Mild cerebellar injury does not significantly affect cerebral white matter microstructural organization and neurodevelopmental outcome in a contemporary cohort of preterm infants

Senden, Richelle E M; Keunen, Kristin; Aa, Niek E. van der; Leemans, Alexander; Išgum, Ivana; Viergever, Max A.; Dudink, Jeroen; Vries, Linda S. de; Groenendaal, Floris; Benders, Manon J. N. L.

doi:10.1038/pr.2018.10

Cited by 7 publications

(6 citation statements)

References 41 publications

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“…More recent cohort studies of neonates with mostly punctate CBH have not detected a higher rate of neurodevelopmental impairment in those with CBH. 5,6,11 In quantifying the size of the CBH, we were able to demonstrate that the precise dose of CBH is important. Given that volumetric quantification of CBH is not practical on routine clinical imaging, we also measured the 2-dimensional imprint of CBH and found that the CBH greatest extent was similarly associated with childhood neurodevelopment.…”

Section: Discussionmentioning

confidence: 90%

“…1,2 Reported rates of CBH diagnosed by magnetic resonance imaging (MRI) range from 14 to 37% in recent preterm cohort studies. [3][4][5][6] The hemorrhages likely originate from the germinal matrices of the developing cerebellum, and in particular the subpially located external granular layer (EGL), which experiences peak cellular proliferation in a rostral to caudal direction during the early 3rd trimester. [7][8][9] The earliest reports of CBH in preterm neonates relied on postmortem examinations and cranial ultrasound via the mastoid fontanelle and described large hemorrhages that were associated with death and severe motor and behavioral impairments.…”

Section: Introductionmentioning

confidence: 99%

“…2,10 More recently, large CBHs have become less common with improvements in neonatal care, and punctate CBHs have been increasingly reported with the application of MRI. [3][4][5][6]11 These punctate CBHs are most often defined as those only visualizable on MRI and measuring <4mm in diameter on any given imaging plane. 6,[12][13][14] A recent systematic review identified 15 subjects across 8 cohort studies with isolated punctate CBH and found that 13 to 20% of them manifested severe neurodevelopmental impairment, a proportion that may not differ from the general very preterm population.…”

Section: Introductionmentioning

confidence: 99%

“…Cerebellar hemorrhage (CBH) is a common early complication of preterm birth and affects the youngest born neonates 1,2 . Reported rates of CBH diagnosed by magnetic resonance imaging (MRI) range from 14 to 37% in recent preterm cohort studies 3–6 . The hemorrhages likely originate from the germinal matrices of the developing cerebellum, and in particular the subpially located external granular layer (EGL), which experiences peak cellular proliferation in a rostral to caudal direction during the early 3rd trimester 7–9 .…”

Section: Introductionmentioning

confidence: 99%

“…More recently, large CBHs have become less common with improvements in neonatal care, and punctate CBHs have been increasingly reported with the application of MRI 3–6,11 . These punctate CBHs are most often defined as those only visualizable on MRI and measuring <4mm in diameter on any given imaging plane 6,12–14 .…”

Section: Introductionmentioning

confidence: 99%

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Location and Size of Preterm Cerebellar Hemorrhage and Childhood Development

Garfinkle

Guo

Synnes

et al. 2020

Annals of Neurology

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Objective: To examine the association between cerebellar hemorrhage (CBH) size and location and preschool-age neurodevelopment in very preterm neonates. Methods: Preterm magnetic resonance images of 221 very preterm neonates (median gestational age = 27.9 weeks) were manually segmented for CBH quantification and location. Neurodevelopmental assessments at chronological age 4.5 years included motor (Movement Assessment Battery for Children, 2nd Edition [MABC-2]), visuomotor integration (Beery-Buktenica Developmental Test of Visual-Motor Integration, 6th Edition), cognitive (Wechsler Primary and Preschool Scale of Intelligence, 3rd Edition), and behavioral (Child Behavior Checklist) outcomes. Multivariable linear regression models examined the association between CBH size and 4.5-year outcomes accounting for sex, gestational age, and supratentorial injury. Probabilistic maps assessed CBH location and likelihood of a lesion to predict adverse outcome. Results: Thirty-six neonates had CBH: 14 (6%) with only punctate CBH and 22 (10%) with ≥1 larger CBH. CBH occurred mostly in the inferior aspect of the posterior lobes. CBH total volume was independently associated with MABC-2 motor scores at 4.5 years (β = −0.095, 95% confidence interval = −0.184 to −0.005), with a standardized β coefficient (−0.16) that was similar to that of white matter injury volume (standardized β = −0.22). CBH size was similarly associated with visuomotor integration and externalizing behavior but not cognition. Voxelwise odds ratio and lesionsymptom maps demonstrated that CBH extending more deeply into the cerebellum predicted adverse motor, visuomotor, and behavioral outcomes. Interpretation: CBH size and location on preterm magnetic resonance imaging were associated with reduced preschool motor and visuomotor function and more externalizing behavior independent of supratentorial brain injury in a dose-dependent fashion. The volumetric quantification and localization of CBH, even when punctate, may allow opportunity to improve motor and behavioral outcomes by providing targeted intervention.

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Section: Discussionmentioning

confidence: 90%