life among multiple sclerosis patients. Clin Neurol Neurosurg 2015; 139: 35–40.
24.
Hobart J, Blight AR, Goodman A, Lynn F, Putzki N: Timed 25-foot walk: direct evidence that improving 20% or greater is clinically meaningful in MS. Neurology 2013; 80: 1509–1517.
25.
Rabadi MH, Kreymborg K, Vincent AS: Sustained-release fampridine (4-aminopyridine) in multiple sclerosis: efficacy and impact on motor function. Drugs R D 2013; 13: 175–181.
26.
Zörner B, Filli L, Reuter K, Kapitza S, Lörincz L, Sutter T, et al: Prolonged-release fampridine in multiple sclerosis: Improved ambulation effected by changes in walking pattern. Mult Scler 2016; 22: 1463–1475.
27.
Cameron MH, Fitzpatrick M, Overs S, Murchison C, Manning J, Whitham R: Dalfampridine improves walking speed, walking endurance, and community participation in veterans with multiple sclerosis: a longitudinal cohort study. Mult Scler 2014; 20: 733–738.
28.
Lo AC, Ruiz JA, Koenig CM, Anderson BM, Olson KM, Triche EW: Effects of dalfampridine on multi-dimensional aspects of gait and dexterity in multiple sclerosis among timed walk responders and non-responders. J Neurol Sci 2015; 356: 77–82.
29.
Zörner B, Filli L, Reuter K, Kapitza S, Lörincz L, Sutter T, et al: Prolonged-release fampridine in multiple sclerosis: improved ambulation effected by changes in walking pattern. Mult Scler 2016; 22: 1463–1475.
30.
Prugger M, Berger T: Assessing the long-term clinical benefit of prolonged-release fampridine tablets in a real-world setting: a review of 67 cases. Patient Relat Outcome Meas 2013; 4: 75–85.
31.
Eroglu S, Inal EE, Eroglu M, Oruc S, Ulasli AM, Cevik H, et al: Ultrasound detection of knee joint degeneration in patients with multiple sclerosis. J Rehabil Med 2016; 48: 604–608.
32.
Allali G, Laidet M, Assal F, Armand S, Lalive PH: Walking while talking in patients with multiple sclerosis: the impact of specific cognitive loads. Neurophysiol Clin 2014; 44: 87–93.
33.
Downer MB, Kirkland MC, Wallack EM, Ploughman M: Walking impairs cognitive performance among people with multiple sclerosis but not controls. Hum Mov Sci 2016; 49: 124–131.
34.
Goodman AD, Stone RT: Enhancing neural transmission in multiple sclerosis (4-aminopyridine therapy). Neurotherapeutics 2013; 10: 106–110.
35.
Kaufman M, Moyer D, Norton J: The significant change for the Timed 25-foot walk in the multiple sclerosis functional composite. Mult Scler 2000; 6: 286–290.
36.
Schwid SR, Goodman AD, McDermott MP, Bever CF, Cook SD: Quantitative functional measures in MS: what is a reliable change? Neurology 2002; 58: 1294–1296.
37.
Kragt JJ, Linden van der FA, Nielsen JM, Uitdehaag BM, Polman CH: Clinical impact of 20% worsening on timed 25-foot walk and 9-hole Peg Test in multiple sclerosis. Mult Scler 2006; 12: 594–598.
38.
Hoogervorst EL, Kalkers NF, Cutter GR, Uitdehaag BM, Polman CH: The patient’s perception of a (reliable) change in the multiple sclerosis functional composite. Mult Scler 2004; 10: 55–60.
39.
Goldman MD, Marrie RA, Cohen JA: Evaluation of the six-minute walk in multiple sclerosis subjects and healthy controls. Mult Scler 2008; 14: 383–390.
40.
Savci S, Inal-Ince D, Arikan H, Guclu-Gunduz A, Cetisli-Korkmaz N, Armutlu K, et al: Six-minute walk distance as a measure of functional exercise capacity in multiple sclerosis. Disabil Rehabil 2005; 27: 1365–1371.
41.
Feys P, Bibby B, Romberg A, Santoyo C, Gebara B, de Noordhout BM, et al: Within-day variability on short and long walking tests in persons with multiple sclerosis. J Neurol Sci 2014; 338: 183–187.
42.
Studenski S, Perera S, Patel K, Rosano C, Faulkner K, Inzitari M, et al: Gait speed and survival in older adults. J Am Med Assoc 2011; 305: 50–58.
43.
Kantor D, Chancellor MB, Snell CW, Henney HR 3rd, Rabinowicz AL: Assessment of confirmed urinary tract infection in patients treated with dalfampridine for multiple sclerosis. Postgrad Med 2015; 127: 218–222.
44.
Van Diemen HA, Polman CH, Koetsier JC, Van Loenen AC, Nauta JJ, Bertelsmann FW: 4-Aminopyridine in patients with multiple sclerosis: dosage and serum level related to efficacy and safety. Clin Neuropharmacol 1993; 16: 195–204.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.