Brain injury pathophysiology study by a multimodal approach in children with sickle cell anemia with no intra or extra cranial arteriopathy
Valentine Brousse,
Corinne Pondarre,
Manoelle Kossorotoff,
Cecile Arnaud,
Annie Kamdem,
Mariane de Montalembert,
Benedicte Boutonnat-Faucher,
Slimane Allali,
Hélène Bourdeau,
Keyne Charlot,
Sebastien Bertil,
Lydie da Costa,
Philippe Connes,
David Grévent,
Suzanne Verlhac
Affiliations
Valentine Brousse
AP-HP, Hôpital Necker Enfants Malades, Service de Pédiatrie Générale et Maladies infectieuses, Paris, France; LABEX GR-Ex, F-75015, France; Institut National de la transfusion sanguine, UMR_S1134, Inserm, F-75015 Paris, France; AP-HP, Hôpital Universitaire Robert Debré, Immuno-hématologie, Paris
Corinne Pondarre
Centre Intercommunal de Créteil, Service de Pédiatrie, Créteil, France; Inserm U955, Paris XII University, Créteil
Manoelle Kossorotoff
AP-HP, Hôpital Necker Enfants Malades, Service de Neurologie Pédiatrique, Paris
Cecile Arnaud
Centre Intercommunal de Créteil, Service de Pédiatrie, Créteil
Annie Kamdem
Centre Intercommunal de Créteil, Service de Pédiatrie, Créteil
Mariane de Montalembert
AP-HP, Hôpital Necker Enfants Malades, Service de Pédiatrie Générale et Maladies infectieuses, Paris, France; LABEX GR-Ex, F-75015
Benedicte Boutonnat-Faucher
AP-HP, Hôpital Necker Enfants Malades, Service de Pédiatrie Générale et Maladies infectieuses, Paris
Slimane Allali
AP-HP, Hôpital Necker Enfants Malades, Service de Pédiatrie Générale et Maladies infectieuses, Paris, France; LABEX GR-Ex, F-75015, France; Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeu_cal Implica_ons, Paris Descartes – Sorbonne Paris Cite ́ University, Imagine Institute, Inserm U1163, Paris
Hélène Bourdeau
AP-HP, Hôpital Robert Debré, service d’Hématologie Biologique, F-75019, Paris
Keyne Charlot
Unité de Physiologie des Exercices et Activités en Conditions Extrêmes, Département Environnements Opérationnels Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge
Sebastien Bertil
AP-HP, Service d’hématologie biologique, Hôpital Européen Georges Pompidou, Paris
Lydie da Costa
LABEX GR-Ex, F-75015, France; AP-HP, Hôpital Robert Debré, service d’Hématologie Biologique, F-75019, Paris, France; Université de Paris, F-75010 Paris; Hematim UR 4666, F-80000 Amiens
Philippe Connes
LABEX GR-Ex, F-75015, France; Laboratoire LIBM EA7424, Equipe « Biologie Vasculaire et du Globule Rouge », Université Claude Bernard Lyon 1, 69100 Villeurbanne, France; Institut Universitaire de France, Paris
David Grévent
AP-HP, Hôpital Necker Enfants Malades, Service d’Imagerie Pédiatrique, Paris
Suzanne Verlhac
Centre Hospitalier Intercommunal de Créteil, Service d’Imagerie Médicale, Créteil, France; AP-HP, Hôpital Universitaire Robert Debré, Service d’Imagerie Médicale, Paris
Despite its high prevalence in children with sickle cell anemia (SCA), the pathophysiology of silent cerebral infarcts (SCI) remains elusive. The main objective of this study was to explore the respective roles of major determinants of brain perfusion in SCA children with no past or current history of intracranial or extracranial vasculopathy. We used a multimodal approach based notably on perfusion imaging arterial spin labeling (ASL) magnetic resonance imaging (MRI) and near infra-red spectroscopy (NIRS), as well as biomarkers reflecting blood rheology and endothelial activation. Out of 59 SCA patients (mean age 11.4±3.9 yrs), eight (13%) had a total of 12 SCI. Children with SCI had a distinctive profile characterized by decreased blood pressure, impaired blood rheology, increased P-selectin levels, and marked anemia. Although ASL perfusion and oximetry values did not differ between groups, comparison of biological and clinical parameters according to the level of perfusion categorized in terciles showed an independent association between high perfusion and increased sP-selectin, decreased red blood cell deformability, low hemoglobin F level, increased blood viscosity and no a-thalassemia deletion. NIRS measurements did not yield additional novel results. Altogether, these findings argue for early MRI detection of SCI in children with no identified vasculopathy and suggest a potential role for ASL as an additional screening tool. Early treatment targeting hemolysis, anemia and endothelial dysfunction should reduce the risk of this under diagnosed and serious complication.
