Dalfampridine Combined with Physical Therapy May Improve Treatment Effects in Dalfampridine Non-Responders with Multiple Sclerosis: A Case Study Focused on Balance and Falls Prevention.

Background: 

Multiple Sclerosis (MS) is a progressive immune-mediated neurological disorder that results in episodes of inflammation which cause demyelination of nerve fibers leading to lesions within the central nervous system.¹ Demyelination slows or disrupts the transmission of nerve conduction causing a wide range of symptoms including muscular weakness, spasticity, poor balance and coordination, and fatigue.^2,3   Additionally, a decrease in gait speed has been used as a clinical benchmark of the extent of disease progression and the impact of MS on a person’s daily activities and function.

Statement of Need: 

Dalfampridine extended release (D-ER, Ampyra®, 10 mg twice daily), is a pharmacological intervention that has been shown to improve gait speed in people with multiple sclerosis and is frequently prescribed to patients with gait difficulties.⁴ D-ER is a voltage-gated potassium channel blocker that functions by increasing action potential conduction in demyelinated axons in patients with MS.⁵ Two phase 3 clinical trials have demonstrated a clinically important improvement in gait speed (≥20% increase on Timed 25-foot Walk test) for individuals taking D-ER, but only in 38% of people who take it (“responders”). More than 60% of people who take this medication do not demonstrate clinically relevant gait speed improvement, (“non-responders”).⁴   The hope is that this case report will lay a foundation for future studies to help develop alternative interventions to help improve gait, balance and mobility in people with MS. Thus, this study addresses a need to investigate best practice options for managing gait impairments in people with MS.

This year I had the opportunity to collaborate with Lexi Williams and Corinne Bohling on a research project led by Dr. Prue Plummer, PhD, PT. This research experience culminated in a case report examining the effects of dalfampridine extended release (D-ER) combined with gait training in people with MS. We evaluated functional outcomes including gait speed, dual-task-performance, cognitive processing speed and balance. Additionally, we intend to publish the case report in order to meet a real need in furthering clinician’s knowledge of the effects of pharmaceutical interventions and physical therapy in terms of a number of different functional assessments.

Balance deficits, resulting in increased fall risk, decreased physical activity and functional decline are common in individuals with MS.⁶ Throughout the fall of 2015 I completed my Critically Appraised Topic (CAT) on evidence comparing the effects of D-ER to yoga training in reducing falls risk or improving balance in individuals with MS. Therapeutic exercise interventions such as resistance exercise, yoga, aerobic training programs including treadmill walking have been shown to improve balance impairments and reduce falls risk.^6-9 There is also evidence that D-ER can produce favorable balance and mobility outcomes for people with MS.¹⁰ Because there has not been any research to determine if PT can augment the effects of D-ER on balance and mobility, I chose to focus on assessing changes in balance and falls risk evaluation in this case study.

This pilot case report aims to set a foundation to help guide future research comparing the effects of gait training alone on gait speed and dual-task performance, in people with MS. The study will provide preliminary information regarding the feasibility of gait training intervention and help to establish protocol and design for future studies. After data collection and analysis was complete we submitted an HMSC Abstract, which was selected to be a platform presentation at the Human Movement Science and Biomechanics Research Symposium at UNC-Chapel Hill. (see poster below). Additionally, the paper will be submitted for publication to the International Journal of Multiple Sclerosis Care (IJMSC). Please check back to view the full paper once submitted for publication.

HMSC Poster

Self-Assessment/Evaluations:

This experience expanded upon my interest in clinical research and provided me with extra experience in gait training with individuals with multiple sclerosis. I worked closely with Dr. Prue Plummer as well as my research teammates, Lexi and Corinne. This process involved collaboration from the initiation of the project, establishing goals and aims of the study, deciding on components to assess and developing a research protocol. Everyone involved worked together to develop the intervention protocol with evidence based training activities and progressions. We communicated well and maintained consistency throughout the entire process in terms of gait training and working with our research participant.

I strongly believe this research is clinically relevant and was happy to contribute to the effort of expanding the available evidence on a topic of strong clinical relevance. I hope that the work that was done will lay the groundwork for exciting further research that will help guide clinical practice for patients with MS.  I believe that was I have learned from this process will enhance my skills as a researcher and clinician.

We created a poster presentation evaluation form to provide to people attending our presentation in order to gain feedback. A summary of evaluations can be viewed Here. We will also be seeking final evaluations/feedback from our capstone committee, as well as our readers once published in IJMSC.

Acknowledgments:

I am grateful to have had the opportunity to work under the guidance of Dr. Prue Plummer. She is extremely knowledgeable and an excellent mentor. She was helpful in guiding us throughout the process to maximize learning and involvement in all aspects of a research experience. She provided constructive feedback, guidance with data collection and analysis, and excellent feedback on all of our projects from the poster presentation abstract to final paper. This opportunity has undoubtedly confirmed my interest in research as well as the importance of evidence-based practice. I also acknowledge the hard work of research colleagues, Corinne Bohling and Lexi Williams. I am grateful for classmates who are passionate about advancing research in physical therapy, committed to quality of clinical care, and excellent team players. Many thanks to those who provided feedback and attended and/or participated in the 2016 Human Movement Science and Biomechanics Research Symposium. And thank you to our committee members Catherine Jacobs and Amy Thomas for their review our final project.

Resources: 

1. National Multiple Sclerosis Society. What is MS: Definition of MS. National Multiple Sclerosis Society Website. http://www.nationalmssociety.org/What-is-MS/Definition-of-MS. Accessed December 4, 2016.
2. National Multiple Sclerosis Society. Symptoms and Diagnosis: MS Symptoms. National Multiple Sclerosis Society Website. http://www.nationalmssociety.org/Symptoms-Diagnosis/MS-Symptoms. Accessed December 4, 2016.
3. Plow MA, Resnik L, Allen SM. Exploring physical activity behaviour of persons with multiple sclerosis: a qualitative pilot study. Disabil Rehabil. 2009;31(20):1652-1665.
4. Goodman AD, Brown TR, Schapiro R, T., et al. A pooled analysis of two phase 3 clinical trials of dalfampridine in patients with multiple sclerosis. International Journal of Multiple Sclerosis Care 2014;16:153-160.
5. Bostock H, Sears T, and Sherratt R. The Effects of 4-aminopyridine and Tetraethylammonium Ions on Normal and Demyelinated Mammalian Nerve Fibers. J Physiol. 1981;313:301-315.

6. Kasser S. and Jacobs J. Understanding and Treating Balance Impairments in Multiple Sclerosis. JCOM. 2014;21(9):419-432.

7. Giacobbi Peter R. J, Dietrich F, Larson R, White J. L. Exercise and Quality of Life in Women With Multiple Sclerosis. Adapt Phys Act Q. 2012;29(3):224-242.

8. Ahmadi A, Arastoo AA, Nikbakht M, Zahednejad S. Comparison of the Effect of 8 weeks Aerobic and Yoga Training on Ambulatory Function, Fatigue and Mood Status in MS Patients. 2013; 15(6): 449-454.

9. Hogan N, Kehoe M, Larkin A, Coote S. Clinical Study The Effect of Community Exercise Interventions for People with MS Who Use Bilateral Support for Gait. 2014; 2014.
10. Hupperts R, Lycke J, Short C, et al. Prolonged-release fampridine and walking and balance in MS: randomised controlled MOBILE trial. Mult Scler J. 2015:1-10.