Ana Filipa Geraldo1,2, Cesar Augusto P F Alves3, Aysha Luis4,5, Domenico Tortora6, Joana Guimarães7,8, Daisy Abreu9, Sofia Reimão2,10, Marco Pavanello11, Patrizia de Marco12, Marcello Scala13,14, Valeria Capra12, Rui Vaz8,15, Andrea Rossi16,17, Erin Simon Schwartz3, Kshitij Mankad4, Mariasavina Severino6. 1. Diagnostic Neuroradiology Unit, Department of Radiology, Centro Hospitalar Vila Nova de Gaia/Espinho (CHVNG/E), Vila Nova de Gaia, Portugal. 2. Clínica Universitária de Imagiologia, Faculty of Medicine of the University of Lisbon, Lisbon, Portugal. 3. Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA. 4. Department of Radiology, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK. 5. Department of Radiology, King's College London, London, UK. 6. Neuroradiology Unit, IRCCS Istituto Giannina Gaslini, Genova, Italia. 7. Department of Neurology, Centro Hospitalar Universitário de São João, Porto, Portugal. 8. Department of Clinical Neurosciences and Mental Health, Faculty of Medicine of the University of Porto, Porto, Portugal. 9. Instituto de Medicina Molecular João Lobo Antunes, Lisbon, Portugal. 10. Neurological Imaging Department, Hospital de Santa Maria, Lisbon, Portugal. 11. Neurosurgery Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy. 12. Medical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy. 13. Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Università Degli Studi Di Genova, Genoa, Italy. 14. Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy. 15. Neurosurgical Department, Centro Hospitalar Universitário de São João, Porto, Portugal. 16. Neuroradiology Unit, IRCCS Istituto Giannina Gaslini, Genova, Italia. andrearossi@gaslini.org. 17. Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy. andrearossi@gaslini.org.
Abstract
PURPOSE: There is limited data concerning neuroimaging findings and longitudinal evaluation of familial cerebral cavernous malformations (FCCM) in children. Our aim was to study the natural history of pediatric FCCM, with an emphasis on symptomatic hemorrhagic events and associated clinical and imaging risk factors. METHODS: We retrospectively reviewed all children diagnosed with FCCM in four tertiary pediatric hospitals between January 2010 and March 2022. Subjects with first available brain MRI and [Formula: see text] 3 months of clinical follow-up were included. Neuroimaging studies were reviewed, and clinical data collected. Annual symptomatic hemorrhage risk rates and cumulative risks were calculated using survival analysis and predictors of symptomatic hemorrhagic identified using regression analysis. RESULTS: Forty-one children (53.7% males) were included, of whom 15 (36.3%) presenting with symptomatic hemorrhage. Seven symptomatic hemorrhages occurred during 140.5 person-years of follow-up, yielding a 5-year annual hemorrhage rate of 5.0% per person-year. The 1-, 2-, and 5-year cumulative risks of symptomatic hemorrhage were 7.3%, 14.6%, and 17.1%, respectively. The latter was higher in children with prior symptomatic hemorrhage (33.3%), CCM2 genotype (33.3%), and positive family history (20.7%). Number of brainstem (adjusted hazard ratio [HR] = 1.37, P = 0.005) and posterior fossa (adjusted HR = 1.64, P = 0.004) CCM at first brain MRI were significant independent predictors of prospective symptomatic hemorrhage. CONCLUSION: The 5-year annual and cumulative symptomatic hemorrhagic risk in our pediatric FCCM cohort equals the overall risk described in children and adults with all types of CCM. Imaging features at first brain MRI may help to predict potential symptomatic hemorrhage at 5-year follow-up.
PURPOSE: There is limited data concerning neuroimaging findings and longitudinal evaluation of familial cerebral cavernous malformations (FCCM) in children. Our aim was to study the natural history of pediatric FCCM, with an emphasis on symptomatic hemorrhagic events and associated clinical and imaging risk factors. METHODS: We retrospectively reviewed all children diagnosed with FCCM in four tertiary pediatric hospitals between January 2010 and March 2022. Subjects with first available brain MRI and [Formula: see text] 3 months of clinical follow-up were included. Neuroimaging studies were reviewed, and clinical data collected. Annual symptomatic hemorrhage risk rates and cumulative risks were calculated using survival analysis and predictors of symptomatic hemorrhagic identified using regression analysis. RESULTS: Forty-one children (53.7% males) were included, of whom 15 (36.3%) presenting with symptomatic hemorrhage. Seven symptomatic hemorrhages occurred during 140.5 person-years of follow-up, yielding a 5-year annual hemorrhage rate of 5.0% per person-year. The 1-, 2-, and 5-year cumulative risks of symptomatic hemorrhage were 7.3%, 14.6%, and 17.1%, respectively. The latter was higher in children with prior symptomatic hemorrhage (33.3%), CCM2 genotype (33.3%), and positive family history (20.7%). Number of brainstem (adjusted hazard ratio [HR] = 1.37, P = 0.005) and posterior fossa (adjusted HR = 1.64, P = 0.004) CCM at first brain MRI were significant independent predictors of prospective symptomatic hemorrhage. CONCLUSION: The 5-year annual and cumulative symptomatic hemorrhagic risk in our pediatric FCCM cohort equals the overall risk described in children and adults with all types of CCM. Imaging features at first brain MRI may help to predict potential symptomatic hemorrhage at 5-year follow-up.
Authors: Athanasios K Manole; Vernon J Forrester; Barrett J Zlotoff; Blaine L Hart; Leslie A Morrison Journal: Am J Med Genet A Date: 2020-02-26 Impact factor: 2.802
Authors: Gregoire Boulouis; Thomas Blauwblomme; Jean François Hak; Sandro Benichi; Adam Kirton; Philippe Meyer; Mathilde Chevignard; Elisabeth Tournier-Lasserve; Mark T Mackay; Stéphane Chabrier; Charlotte Cordonnier; Manoëlle Kossorotoff; Olivier Naggara Journal: Stroke Date: 2019-10-22 Impact factor: 7.914
Authors: Atif Zafar; Syed A Quadri; Mudassir Farooqui; Asad Ikram; Myranda Robinson; Blaine L Hart; Marc C Mabray; Catherine Vigil; Alan T Tang; Mark L Kahn; Howard Yonas; Michael T Lawton; Helen Kim; Leslie Morrison Journal: Stroke Date: 2019-05 Impact factor: 7.914
Authors: M C Mabray; J Starcevich; J Hallstrom; M Robinson; M Bartlett; J Nelson; A Zafar; H Kim; L Morrison; B L Hart Journal: AJNR Am J Neuroradiol Date: 2020-05-28 Impact factor: 3.825
Authors: Aileen A Ren; Daniel A Snellings; Yourong S Su; Courtney C Hong; Marco Castro; Alan T Tang; Matthew R Detter; Nicholas Hobson; Romuald Girard; Sharbel Romanos; Rhonda Lightle; Thomas Moore; Robert Shenkar; Christian Benavides; M Makenzie Beaman; Helge Müller-Fielitz; Mei Chen; Patricia Mericko; Jisheng Yang; Derek C Sung; Michael T Lawton; J Michael Ruppert; Markus Schwaninger; Jakob Körbelin; Michael Potente; Issam A Awad; Douglas A Marchuk; Mark L Kahn Journal: Nature Date: 2021-04-28 Impact factor: 49.962