Clinical significance of periventricular leukomalacia in the formation cerebral palsy

   Background. Cerebral palsy is one of the main causes of childhood disability. In this case, the main form of brain damage is periventricular leukomalacia, the preferred diagnostic method for which is ultrasound.

   Objective. Objective of the study: to study the features of the course, the nature of structural changes and the clinical significance of periventricular leukomalacia in the formation of cerebral palsy. The study design wasa prospective, observational, single-center study.

   All patients were initially in the intensive care unit due to the presence of multiple organ failure. Inclusion criteria: newborns with perinatal lesions of the central nervous system in combination with structural changes in the brain according to ultrasound. Exclusion criteria: newborns with perinatal lesions of the central nervous system with no structural changes in the brain according to ultrasound. Clinical observation of patients began in the neonatal period. Subsequently, dynamic observation was carried out with an assessment of the state of the nervous system up to 4 years. For an objective assessment of the psychomotor development of children in the first year of life, the method of quantitative assessment of the child's age development according to the L. T. Zhurba and E. A. Mastyukova.

   Results. 115 patients were under observation (full-term – 31, premature – 84). Forming and formed cerebral palsy was diagnosed in 20 patients. The leading nosological form of damage to the central nervous system in the neonatal period in patients was cerebral ischemia (95 %). In 80 % of patients, structural changes in the brain, according to ultrasound, were in the form of periventricular leukomalacia. Both non-cystic forms (10 patients) and cystic forms (6) were identified. The level of psychomotor development according to L. T. Zhurba and E. A. Mastyukova at the age of 3 months was 6.8 ± 0.65 points; at 6 months – 8.9 ± 0.77 points; at 1 year – 12.2 ± 0.78, which indicated a total gross delay in psychomotor development in the first year of life. In patients with cerebral palsy at the age of 1-year, atrophic dropsy of the brain was recorded with the presence of a pathognomonic sign – expansion of the third ventricle in proportion to the lateral ventricles of the brain, which is associated with a deficiency of oligodendroglia and myelin in periventricular leukomalacia. In 16 surviving children, the following organic lesions of the central nervous system were formed: cerebral palsy, severe double hemiplegia, symptomatic epilepsy (5 children; 31.3 %); cerebral palsy, severe double hemiplegia (5 children; 31.3 %); cerebral palsy, spastic diplegia (6 children; 37.4 %).

1. Back S. A. White matter injury in the preterm infant: pathology and mechanisms. Acta Neuropathol. 2017; 134 (8): 331-349.

2. Wilson-Costello D., Friedman H., Minich N., et al. Improved survival rates with increased neurodevelopmental disability for extremely low birth weight infants in the 1990^s. Pediatrics. 2005; 115 (4): 997-1003.

3. Beaino G., Khoshnood B., Kaminski M., et al. Predictors of cerebral palsy in very preterm infants: the EPIPAGE prospective population-based cohort study. Dev Med Child Neurol. 2010; 52 (6): 119-125.

4. Vinall J., Miller S. P., Chau V., et al. Neonatal pain in relation to postnatal growth in infants born very preterm. Pain. 2012; 153 (7): 1374-1381.

5. Romero-Guzman G. J., Lopez-Munoz F. Prevalencia y factores de riesgo de leucomalacia periventricular en recien nacidos prematuros. Revision sistematica [Prevalence and risk factors for periventricular leukomalacia in preterm infants. A systematic review]. Rev Neurol. 2017; 65 (2): 57-62.

6. Volpe J. J. Cerebral white matter injury of the premature infant-more common than you think. Pediatrics. 2003; 112 (1): 176-180.

7. Lee Y., Morrison B. M., Li Y., et al. Oligodendroglia metabolically supports axons and contribute to neurodegeneration. Nature. 2012; 26 (487): 443-448.

8. O'Gorman R. L, Bucher H. U, Held U., et al. Tract-based spatial statistics to assess the neuroprotective effect of early erythropoietin on white matter development in preterm infants. Brain. 2015; 138 (Pt 2): 388-397.

9. Shatrov J. G., Birch S. C. M., Lam L. T., et al. Chorioamnionitis and cerebral palsy: a meta-analysis. Obstet Gynecol. 2010; 116 (2 Pt 1): 387-392.

10. Maisonneuve E., Ancel P. Y., Foix-L'Hélias L., et al. Impact of clinical and/or histological chorioamnionitis on neurodevelopmental outcomes in preterm infants: A literature review. J Gynecol Obstet Hum Reprod. 2017; 46 (4): 307-316.

11. Lu H. Y., Zhang Q., Wang Q. X., et al. Contribution of Histologic Chorioamnionitis and Fetal Inflammatory Response Syndrome to Increased Risk of Brain Injury in Infants With Preterm Premature Rupture of Membranes. Pediatr Neurol. 2016; 61: 94-98.

12. Yap V., Perlman J. M. Mechanisms of brain injury in newborn infants associated with the fetal inflammatory response syndrome. Semin Fetal Neonatal Med. 2020; 25 (4):101110.

13. Felderhoff-Mueser U., Bittigau P., Sifringer M., et al. Oxygen causes cell death in the developing brain. Neurobiol Dis. 2004; 17 (2): 73-82.

14. Gerstner B., DeSilva T. M., Genz K., et al. Hyperoxia causes maturation-dependent cell death in the developing white matter. J Neurosci. 2008; 28 (5): 1236-12145.

15. Agut T., Alarcon A., Cabañas F., et al. Preterm white matter injury: ultrasound diagnosis and classification. Pediatr Res. 2020; 87 (Suppl 1): 37-49.

16. Jongmans M., Henderson S., de Vries L., et al. Duration of periventricular densities in preterm infants and neurological outcome at 6 years of age. Arch Dis Child. 1993; 69 (1 Spec No): 9-13.

17. Ancel P. Y, Livinec F., Larroque B., et al. Cerebral palsy among very preterm children in relation to gestational age and neonatal ultrasound abnormalities: the EPIPAGE cohort study. Pediatrics. 2006; 117 (3): 828-835.

18. Sarkar S., Shankaran S., Barks J., et al. Outcome of Preterm Infants with Transient Cystic Periventricular Leukomalacia on Serial Cranial Imaging Up to Term Equivalent Age. J Pediatr. 2018; 195: 59-65.

19. Resić B., Tomasović M., Kuzmanić-Samija R., et al. Neurodevelopmental outcome in children with periventricular leukomalacia. Coll Antropol. 2008; 32 Suppl 1: 143-147.

20. Ringelberg J., van de Bor M. Outcome of transient periventricular echodensities in preterm infants. Neuropediatrics. 1993; 24 (5): 269-273.

21. Gotardo J. W, Volkmer N. F. V., Stangler G. P., et al. Impact of peri-intraventricular haemorrhage and periventricular l eukomalacia in the neurodevelopment of preterms: A systematic review and meta-analysis. PLoS One. 2019; 14 (1): e0223427.

22. Strahle J. M., Triplett R. L., Alexopoulos D., et al. Impaired hippocampal development and outcomes in very preterm infants with perinatal brain injury. Neuroimage Clin. 2019; 22: 101787.

23. Tinelli F., Guzzetta A., Purpura G., et al. Structural brain damage and visual disorders in children with cerebral palsy due to periventricular leukomalacia. Neuroimage Clin. 2020; 28: 102430.

24. Zhurba L. T., Mastyukova E. M. Violation of psychomotor development of children of the first year of life. Moscow: Medicine, 1981. 272 p. (In Russ.)