IMAGINE-study (Imaging study in epilepsy)
Is there a neuronal correlate for cognitive impairment and response to antiepileptic drugs in children with frontal lobe epilepsy?

Rationale: Frontal lobe epilepsy (FLE), i.e. epilepsy with a frontal epileptic
focus, represents a substantial proportion of all partial epilepsies. After the
diagnosis FLE is made, the prognosis is still uncertain. Part of the children
responds well to antiepileptic drug (AED) treatment, while others will become
refractory and have frequent and disabling seizures. A second problem next to
response to medication is that part of the children with FLE will suffer from
cognitive impairment. The nature and severity of this impairment is highly
variable. Up to now, no clear patient or epilepsy-related factors responsible
for refractoriness and cognitive changes have been identified, and structural
MRI scans often reveal no abnormalities. Therefore, no currently known markers
enable clinicians to recognise this patient category. Hence, a tool for the
recognition of patients at risk for refractory epilepsy and cognitive
impairment is needed to increase our understanding of the neuronal substrate
and thus aetiology of refractoriness as well as cognitive impairment. This, in
turn, may open new possibilities for pro-active therapy, including drug
development.
As micro-structural and functional changes at the cellular level expectedly
precede macro-structural changes, we hypothesize that new MRI techniques,
diffusion tensor imaging (DTI) task related functional magnetic resonance
imaging (fMRI) and resting state fMRI, are potentially more suitable to
identify any neuronal changes associated with cognitive decline and/or
refractoriness relative to structural MRI.

Objectives: In this study we investigate possible correlations between
cognitive impairment as well as response to AED treatment in children with FLE
and abnormalities in brain micro-structure, function and neuronal connectivity.
Therefore, we apply new MRI-techniques, including DTI, task related fMRI and
resting state fMRI.

Study design: Cohort study

Nature and extent of the burden and risks associated with participation,
benefit and group relatedness: The purposed MRI-techniques are non-invasive,
the burden minimal. The risks are negligible because we do not use contrast
agents or anaesthetics. The main burden is that children have to lay down
quietly in the noisy MRI scan for one hour.
Though, in theory, it is possible that structural abnormalities will be found
during MRI in the healthy control group. Therefore, study participation will
only be allowed if people give their approval that whenever structural
abnormalities are found, they and their general practitioner will be informed.
Recruitment of children is essential to the subject matter of the study, as
frontal lobe epilepsy is basically a disease of childhood. The core aspects of
our study, the emergence of cognitive impairment as well as refractoriness, are
both observed early in the course of FLE, thus at childhood. Both conditions
have a lasting impact on mental and social functioning. To elucidate their
causative mechanisms demands their study during their time of emergence.
The study of possible neuronal correlates of cognitive impairment and
refractoriness in FLE demands the inclusion of an age-matched control group.
The imaging of the normally developing brain provides a baseline for
comparisons, both with FLE and FLE complicated by cognitive impairment or
refractoriness.