PET Study of the Nicotinic System in Epilepsy
Condition: Epilepsy
MeSH terms: Epilepsy
Study type: Interventional

Summary: 
      Mutations in neuronal nicotinic acetylcholine receptors (nAChRs) have been identified in the
      autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Despite the demonstration of a
      gain of function of the mutated receptors, the precise mechanisms leading to this nocturnal
      epilepsy are still unknown. In 2006 the investigators studied the nAChR cerebral distribution
      in a group of patients with ADNFLE carrying a nAChR mutation, by a PET-scan using
      [18F]-F-A-85380, a ligand with a high affinity and specificity for alpha4beta2 nicotinic
      receptors. The study showed a different pattern of brain distribution of the radiotracer in
      the ADNFLE patients when compared to a group of control subjects, with a significant increase
      of nicotinic receptor density in the patients in mesencephalon and cerebellum (Picard et al.,
      Brain 2006). Based on the known biochemical and cellular circuits in the brainstem, these
      results suggest that the nAChR density increase in mesencephalon is involved in the
      pathophysiology of ADNFLE through the role of brainstem ascending cholinergic systems in
      arousal. The follow-up step consists of extending this examination to other forms of
      epilepsy, in order to verify the specificity of the hyperfixation pattern for ADNFLE, and
      search for a potential involvement of nicotinic receptors in other forms of epilepsy. The
      investigators aim to study 5 groups of subjects: control subjects (Group 1, 20 subjects);
      patients with a non lesional partial epilepsy and a predominance of diurnal seizures (Group
      2, 12 subjects); patients with an idiopathic generalized epilepsy (Group 3, 12 subjects);
      patients with nocturnal frontal lobe epilepsy (Group 4, 3 subjects) and epileptic patients
      with vagal nerve stimulation (Group 5, 1 subject). For each patient, a cerebral MRI, [18F]-
      fluorodeoxyglucose (FDG) PET/CT and [18F]-F-A-85380 PET/CT examinations are planned. The
      investigators will perform data analyses on volume of distribution (Vt) parametric images
      which will be based on the ratio of brain tissue to unchanged F-A-85380 plasma at
      equilibrium. Statistical parametric mapping (SPM2) will be used to further study the
      parametric PET images. This study is primarily dedicated to demonstrate that the pattern of
      hyperfixation that was obtained in ADNFLE patients is specific for this disorder and does not
      constitute a common pattern to various forms of epilepsy. The investigators will also search
      for a possible involvement of the nAChRs in other forms of epilepsy.
    


Intervention name(s): MRI of the brain; PET scan [18F]F-A-85380; PET scan [18F]FDG
Intervention type(s): Radiation; Radiation; Radiation
Intervention description(s): to eliminate a structural intra-cerebral lesion; exam performed after iv injection of 200 MBq [18F]F-A-85380; exam performed after iv injection of 200 MBq [18F]FDG
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science