-
Journal of Neurodevelopmental Disorders Aug 2023Leukomalacia is a serious form of neonatal brain injury that often leads to neurodevelopmental impairment, and studies on neonatal leukomalacia and its long-term...
BACKGROUND
Leukomalacia is a serious form of neonatal brain injury that often leads to neurodevelopmental impairment, and studies on neonatal leukomalacia and its long-term outcomes are lacking. The aim of this study was to analyze the clinical manifestations, imaging features, and long-term neurodevelopmental outcomes in preterm infants and term infants with leukomalacia.
METHODS
Newborns diagnosed with leukomalacia by head magnetic resonance imaging (MRI) and who were admitted to intensive care units from January 2015 to June 2020 were enrolled. All infants were followed up to June 2022 (2-7 years old), and their neurodevelopmental outcomes were evaluated. The clinical data and long- term outcomes of preterm infants and term infants was analyzed by Chi-square tests.
RESULTS
A total of 218 surviving infants with leukomalacia including 114 preterm infants and 104 term infants completed the follow-up. The major typesof leukomalacia on MRI were periventricular leukomalacia in the preterm group and subcortical cystic leukomalacia in the term group, respectively (χ = 55.166; p < 0.001). When followed up to 2-7 years old, the incidence of neurodevelopmental impairment in the preterm group and term group was not significantly different (χ = 0.917; p = 0.338). However, the incidence of cerebral palsy (CP) in the preterm group was significantly higher (χ = 4.896; p = 0.027), while the incidence of intellectual disability (ID) (χ = 9.445; p = 0.002), epilepsy (EP) (χ = 23.049; p < 0.001), and CP combined with ID andEP (χ = 4.122; p = 0.042) was significantly lower than that in the term group.
CONCLUSIONS
Periventricular leukomalacia mainly occurred in preterm infants while subcortical cystic leukomalacia was commonly seen in term infants. Although the long-term neurodevelopmental outcomes of leukomalacia were both poor, preterm infants were more prone to CP, while term infants were more prone to ID, EP, and the combination of CP with ID and EP.
Topics: Infant, Newborn; Infant; Humans; Child, Preschool; Child; Infant, Premature; Cohort Studies; Leukomalacia, Periventricular; Cerebral Palsy; Epilepsy
PubMed: 37550616
DOI: 10.1186/s11689-023-09489-7 -
International Journal of Molecular... Jun 2023Germinal matrix hemorrhage (GMH) is a pathology that occurs in infancy, with often devastating long-term consequences. Posthemorrhagic hydrocephalus (PHH) can develop...
Germinal matrix hemorrhage (GMH) is a pathology that occurs in infancy, with often devastating long-term consequences. Posthemorrhagic hydrocephalus (PHH) can develop acutely, while periventricular leukomalacia (PVL) is a chronic sequala. There are no pharmacological therapies to treat PHH and PVL. We investigated different aspects of the complement pathway in acute and chronic outcomes after murine neonatal GMH induced at postnatal day 4 (P4). Following GMH-induction, the cytolytic complement membrane attack complex (MAC) colocalized with infiltrating red blood cells (RBCs) acutely but not in animals treated with the complement inhibitor CR2-Crry. Acute MAC deposition on RBCs was associated with heme oxygenase-1 expression and heme and iron deposition, which was reduced with CR2-Crry treatment. Complement inhibition also reduced hydrocephalus and improved survival. Following GMH, there were structural alterations in specific brain regions linked to motor and cognitive functions, and these changes were ameliorated by CR2-Crry, as measured at various timepoints through P90. Astrocytosis was reduced in CR2-Crry-treated animals at chronic, but not acute, timepoints. At P90, myelin basic protein and LAMP-1 colocalized, indicating chronic ongoing phagocytosis of white matter, which was reduced by CR2-Crry treatment. Data indicate acute MAC-mediated iron-related toxicity and inflammation exacerbated the chronic effects of GMH.
Topics: Mice; Animals; Hydrocephalus; Complement System Proteins; Cerebral Hemorrhage; Inflammation; Complement Membrane Attack Complex; Iron; Recombinant Fusion Proteins
PubMed: 37373319
DOI: 10.3390/ijms241210171 -
Epilepsy Research Aug 2020Collagen type IV, alpha-1 (COL4A1) variants can cause cerebrovascular diseases, such as porencephaly and cerebral hemorrhage, in addition to other autosomal dominant...
Collagen type IV, alpha-1 (COL4A1) variants can cause cerebrovascular diseases, such as porencephaly and cerebral hemorrhage, in addition to other autosomal dominant hereditary diseases. Patients with COL4A1 variants can present with epilepsy, most commonly focal epilepsy. In this paper, we present five patients, three of whom were examined by the authors, and two who were previously reported. Clinically, these five patients were characterized by the presence of West syndrome (WS), periventricular leukomalacia (PVL), and microcephaly, but none had a history of premature birth or hypoxic ischemic encephalopathy (HIE). Genetic testing results indicated that all patients had heterozygous variants of COL4A1. Genetic testing for the COL4A1 variants should be considered when a patient without a history of prematurity or HIE develops WS with PVL and microcephaly.
Topics: Cerebral Hemorrhage; Child; Child, Preschool; Collagen Type IV; Female; Heterozygote; Humans; Infant; Male; Mutation; Spasms, Infantile
PubMed: 32446163
DOI: 10.1016/j.eplepsyres.2020.106349 -
Pediatric Research Mar 2020In the past three decades, cerebral ultrasound (CUS) has become a trusted technique to study the neonatal brain. It is a relatively cheap, non-invasive, bedside... (Review)
Review
In the past three decades, cerebral ultrasound (CUS) has become a trusted technique to study the neonatal brain. It is a relatively cheap, non-invasive, bedside neuroimaging method available in nearly every hospital. Traditionally, CUS was used to detect major abnormalities, such as intraventricular hemorrhage (IVH), periventricular hemorrhagic infarction, post-hemorrhagic ventricular dilatation, and (cystic) periventricular leukomalacia (cPVL). The use of different acoustic windows, such as the mastoid and posterior fontanel, and ongoing technological developments, allows for recognizing other lesion patterns (e.g., cerebellar hemorrhage, perforator stroke, developmental venous anomaly). The CUS technique is still being improved with the use of higher transducer frequencies (7.5-18 MHz), 3D applications, advances in vascular imaging (e.g. ultrafast plane wave imaging), and improved B-mode image processing. Nevertheless, the helpfulness of CUS still highly depends on observer skills, knowledge, and experience. In this special article, we discuss how to perform a dedicated state-of-the-art neonatal CUS, and we provide suggestions for structured reporting and quality assessment.
Topics: Animals; Asphyxia; Brain; Brain Diseases; Cerebral Hemorrhage; Cerebral Infarction; Echoencephalography; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Infant, Premature, Diseases; Leukomalacia, Periventricular
PubMed: 32218539
DOI: 10.1038/s41390-020-0776-y -
Pediatric Radiology Apr 2022Neurosonography has become an essential tool for diagnosis and serial monitoring of preterm brain injury. Preterm infants are at significantly higher risk of... (Review)
Review
Neurosonography has become an essential tool for diagnosis and serial monitoring of preterm brain injury. Preterm infants are at significantly higher risk of hypoxic-ischemic injury, intraventricular hemorrhage, periventricular leukomalacia and post-hemorrhagic hydrocephalus. Neonatologists have become increasingly dependent on neurosonography to initiate medical and surgical interventions because it can be used at the bedside. While brain MRI is regarded as the gold standard for detecting preterm brain injury, neurosonography offers distinct advantages such as its cost-effectiveness, diagnostic utility and convenience. Neurosonographic signatures associated with poor long-term outcomes shape decisions regarding supportive care, medical or behavioral interventions, and family members' expectations. Within the last decade substantial progress has been made in neurosonography techniques, prompting an updated review of the topic. In addition to the up-to-date summary of neurosonography, this review discusses the potential roles of emerging neurosonography techniques that offer new functional insights into the brain, such as superb microvessel imaging, elastography, three-dimensional ventricular volume assessment, and contrast-enhanced US.
Topics: Brain; Brain Injuries; Cerebral Hemorrhage; Humans; Infant; Infant, Newborn; Infant, Premature; Leukomalacia, Periventricular; Ultrasonography
PubMed: 34648071
DOI: 10.1007/s00247-021-05191-9 -
JPEN. Journal of Parenteral and Enteral... Feb 2020Neonates have limited antioxidative capacity and are at increased risk of infection and inflammation-a situation that is exacerbated in preterm neonates. Together,... (Review)
Review
Neonates have limited antioxidative capacity and are at increased risk of infection and inflammation-a situation that is exacerbated in preterm neonates. Together, oxidative stress and inflammation are implicated in many serious conditions affecting neonates, such as bronchopulmonary dysplasia and periventricular leukomalacia. Neonates requiring parenteral nutrition have certain nutritional requirements. For example, very long-chain ω-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are regarded as conditionally essential with critical roles during early retinal and brain development, and may also have other benefits such as anti-inflammatory effects. Because of these factors, the choice of lipid emulsion used as part of parenteral nutrition support may influence clinical outcomes in neonates. There are concerns that lipid emulsions based purely on soybean oil may increase lipid peroxidation, oxidative stress, and inflammation because of their high ω-6 PUFA and low ω-3 PUFA concentrations. Composite fish-oil containing lipid emulsions may provide advantages for neonates owing to their high DHA and EPA content and high antioxidant (α-tocopherol) levels. Here, we discuss clinical trials of lipid emulsions in preterm and term neonatal populations, with a particular emphasis on markers of oxidative stress and DHA and EPA levels. Olive oil/soybean oil lipid emulsions have shown few advantages in neonates over other lipid emulsions. However, compared with either pure soybean or soybean/olive-oil based emulsions, composite fish-oil containing lipid emulsions reduce oxidative stress/lipid peroxidation and also increase DHA and EPA levels. These advantages may translate into clinical benefits for neonates requiring parenteral nutrition.
Topics: Animals; Fat Emulsions, Intravenous; Fatty Acids, Omega-3; Fish Oils; Humans; Infant, Newborn; Olive Oil; Parenteral Nutrition; Soybean Oil
PubMed: 32049399
DOI: 10.1002/jpen.1759 -
JAMA Network Open May 2023Preterm birth and socioeconomic status (SES) are associated with brain structure in childhood, but the relative contributions of each during the neonatal period are...
IMPORTANCE
Preterm birth and socioeconomic status (SES) are associated with brain structure in childhood, but the relative contributions of each during the neonatal period are unknown.
OBJECTIVE
To investigate associations of birth gestational age (GA) and SES with neonatal brain morphology by testing 3 hypotheses: GA and SES are associated with brain morphology; associations between SES and brain morphology vary with GA; and associations between SES and brain structure and morphology depend on how SES is operationalized.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study recruited participants from November 2016 to September 2021 at a single center in the United Kingdom. Participants were 170 extremely and very preterm infants and 91 full-term or near-term infants. Exclusion criteria were major congenital malformation, chromosomal abnormality, congenital infection, cystic periventricular leukomalacia, hemorrhagic parenchymal infarction, and posthemorrhagic ventricular dilatation.
EXPOSURES
Birth GA and SES, operationalized at the neighborhood level (using the Scottish Index of Multiple Deprivation), the family level (using parental education and occupation), and subjectively (World Health Organization Quality of Life measure).
MAIN OUTCOMES AND MEASURES
Brain volume (85 parcels) and 5 whole-brain cortical morphology measures (gyrification index, thickness, sulcal depth, curvature, surface area) at term-equivalent age (median [range] age, 40 weeks, 5 days [36 weeks, 2 days to 45 weeks, 6 days] and 42 weeks [38 weeks, 2 days to 46 weeks, 1 day] for preterm and full-term infants, respectively).
RESULTS
Participants were 170 extremely and very preterm infants (95 [55.9%] male; 4 of 166 [2.4%] Asian, 145 of 166 [87.3%] White) and 91 full-term or near-term infants (50 [54.9%] male; 3 of 86 [3.5%] Asian, 78 of 86 [90.7%] White infants) with median (range) birth GAs of 30 weeks, 0 days (22 weeks, 1 day, to 32 weeks, 6 days) and 39 weeks, 4 days (36 weeks, 3 days, to 42 weeks, 1 day), respectively. In fully adjusted models, birth GA was associated with a higher proportion of brain volumes (27 of 85 parcels [31.8%]; β range, -0.20 to 0.24) than neighborhood-level SES (1 of 85 parcels [1.2%]; β = 0.17 [95% CI, -0.16 to 0.50]) or family-level SES (maternal education: 4 of 85 parcels [4.7%]; β range, 0.09 to 0.15; maternal occupation: 1 of 85 parcels [1.2%]; β = 0.06 [95% CI, 0.02 to 0.11] respectively). There were interactions between GA and both family-level and subjective SES measures on regional brain volumes. Birth GA was associated with cortical surface area (β = 0.10 [95% CI, 0.02 to 0.18]) and gyrification index (β = 0.16 [95% CI, 0.07 to 0.25]); no SES measure was associated with cortical measures.
CONCLUSIONS AND RELEVANCE
In this cohort study of UK infants, birth GA and SES were associated with neonatal brain morphology, but low GA had more widely distributed associations with neonatal brain structure than SES. Further work is warranted to elucidate the mechanisms underlying the association of both GA and SES with early brain development.
Topics: Infant; Female; Infant, Newborn; Humans; Male; Infant, Premature; Premature Birth; Cohort Studies; Quality of Life; Brain; Infant, Premature, Diseases; Social Class
PubMed: 37256618
DOI: 10.1001/jamanetworkopen.2023.16067 -
Bioengineered Apr 2022Studies have shown that periventricular leukomalacia (PVL) is a distinctive form of cerebral white matter injury that pertains to myelination disturbances. Maternal...
Studies have shown that periventricular leukomalacia (PVL) is a distinctive form of cerebral white matter injury that pertains to myelination disturbances. Maternal inflammation is a main cause of white matter injury. Intrauterine inflammation cellular will be propagated to the developing brain by the entire maternal-placental-fetal axis, and triggers neural immune injury. As a low-affinity receptor, adenosine A receptor (AAR) requires high concentrations of adenosine to be significantly activated in pathological conditions. We hypothesized that in the maternal inflammation-induced PVL model, a selective AAR antagonist PSB0788 had the potential to prevent the injury. In this work, a total of 18 SD pregnant rats were divided into three groups, and treated with intraperitoneal injection of phosphate buffered saline (PBS), lipopolysaccharide (LPS), or LPS+PSB0788. Placental infection was determined by H&E staining and the inflammatory condition was determined by ELISA. Change of MBP, NG2 and CC-1 in the brain of the rats' offspring were detected by western blot and immunohistochemistry. Furthermore, LPS-induced maternal inflammation reduced the expression of MBP, which related to the decrease in the numbers of OPCs and mature oligodendrocytes in neonate rats. After treatment with PSB0788, the levels of MBP proteins increased in the rats' offspring, improved the remyelination. In conclusion, our study shows that the selective AAR antagonist PSB0788 plays an important role in promoting the normal development of OPCs by the maternal inflammation-induced PVL model. Future studies will focus on the mechanism of PSB0788 in this model.
Topics: Animals; Animals, Newborn; Brain; Brain Injuries; Disease Models, Animal; Female; Humans; Infant, Newborn; Inflammation; Leukomalacia, Periventricular; Lipopolysaccharides; Placenta; Pregnancy; Rats
PubMed: 35436416
DOI: 10.1080/21655979.2022.2061296 -
Pediatrics Feb 2021Cerebral palsy (CP) is the most common childhood motor disability. The emergence of genetic CP etiologies, variable inclusion of hypotonic CP in international...
BACKGROUND
Cerebral palsy (CP) is the most common childhood motor disability. The emergence of genetic CP etiologies, variable inclusion of hypotonic CP in international registries, and involvement of different medical disciplines in CP diagnosis can promote diagnostic variability. This variability could adversely affect patients' understanding of their symptoms and access to care. Therefore, we sought to determine the presence and extent of practice variability in CP diagnosis.
METHODS
We surveyed physicians in the United States and Canada interested in CP on the basis of membership in the American Academy of Cerebral Palsy and Developmental Medicine or the Child Neurology Society Neonatal Neurology, Movement Disorders, or Neurodevelopmental Disabilities Special Interest Groups. The survey included the 2007 consensus definition of CP and 4 hypothetical case scenarios.
RESULTS
Of 695 contacted physicians, 330 (47%) completed the survey. Two scenarios yielded consensus: (1) nonprogressive spastic diplegia after premature birth with periventricular leukomalacia on brain MRI (96% would diagnose CP) and (2) progressive spastic diplegia (92% would not diagnose CP). Scenarios featuring genetic etiologies or hypotonia as the cause of nonprogressive motor disability yielded variability: only 46% to 67% of practitioners would diagnose CP in these settings.
CONCLUSIONS
There is practice variability in whether a child with a nonprogressive motor disability due to a genetic etiology or generalized hypotonia will be diagnosed with CP. This variability occurred despite anchoring questions with the 2007 consensus definition of CP. On the basis of these results, we have suggested ways to reduce diagnostic variability, including clarification of the consensus definition.
Topics: Adolescent; Canada; Cerebral Palsy; Child; Child, Preschool; Cross-Sectional Studies; Female; Humans; Male; Physicians; Surveys and Questionnaires; United States; Young Adult
PubMed: 33402528
DOI: 10.1542/peds.2020-010066 -
Journal of the College of Physicians... Sep 2023To investigate the importance and diagnostic yield of genetic and radiological evaluations in children with hypotonia. (Observational Study)
Observational Study
OBJECTIVE
To investigate the importance and diagnostic yield of genetic and radiological evaluations in children with hypotonia.
STUDY DESIGN
Comparative observational study. Place and Duration of the Study: Department of Pediatrics Neurology, Namik Kemal University, Tekirdag, Turkey, between 2019 and 2022.
METHODOLOGY
Patients' medical histories, laboratory results, radiological examinations, and genetic tests, if any, were obtained retrospectively from the patients' clinic files. Children with hypotonia detected since the infantile period and who were on regular follow-up were included in the study. Patients who lost the follow-up were excluded.
RESULTS
Out of one hundred and seventy patients, 61.8% (n=105) were boys and 38.2% (n=65) were girls. The admission age of the patients ranged from 1 to 121 months; the mean age at presentation was 13.52±17.35 months. Hypotonia was central in 85.3% (n=145), peripheral in 12.4% (n=21), and mixed in 2.3% (n=4). Cerebral palsy was the predominant, non-genetic clinical cause of hypotonia (n=66, 39%). Brain magnetic resonance imaging (MRI) was normal in 48.2% (n=82). The most common MRI abnormality was periventricular leukomalacia in 15.9% (n=27). Sixty-five (38.2%) patients were diagnosed genetically. More than half of the patients with a genetic diagnosis were diagnosed by whole exome sequencing (WES).
CONCLUSION
Brain MRI is the first choice for the patients with central hypotonia. Patients who cannot be diagnosed with clinical findings and brain MRI should undergo WES. This is helpful for the long-term prognosis and management.
KEY WORDS
Hypotonia, Whole exome sequencing, Magnetic resonance, Spinal muscular atrophy, Cerebral palsy.
Topics: Child; Child, Preschool; Female; Humans; Infant; Male; Cerebral Palsy; Muscle Hypotonia; Radiology; Retrospective Studies; Brain; Magnetic Resonance Imaging; Exome Sequencing
PubMed: 37691366
DOI: 10.29271/jcpsp.2023.09.1028