Functional electrical stimulation of the ankle dorsiflexors during walking in children with unilateral spastic cerebral palsy: a randomized crossover intervention study.

Cerebral palsy (CP) is the most common upper motor neuron disorder in children
and the main cause of disability in childhood (1) CP describes a group of
disorders of the musculoskeletal system, which are permanently but not
unchangeable. CP is caused by congenital or acquired non-progressive disorders
of the developmental brain in the first year of life. (2, 3)

Children with spastic CP often walk with insufficient ankle dorsiflexion (in
the swing phase) or with eversion of the foot,. A pathological gait, known as
drop-foot gait, can be the result and this has 2 major complications: foot-slap
during loading response and toe-drag during swing. This partlyis partly caused
by weakness of the anterior tibial muscle and partly due to co-contraction of
both the fibular- and anterior tibial muscle. So there is a combination of a
lack of selectivity and decreased strength, making walking at various stages
deviant. Furthermore, there is an imbalance noticeable while walking. In time,
the disorder appears to be progressive due to atrophy and contractures of the
muscle and increasing bodyweight . For classification of gait, the Winters
scale can be used (figure 1), where unilateral CP with dropfoot is classified
as type I (4).
In daily life these problems cause limited walking distance and frequent falls.
This can lead to restrictions in participating in daily activities at school
and in leisure.
The current guideline for spastic cerebral palsy describes the different
interventions in relation to the age of the child as follows:
The first step is conservative therapy, which includes physiotherapy,
orthopaedic shoes and orthoses. (5)
The second step includes systemically and locally applied drugs. Diazepam,
Dantrolene, Clonidine and Baclofen are the most widely used drugs. These drugs,
with the exception of Dantrolene, suppress the spasticity by inhibition of
excitatory neurotransmitters, or by stimulation of the inhibitory
neurotransmitters. Botulinum toxin A (Bont-A) is an intramuscularly applied
drug, which causes a chemical denervation at the level of the motor end plate
of the muscle causing weakness. It is therefore administered in those muscles
that show undesirable co-activation. Because the effect is only temporarily,
the treatment has to be repeated every 3 - 9 months. Using training, the effect
of Bont-A can be prolonged. To be able to administer the Bont-A injections in a
muscle of a severely disabled child, general anaesthetic is required. Treatment
with an orthosis can be very functional, however active movement is impossible.
This is a restriction especially in patients with light symptoms; GMFCS level I
and II. Furthermore, it has a proper effect in one phase of a step, but not in
the other, while it is used for correction of a dynamic event. Negative effects
may be muscle weakness and atrophy.
The third step includes surgical interventions, e.g. tenotomy, transposition
and osteotomy. This is often followed by a conservative plaster program with
good post-operative counselling (physiotherapy and splints) to prevent or
postpone bone deformities. More importantly, however, is to perform soft tissue
surgery at a younger age. Malformations and associated operations can therefore
be prevented or postponed to a later age, when they do not interfere with the
growth of the child. In each intervention, there is the risk of side effects,
such as sedation with oral medications, pressure sores and atrophy in a static
orthosis, temporary effect in a Bont-A treatment and surgical complications due
to a result of the surgery, and on the other hand as a result of the
execution(6).
Functional electrical stimulation (FES) may be an effective alternative
treatment for children with spastic CP and a drop foot. By stimulating the
fibular nerve or the anterior tibial muscle during the swing phase,
dorsiflexion of the foot is stimulated. In contrast to bracing, FES does not
restrict motion, but does produce muscle contraction, and thus has the
potential to increase strength and motor control through repetitive neural
stimulation over time(2). Two types of effects can be identified: 1) a direct
effect of stimulation of the fibular nerve or the anterior tibial muscle (i.e
*orthotic*) and 2) a therapeutic effect of repeated electrical stimulation
resulting in sustained effect on muscles and/ or joints. In preparation of this
study we performed a systematic research (Moll et al. accepted) and we found
that FES immediately improves ankle dorsal flexion and falls (table 1). In
addition we showed longer sustained effects of FES on ankle dorsal flexion and
falls (table 1). However, it should be noted only two study studies (4
articles) were of level II class evidence (small RCT) and all other studies
used a single subject design.
(Table 1. see appendix) Until now, the use of FES in CP is limited and no data
exist about the effects on walking distance (activity level) and participation
level.
The overall objective of this study is to conduct a randomised cross-over
intervention trial in children with unilateral spastic CP with 12 weeks of FES
for every participant and 18-24 weeks of conventional therapy. The
effectiveness of FES will be examined at an individual goal level. For every
individual a goal at walking distance will be set, next to possible other
goals. Next to that, results will be measured at the activity and functional
level: the effect at gait kinematics (such as ankle dorsiflexion and balance),
walking distance, falls, spasticity and muscle force. Both the short and
mid-long term effects will be studied (initial study, 12 weeks of FES
treatment) as the long-term effects (3 year follow-up of patients continuing
FES treatment). We will also take in to account the type of brain damage of the
patients. An addition al goal is to investigate the cost effectiveness of FES,
which, in case of a positive effect, may support allowance by insurance
companies.

The primary objective of this study is to evaluate the effect of FES on
participation level: achieving of individual goals, using the goal attainment
scale (GAS)), and the Canadian Occupational Performance Measure (COPM) for the
long term. Secondary objectives are to study effects at the body and function
level; improvement of gait characteristics, improvement of balance and muscle
force, and also effects on activity level like walking distance and number of
falls. Next to this, the donning and doffing of FES versus conventional
treatment (e.g. ankle-foot orthoses) and patient satisfaction will be studied.

In the end evidence should be provided about whether FES is a feasible
treatment option for foot drop in children with sCP, and if yes, for which
specific patients. This evidence could be used to apply for insurance
reimbursement for the FES apparatus.

The study will be a randomised controlled crossover study. Patients will be
randomised for the
conventional or the FES group, to decide with which treatment they will start.

FES group
This group will start with FES treatment: 4 weeks *adaptation phase* and 8
weeks *FES phase*. During the adaption phase, the stimulus (in Volt) will
gradually be increased up to an effective level. The participants have to
increase the wear time during this phase from 30 minutes to 6 hours a day.
During the 8 weeks FES phase, the participants have to wear the FES device for
minimal 6 hours a day during walking. After the FES phase, this group will
enter the *wash-out* period of 6 weeks. This period is meant to let the
therapeutic effects of FES fade, to prevent disturbance of the assessments
during the conventional therapy. After this period, 12 weeks of conventional
therapy will follow (orthoses/shoes and usual physiotherapy)

Conventional (control) group
This group will be instructed to wear their orthoses/shoes on a daily basis for
the first 12 weeks of the study. Usual physiotherapy can be continued. After
the first 12-week period, the control group will enter a 6 week wash-out period
(second baseline) and then be switched to FES treatment for 12 weeks in total.
(see fig 1 for a diagram of the study design).

Long term clinical follow-up
For patients who continue FES therapy after they completed the study, the long
term follow-up will be described. This long term follow-up resembles the
follow-up in the case of conventional orthotic therapy . However, because
little literature reports on the long term effects of FES, we specifically aim
to collect and publish data on the long term effects. The follow-up will
consist of 4 visits: at the start of the follow-up and 3 visits each a year
later (3 years follow-up in total). The assessments are mostly the same as the
assessments of the initial study, but a bit shorter.

Assessments
Patients will undergo four complete assessments. A complete assessment will
exist of: physical examination, gait analysis, strength analysis, 7 day
activity measurement, goal attainment score and the CPQoL questionnaire. These
assessments include the 1) assessments at baseline (time 0) with current
intervention (week 0), 2) at week 12), 3) at week 18 at the end of wash-out
and start of next treatment 4) at week 30, the end of the last treatment
phase. (see fig. 1 for a diagram of the study design). In the case of
continuation of FES therapy, a 3-year follow-up will follow, including 4
measurements in total.

Current (control) treatment: Individuals suffering from stroke and other
neurological disorders often experience inadequate dorsiflexion during swing
phase of the gait cycle due to dorsiflexor muscle weakness. This type of
pathological gait, mostly known as drop-foot gait, has two major complications:
foot-slap during loading response and toe-drag during swing. Physiotherapy and
special shoes are the first treatment options. Also ankle foot orthotic (AFO)
devices are prescribed to resolve these complications. Existing AFOs are
designed with or without articulated joint with various motion control elements
like springs, dampers, four-bar mechanism, series elastic actuator, and so
forth. (10) In the first assessment we will analyze the current treatment of
the children; for instance whether they have properly aligned and fitted
orthoses and shoes. If the orthosis or shoes are not well fitting, we will
first adjust and optimize this before starting the trial. We will use a
systematic approach as described by Kerkum et al (11) using the *shank-
to-vertical* angle. This tibia inclination angle is responsive to changes in
heel height of the AFO-footwear combination and reflects the accompanying
changes in the lower limb angles and movements. In addition we will look at
pre-positioning, the ankle angle at heelstrike and knee extension in
mid-stance. Of course the type of orthoses will influence the assessment.
FES intervention: The FES device used (WalkAide; Innovative Neurotronics,
Austin, Texas, USA) delivers asymmetrical biphasic surface electrical
stimulation to the common fibular (formerly common peroneal) nerve, triggered
by an individually programmed tilt sensor, to improve foot clearance during the
swing phase of gait. The major dorsiflexor of the ankle is the tibialis
anterior muscle, which lifts and inverts the foot. The fibular (formerly
peroneal) muscle group primarily everts the foot, with some contribution to
plantar flexion. (12) Minor adjustments in placement of the stimulating
electrodes can more selectively activate the anterior tibial and * or the
fibular muscles to achieve the desired motion in both the sagittal and frontal
planes. In addition to the user-controlled amplitude dial, the stimulation
parameters that are adjustable by the clinician include pulse frequency (16.7-
33 Hz), pulse width (25-300ms), tilt angles to trigger stimulation off and on,
presence of ramps up or down, minimum and maximum stimulation times, and a wait
time in between consecutive stimulations. Software provided with the device is
able to record walking data to guide decision making around these parameters.
Initial setup of the FES device will be done after the baseline assessment. In
the first 4 weeks the settings of the FES will be adapted. Participants will be
instructed to increase wear time from 30 minutes per day to 6 hours per day.
During the following 8 weeks FES phase, participants will be asked to wear the
device daily for at least 6 hours, during the times when they are walking the
most. During this period, patients can continue their conventional therapy
(except for AFO), for example physiotherapy if they are used to do so.
After the initial 12 weeks the FES group will be reassigned to the orthosis -
after a 6 week wash-out period - and the orthosis group to the FES group.

After completion of the initial study, patients can choose to continue FES
therapy - a decision that will be made together with the treating physician.

Most AFOs (current treatment) induce mobility restriction. By restricting ankle
movement, AFOs may exacerbate muscle weakness and atrophy, potentially leading
to further loss of function over time. Furthermore, especially patients treated
with AFOs may suffer from pressure sores. FES does not restrict motion, but
does produce muscle contraction, and thus has the potential to increase
strength and motor control through repetitive neural stimulation over time. The
risk of this treatment is negligible and the burden minimal. The study can only
be done using this patients group.