Treatment of Gait Disorders in Children With Dravet Syndrome

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: