Neonatal brain injury causes cerebellar learning deficits and Purkinje cell dysfunction

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.

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.

Infants who are very preterm (born < or = 32 weeks of gestation) and very low birth weight (VLBW) (weighing < or = 1500 g) are at risk for poor developmental outcomes. There is increasing evidence that very preterm birth and VLBW have a considerable effect on motor development, although findings are inconsistent. To investigate the relationship between very preterm birth and VLBW and motor development. The computerized databases EMBASE, PubMed, and Web of Knowledge were used to search for English-language peer-reviewed articles published between January 1992 and August 2009. Studies were included if they reported motor scores of very preterm and VLBW children without congenital anomalies using 1 of 3 established and widely used motor tests: the Bayley Scales of Infant Development II (BSID-II), the Movement Assessment Battery for Children (MABC), and the Bruininks-Oseretsky Test of Motor Proficiency (BOTMP). Forty-one articles were identified, encompassing 9653 children. In comparison with term-born peers, very preterm and VLBW children obtained significantly lower scores on all 3 motor tests: BSID-II: d = -0.88 (95% confidence interval [CI], -0.96 to -0.80; P < .001), MABC: d = -0.65 (95% CI, -0.70 to -0.60; P < .001), and BOTMP: d = -0.57 (95% CI, -0.68 to -0.46; P < .001). Whereas motor outcomes on the BSID-II show a catch-up effect in the first years of development (r = 0.50, P = .01), the results on the MABC demonstrate a nonsignificantly greater deficit with increasing age during elementary school and early adolescence (r = -0.59, P = .07). Being born preterm or VLBW is associated with significant motor impairment persisting throughout childhood.