An observational study in Dravet Syndrome and Severe Myoclonic Epilepsy of Infancy, sponsored by Universiteit Antwerpen. Completed at 3 sites in Belgium. Open to participants aged 3 Years to 25 Years. Per ClinicalTrials.gov, last updated 2022-04-14.
Sponsored by Universiteit Antwerpen · Observational
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.
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:
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.
90 studies on the registry are indexed under Epilepsies, Myoclonic; 21 are open to participants now.
This study's enrollment of 50 is below the median of 75 across 20 observational studies indexed under Epilepsies, Myoclonic.
Browse Epilepsies, Myoclonic studies →Universiteit Antwerpen is the lead sponsor of 132 studies on the registry; 29 are open to participants now.
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All children and adolescents with Dravet syndrome living in Flanders and the Netherlands
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Three dimensional gait analysis consisting of joint kinematics, kinetics and dynamic EMG data will be introduced into the diagnostic scheme
Lower limb kinematics during walking in degrees
The gait pattern is assessed by instrumented 3D gait analysis using the standardized Vicon Clinical Gait Model. Joint rotation angles of the major joints of the lower limbs will be described during walking
Time frame: baseline (at intake in year 1 of the study, T0)
Lower limb kinematics during walking in degrees
The gait pattern is assessed by instrumented 3D gait analysis using the standardized Vicon Clinical Gait Model. Joint rotation angles of the major joints of the lower limbs will be described during walking.
Time frame: after 12 months (T1), after 24 months (T2) and after 36 months (T3) from intake
Lower limb kinetics during walking
The gait pattern is assessed by instrumented 3D gait analysis using the standardized Vicon Clinical Gait Model. Net forces acting around the major joints of the lower limbs will be calculated.
Time frame: baseline (at intake in year 1 of the study, T0), after 12 months (T1), after 24 months (T2) and after 36 months (T3) from intake
Muscle activation patterns during gait in microvolts
Surface electromyography signals (microvolts) will be recorded during gait.
Time frame: baseline (at intake in year 1 of the study, T0), after 12 months (T1), after 24 months (T2) and after 36 months (T3) from intake
Functional strength on the Functional Strength Measurement.
Functional muscle strength will be assessed during clinical examination using the Functional Strength Measurement (FSM). The FSM consists of eight items: overarm throwing (centimeters), chest pass (centimeters), standing long jump (centimeters), sit to stand (number of repetitions in 30 seconds), underarm throwing (centimeters), lifting a box (number of repetitions in 30 seconds), lateral step-up (numer of repetitions in 30 seconds) and stair climbing (number of steps in 30 seconds). Norm reference values are available.
Time frame: baseline (at intake in year 1 of the study, T0), after 12 months (T1), after 24 months (T2) and after 36 months (T3) from intake
Functional Mobility Scale
Functional mobility will be assessed during parent interview using the Functional Mobility Scale (FMS). The FMS is a 6-point scale with maximum score of 6 being the most functional outcome (independent on all surfaces) and minimum score of 1 being the least functional outcome (uses wheelchair)
Time frame: baseline (at intake in year 1 of the study, T0), after 12 months (T1), after 24 months (T2) and after 36 months (T3) from intake
Mobility Questionnaire 28
Mobility limitations during daily activities inside and outside of the house will be assessed during parent interview using the validated Dutch translation of the Mobility Questionnaire 28 (MobQuest28), Dutch version: MobiliteitsVragenlijst 28 (MoVra28). The MobQuest28/MoVra28 consists of 28 items with a 5-point rating scale (0 = without any difficulties to 4 = impossible without help). A total score (0-100) indicates the mobility limitations.
Time frame: baseline (at intake in year 1 of the study, T0), after 12 months (T1), after 24 months (T2) and after 36 months (T3) from intake
heigth in meters
Total body height will be measured during clinical examination
Time frame: baseline (at intake in year 1 of the study, T0), after 12 months (T1), after 24 months (T2) and after 36 months (T3) from intake
body weigth in kilogram
Body weight will be measured during clinical examination
Time frame: baseline (at intake in year 1 of the study, T0), after 12 months (T1), after 24 months (T2) and after 36 months (T3) from intake
passive joint range of motion in degrees
Passive joint range of motion (°) will be measured during clinical examination using a goniometer
Time frame: baseline (at intake in year 1 of the study, T0), after 12 months (T1), after 24 months (T2) and after 36 months (T3) from intake
skeletal alignment in degrees
Skeletal alignment will be measured during clinical examination using a goniometer
Time frame: baseline (at intake in year 1 of the study, T0), after 12 months (T1), after 24 months (T2) and after 36 months (T3) from intake
Muscle length in degrees
Hamstrings length (popliteal angle in degrees) and iliopsoas length (Thomas test in degrees) will be measured during clinical examination using a goniometer
Time frame: baseline (at intake in year 1 of the study, T0), after 12 months (T1), after 24 months (T2) and after 36 months (T3) from intake
Selective muscle strength on the Medical Research Council muscle scale
The Medical Research Council muscle scale is a 6-point scale with minimum score 0 = no muscle contraction and maximum score 5 = normal muscle power.
Time frame: baseline (at intake in year 1 of the study, T0), after 12 months (T1), after 24 months (T2) and after 36 months (T3) from intake
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