Muscle Ultrasound Measures as Biomarkers of Upper Motor Neuron Function
Condition: Muscle Spasticity
MeSH terms: Muscle Spasticity
Study type: Observational

Summary: 
      Background:

      - Primary lateral sclerosis (PLS) is a rare disease. It leads to weakness in the muscle of
      the arms, legs, and face. People with PLS develop muscle stiffness called spasticity.
      Researchers want to find a better way to measure this. They want to see if ultrasound, which
      uses sound waves to look at parts of the body, can measure spasticity and stiffness in
      muscles.

      Objective:

      - To see if ultrasound can detect and measure muscle spasticity in people with PLS.

      Eligibility:

        -  People ages 18 75 who have a diagnosis of PLS and are enrolled in protocol 01-N-0145.

        -  Healthy volunteers ages 18 75.

      Design:

        -  Participants with PLS will have 1 study visit. Healthy participants will have upto 5
           visits. Each visit will be about 2 hours.

        -  Participants will have tests of muscle strength. They will be examined. They will push
           their arms and legs against researchers in different positions.

        -  Participants will have tests of muscle stiffness. Their arms and legs will be moved
           while they relax.

        -  Participants will have a muscle ultrasound test. They will lie on a table. Gel will be
           placed on the skin over the muscles of the arms and legs. A probe, like a microphone,
           will be moved over the skin. Researchers will look at several muscles.

        -  Participants should try to stay still during the ultrasound. It may be done several
           times and may be done by different examiners.
    

Detailed description: 
      Objective

      Persons with corticospinal, or upper motor neuron dysfunction have increased muscle stiffness
      from spasticity. Spasticity is established by clinical examination, but there are few
      reliable objective measures of spasticity. New ultrasound techniques to measure the elastic
      properties of tissue represent a potential measure of spasticity. The ultrasound measures of
      tissue elasticity are painless and quick to perform, but their ability to detect changes
      resulting from spasticity is uncertain. The goal of this pilot study is to see how much
      ultrasound measures of muscle elasticity differ between patients with spasticity and healthy
      controls. Secondary objectives are to correlate muscle elasticity measures with a clinical
      rating scale of spasticity and to assess intra and inter-rater reliability. This is a
      protocol for primary lateral sclerosis (PLS) patients who are enrolled in another NIH study
      in which they have been diagnosed with spasticity.

      Study Population

      23 adult PLS patients with arm or leg spasticity currently enrolled in an NIH protocol

      30 healthy adult controls with normal neurological exams.

      Design

      The first phase, an investigator training phase, is aimed to become familiar with the Siemens
      Acuson S2000 after the upgrade. The two investigators will train with 5 healthy volunteers.
      In the second phase inter-observer variability of the ultrasound and Ashworth scale will be
      assessed by having healthy volunteers and patients evaluated by the different investigators.
      Since spasticity does fluctuate throughout the day, subjects will be consecutively assessed
      for inter-observer variability and within a few hours or around the same time the following
      day (depending on patient availability) for intra-observer variability. Each investigator
      will do the Ashworth scale independent of the other. Each investigator will do the ultrasound
      independent of the other. In the third phase, we will assess patients and volunteers to reach
      the sample size that a power analysis suggested that we would need to measure differences
      between patients with spasticity and controls.

      Outcome Measures

      The primary outcome will be measuring muscle stiffness from the biceps brachii using
      ultrasound elastography, which will be compared between patient groups and control groups. A
      secondary outcome will be the correlation of muscle stiffness at rest with the modified
      Ashworth score for elbow flexion. Measures of muscle strength and ultrasound measures of
      density and thickness will be examined in an exploratory fashion. Elastography of the
      tibialis anterior will be examined in an exploratory fashion.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Keywords: Spasticity; Primary Lateral Sclerosis; Elastography; Ultrasound