Treatment of Gait Disorders in Children With Dravet Syndrome
Conditions: Dravet Syndrome, Severe Myoclonic Epilepsy of Infancy
Sponsor: Universiteit Antwerpen

Identification and treatment of gait 
abnormalities in children and adolescents 
with Dravet syndrome   
 
Research Protocol for posting on ClinicalTrials.gov PRS 
Protocol Registration number: NCT03857451 
 
Date: 07 February 2017 
 
 

Research protocol version 3 
 
07 February 2017 
1. Background 
The gait pattern in children and adolescents with DS was first described as "crouch gait" by 
Rodda et al., using 2D video analysis, clinical examination and X-ray of the lower limbs [1]. 
Later, Rilstone et al confirmed this "crouch" pattern in adults   [2]. In addition to the gait 
deviations described, the children with DS also showed an enlarged internal hip rotation and 
a decreased passive knee and hip extension and an increased external tibial torsion and pes 
plano valgus observed with increasing age [1]. Based on these observations, Rodda 
hypothesised that a combination of malalignment and muscle weakness of the lower limbs 
lies at the root of the observed gait disorders [1]. However, this hypothesis can only be 
confirmed by 3D gait analysis in combination with measurements of muscle strength, which 
has not yet been carried out. 
From the study of Rodda et al.  "crouch gait" appears to develop in children with DS between 
6 and 12 years [1], followed by a progressive decline in the gait pattern with increasing age   
[1, 2]. As mentioned, the passive movement limitations and the bony deformities aggravate 
by  increasing age [1]. It is known that "crouch gait" in other patient populations usually arises 
in early adolescence   [3]. This period is characterized by a growth spurt, in which body length 
and weight increase faster than muscle strength, reflecting the "crouch" pattern   [3]. "Crouch 
gait" is known as a very complex, progressive disorder, profound understanding of the various 
causal factors is required to adequately treat this pattern. In order to gain full insight into the 
causes of the abnormal gait pattern, a longitudinal follow-up of patients is therefore necessary 
to monitor the influence of various factors, such as growth, a possible decrease in muscle 
force, but also the characteristic psychomotor retardation. 
No literature is known on the treatment of gait disorders in patients with DS. Researchers do 
mention the use of corrective insoles [4], orthopaedic shoes and ankle-foot orthosis  [1], 
mainly based on clinical expertise and results of scientific research in other populations. 
Orthopaedic procedures are also applied to correct bone-like abnormalities with the aim of 
optimizing  the gait pattern [1]. The effectiveness of these interventions in patients with DS is 
unknown. To increase the quality of life of the individual patient, it is essential to keep patients 
with DS active and mobile for as long as possible. Interventions can focus on improving the 
strength and/or correction of the biomechanics of the gait pattern. It is extremely important 
to also think about prevention and determine at what age one can already intervene to correct 
small deviations in biomechanics (e.g. by splints) to prevent children from entering a vicious 
circle of serious gait disorders, such as "crouch". When drawing up a treatment plan, it is 
possible to rely on the expertise of the treatment of gait abnormalities in other neuromotor 
disorders (cerebral palsy, spina bifida), but it is essential to adapt the proposed treatment plan 
to the specific characteristics of patients with Dravet syndrome. 
2. Purpose of the research 
The ultimate objective of this project is to draw up adequate, scientifically based, treatment 
for reduction and, if possible, prevention of gait disorders in children with DS. 

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3. Method 
The research consists of 2 parts: a retrospective part and a prospective part. In the 
retrospective part, children's developmental status and potential developmental delay is 
described based on file data. In the prospective part, the children with DS are contacted and 
their gait pattern is evaluated. 
Patient Recruitment: 
Dravet syndrome has a prevalence of 1/15,000 to 1/30,000. In Flanders, an estimated 380 
people would have been diagnosed with Dravet syndrome. In 2016, 70 patients were 
medically and paramedically monitored at the University Hospital Antwerp (UZA), at the Child 
Neurology Department. As this is a rather small patient population, attempts are made to 
reach all patients within the age range of 3 – 25 years with Dravet syndrome in the 
geographical area of Flanders and the south of the Netherlands. Approximately 50 participants 
are being sought, 30 of which are from UZA and 20 from other centres. Children can 
participate in the study if they are (1) diagnosed with Dravet syndrome, based on the criteria 
defined by Ceulemans and Cras in 2004 [5]   and (2) are 3 years or older, have at least one year 
of walking experience and are up to 25 years at first inclusion. Exclusion criteria for 
participation are the prevention of a heavy epileptic seizure (status epilepticus or tonic-clonic 
seizure for more than 3 minutes) in the 24 hours prior to the study and/or insufficient 
cooperative for the removal of a 3D gang analysis. 
A study officer from the UZA will invite patients who arrive at the Dravet consultation at the 
Child Neurology Service to participate in the study. In addition, a written call is launched via 
the newsletter of the parent association Stichting Dravet Syndrome Nederland/Vlaanderen. 
Interested parties can contact the aforementioned research officer who will provide further 
information. 
Written consent is requested to the parent(s) or legal guardian of the children. The parents 
and the child are informed prior about the course of the study, expectations and risks. 
A control population in accordance with the size and characteristics of the pilot group, of 
children and (young) adults with typical development or cerebral palsy will be composed of 
available data from previous research. UZ Leuven makes a database available to this end of 
gait analyses carried out for research at the KU Leuven [6] .   In addition, a second control 
group will be composed of children and young adults who also have motor and developmental 
problems, whether or not in combination with epilepsy, due to a genetic condition that is not 
a mutation in the SCN1A gene.  
Research Setting 
All studies carried out for this study will take place in the M²OCEAN lab, UZA. 
Data Collection Procedures 
The research protocol is Figure 1and a schematic view can be found in the addendum to this 
research protocol. Prior to the physical examination, parents are asked about the use of 
technical aids as well as the distance that the child can walk independently, and a classification 
is  made according to the Functional Mobility Scale [7]. The Mobility Questionnaire, research 
version (MoVra28) is also taken  [8]. 

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An essential part of a gait analysis is an extensive physical neurological and clinical 
physiotherapeutic examination [9]collecting information on joint range of motion, alignment 
(femoral anteversion, bimalleolar and tibiofemoral angle via goniometry), muscle strength of 
the lower limbs, as well as about possible foot abnormalities (varus or valgus abnormalities of 
rear foot) and and hypermobility (Beighton hypermobility scale). Children with DS usually have 
a severe mental retardation which makes instructions for manual muscle strength tests 
difficult to understand. The physiotherapeutic exam will therefore be supplemented by the 
Functional Strength Measurement [10], a strength test designed especially for children with 
easy to understand assignments. The results of the FSM in children with Dravet syndrome can 
be compared with available normative values from the literature  [10]. 
 
Figure 1: Schematic overview of the research protocol 
In order to characterize the biomechanics of the gang pattern, the children will be subjected 
to an extensive 3D gait analysis. The experimental set-up used has already been validated in 
several studies [11-13]   and consists of an instructed walkway (16 m long), surrounded by 8 
cameras (Vicon Motion Systems, T10, 100Hz), in which four force platforms (AMTI type OR 6-
7, 0.5 x 0.4 m, 1000 Hz), were built in to register the ground reaction forces of the left and 
right foot separately. The Helen-Hayes marker set-up   [14]   (see fig. 2) will be used to follow 
the kinematics of the lower limbs. The reflective markers (14 mm) are applied to the skin using 
hypoallergenic tape. The children will be encouraged to walk barefoot on the hiking trail at 
preferential speed. The over and over again steps are repeated until 3 good left and 3 good 
right-wing foot contacts are collected on the power plates. In order to achieve a pattern as 
naturally as possible, the children will receive small assignments (e.g. bringing small cubes or 
puzzle pieces back and forth) to divert attention from stepping. 

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Figure 2: The marker set 
Data analysis 
Kinematic data, such as the range of motion of the different joints, describe the gait pattern 
and a comparison with age-specific reference data may determine gait abnormalities. The 
Vicon Clinical Model (based on the   Kadaba [15]   and Davis   [14]) is used to reconstruct 
movements of the different body segments and describe and analyze the kinematic time 
profiles. Joint angles are expressed as YXZ Cardan angles of the most distal compared to the 
most proximal segment. The angles are zero during the upright stance. These angles display 
flexion/extension, ad/abduction and internal/external rotation of the joints. 
To detect the biomechanical causes of the gait disorder, it is important, using an integrated 
inverse-dynamic model (Vicon Clinical Model), to determine the forces that control the 
observed movement. From measured joint kinematics and the ground reaction forces, net 
joint moments are calculated, which may be considered the cause of the observed movement 
pattern in a specific joint. The net joint moment is the resulting moment generated by all the 
structures that span the joint (muscles, ligaments, capsule, skin) [16]. To fully understand how 
active (muscles) and passive (gravity, ligaments and capsule) forces work together during 
movement, the inverse dynamic analysis must be supplemented by electromyography (EMG). 
To the extent of the possible, we will therefore attempt to collect EMG data from the hip 
extensors, knee flexors and extensors and ankle plantar flexors. 
Interventions 
No literature has been known to date on the treatment of arising disorders in patients with 
DS. There are three possible approaches to the prevention and treatment of gait disorders (1) 
the changes in passive anatomy; (2) changes in active anatomy and (3) the changes in the gait 

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pattern due to change in internal forces (active and passive anatomical changes) and external 
forces (ground reaction force, gravity). 
Passive changes mean muscle contractures and bone-like abnormalities. Previous research 
identified both flexion and extension defects, as well as malrotations in children with DS [1]. 
Prevention of muscle contractures can be done by stretching during physiotherapy as well as 
by using night equipment for positioning. Active changes mean that we have a loss of strength 
that was suggested in children with DS   [1]. Here too, after sufficient insights into the natural 
course, preventive, but also corrective action can be done using physiotherapy. Finally, there 
are also possibilities to directly affect the gait pattern, for example, by using orthotics that can 
restore biomechanical functions. 
Use of orthotics as well as frequency of physiotherapeutic interventions will be listed. On the 
basis of the results of the 3D gait analysis and the longitudinal follow-up of patients, a decision 
will be taken on the usefulness and application of any interventions in consultation with the 
treating neurologist and physiotherapist. 
Statistical analysis plan 
The statistical analysis will mainly include descriptive statistics. Gait parameters will be 
compared between DS and healthy controls using a t-test or a non-parametric alternative. 
Changes in gait pattern, detected by annual retesting, will be evaluated using a mixed models 
design. 
4. Relevance of the research 
Knowledge and insights from this project will directly improve quality of life in patients with 
Dravet syndrome by optimizing the treatment of gait abnormalities, allowing the individual to 
remain mobile for longer and thus contribute to increased independence and self-reliance of 
the individual. This sets the research within the strategic cluster 'Health & Well-being' with a 
focus on prevention and treatment of gait problems in brain disorders based on personalized 
therapy. A personalised treatment plan can only be achieved if a thorough identification of 
the gait defects and its causes have been carried out, which can only be done on the basis of 
3D gait analysis. Moreover, prevention can only be done and intervened early, when the data 
of a longitudinal follow-up of the gait pattern are available in children with DS.  
5. References 
1.Rodda, J.M., et al.,Progressive gait deterioration in adolescents with Dravet syndrome. Arch 
Neurol, 2012. 69(7): p. 873-8. 
2.Rilstone, J.J., et al., Dravet syndrome: seizure control and gait in adults with different SCN1A 
mutations.  Epilepsia, 2012.  53(8): p. 1421-8. 
3.Gage, J., et al., The identification and treatment of gait problems in cerebral palsy.  Vol. 2nd. 
2009: Wiley. 
4.Verheyen, K., Motor skills and arising pattern in children with severe myoclone epilepsy as 
part of Dravet syndrome. 2010. 

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5.Ceulemans, B. and P. Cras, "Severe myoclonic epilepsy in infancy". Relevance for the clinician 
of severe epilepsy starting in infancy.  Acta Neurol Belg, 2004.  104(3): p. 95-9. 
6.Van de Walle, P., et al., Age-related changes in mechanical and metabolic energy during 
typical gait.  Gait & Posture, 2010.  31(4): p. 495-501. 
7.Graham, H.K., et al., The Functional Mobility Scale (FMS).  J Pediatr Orthop, 2004.  24(5): p. 
514-20. 
8.Dallmeijer, A.J., et al., Measuring mobility limitations in children with cerebral palsy: Rasch 
model fit of a mobility questionnaire, MobQues28.  Arch Phys Med Rehabil, 2011.  92(4): p. 
640-5. 
9.Desloovere, K., et al., Do dynamic and static clinical measurements correlate with gait 
analysis parameters in children with cerebral palsy?  Gait Posture, 2006.  24(3): p. 302-13. 
10.Aertssen, W.F., G.D. Ferguson, and B.C. Smits-Engelsman, Reliability and Structural and 
Construct Validity of the Functional Strength Measurement in Children Aged 4 to 10 Years.  
Phys Ther, 2015. 
11.Hallemans, A., et al., 3D joint dynamics of walking in toddlers A cross-sectional study 
spanning the first rapid development phase of walking.  Gait Posture., 2005.  22(2): p. 107-
118. 
12.Hallemans, A., et al., Changes in foot-function parameters during the first 5 months after 
the onset of independent walking: a longitudinal follow-up study.  Gait & Posture, 2006.  23(2): 
p. 142-148. 
13.Hallemans, A., D. De Clercq, and P. Aerts, Changes in 3D joint dynamics during the first 5 
months after the onset of independent walking: a longitudinal follow-up study.  Gait Posture, 
2006.  24(3): p. 270-9. 
14.Davis, R.B., et al., A gait analysis data collection and reduction technique.  Hum Mov Sci, 
1991.  10: p. 575-587. 
15.Kadaba, M.P., H.K. Ramakrishnan, and M.E. Wootten, Measurement of lower extremity 
kinematics during level walking.  J Orthop Res, 1990.  8: p. 383-392. 
16.Winter, D.A., Biomechanics of motor control and human movement.  Vol. 2nd. 1990, USA: 
John Whiley & Sons Inc.