Neuromusculoskeletal Modeling of Muscle Spasticity

Cerebral palsy (CP) is a movement and posture disorder caused by an injury to the developing brain, with a prevalence in Sweden of about 2/1000 live births. Children with CP have walking difficulties, and decreased muscle mass and muscle function as compared to typically developing (TD) children. The extent of disability in CP depends on the severity and timing of the primary cerebral lesion and can be classified with the gross motor function classification system (GMFCS E\&R) that ranges from walking without limitations (I) to being transported in a wheelchair (V).

Muscle function commonly deteriorates with age and contracture development is often clinically evident as early as at 4 years of age. In addition to being thinner and weaker, skeletal muscle in children with CP develop poor quality, i.e., increasingly higher amounts of fat and connective tissue at the expense of functional, contractile proteins.

How long-term standard treatments for children with spastic CP including, training and orthotics use, with botulinum toxin (BoNT-A) treatment as an adjunct, affects muscle on functional, structural, and microscopic level in CP has not yet been published. Therefore, we will investigate the muscle function as well as functional mobility, structure, and spasticity. We will conduct functional mobility tests. Muscle strength will be measured with a rig-fixed dynamometer, and muscle structure will be measured with magnetic resonance imaging. The spasticity will be instrumentally assessed by the NeuroflexorTM, a machine measuring resistance in a muscle when a pedal is passively moving the participants foot at two different speeds. We will follow participants, for 1 year, with 4 measurements during this period.

In order to better treat these children, we need to better understand the complex, interrelated interactions of musculoskeletal properties and function in children with CP. Our hypothesis is that muscle structure and function is affected by standard clinical treatments sessions including routine botulinum toxin treatment. Analyzing the effect of standard care may help planning of more effective clinical treatments in the future.

How long-term standard treatments for children with spastic cerebral palsy (CP), including training and orthotics use, with botulinum toxin (BoNT-A) treatment as an adjunct, affects muscle on functional, structural, and microscopic level in CP has not yet been published. Therefore, we will investigate the muscle function as well as functional mobility, structure, and spasticity.

Research questions:

* How is muscle structure, muscle strength, spasticity and, stiffness of the calf muscle in CP related to motor function, and how does it differ to typically developing (TD) children?
* What is the long-term effect of a standard care with BoNT-A as an adjunct on motor function, muscle structure, muscle strength, spasticity, and stiffness?

Participants with spastic CP, aged between 5-17 years, are recruited from the Dept of Pediatric Orthopaedics, when clinically motivated plans for the first BoNT-A treatment session of the calf (plantar flexors) are set. Typically developing children at same ages are recruited through convenient sample and will take part of the assessments once. The children with CP will go through the following assessments at four different time-points; before, 3 months, 6 months, and one year after the first BoNT-A injection:

* Spasticity will be measured with clinical tests: Modified Tardieu scale and Modified Ashworth scale and with a instrumented device measuring muscle resistance, the NeuroflexorTM.
* Isometric strength measurements of plantar flexors and ankle dorsiflexors using a dynamometer (ChatillonTM) fixed in a custom-built testing frame while surface EMG is captured.
* Functional mobility in walking for example the Timed-Up-and-Go test (TUG-test) i.e. the time it takes for the child to stand up from a chair, walk 3 m, turn around, walk back, and sit down.
* Active and passive range of motion (ROM) measured with a goniometer

Before the first injection, the children with CP will be examined with magnetic resonance imaging (MRI) providing complex 3D structural information of individual muscles. One year after first injection, another examination with MRI will be conducted.

This explorative, observational, prospective, long time follow up study will be conducted at the Motion analysis laboratory at Astrid Lindgren's children's hospital and Huddinge Karolinska in collaboration with KTH Royal Institute of Technology.

Parametric and/or non-parametric statistical tests for within and between group comparisons, and correlations will be performed. Based on the pilot data from TD children the CP group and previous literature we need a sample size of 10-15 participants in each group.

Eligibility Criteria:
Inclusion Criteria:

* Unilateral/Bilateral spastic CP without Botulinum toxin injection history
* Understanding study protocol and expressing voluntary consent of the family
* Dorsiflexion to at least a neutral position of the foot

Exclusion Criteria:

* Contraindication to MRI scanning: metal fragments in the body, surgically implanted devices containing metal, severe claustrophobia, or inability to lie down in the MRI scanner, presence of pacemaker or other stimulators, shunts etc.
* Total range of ankle movement less than 35°