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      Perinatal Cerebellar Injury in Human and Animal Models

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          Abstract

          Cerebellar injury is increasingly recognized through advanced neonatal brain imaging as a complication of premature birth. Survivors of preterm birth demonstrate a constellation of long-term neurodevelopmental deficits, many of which are potentially referable to cerebellar injury, including impaired motor functions such as fine motor incoordination, impaired motor sequencing and also cognitive, behavioral dysfunction among older patients. This paper reviews the morphogenesis and histogenesis of the human and rodent developing cerebellum, and its more frequent injuries in preterm. Most cerebellar lesions are cerebellar hemorrhage and infarction usually leading to cerebellar abnormalities and/or atrophy, but the exact pathogenesis of lesions of the cerebellum is unknown. The different mechanisms involved have been investigated with animal models and are primarily hypoxia, ischemia, infection, and inflammation Exposure to drugs and undernutrition can also induce cerebellar abnormalities. Different models are detailed to analyze these various disturbances of cerebellar development around birth.

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          Most cited references88

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          Cerebellum of the premature infant: rapidly developing, vulnerable, clinically important.

          J Volpe (2009)
          Brain abnormality in surviving premature infants is associated with an enormous amount of neurodevelopmental disability, manifested principally by cognitive, behavioral, attentional, and socialization deficits, most commonly with only relatively modest motor deficits. The most recognized contributing neuropathology is cerebral white matter injury. The thesis of this review is that acquired cerebellar abnormality is a relatively less recognized but likely important cause of neurodevelopmental disability in small premature infants. The cerebellar disease may be primarily destructive (eg, hemorrhage, infarction) or primarily underdevelopment. The latter appears to be especially common and relates to a particular vulnerability of the cerebellum of the small premature infant. Central to this vulnerability are the extraordinarily rapid and complex developmental events occurring in the cerebellum. The disturbance of development can be caused either by direct adverse effects on the cerebellum, especially the distinctive transient external granular layer, or by indirect remote trans-synaptic effects. This review describes the fascinating details of cerebellar development, with an emphasis on events in the premature period, the major types of cerebellar abnormality acquired during the premature period, their likely mechanisms of occurrence, and new insights into the relation of cerebellar disease in early life to subsequent cognitive/behavioral/attentional/socialization deficits.
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            Does cerebellar injury in premature infants contribute to the high prevalence of long-term cognitive, learning, and behavioral disability in survivors?

            Although cerebellar hemorrhagic injury is increasingly diagnosed in infants who survive premature birth, its long-term neurodevelopmental impact is poorly defined. We sought to delineate the potential role of cerebellar hemorrhagic injury in the long-term disabilities of survivors of prematurity. We compared neurodevelopmental outcome in 3 groups of premature infants (N = 86; 35 isolated cerebellar hemorrhagic injury, 35 age-matched controls, 16 cerebellar hemorrhagic injury plus supratentorial parenchymal injury). Subjects underwent formal neurologic examinations and a battery of standardized developmental, functional, and behavioral evaluations (mean age: 32.1 +/- 11.1 months). Autism-screening questionnaires were completed. Neurologic abnormalities were present in 66% of the isolated cerebellar hemorrhagic injury cases compared with 5% of the infants in the control group. Infants with isolated cerebellar hemorrhagic injury versus controls had significantly lower mean scores on all tested measures, including severe motor disabilities (48% vs 0%), expressive language (42% vs 0%), delayed receptive language (37% vs 0%), and cognitive deficits (40% vs 0%). Isolated cerebellar hemorrhagic injury was significantly associated with severe functional limitations in day-to-day activities. Significant differences were noted between cases of cerebellar hemorrhagic injury versus controls on autism screeners (37% vs 0%) and internalizing behavioral problems (34% vs 9%). Global developmental, functional, and social-behavioral deficits were more common and profound in preterm infants with injury to the vermis. Preterm infants with cerebellar hemorrhagic injury and supratentorial parenchymal injury were not at overall greater risk for neurodevelopmental disabilities, although neuromotor impairment was more severe. Cerebellar hemorrhagic injury in preterm infants is associated with a high prevalence of long-term pervasive neurodevelopment disabilities and may play an important and underrecognized role in the cognitive, learning, and behavioral dysfunction known to affect survivors.
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              Neuronal migration, with special reference to developing human brain: a review.

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                Author and article information

                Journal
                Neurol Res Int
                Neurol Res Int
                NRI
                Neurology Research International
                Hindawi Publishing Corporation
                2090-1852
                2090-1860
                2012
                23 February 2012
                : 2012
                : 858929
                Affiliations
                1Departments of Neurology and Pediatrics, Newborn Brain Institute, University of California San Francisco, San Francisco, CA 94143, USA
                2U676 Inserm, Paris, France
                3Faculté de Médecine Denis Diderot, Université Paris 7, 75010 Paris, France
                4Assistance Publique Hôpitaux de Paris, Service de Pédiatrie et Réanimation Néonatales, Hôpital Robert Debré, 48 Baulevard Sérurier, 75019 Paris, France
                5PremUP, Paris, France
                Author notes

                Academic Editor: Tara DeSilva

                Article
                10.1155/2012/858929
                3317029
                22530126
                5963c486-531f-4e26-a8f6-6d0dd81ee28c
                Copyright © 2012 Valerie Biran et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 September 2011
                : 29 November 2011
                Categories
                Review Article

                Neurology
                Neurology

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