title: Presence of cerebral microbleeds is associated with worse executive function in pediatric brain tumor survivors.
abstract: A specific form of small-vessel vasculopathy-cerebral microbleeds (CMBs)-has been linked to various types of dementia in adults. We assessed the incidence of CMBs and their association with neurocognitive function in pediatric brain tumor survivors.
  
  
  
  In a multi-institutional cohort of 149 pediatric brain tumor patients who received cranial radiation therapy (CRT) between 1987 and 2014 at age <21 years and 16 patients who did not receive CRT, we determined the presence of CMBs on brain MRIs. Neurocognitive function was assessed using a computerized testing program (CogState). We used survival analysis to determine cumulative incidence of CMBs and Poisson regression to examine risk factors for CMBs. Linear regression models were used to assess effect of CMBs on neurocognitive function.
  
  
  
  The cumulative incidence of CMBs was 48.8% (95% CI: 38.3-60.5) at 5 years. Children who had whole brain irradiation developed CMBs at a rate 4 times greater than those treated with focal irradiation (P < .001). In multivariable analysis, children with CMBs performed worse on the Groton Maze Learning test (GML) compared with those without CMBs (Z-score -1.9; 95% CI: -2.7, -1.1; P < .001), indicating worse executive function when CMBs are present. CMBs in the frontal lobe were associated with worse performance on the GML (Z-score -2.4; 95% CI: -2.9, -1.8; P < .001). Presence of CMBs in the temporal lobes affected verbal memory (Z-score -2.0; 95% CI: -3.3, -0.7; P = .005).
  
  
  
  CMBs are common and associated with neurocognitive dysfunction in pediatric brain tumor survivors treated with radiation.
authors.affiliation: School of Medicine University of California San Francisco (UCSF), San Francisco, California (E.R.); Department of Neurology UCSF, San Francisco, California (K.S., E.F., B.D.B., H.J.F., S.M.); D epartment of Radiology Children's Hospital Los Angeles, Los Angeles, California (B.T.); Department of Pediatrics, Washington University, St Louis, Missouri (K.G.); Department of Pediatrics, Benioff Children's Hospital Oakland, Oakland, California (J.T.); Department of Pediatrics, Valley Children's Hospital, Madera, California (D.S.); Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology UCSF, San Francisco, California (J.C.); Department of Pediatrics UCSF, San Francisco, California (R.E.G., A.B., S.M.); Department of Neurological Surgery UCSF, San Francisco, California (A.B., A.M.M., S.M.); Department of Radiology and Biomedical Imaging UCSF, San Francisco, California (J.M.L.); Department of Biostatistics and Epidemiology UCSF, San Francisco, California (A.M.M.).
authors.forename: Erika
authors.initials: E
authors.lastname: Roddy
authors.affiliation: School of Medicine University of California San Francisco (UCSF), San Francisco, California (E.R.); Department of Neurology UCSF, San Francisco, California (K.S., E.F., B.D.B., H.J.F., S.M.); D epartment of Radiology Children's Hospital Los Angeles, Los Angeles, California (B.T.); Department of Pediatrics, Washington University, St Louis, Missouri (K.G.); Department of Pediatrics, Benioff Children's Hospital Oakland, Oakland, California (J.T.); Department of Pediatrics, Valley Children's Hospital, Madera, California (D.S.); Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology UCSF, San Francisco, California (J.C.); Department of Pediatrics UCSF, San Francisco, California (R.E.G., A.B., S.M.); Department of Neurological Surgery UCSF, San Francisco, California (A.B., A.M.M., S.M.); Department of Radiology and Biomedical Imaging UCSF, San Francisco, California (J.M.L.); Department of Biostatistics and Epidemiology UCSF, San Francisco, California (A.M.M.).
authors.forename: Katherine
authors.initials: K
authors.lastname: Sear
authors.affiliation: School of Medicine University of California San Francisco (UCSF), San Francisco, California (E.R.); Department of Neurology UCSF, San Francisco, California (K.S., E.F., B.D.B., H.J.F., S.M.); D epartment of Radiology Children's Hospital Los Angeles, Los Angeles, California (B.T.); Department of Pediatrics, Washington University, St Louis, Missouri (K.G.); Department of Pediatrics, Benioff Children's Hospital Oakland, Oakland, California (J.T.); Department of Pediatrics, Valley Children's Hospital, Madera, California (D.S.); Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology UCSF, San Francisco, California (J.C.); Department of Pediatrics UCSF, San Francisco, California (R.E.G., A.B., S.M.); Department of Neurological Surgery UCSF, San Francisco, California (A.B., A.M.M., S.M.); Department of Radiology and Biomedical Imaging UCSF, San Francisco, California (J.M.L.); Department of Biostatistics and Epidemiology UCSF, San Francisco, California (A.M.M.).
authors.forename: Erin
authors.initials: E
authors.lastname: Felton
authors.affiliation: School of Medicine University of California San Francisco (UCSF), San Francisco, California (E.R.); Department of Neurology UCSF, San Francisco, California (K.S., E.F., B.D.B., H.J.F., S.M.); D epartment of Radiology Children's Hospital Los Angeles, Los Angeles, California (B.T.); Department of Pediatrics, Washington University, St Louis, Missouri (K.G.); Department of Pediatrics, Benioff Children's Hospital Oakland, Oakland, California (J.T.); Department of Pediatrics, Valley Children's Hospital, Madera, California (D.S.); Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology UCSF, San Francisco, California (J.C.); Department of Pediatrics UCSF, San Francisco, California (R.E.G., A.B., S.M.); Department of Neurological Surgery UCSF, San Francisco, California (A.B., A.M.M., S.M.); Department of Radiology and Biomedical Imaging UCSF, San Francisco, California (J.M.L.); Department of Biostatistics and Epidemiology UCSF, San Francisco, California (A.M.M.).
authors.forename: Benita
authors.initials: B
authors.lastname: Tamrazi
authors.affiliation: School of Medicine University of California San Francisco (UCSF), San Francisco, California (E.R.); Department of Neurology UCSF, San Francisco, California (K.S., E.F., B.D.B., H.J.F., S.M.); D epartment of Radiology Children's Hospital Los Angeles, Los Angeles, California (B.T.); Department of Pediatrics, Washington University, St Louis, Missouri (K.G.); Department of Pediatrics, Benioff Children's Hospital Oakland, Oakland, California (J.T.); Department of Pediatrics, Valley Children's Hospital, Madera, California (D.S.); Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology UCSF, San Francisco, California (J.C.); Department of Pediatrics UCSF, San Francisco, California (R.E.G., A.B., S.M.); Department of Neurological Surgery UCSF, San Francisco, California (A.B., A.M.M., S.M.); Department of Radiology and Biomedical Imaging UCSF, San Francisco, California (J.M.L.); Department of Biostatistics and Epidemiology UCSF, San Francisco, California (A.M.M.).
authors.forename: Karen
authors.initials: K
authors.lastname: Gauvain
authors.affiliation: School of Medicine University of California San Francisco (UCSF), San Francisco, California (E.R.); Department of Neurology UCSF, San Francisco, California (K.S., E.F., B.D.B., H.J.F., S.M.); D epartment of Radiology Children's Hospital Los Angeles, Los Angeles, California (B.T.); Department of Pediatrics, Washington University, St Louis, Missouri (K.G.); Department of Pediatrics, Benioff Children's Hospital Oakland, Oakland, California (J.T.); Department of Pediatrics, Valley Children's Hospital, Madera, California (D.S.); Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology UCSF, San Francisco, California (J.C.); Department of Pediatrics UCSF, San Francisco, California (R.E.G., A.B., S.M.); Department of Neurological Surgery UCSF, San Francisco, California (A.B., A.M.M., S.M.); Department of Radiology and Biomedical Imaging UCSF, San Francisco, California (J.M.L.); Department of Biostatistics and Epidemiology UCSF, San Francisco, California (A.M.M.).
authors.forename: Joseph
authors.initials: J
authors.lastname: Torkildson
authors.affiliation: School of Medicine University of California San Francisco (UCSF), San Francisco, California (E.R.); Department of Neurology UCSF, San Francisco, California (K.S., E.F., B.D.B., H.J.F., S.M.); D epartment of Radiology Children's Hospital Los Angeles, Los Angeles, California (B.T.); Department of Pediatrics, Washington University, St Louis, Missouri (K.G.); Department of Pediatrics, Benioff Children's Hospital Oakland, Oakland, California (J.T.); Department of Pediatrics, Valley Children's Hospital, Madera, California (D.S.); Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology UCSF, San Francisco, California (J.C.); Department of Pediatrics UCSF, San Francisco, California (R.E.G., A.B., S.M.); Department of Neurological Surgery UCSF, San Francisco, California (A.B., A.M.M., S.M.); Department of Radiology and Biomedical Imaging UCSF, San Francisco, California (J.M.L.); Department of Biostatistics and Epidemiology UCSF, San Francisco, California (A.M.M.).
authors.forename: Benedict Del
authors.initials: BD
authors.lastname: Buono
authors.affiliation: School of Medicine University of California San Francisco (UCSF), San Francisco, California (E.R.); Department of Neurology UCSF, San Francisco, California (K.S., E.F., B.D.B., H.J.F., S.M.); D epartment of Radiology Children's Hospital Los Angeles, Los Angeles, California (B.T.); Department of Pediatrics, Washington University, St Louis, Missouri (K.G.); Department of Pediatrics, Benioff Children's Hospital Oakland, Oakland, California (J.T.); Department of Pediatrics, Valley Children's Hospital, Madera, California (D.S.); Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology UCSF, San Francisco, California (J.C.); Department of Pediatrics UCSF, San Francisco, California (R.E.G., A.B., S.M.); Department of Neurological Surgery UCSF, San Francisco, California (A.B., A.M.M., S.M.); Department of Radiology and Biomedical Imaging UCSF, San Francisco, California (J.M.L.); Department of Biostatistics and Epidemiology UCSF, San Francisco, California (A.M.M.).
authors.forename: David
authors.initials: D
authors.lastname: Samuel
authors.affiliation: School of Medicine University of California San Francisco (UCSF), San Francisco, California (E.R.); Department of Neurology UCSF, San Francisco, California (K.S., E.F., B.D.B., H.J.F., S.M.); D epartment of Radiology Children's Hospital Los Angeles, Los Angeles, California (B.T.); Department of Pediatrics, Washington University, St Louis, Missouri (K.G.); Department of Pediatrics, Benioff Children's Hospital Oakland, Oakland, California (J.T.); Department of Pediatrics, Valley Children's Hospital, Madera, California (D.S.); Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology UCSF, San Francisco, California (J.C.); Department of Pediatrics UCSF, San Francisco, California (R.E.G., A.B., S.M.); Department of Neurological Surgery UCSF, San Francisco, California (A.B., A.M.M., S.M.); Department of Radiology and Biomedical Imaging UCSF, San Francisco, California (J.M.L.); Department of Biostatistics and Epidemiology UCSF, San Francisco, California (A.M.M.).
authors.forename: Daphne A
authors.initials: DA
authors.lastname: Haas-Kogan
authors.affiliation: School of Medicine University of California San Francisco (UCSF), San Francisco, California (E.R.); Department of Neurology UCSF, San Francisco, California (K.S., E.F., B.D.B., H.J.F., S.M.); D epartment of Radiology Children's Hospital Los Angeles, Los Angeles, California (B.T.); Department of Pediatrics, Washington University, St Louis, Missouri (K.G.); Department of Pediatrics, Benioff Children's Hospital Oakland, Oakland, California (J.T.); Department of Pediatrics, Valley Children's Hospital, Madera, California (D.S.); Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology UCSF, San Francisco, California (J.C.); Department of Pediatrics UCSF, San Francisco, California (R.E.G., A.B., S.M.); Department of Neurological Surgery UCSF, San Francisco, California (A.B., A.M.M., S.M.); Department of Radiology and Biomedical Imaging UCSF, San Francisco, California (J.M.L.); Department of Biostatistics and Epidemiology UCSF, San Francisco, California (A.M.M.).
authors.forename: Josephine
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Medicine University of California San Francisco (UCSF), San Francisco, California (E.R.); Department of Neurology UCSF, San Francisco, California (K.S., E.F., B.D.B., H.J.F., S.M.); D epartment of Radiology Children's Hospital Los Angeles, Los Angeles, California (B.T.); Department of Pediatrics, Washington University, St Louis, Missouri (K.G.); Department of Pediatrics, Benioff Children's Hospital Oakland, Oakland, California (J.T.); Department of Pediatrics, Valley Children's Hospital, Madera, California (D.S.); Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology UCSF, San Francisco, California (J.C.); Department of Pediatrics UCSF, San Francisco, California (R.E.G., A.B., S.M.); Department of Neurological Surgery UCSF, San Francisco, California (A.B., A.M.M., S.M.); Department of Radiology and Biomedical Imaging UCSF, San Francisco, California (J.M.L.); Department of Biostatistics and Epidemiology UCSF, San Francisco, California (A.M.M.).
authors.forename: Robert E
authors.initials: RE
authors.lastname: Goldsby
authors.affiliation: School of Medicine University of California San Francisco (UCSF), San Francisco, California (E.R.); Department of Neurology UCSF, San Francisco, California (K.S., E.F., B.D.B., H.J.F., S.M.); D epartment of Radiology Children's Hospital Los Angeles, Los Angeles, California (B.T.); Department of Pediatrics, Washington University, St Louis, Missouri (K.G.); Department of Pediatrics, Benioff Children's Hospital Oakland, Oakland, California (J.T.); Department of Pediatrics, Valley Children's Hospital, Madera, California (D.S.); Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology UCSF, San Francisco, California (J.C.); Department of Pediatrics UCSF, San Francisco, California (R.E.G., A.B., S.M.); Department of Neurological Surgery UCSF, San Francisco, California (A.B., A.M.M., S.M.); Department of Radiology and Biomedical Imaging UCSF, San Francisco, California (J.M.L.); Department of Biostatistics and Epidemiology UCSF, San Francisco, California (A.M.M.).
authors.forename: Anuradha
authors.initials: A
authors.lastname: Banerjee
authors.affiliation: School of Medicine University of California San Francisco (UCSF), San Francisco, California (E.R.); Department of Neurology UCSF, San Francisco, California (K.S., E.F., B.D.B., H.J.F., S.M.); D epartment of Radiology Children's Hospital Los Angeles, Los Angeles, California (B.T.); Department of Pediatrics, Washington University, St Louis, Missouri (K.G.); Department of Pediatrics, Benioff Children's Hospital Oakland, Oakland, California (J.T.); Department of Pediatrics, Valley Children's Hospital, Madera, California (D.S.); Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology UCSF, San Francisco, California (J.C.); Department of Pediatrics UCSF, San Francisco, California (R.E.G., A.B., S.M.); Department of Neurological Surgery UCSF, San Francisco, California (A.B., A.M.M., S.M.); Department of Radiology and Biomedical Imaging UCSF, San Francisco, California (J.M.L.); Department of Biostatistics and Epidemiology UCSF, San Francisco, California (A.M.M.).
authors.forename: Janine M
authors.initials: JM
authors.lastname: Lupo
authors.affiliation: School of Medicine University of California San Francisco (UCSF), San Francisco, California (E.R.); Department of Neurology UCSF, San Francisco, California (K.S., E.F., B.D.B., H.J.F., S.M.); D epartment of Radiology Children's Hospital Los Angeles, Los Angeles, California (B.T.); Department of Pediatrics, Washington University, St Louis, Missouri (K.G.); Department of Pediatrics, Benioff Children's Hospital Oakland, Oakland, California (J.T.); Department of Pediatrics, Valley Children's Hospital, Madera, California (D.S.); Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology UCSF, San Francisco, California (J.C.); Department of Pediatrics UCSF, San Francisco, California (R.E.G., A.B., S.M.); Department of Neurological Surgery UCSF, San Francisco, California (A.B., A.M.M., S.M.); Department of Radiology and Biomedical Imaging UCSF, San Francisco, California (J.M.L.); Department of Biostatistics and Epidemiology UCSF, San Francisco, California (A.M.M.).
authors.forename: Annette M
authors.initials: AM
authors.lastname: Molinaro
authors.affiliation: School of Medicine University of California San Francisco (UCSF), San Francisco, California (E.R.); Department of Neurology UCSF, San Francisco, California (K.S., E.F., B.D.B., H.J.F., S.M.); D epartment of Radiology Children's Hospital Los Angeles, Los Angeles, California (B.T.); Department of Pediatrics, Washington University, St Louis, Missouri (K.G.); Department of Pediatrics, Benioff Children's Hospital Oakland, Oakland, California (J.T.); Department of Pediatrics, Valley Children's Hospital, Madera, California (D.S.); Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology UCSF, San Francisco, California (J.C.); Department of Pediatrics UCSF, San Francisco, California (R.E.G., A.B., S.M.); Department of Neurological Surgery UCSF, San Francisco, California (A.B., A.M.M., S.M.); Department of Radiology and Biomedical Imaging UCSF, San Francisco, California (J.M.L.); Department of Biostatistics and Epidemiology UCSF, San Francisco, California (A.M.M.).
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Fullerton
authors.affiliation: School of Medicine University of California San Francisco (UCSF), San Francisco, California (E.R.); Department of Neurology UCSF, San Francisco, California (K.S., E.F., B.D.B., H.J.F., S.M.); D epartment of Radiology Children's Hospital Los Angeles, Los Angeles, California (B.T.); Department of Pediatrics, Washington University, St Louis, Missouri (K.G.); Department of Pediatrics, Benioff Children's Hospital Oakland, Oakland, California (J.T.); Department of Pediatrics, Valley Children's Hospital, Madera, California (D.S.); Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology UCSF, San Francisco, California (J.C.); Department of Pediatrics UCSF, San Francisco, California (R.E.G., A.B., S.M.); Department of Neurological Surgery UCSF, San Francisco, California (A.B., A.M.M., S.M.); Department of Radiology and Biomedical Imaging UCSF, San Francisco, California (J.M.L.); Department of Biostatistics and Epidemiology UCSF, San Francisco, California (A.M.M.) sabine.mueller@ucsf.edu.
authors.forename: Sabine
authors.initials: S
authors.lastname: Mueller
mesh_terms: D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000150:complications / Q000000981:diagnostic imaging / Q000523:psychology* / Q000532:radiotherapy*; D002543:Cerebral Hemorrhage / Q000150:complications / Q000000981:diagnostic imaging / Q000523:psychology*; D002648:Child; D002675:Child, Preschool; D056344:Executive Function; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D011878:Radiotherapy / Q000009:adverse effects*; D012307:Risk Factors; D017741:Survivors; D055815:Young Adult
keywords: cerebral microbleeds; cranial radiation therapy; late effects of tumor therapy; neurocognitive function; pediatric brain tumor survivors.