Treatment of Gait Disorders in Children With Dravet Syndrome
Treatment of Gait Disorders in Children With Dravet Syndrome
Dravet syndrome is a severe infantile onset epilepsy syndrome with a prevalence of 1/15.000
 to 1/30.000. An infant with an apparently normal development presents around 6 months of age
 with a convulsive status epilepticus. Seizures can be triggered by fever, illness or
 vaccination. Because of its drug-resistance, in the past, most attention has been paid to
 seizure control. However, developmental and behavioural problems also become a serious
 concern during the second year of life. Outcome is poor, with intellectual disability and
 ongoing seizures. On the long term, the deterioration in gait is very characteristic. A
 crouch gait pattern develops that largely impacts the daily life functioning. Most children
 maintain the ability to walk around the house, but for longer distances they must rely on
 wheelchair use, which further negatively affects their mobility. Gait analysis, when combined
 with physical examination, provides quantitative information to guide treatment of gait
 disorders and assess its outcome. The goal of this project is the development of a clinical
 decision framework based upon 3D gait analysis to diagnose and treat mobility problems in
 children with Dravet syndrome. Two major university hospitals in Flanders (UZA and UZ Leuven)
 are partners in this project. The parent organisation "Stichting Dravetsyndroom
 Nederland/Vlaanderen" will also participate, as intermediate partner to facilitate contacts
 between all parties being patients and their caregivers, clinical gait labs and treating
 physicians.
The problem under investigation is the reduced functional mobility of patients with Dravet
 syndrome resulting from a crouch gait pattern. The solution, proposed in this research
 project, is the development of a decision framework based upon clinical gait analysis to
 identify the main problems and subsequently use this knowledge to select the appropriate
 treatment for the observed gait disorder.

 Dravet syndrome is a severe infantile onset epilepsy syndrome with a prevalence of 1/15.000
 to 1/30.000. In 80% of the cases it is associated with mutations in the gene encoding the
 alpha-subunit of the sodium channel SCN1A that is expressed in the frontal lobe, basal
 ganglia and cerebellum. An infant with an apparently normal development presents around 6
 months of age with a convulsive status epilepticus. Seizures can be triggered by fever,
 illness or vaccination. Because of its drug-resistance, in the past, most attention has been
 paid to seizure control. However, developmental and behavioural problems also become a
 serious concern during the second year of life. Outcome is poor, with intellectual disability
 and ongoing seizures. On the long term, the deterioration in gait is very characteristic. A
 crouch gait pattern develops that largely impacts the daily life functioning. Most children
 maintain the ability to walk around the house, but for longer distances they must rely on
 wheel-chair use, which further negatively affects their mobility. In general, Dravet syndrome
 is a very severe epileptic encephalopathy with a negative impact on the health and quality of
 life of both the patients and their caregivers.

 Crouch gait refers to a sustained flexion of the hip, knee and ankle throughout the stance
 phase of gait. This is a very inefficient walking pattern with increased energy expenditure.
 Crouch gait is also observed in children with cerebral palsy (CP). In this population,
 ankle-foot orthoses (AFOs) show effective in resolving the underlying biomechanical
 deviations and improving functional mobility. Similar benefits can be expected in children
 with Dravet. However, before AFOs can be routinely applied in clinical practice, more
 research is necessary to identify the cause of crouch gait in patients with Dravet syndrome.
 The hypothesis was formulated that the crouch pattern in children with Dravet might develop
 as a consequence of lever arm dysfunctions in the lower limbs resulting from skeletal
 malalignment in combination with muscle weakness. The first objective in this study is to
 confirm this hypothesis. The second objective is to determine the effectiveness of AFOs in
 relieving the biomechanical problems, thereby reducing crouch gait and improving functional
 mobility. Pilot work in 10 children show primary problems situated around the ankle joint,
 providing proof of concept for the use of AFOs. In the first phase of the project, two
 research questions will be addressed.

 1. Which biomechanical problems contribute to the crouch gait in children with Dravet
 syndrome?

 2. Can AFO improve musculoskeletal alignment and reduce knee flexion in children with
 Dravet syndrome?

 Gait analysis, when combined with physical examination, provides quantitative information to
 guide treatment of gait disorders and assess its outcome. At the University of Antwerp a
 state-of-the-art gait lab, the Multidisciplinary Motor Center Antwerp (M²OCEAN) was
 established in 2010 by means of a Hercules grant type 2 (AUHA/09/006). Since the Dravet
 consultation follows 80% of the children with Dravet syndrome in Flanders, the University of
 Antwerp is best placed to incorporate clinical gait analysis in the diagnostic scheme of
 these children. However, as a result of the mental retardation observed in these children,
 lengthy and time consuming protocols are a problem that can negatively affect the
 attainability of a good measurement. The mental retardation also becomes a problem when the
 children do not understand the instructions during physical examination. The challenge is to
 develop adequate protocols for both data collection and processing that specifically target
 the problems faced in this population. These protocols need to be feasible and understandable
 in children with low intelligence quotient. Information from the first phase of this project
 serves as input for this second phase that aims at answering the following questions:

 1. Which protocols for clinical gait analysis are most suitable in children with Dravet
 syndrome?

 2. What are the mobility benefits of applying the selected protocols for 3D gait analysis
 in clinical practice for children with Dravet syndrome? This project consists of 2
 phases. The first phase (month 1 - 36) is directed at scientific research to validate
 the proof of concept for treatment of crouch gait in children with Dravet syndrome. The
 second phase (month 12 - 48) is dedicated to methodological developments that will
 enhance the routinely application of clinical gait analysis in the diagnostic scheme of
 children with Dravet syndrome and will provide proof that clinical gait analysis is a
 useful tool to identify main gait problems and set appropriate treatment goals in
 children with Dravet syndrome.

 The overall design of choice for the first phase is a mixed longitudinal design. A cohort of
 children with Dravet syndrome will be subjected to follow-up for a period of 3 years annually
 receiving a physical examination and instrumented 3D clinical gait analyses (kinematics,
 kinetics, EMG). Two age-matched control groups will be retrospectively included. Control
 groups consist of a sample of age-matched typically developing children and a sample of
 age-matched children with cerebral palsy walking without and with AFO.

 The work is organised into four work packages. The first work package (WP1) is dedicated to
 data collection and comprises the longitudinal follow up of the cohort of children with
 Dravet syndrome and the retrospective data collection in the control groups. Data will be
 collected throughout the first 3 years of the project. Case - control studies related to
 scientific goals 1 and 2 are organised in the second work package (WP2) whereby WP2.1
 focusses on the identification of the biomechanical factors that contribute to the
 development of crouch gait and WP2.2 is directed at providing evidence that AFO can improve
 gait. The third work package (WP3) occurs synchronously in time and is related to the third
 research goal aiming at providing evidence for the benefit of including clinical gait
 analysis in the diagnostic scheme of children with Dravet syndrome. The last work package
 (WP4), the protocol selection and optimization, can start when the main biomechanical
 problems are identified in WP2.1.
Inclusion Criteria:

 -  diagnosed with Dravet syndrome according to the criteria of Ceulemans and Cras (2004)

 -  aged minimum 3 years and maximum 25 years at inclusion

 -  having minimum 1 year of walking experience

 Exclusion Criteria:

 -  severe epileptic seizure (status epilepticus or tonic-clonic insult over 3 min) within
 the 24 hours before the assessment

 -  insufficient cooperation to perform 3D gait analysis

 -  comorbidities of other neurological and/or orthopedic disorders not linked to Dravet
 syndrome