Looking For Genetic and Environmental Risk Factors and Therapeutic Aspects in Cervical Artery Dissections (CADISP)

• association of environmental risk factors with cervical artery dissections [ Time Frame: 2009 ] [ Designated as safety issue: No ]
• gene-environment interactions [ Time Frame: 2009 ] [ Designated as safety issue: No ]

The main purpose of this study is to look for genetic and environmental risk factors of cervical artery dissections, a major cause of ischemic stroke in young adults, in a large multicenter case-control trial

Background: Cervical artery dissections (CAD) are a major cause of ischemic stroke, longstanding disability, and occasionally death in young adults. Several lines of evidence suggest genetic predisposition for CAD. Previous genetic studies were, however, inconclusive mainly due to insufficient numbers of patients. Our hypothesis is that CAD is a multifactorial disease caused by yet largely unidentified genetic variants and environmental factors, which may interact.

Aim: Our main aim is to look for genetic and environmental risk factors and gene-environment interactions potentially underlying CAD. In addition, therapeutic aspects are addressed in the setting of a multicenter registry.

Methods: We organized a multinational European network, CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) which targets at increasing our knowledge on the pathophysiological mechanisms of this disease in a large, representative patient population. Within this network, we are aiming to perform a de novo genetic association analysis using both a genome-wide and a candidate gene approach. For this purpose, 1130 patients with CAD, 1130 patients with non-CAD ischemic stroke, and 1890 healthy controls are being recruited, and detailed clinical, laboratory, diagnostic, therapeutic and outcome data are being collected from all participating patients. We are expecting to reach the above numbers of subjects by the end of 2008. Analyses of the CADISP database might clarify a number of debated issues, including risk factors, stroke preventive treatment, and outcome predictors of CAD.

We present the strategy of a collaborative project searching for genetic risk factors of cervical artery dissections. We hope that the CADISP network will provide detailed and novel data on risk factors and treatment aspects of CAD.

groups 1 and 2: hospital-based, neurology departments group 3: community samples

• Cervical Artery Dissection
• Stroke
• Brain Infarction

• 1
  CAD-group (Cervical Artery Dissection - group): consecutive patients with cervical artery dissection, with or without associated cerebral ischemia, hospitalized in one of the participating neurological centers; standardized inclusion and exclusion criteria apply
• 2
  IS-group (Ischemic Stroke - Group): patients selected among consecutive patients hospitalized for an ischemic stroke without CAD, in the same centers as patients from group1, frequency-matched on age and gender with group1; standardized inclusion and exclusion criteria apply
• 3
  HC-group (Healthy Control - Group): DNA of healthy individuals from existing DNA-databases will be used as controls for the Belgian, French, German and Swiss centers; the other centers are recruiting their own age- and sex-matched healthy controls; individuals from the 3 groups (CAD, IS and HC) are strictly matched on geographical origin in order to avoid stratification bias

• Engelter ST, Brandt T, Debette S, Caso V, Lichy C, Pezzini A, Abboud S, Bersano A, Dittrich R, Grond-Ginsbach C, Hausser I, Kloss M, Grau AJ, Tatlisumak T, Leys D, Lyrer PA; for the Cervical Artery Dissection in Ischemic Stroke Patients (CADISP) Study Group. Antiplatelets versus anticoagulation in cervical artery dissection. Stroke. 2007 Sep;38(9):2605-11. Epub 2007 Jul 26. Review.
• Debette S, Metso TM, Pezzini A, Engelter ST, Leys D, Lyrer P, Metso AJ, Brandt T, Kloss M, Lichy C, Hausser I, Touzé E, Markus HS, Abboud S, Caso V, Bersano A, Grau A, Altintas A, Amouyel P, Tatlisumak T, Dallongeville J, Grond-Ginsbach C; CADISP-group. CADISP-genetics: an International project searching for genetic risk factors of cervical artery dissections. Int J Stroke. 2009 Jun;4(3):224-30.

GROUP1:

Inclusion Criteria:

• Typical radiological aspect of dissection* in a cervical artery (carotid and/or vertebral);* Mural hematoma, pseudoaneurysm, long tapering stenosis, intimal flap, double lumen, or occlusion > 2 cm above the carotid bifurcation revealing a pseudo aneurysm or a long tapering stenosis after recanalisation
• Written informed consent

Exclusion Criteria:

• Purely intracranial dissection
• Dissection occurring after an endovascular procedure
• Known mendelian genetic disorder that can explain the dissection (e.g. vascular Ehlers-Danlos syndrome)

GROUP2:

Inclusion Criteria:

• Recent ischemic stroke
• No signs of CAD on extracranial duplex sonography and angiography (digital subtraction or magnetic resonance or CT), performed < 7 days after the stroke
• Written informed consent

Exclusion Criteria:

• Possible cerebral ischemia but normal cerebral imaging
• CAD cannot be ruled out (e.g.persistent arterial occlusion without mural hematoma)
• Endovascular or surgical procedure on the coronary, cervical or cerebral arteries during the 48 hours preceding the cerebral infarction
• Cardiopathies with a very high embolic risk (Mechanical prosthetic valves, mitral stenosis with atrial fibrillation, intracardiac tumor, infectious endocarditis, myocardial infarction<4 months)
• Arterial vasospasm following a subarachnoid haemorrhage
• Auto-immune disease possibly responsible for the cerebral infarction
• Known monogenic disease responsible for the cerebral infarction

GROUP3:

Inclusion criteria:

• Individuals from the general population without history of stroke, dissections in any artery, transient ischemic attack, coronary artery disease, peripheral artery disease
• Written informed consent