Short summary

The present study aim to validate ultrasound speckle tracking (UST) to measure and monitor muscle function in multiple sclerosis patients receiving vs. not receiving fampridine treatment. UST is a non-invasive ultrasound technique, with the potential to measure muscle function, including muscle contractility (through strain). 

Furthermore, we wish to relate these results to biomarkers in blood and urine to examine disease progression and muscle activity.

Rationale

Despite effective treatments, two thirds of all multiple sclerosis (MS) patients experience gait difficulties to a degree where walking aids or a wheelchair is required [1]. The gait function is particularly impaired in the progressive phases of the disease, where diagnostic and prognostic markers are still inadequate [2]. Patients with impaired gait function are highly dependent on strong upper extremities for transfer and mobility, including a well-functioning rotator cuff [3]. Unfortunately, dysfunction in the upper extremities is a frequent but often underestimated problem in MS patients [4].

Since 2009, medical treatment of gait impairments has been possible with fampridine. Fampridine alleviates the axonal conductance block in the demyelinated axons through inhibition of voltage-dependent potassium channels. This allows fpor an enhanced release of neurotransmitters in the neuromuscular junction and improved muscle contraction. The result is improved walking speed, coordination and balance in approximately 40% of treated MS patients, assessed through functional walking tests [5-7]. Similar results are seen for the function of the upper extremities in patients with MS [8-10]. Nonetheless, fampridine treatment is currently reserved for MS patients with symptomatic gait difficulties, due to present clinical guidelines where an objective measurable improved gait function of 20 % after 14 days of treatment is required.

Patients without a gait function could still experience a positive effect of fampridine treatment on their arm function and thereby activities of daily life such as personal transfer, dressing or personal hygiene hence, enhancing their quality of life. However, these patients are currently not eligible for subsidized fampridine treatment due to the requirements of an objective measurable effect.

The existing diagnostic imaging methods used for indicating muscle function determines muscle elasticity (elastrography) as an indirect expression of muscle activity. They are associated with a great variation [11, 12] and do not have the necessary precision to assess the clinical effect of a specific treatment like fampridine. Furthermore, they are difficult to implement in the daily clinical setting. Ultrasound speckle tracking (UST) is a new, in-house-invented and patented (EP17154342.4) ultrasound technique that non-invasively allows an objective and quantitative evaluation of a localized muscle contraction (muscle strain). UST is originally developed for dynamic cardiac muscle examination [13], but is used in our modified and patented version for skeletal muscle examination [14].

Aim:

The purpose of the present study is to validate UST for clinical assessment of muscle function in MS patients, before and during fampridine treatment. It is our hypothesis that UST has the potential to quantitatively evaluate muscle function and monitor the treatment response in fampridine-treated MS patients.

Description of the cohort

Multiple sclerosis patients, between 18 and 100 years, who fullfill the Fampridine treatment criteria.

Data and biological material

Muscle strain measured by ultrasound speckle tracking

Functional tests

Questionnaires

Kinematic, kinetic, gait summary measures and temporo spatielle outcomes will be collected in a three-dimensional gait laboratory.

Blood

Urine

Collaborating researchers and departments

BRIDGE – Brain Research – Inter-Disciplinary Guided Excellence, Department of Clinical Research – University of Southern Denmark.

Department of Orthopaedics and Traumatology, Odense University Hospital,

• Physician, Lars Henrik Frich, PhD
• Associate Professor Anders Holsgaard-Larsen, PhD. 

Department of Neurobiology Research, University of Southern Denmark

• Associate Professor, Kate Lykke Lambertsen, PhD

Department of Neurology, Lillebaelt Hospital,

• Physician, Henrik Boye Jensen, PhD

Department of Cardiology, Odense University Hospital

• Physician, Jordu Sanchez Dahl, PhD

Department of Radiology, Odense University Hospital

• Physician, John Hjarbæk, PhD

The Miami Project to Cure Paralysis, Miami University, USA

• Associate Professor, Roberta Bramilla, PhD

Publications associated with the project