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Pediatric Neurology Nov 2021We analyzed the certainty of evidence (CoE) for risk factors of periventricular leukomalacia (PVL) in preterm neonates, a common morbidity of prematurity. (Meta-Analysis)
Meta-Analysis
BACKGROUND
We analyzed the certainty of evidence (CoE) for risk factors of periventricular leukomalacia (PVL) in preterm neonates, a common morbidity of prematurity.
METHODS
Medline, CENTRAL, Embase, and CINAHL were searched. Cohort and case-control studies and randomised randomized controlled trials were included. Data extraction was performed in duplicate. A random random-effects meta-analysis was utilizedused. CoE was evaluated as per Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines.
RESULTS
One hundred eighty-six studies evaluating 95 risk factors for PVL were included. Of the 2,509,507 neonates assessed, 16,569 were diagnosed with PVL. Intraventricular hemorrhage [adjusted odds ratio: 3.22 (2.52-4.12)] had moderate CoE for its association with PVL. Other factors such as hypocarbia, chorioamnionitis, PPROM >48 hour, multifetal pregnancy reduction, antenatal indomethacin, lack of antenatal steroids, perinatal asphyxia, ventilation, shock/hypotension, patent ductus arteriosus requiring surgical ligation, late-onset circulatory collapse, sepsis, necrotizing enterocolitis, and neonatal surgery showed significant association with PVL after adjustment for confounders (CoE: very low to low). Amongst the risk factors associated with mother placental fetal (MPF) triad, there was paucity of literature related to genetic predisposition and defective placentation. Sensitivity analysis revealed that the strength of association between invasive ventilation and PVL decreased over time (P < 0.01), suggesting progress in ventilation strategies. Limited studies had evaluated diffuse PVL.
CONCLUSION
Despite decades of research, our findings indicate that the CoE is low to very low for most of the commonly attributed risk factors of PVL. Future studies should evaluate genetic predisposition and defective placentation in the MPF triad contributing to PVL. Studies evaluating exclusively diffuse PVL are warranted.
Topics: Humans; Infant, Newborn; Infant, Premature, Diseases; Leukomalacia, Periventricular; Risk Factors
PubMed: 34537463
DOI: 10.1016/j.pediatrneurol.2021.08.003 -
Journal of Visualized Experiments : JoVE May 2010We describe a protocol for establishing mouse models of periventricular leukomalacia (PVL). PVL is the predominant form of brain injury in premature infants and the most...
We describe a protocol for establishing mouse models of periventricular leukomalacia (PVL). PVL is the predominant form of brain injury in premature infants and the most common antecedent of cerebral palsy. PVL is characterized by periventricular white matter damage with prominent oligodendroglial injury. Hypoxia/ischemia with or without systemic infection/inflammation are the primary causes of PVL. We use P6 mice to create models of neonatal brain injury by the induction of hypoxia/ischemia with or without systemic infection/inflammation with unilateral carotid ligation followed by exposure to hypoxia with or without injection of the endotoxin lipopolysaccharide (LPS). Immunohistochemistry of myelin basic protein (MBP) or O1 and electron microscopic examination show prominent myelin loss in cerebral white matter with additional damage to the hippocampus and thalamus. Establishment of mouse models of PVL will greatly facilitate the study of disease pathogenesis using available transgenic mouse strains, conduction of drug trials in a relatively high throughput manner to identify candidate therapeutic agents, and testing of stem cell transplantation using immunodeficiency mouse strains.
Topics: Animals; Brain Ischemia; Disease Models, Animal; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Leukomalacia, Periventricular; Mice; Mice, Transgenic; Myelin Basic Protein
PubMed: 20485263
DOI: 10.3791/1951 -
Developmental Medicine and Child... Jan 2023To determine the prevalence of dystonia in individuals with periventricular leukomalacia (PVL) and spastic cerebral palsy (CP), but without basal ganglia and thalamic...
AIM
To determine the prevalence of dystonia in individuals with periventricular leukomalacia (PVL) and spastic cerebral palsy (CP), but without basal ganglia and thalamic injury (BGTI) on brain magnetic resonance imaging (MRI).
METHOD
This was a retrospective study of individuals with spastic CP and PVL on MRI evaluated between 2005 and 2018 in a CP center. Individuals with non-PVL brain lesions on MRI, including BGTI, were excluded. Dystonia was assessed via blinded review of neurological exam videos by pediatric movement disorders specialists.
RESULTS
Eighty-five participants (45 males, 40 females; mean age at videotaping 12 years [standard deviation 5 years 6 months], range 4-26 years) met inclusion and exclusion criteria. Of these participants, 50 (59%) displayed dystonia in their exam videos. The most common locations of dystonia were the fingers and hip adductors. The prevalence of dystonia was unaffected by the gestational age or severity of PVL, and was affected by Gross Motor Function Classification System level.
INTERPRETATION
Dystonia is common in individuals with spastic CP and PVL, even without BGTI on MRI. Our findings suggest vigilance for dystonia in individuals with spastic CP should remain high, even without MRI evidence of BGTI.
WHAT THIS PAPER ADDS
Individuals with spastic cerebral palsy and isolated periventricular leukomalacia on magnetic resonance imaging commonly display dystonia. Common sites of dystonia are in the fingers and hip adductors.
Topics: Infant, Newborn; Male; Female; Child; Humans; Infant; Child, Preschool; Leukomalacia, Periventricular; Cerebral Palsy; Muscle Spasticity; Dystonia; Retrospective Studies; Magnetic Resonance Imaging; Dystonic Disorders
PubMed: 35661146
DOI: 10.1111/dmcn.15300 -
AJR. American Journal of Roentgenology Mar 1989Eight children with clinical and radiologic abnormalities consistent with periventricular leukomalacia were investigated with MR imaging of the brain that employed both... (Comparative Study)
Comparative Study
Eight children with clinical and radiologic abnormalities consistent with periventricular leukomalacia were investigated with MR imaging of the brain that employed both inversion-recovery and T2-weighted spin-echo imaging sequences. The more precise delineation of white and gray matter on inversion-recovery images as compared with CT allows a detailed demonstration of the anatomic features of periventricular leukomalacia; specifically, a reduced quantity of white matter in the periventricular region and centrum semiovale and, in more severe cases, cavitated infarcts that replace the immediate periventricular white matter. The T2-weighted spin-echo and short inversion time inversion-recovery images demonstrated abnormally increased signal in white matter that appeared normal on CT scans and only minimally abnormal on conventional inversion-recovery images. These abnormalities most probably represent white matter gliosis that extends beyond the immediate periventricular regions. MR recognition of cerebral white matter abnormalities associated with periventricular leukomalacia may confirm the clinical suspicion of this diagnosis in children with spastic diplegia or quadriplegia.
Topics: Adolescent; Brain; Child; Child, Preschool; Encephalomalacia; Female; Humans; Infant, Newborn; Leukomalacia, Periventricular; Magnetic Resonance Imaging; Male; Tomography, X-Ray Computed
PubMed: 2783813
DOI: 10.2214/ajr.152.3.583 -
Developmental Medicine and Child... Aug 1998
Review
Topics: Brain Ischemia; Humans; Infant, Newborn; Infant, Premature; Leukomalacia, Periventricular
PubMed: 9746011
DOI: 10.1111/j.1469-8749.1998.tb15417.x -
Journal of Child Neurology Sep 2009Intraventricular hemorrhage and cystic periventricular leukomalacia are often co-occurring characteristics of brain damage in preterm infants. Using data from 1016...
Intraventricular hemorrhage and cystic periventricular leukomalacia are often co-occurring characteristics of brain damage in preterm infants. Using data from 1016 infants born before 30 completed weeks' gestational age, we sought to clarify the relationship between severe intraventricular hemorrhage and cystic periventricular leukomalacia, with special emphasis on common antecedents and potential confounding. After comparing risk factors for intraventricular hemorrhage grades 1 through 4 and cystic periventricular leukomalacia, it appears the risk patterns for intraventricular hemorrhage grade 3, intraventricular hemorrhage grade 4, and cystic periventricular leukomalacia differ. The association between intraventricular hemorrhage grade 3 and cystic periventricular leukomalacia differs appreciably from the association between intraventricular hemorrhage grade 4 and cystic periventricular leukomalacia, supporting the notion that intraventricular hemorrhage grade 3 and intraventricular hemorrhage grade 4 are different entities. The presence of intraventricular hemorrhage grade 3 and intraventricular hemorrhage grade 4 increases the risk of cystic periventricular leukomalacia, even after adjusting for potential confounders. This raises the possibility that intraventricular hemorrhage grade 3 and intraventricular hemorrhage grade 4 cause cystic periventricular leukomalacia.
Topics: Cerebral Hemorrhage; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Leukomalacia, Periventricular; Logistic Models; Male; Odds Ratio; Premature Birth; Respiration; Retrospective Studies; Risk Factors
PubMed: 19745088
DOI: 10.1177/0883073809338064 -
Developmental Medicine and Child... Jan 1996The authors studied the clinical course and electroencephalograms (EEGs) of 27 patients with periventricular leukomalacia (PVL), to investigate the relation between PVL...
The authors studied the clinical course and electroencephalograms (EEGs) of 27 patients with periventricular leukomalacia (PVL), to investigate the relation between PVL and West syndrome. Seven of the 27 patients with PVL developed WS; in all seven the PVL was severe. Bilateral parieto-occipital dominant irregular polyspike-and-wave (PO-polySpW) bursts were seen in eight of the 21 patients whose EEGs were recorded within the age of one year (corrected for preterm birth). All eight had severe PVL, and in six, bilateral PO-polySpW bursts were followed by hypsarrhythmia and spasms. None of the 12 patients without polyspike-and-wave bursts developed West syndrome, the study shows that West syndrome is a common complication of severe PVL and that it correlates strongly with the occurrence of bilateral PO-polySpW bursts on follow-up EEGs.
Topics: Birth Weight; Child; Child, Preschool; Electroencephalography; Female; Follow-Up Studies; Gestational Age; Humans; Infant; Infant, Newborn; Leukomalacia, Periventricular; Magnetic Resonance Imaging; Male; Risk Factors; Severity of Illness Index; Spasms, Infantile
PubMed: 8606011
DOI: 10.1111/j.1469-8749.1996.tb15027.x -
American Journal of Perinatology Oct 2008Periventricular leukomalacia (PVL) in premature infants is a major cause of mortality and disability. However, while China is the largest developing country, there is an... (Comparative Study)
Comparative Study
Periventricular leukomalacia (PVL) in premature infants is a major cause of mortality and disability. However, while China is the largest developing country, there is an absence of data concerning PVL. This study was carried out in order to explore the incidence rate and analyze the high-risk factors of PVL in premature infants, and to suggest a working protocol for the prevention of PVL in newborns at risk. The cohort prospective study included 921 premature infants < 37 weeks' gestation from January 2004 to July 2007. The study group was comprised of 271 premature infants with an ultrasound diagnosis of PVL and the control group was comprised of 650 premature infants who were submitted to the same evaluation protocol but did not show any echographic signs of PVL. The results showed that the incidence rate of PVL was 29.4% in China. High-degree PVL accounted for < 12% and > 88% of PVL was low-degree. The incidence rate was much higher when premature infants were accompanied by the following complications: low gestational age, low birth weight, prolonged rupture of membranes, chorionitis, mechanical ventilation, periventricular-ventricular hemorrhage, hypocapnia, and hyperlactacidemia. Severe complications that occur in premature infants also significantly increase the incidence of PVL. Antenatal corticosteroids can significantly decrease the incidence rate of PVL. This investigation provided a theoretical reference for the prevention of premature PVL.
Topics: Cause of Death; China; Cohort Studies; Confidence Intervals; Female; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Incidence; Infant, Newborn; Infant, Premature; Leukomalacia, Periventricular; Logistic Models; Male; Odds Ratio; Pregnancy; Prognosis; Prospective Studies; Risk Assessment; Severity of Illness Index; Survival Analysis; Ultrasonography, Doppler
PubMed: 18843588
DOI: 10.1055/s-0028-1083841 -
Developmental Medicine and Child... Dec 1996The dramatic improvement in neonatal care during the last decade did not succeed in reducing the incidence of periventricular leukomalacia (PVL), suggesting that...
The dramatic improvement in neonatal care during the last decade did not succeed in reducing the incidence of periventricular leukomalacia (PVL), suggesting that prenatal events may be the main target for PVL prevention. The studied cohort included 753 very preterm infants born between 24 and 32 weeks of gestational age, admitted to the intensive care unit and surviving at least 7 days; 69 (9.2%) of these infants had a diagnosis of cystic PVL. The highest PVL frequency was observed among the infants born at 28 weeks of gestation (16%). Inflammatory prenatal events occurring during the last days or weeks before delivery and PVL occurrence are strongly correlated. Indeed, the combination of intra-uterine infection and premature rupture of membranes is associated with a very high risk (22%). Prolongation of pregnancy with tocolysis for more than 24 hours also carries a significant 8% risk of PVL. In contrast, chronic fetal distress of long duration, such as severe intra-uterine growth retardation and pre-eclampsia, is seldom followed by PVL (< 2% risk). Similarly, rapid unexpected deliveries entail a minimal PVL risk (4%). Experimental and epidemiological confirmations of these data would have an influence on the management of both the preterm onset of labour and the premature rupture of membranes.
Topics: Female; Humans; Infant; Infant, Newborn; Leukomalacia, Periventricular; Male; Pregnancy; Risk Factors
PubMed: 8973291
DOI: 10.1111/j.1469-8749.1996.tb15068.x -
Neuroradiology Feb 2024Preterm children with cerebral palsy (CP) often have varying hand dysfunction, while the specific brain injury with periventricular leukomalacia (PVL) cannot quite...
PURPOSE
Preterm children with cerebral palsy (CP) often have varying hand dysfunction, while the specific brain injury with periventricular leukomalacia (PVL) cannot quite explain its mechanism. We aimed to investigate glymphatic activity using diffusion tensor image analysis along the perivascular space (DTI-ALPS) method and evaluate its association with brain lesion burden and hand dysfunction in children with CP secondary to PVL.
METHODS
We retrospectively enrolled 18 children with bilateral spastic CP due to PVL and 29 age- and sex-matched typically developing controls. The Manual Ability Classification System (MACS) was used to assess severity of hand dysfunction in CP. A mediation model was performed to explore the relationship among the DTI-ALPS index, brain lesion burden, and the MACS level in children with CP.
RESULTS
There were significant differences in the DTI-ALPS index between children with CP and their typically developing peers. The DTI-ALPS index of the children with CP was lower than that of the controls (1.448 vs. 1.625, P = 0.003). The mediation analysis showed that the DTI-ALPS index fully mediated the relationship between brain lesion burden and the MACS level (c' = 0.061, P = 0.665), explaining 80% of the effect.
CONCLUSION
This study provides new insights into the neural basis of hand dysfunction in children with CP, demonstrating an important role of glymphatic impairment in such patients. These results suggest that PVL might affect hand function in children with CP by disrupting glymphatic drainage.
Topics: Child; Infant, Newborn; Humans; Cerebral Palsy; Leukomalacia, Periventricular; Glymphatic System; Retrospective Studies; Hand
PubMed: 38129651
DOI: 10.1007/s00234-023-03269-9