Muscle Pathology and Gait in Children with Duchenne Muscular Dystrophy

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Muscle Pathology and Gait in Children with
Duchenne Muscular Dystrophy

• Donovan J. Lott, PT, PhD, CSCS
• May 19, 2009
• Mentors
• Steve Kautz, PhD
• Krista Vandenborne, PhD, PT

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Professional Background

• Clinical work as physical therapist
• PhD studying soft tissue mechanics of neuropathic
  foot
• Quantifying muscle plasticity UF
• Phase I of K12
• Developing aims for K award

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Duchenne Muscular Dystrophy (DMD)

• X-linked recessive disorder
• 40 of cases are spontaneous mutations
• 1 in 3,500 male births
• Shortened life span
• No cure100 lethal

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Pathophysiology
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Pathophysiology
2yr
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Weakness
Pseudohypertrophy
Impaired mobility
Postural changes
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Interests

• How muscle pathology is related to gait function
  in children with DMD
• How/if rehabilitation strategies can favorably
  impact gait mechanics

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• Background and Preliminary Data
• Disease Progression/Pathology
• Quantitative muscle strength testing
• Non-invasive magnetic resonance imaging (MRI) and
  spectroscopy (MRS)
• Gait
• Basic measures
• Kinematics Kinetics
• Brief thoughts on rehabilitation in patients with
  DMD

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Disease Progression/PathologyStrength

• Weakness becomes more evident with increasing age
• Lower extremities weaker than upper extremities
• Proximal weaker than distal
• MMTs inferior to quantitative tests

(Lue et al., 1992 McDonald et al., 1995 Marden
et al., 2005)
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Disease Progression/PathologyStrength
Preliminary Data

• Biodex isokinetic dynamometer
• Isometric tests
• Knee extensors
• Ankle plantarflexors
• Ankle dorsiflexors

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Preliminary Data Participants
29 boys with DMD, 12 healthy controls
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Disease Progression/PathologyStrength
Preliminary Data
Torque of Plantarflexors
Torque of Dorsiflexors
Normalized Torque (Nm/cm2)
Normalized Torque (Nm/cm2)
Torque of Quadriceps
Normalized Torque (Nm/cm2)
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Disease Progression/PathologyWhy MRI/MRS?

• Noninvasive/nondestructive
• Detailed information
• Quantitative
• Sensitive
• MRI
• Cross-sectional area (CSA)
• Qualitative fatty infiltration
• Contractile area
• MRS
• Quantification of
• intramuscular lipids

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Disease Progression/PathologyMRI Preliminary
Data CSA
TA
Sol
MG
LG


1-4 Quadriceps

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1
3
2
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Disease Progression/PathologyMRI Preliminary
Analyses
-

( ) - ( )

T1 weighted gradient echo Image with fat
suppression
T1 weighted gradient echo Image without fat
suppression
Subtraction image
For determining Intramuscular Fat content and
Contractile Area
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Disease Progression/PathologyMRS

• Various metabolites have been quantified with
  1H-MRS in children with DMD (Sharma et al., 2003
  Hsieh et al., 2007 and 2009)
• We have begun to quantify lipids for fatty
  infiltration in patients with DMD

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Disease Progression/PathologyPreliminary Data
1H-MRS
CON
DMD
DMD
CON
Lipid
Water
Water
Lipid
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Disease Progression/PathologyPreliminary Data
1H-MRS
Cross-sectional
Longitudinal
Nonambulatory

DMD subjects D1 - 13.8 y/o D2 - 8.8 y/o D3 8.9
y/o
CON DMD
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Gait

• Little work has been done
• Mostly heterogenous groups or small sample
• More descriptive in nature (Hsu Furumasu, 1993)

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GaitPreliminary DataSpatiotemporal Parameters
Healthy control subject
DMD subject
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GaitPreliminary DataSpatiotemporal Parameters
-Stride and step lengths were shorter in DMD
subjects (p lt 0.05) -Trend for greater base of
support and slower gait velocity (p lt 0.09)

CON DMD
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Gait

• Activity Monitor
• ActiGraph
• Functional Assessment
• 30 foot walk

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GaitActiGraph

• Walking and non-ambulatory activity
• Can estimate energy expenditure (METs)

15 y/o healthy boy
14 y/o boy with DMD
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GaitPreliminary Data for 30 foot walk
Longitudinal
Nonambulatory
DMD subjects D1 - 13.8 y/o D2 - 8.8 y/o D3 8.9
y/o
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GaitPreliminary Data
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Gait

• A few recent studies have utilized state-of-the
  art 3D motion capture systems for kinematics and
  kinetics of gait

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Gait
DMD Control
Pelvic Tilt
Hip Power

• Ankle Plantarflexion - Dorsiflexion

Ankle Power
(DAngelo et al., 2009)
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GaitFuture work needed in DMD

• Better understand how pathology is related to
  gait
• Longitudinal data on gait biomechanics
• Older (9-14 years) participants

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Rehabilitation

• Current thoughts/strategies re physical therapy
  for those with DMD
• Stretch to prevent contractures
• Orthoses for decreasing impact/progression of
  contractures
• Positioning/chest therapy for later stages

• No sufficient data in the literature to justify a
  sound exercise prescription for DMD

(Grange Call, 2007)
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Rehabilitation

• Muscle Damage Disuse Atrophy

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Rehabilitation

• Possible rehabilitation strategies to implement
  and study
• Stretching as a protective mechanism (Koh et al.,
  2003)
• Strengthening (de Lateur Giaconi, 1979 Kaczor
  et al., 2007)
• Trunk control/stabilization

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Overall Objectives

• Examine the relationship between gait and disease
  progression in children with DMD
• Pilot rehabilitation interventions to target
  improvement in gait without enhancing muscle
  pathology

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Thank you

• University of Florida
• Biomechanics
• Steve Kautz
• DMD Imaging team
• Krista Vandenborne
• Glenn Walter
• Claudia Senesac
• Roxanna Bendixen
• Sean Forbes
• Sean Germain
• Ravneet Vohra
• Ishu Arpan
• Jasjit Deol
• Alicia Kinsey
• Jessica Blank

University of Toronto Sunita Mathur University
of Pennsylvania Lee Sweeney
MRI/MRS conducted at the AMRIS facility, McKnight
Brain Institute, UF
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Disease Progression/PathologyMRI Preliminary Data
CSA of Triceps Surae
CSA of TA
CSA of Quads
1-4 Quadriceps
TA
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1
3
2
2
3
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1-3 Triceps Surae