Skeletal Muscle Properties and the Metabolic Cost of Walking Post-stroke
Condition: Stroke
MeSH terms: Stroke
Study type: Observational

Summary: 
      Of the ~700,000 persons who suffer a stroke each year, only 50% recover the ability to
      perform unlimited community walking. One mechanism contributing to locomotor dysfunction
      post-stroke is an increased metabolic cost of walking relative to neurologically healthy
      individuals 2-4. This increased cost likely limits the amount of walking performed, which
      further reduces functional capacity, thus contributing to long-term spiral of disability and
      decreased quality of life in these persons. In addition to increased metabolic cost,
      increased estimates of mechanical work are also characteristic of hemiparetic walking 2,29.
      Interestingly, although estimates of mechanical work reflect work done by locomotor muscles,
      little is known about the impact that peripheral muscle properties have on estimates of
      mechanical work. Furthermore, questions concerning how these properties relate to the
      increased metabolic cost of walking remain unanswered. The short-term objective and purpose
      of the proposed research is to determine the extent to which peripheral muscle
      characteristics, as well as estimates of muscle mechanical energy expenditure (MMEE), relate
      to the metabolic cost of walking post-stroke.
    

Detailed description: 
      A guiding principle of the proposed research is that skeletal muscle is the building block of
      all movement and, as such, muscle dysfunction can ultimately limit the gains possible from
      rehabilitation intervention. Therefore, maximal gains will be made only when central nervous
      system adaptations access peripheral muscle that is fully capable of supporting the increased
      activity.

      The primary hypothesis is that in persons with hemiparesis following stroke, alterations in
      the metabolic properties of peripheral skeletal muscles, in combination with greater
      mechanical work, contribute to the increased metabolic cost of walking. A secondary
      hypothesis is that locomotor training induces adaptations in lower extremity skeletal muscle
      resulting in improved mechanical and metabolic efficiency. In order to test these hypotheses,
      the following three specific aims will be addressed:

      Aim 1: Determine the in-vivo metabolic characteristics of the ankle plantar flexor muscles in
      persons with chronic post-stroke hemiparesis and neurologically healthy individuals. In-vivo
      muscle metabolic properties will be assessed via phosphorous magnetic resonance spectroscopy
      (31P-MRS). Specifically, we will measure the resting phosphorylation potential as well as the
      in-vivo oxidative capacity of the ankle plantar flexor muscles. We hypothesize that
      individuals with chronic hemiparesis will exhibit reductions in oxidative capacity as well as
      an increased resting phosphorylation potential relative to age-, gender-, height- and
      weight-matched control subjects. We suggest these adaptations, which are characteristic of a
      less energetically efficient muscle, contribute to an increased metabolic cost beyond that
      resulting from potential increases in mechanical work performed by locomotor muscles.

      Aim 2: Quantify metabolic cost as well as muscle mechanical energy expenditure during walking
      in persons with chronic post-stroke hemiparesis and neurologically healthy individuals.
      Post-stroke hemiparesis is associated with a variety of motor control problems that include
      abnormal synergistic organization of movement as well as altered temporal sequencing of
      muscle activity 5,10,11. Since muscle excitation during normal walking is believed to be very
      efficient 8,9,33 it is likely that altered muscle coordination post-stroke, reflected in
      increased mechanical work, is one factor contributing to the increased metabolic cost of
      walking. We hypothesize that the metabolic cost of walking post-stroke will be elevated
      relative to controls at matched speeds. Additionally, a measure of mechanical work, muscle
      mechanical energy expenditure (MMEE), will be elevated post-stroke, reflective of
      mechanically inefficient movement strategies and causal to a portion of the increased
      metabolic cost of walking.

      Aim 3: Determine the impact of 12 weeks of locomotor training on in-vivo muscle metabolic
      properties, the metabolic cost of walking as well as MMEE in persons with chronic post-stroke
      hemiparesis. There is emerging evidence that chronic neurologic deficits due to stroke can be
      improved through intensive, repetitive task-oriented motor training (e.g. locomotor
      training). The basis for locomotor training (LT) improvements is thought to involve
      mechanisms of central neuroplasticity that are responsive to fundamental principles of motor
      learning 37,38,39. In addition, our pilot data demonstrate that LT may also result in
      peripheral adaptations in the plantar flexor muscles. Thus, the potential seemingly exists to
      induce both central and peripheral adaptations with this intervention strategy. We expect
      that LT will attenuate existing deficits, resulting in an increased oxidative capacity and a
      decreased resting phosphorylation potential in ankle plantar flexor muscles. In addition, LT
      will result in a reduced MMEE and a reduced metabolic cost of walking, reflective of improved
      mechanical and metabolic efficiency. We believe it will prove important to describe
      adaptations in walking mechanics as well as within peripheral muscle that occur following LT
      and relate them to the metabolic cost of walking. In addition, continued deficits will
      reflect a need for additional or adjunctive intervention strategies, thus providing
      information on how to modify or augment future rehabilitation interventions in order to
      improve individual outcomes.
    

Intervention name(s): Treadmill walking; Magnetic resonance spectroscopy
Intervention type(s): Behavioral; Other
Intervention description(s): Subjects will perform treadmill walking at a self-selected velocity; Muscle oxidative capacity will be assessed via Magnetic resonance spectroscopy (31P-MRS)
Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        community sample
      
Biospecimen description: 
      None retained
    
Keywords: muscles; work; Magnetic Resonance Imaging; control groups