Validation of a Non Invasive Blood Marker of SIDS and Vagal Disorders
Condition: Vagal Syncope
MeSH terms: Syncope
Study type: Observational

Summary: 
      Context

      The investigators recently demonstrated a highly significant increase in muscarinic receptor
      density in the myocardium of infants deceased from sudden infant death syndrome (SIDS)
      compared to those of infants deceased from identified causes 1. Muscarinic receptor
      overexpression was found in all SIDS samples studied to date. It was associated with an
      average increase in acetylcholinesterase activity, appearing as a compensatory mechanism to
      oppose the cardiac muscarinic receptor overexpression. Similar vago-cardiac abnormalities
      were detected in a rabbit model of vagal hyperreactivity that the investigators first
      described some years ago2. In these hyperreactive animals, expression of muscarinic receptors
      was also enhanced in blood white cells. Noticeably, the pattern of changes in these cells
      paralleled the pattern of changes in the heart. Thus, muscarinic abnormalities in cardiac
      tissues could be inferred with high confidence from those measured in lymphocytes.This was
      the first report of a vago-cardiac abnormality in sudden infant death syndrome. The
      investigators findings also provided original and important perspectives for the
      identification and therapeutic management of infants at risk of sudden death. As such, the
      publication of the investigators work raised a major interest from the population and from
      the scientific and medical communities, in particular cardio-pediatricians. ObjectivesThe
      objective of the present clinical project is to validate, in human lymphocytes, muscarinic
      receptor expression level (assessed by quantitative RT-PCR) as a circulating biomarker of
      autonomic nervous system dysfunction and more specifically, of vagal hyperactivity and of
      risk of sudden death. The project will include 2 major items, conducted in parallel:1.
      evaluation of the muscarinic receptor expression in lymphocytes from adults with vagal
      syncopes (n=60 patients from an existing file versus 60 controls) (Cardiology unit + Clinical
      Investigation Centre (CIC) + Laboratory of Neurobiology and Cardiovascular Pharmacology); 2.
      evaluation of the muscarinic receptor expression in lymphocytes from children with vagal
      syncopes (n=60 versus 60 controls) (Pediatry unit + Clinical Investigation Centre +
      Laboratory of Neurobiology and Cardiovascular Pharmacology).PerspectivesThis project
      represents the first step of validation of a circulating marker of vagal hyperactivity and of
      risk of SIDS in human. Once this step is completed, the investigators will start with the
      prospective study " muscarinic receptor expression in lymphocytes and SIDS " (cord blood
      collected at birth and follow up of the new-borns) (Maternity ward + CIC + Laboratory of
      Neurobiology and Cardiovascular Pharmacology). Then therapeutic preventive management becomes
      a realistic objective. A therapeutic clinical study will then be started with atropinic
      drugs, in order to test their potential protective action against sudden death. The final
      objective of the investigators research is the prevention of SIDS through i) identification -
      as soon as birth - of new-borns at high risk and ii) appropriate prophylactic therapy. The
      investigators work also opens exciting perspectives in the field of the still poorly
      understood vagal disorders in children and adults such as vagal pauses.1 Livolsi et coll,
      Plos One 5, e9464, 2010 ; 2 Livolsi et coll, Circulation 106, 2301-2304, 2002
    


Intervention name(s): Blood sampling; ECG-Holter 24 h tape and sino-carotid stimulation test
Intervention type(s): Biological; Other
Intervention description(s): Blood sampling; ECG-Holter 24 h tape and sino-carotid stimulation test
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        University Hospital
      
Biospecimen description: 
      Blood