Cerebellar stimulation to treat refractory epilepsy in children

Epilepsy affects 50 million people worldwide and about 30-40% of these patients
will not be adequately controlled with antiepileptic drugs (AEDs) 1.
Meta-analysis of available data suggest that modern AEDs will benefit only
about 6% of these patients over placebo 2. Once established, overall prognosis
can be very poor; In Lennox Gastaut syndrome (LGS) for example 90% of patients
are mentally retarded and > 80 % have recurring seizures throughout their adult
life 3,4. When surgical intervention is not indicated, possible or where
surgery did not provide relief, deep brain stimulation is an emerging
alternative treatment for refractory epilepsy. New evidence indicates
cerebellum might be a potential target to further improve treatment
possibilities in these patients. It is our hypothesis that stimulation of a
specific cerebellar area, i.e. cerebellar nuclei (CN), will significantly
reduce the number of epileptic seizures and thereby improve cognitive
development and functioning of refractory epilepsy patients.

- Decrease epilepsy
- Improve cognition

- 3 months baseline registration of epilepsy and cognition
- Surgery with implantation of electrical cerebellar leads, followed by a
post-surgical hospitalisation
- 4 weeks after surgery start electrical stimulation
- 6 months after start stimulation first endpoint measurement of epilepsy and
assesment of cognition
- 12 months after start stimulation second endpoint measurement of epilepsy and
cognition

- Electrical stimulation via implanted leads

This study is a heavy burden on the patient population. In brief, participants
are hospitalized pre and post-surgery and are implanted with CS electrodes
coupled to a neuro-stimulation device for which post-operative monitoring is
required. Participants, or their parents, are furthermore required to keep
track of the epilepsy in terms of frequency and severity in a seizure diary.
Pre surgery all participants undergo MRI scanning, 24 hrs EEG monitoring and IQ
and cognitive functioning tests. Post-surgery participants receive MRI scanning
and in different stages EEG monitoring and cognitive functioning tests.
Since the surgery will be a major component of the burden we briefly explain
the procedure:
- Neurosurgical procedure under general anaesthesia for placement of CS
electrodes in CDN using standard stereotactic and neuro-navigation techniques,
implantation of the neurostimulator device (like a pacemaker) subcutaneously
under the clavicular bone and subcutaneously connecting the neurostimulator
with the stimulator by electrical wiring. This entire procedure will last
approximately 5 - 6 hours.
- Hospitalization after the surgical procedure during 3 to 5 days with
post-operative (under general anesthesia) MRI scanning. This post-operative MRI
scanning is essential and crucial to determine if the CS electrode is correctly
positioned.