Investigation of the Serotoninergic System in Multiple System Atrophy: a Positron Emission Tomography (PET) Study

Morphological and Functional Investigation of the Serotoninergic System in Multiple System Atrophy: a 18F-MPPF PET Study

Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder of the adult associated to a poor prognosis. MSA is clinically characterized by the association of extra-pyramidal, dysautonomic, cerebellar and pyramidal symptoms. Histological and biological studies have raised the hypothesis that, beside the well known dopamine deficiency, some of the symptoms could be related to a dysfunction in serotoninergic neurotransmission. Serotonin is involved in the modulation of several functions impaired in MSA, such as mood, motricity or sleep. The recent description of an association between loss of brainstem serotonin neurons and sudden death in patients with MSA reinforced the hypothesis of a critical role played by this neurotransmitter in the pathophysiology of this disease. Autoreceptors called 5-HT1a are strongly involved in the regulation of serotonin neurotransmission. During the last years several radio-ligands allowing in vivo PET quantification of 5-HT1a receptors, such as 18F-MPPF (4-(2'-methoxyphenyl)-1-[2'-(N-2''-piridinyl)-p-fluorobenzamide]methylpiperazine), were developed. Moreover, the investigators recently demonstrated the ability of this brain functional imaging method to investigate, in healthy volunteers, the functional properties of 5-HT1a autoreceptors through an evaluation of their desensitization after a single oral dose of fluoxetine.

Inclusion Criteria:

• Patients with Multiple system atrophy (MSA)

  • MSA possible or probable
  • Male and female
  • Age : 30 to 80
  • No cognitive impairment
  • Unmodified treatment for 2 months
  • Able to give informed consent
  • Affiliated to social insurance

• Patients with idiopathic Parkinson's disease (IPD):

  • Positive clinical criteria for IPD
  • Male and female
  • Age : 30 to 80
  • No cognitive impairment
  • Unmodified treatment for 2 months
  • Able to give informed consent
  • Affiliated to social insurance

• Healthy controls:

  • Absence of neuropsychiatric disorder
  • Male and female
  • Age : 30 to 80
  • Able to give informed consent
  • Affiliated to social insurance

Exclusion Criteria:

• Patients with Multiple system atrophy (MSA)

  • Other Parkinsonian syndrome
  • Dementia
  • Recent intake (< 4 weeks or 8 weeks for fluoxetine) of medication acting on 5-HT1a receptors
  • History of major depression
  • Contraindication to brain MRI
  • Contraindication to PET

• Patients with idiopathic Parkinson's disease

  • Other Parkinsonian syndrome
  • Dementia
  • Recent intake (< 4 weeks or 8 weeks for fluoxetine) of medication acting on 5-HT1a receptors
  • History of major depression
  • Contraindication to brain MRI
  • Contraindication to PET

• Healthy controls:

  • Patient having a neuropsychiatric disease
  • Recent intake (< 4 weeks or 8 weeks for fluoxetine) of medication acting on 5-HT1a receptors
  • History of major depression
  • Contraindication to brain MRI
  • Contraindication to PET