Long-term neurodevelopmental outcome of neonates born at term with perinatal haemorrhagic stroke: A population-based study.

AIM: To assess the long-term neurodevelopmental outcome of neonates born at term diagnosed with perinatal haemorrhagic stroke (PHS) and investigate the associations among brain territorial involvement, clinical risk factors, and neurodevelopmental outcomes. METHOD: We conducted a population-based study enrolling 55 neonates born at term with PHS confirmed by magnetic resonance imaging born between 2007 and 2017. Long-term neurodevelopmental outcome was assessed using the Bayley Scales of Infant Development, Second Edition, the Brunet-Lézine test, and the Stanford-Binet Intelligence Scales, Fifth Edition. RESULTS: Follow-up was available in 50 (91%) of the infants, at a median age of 60 months (interquartile range 35-88). Forty per cent of the infants developed according to population norms, and developmental disabilities were diagnosed less frequently among neonates with frontal lobe PHS. In a multivariable model, parietal lobe PHS increased the risk for cerebral palsy (odds ratio [OR] 6.7; 95% confidence interval [CI] 1.1-41.4) and cognitive impairment (OR: 23.6; 95% CI: 2.9-194.9), while the involvement of the thalamus and/or basal ganglia was associated with epilepsy (OR: 7.0; 95% CI: 1.3-37.7). Seizures on admission were associated with epilepsy (OR: 10.8; 95% CI: 1.8-64.3). Patients with PHS affecting multiple lobes had poor prognosis. INTERPRETATION: Parietal lobe haemorrhage, the involvement of the thalamus/basal ganglia, PHS affecting multiple lobes, and seizures were independent predictors of chronic neurodevelopmental sequelae, suggesting that the stroke territorial involvement and clinical risk factors influence the outcome of PHS.

EPG5 c.1007A > G mutation in a sibling pair with rapidly progressing Vici syndrome.

We report on a sibling pair with the EPG5 c.1007A > G mutation who developed a severe form of Vici syndrome and died in infancy. The c.1007A > G (p.Gln336Arg) mutation, affecting the penultimate nucleotide and the splicing of exon 2 is the most common mutation of EPG5 and is typically associated with a less devastating prognosis: cardiomyopathy and cataract are less frequent consequences and the median survival time is 78 months compared to an overall median survival of 42 months. The less severe course related to c.1007A > G was formerly explained by the preserved canonical splicing in 25% of the transcripts. In contrast, we found the messenger RNA encoded by the c.1007A > G allele to be absent, explaining the severe course of the disease. This family provides another example of phenotypic variability related to a differential splicing.

[Perinatal stroke - from symptoms to follow-up]. / Újszülöttkori stroke - a tünetek megjelenésétol az utánkövetésig.

BACKGROUND AND PURPOSE: We aimed to analyze patient characteristics of term neonates with the diagnosis of stroke between 2006 and 2017 at the 3rd level Neonatal Intensive Care Unit of the Szent János Hospital. METHODS: We conducted a retrospective and prospective analysis including 18 newborns with stroke. Presentation, imaging methods, etiology and clinical context were discussed. All patients had a follow-up at 2 years of age or later. Subject of the study - In the past 10 years 17 term born and one premature neonate born at 36 weeks of age were diagnosed with stroke in our unit. All patients were born at good condition generally with high Apgar scores (9±1). Cesarean section was performed in 4 cases. RESULTS: With an estimated incidence of one in 1600-4000 births, the incidence of perinatal stroke in our unit was found to be the same as mentioned in the international databases. Regarding imaging method, cranial ultrasound scan do not visualise arterial ischaemic stroke therefore head MRI is recommended. Neurological symptoms of the patients presented in the first two days of life. Etiology included thrombophilia (4/18), infection (4/18), vascular malformation (2/18), moderate asphyxia (2/18) and pre-eclampsia (2/18). Middle cerebral artery was involved in 50% while the anterior cerebral artery was affected in 33%. The stroke occured in the left hemisphaerium in 44%, in the right side in 39% and was bilateral in 17%. In two cases the stroke was diagnosed in utero. Early childhood developmental support resulted in average or above average gross and fine motor development and cognitive outcome. CONCLUSION: Presenting neurological symptoms typically occur in the first few days after birth when perinatal stroke need to be considered among the broad spectrum of neonatal illnesses. Normal developmental outcome can be achieved even in cases of extensive brain damage with early childhood developmental support. Severely impaired development was observed in the cases of in utero stroke. Inherited prothrombotic disorders may have implications for subsequent pregnancies of the mother.

Whole lung lavage and GM-CSF use for pulmonary alveolar proteinosis in an infant with lysinuric protein intolerance: a case report.

BACKGROUND: Lysinuric protein intolerance (LPI) is a multi-organ metabolic disorder characterized by the imbalance in absorption and excretion of cationic amino acids like lysine, ornithine and arginine. Infants with LPI typically present with recurrent vomiting, poor growth, interstitial lung disease or renal impairment. The early onset of pulmonary alveolar proteinosis (PAP) has been reported to be associated with a severe form of LPI. Treatment of PAP most commonly consists of whole-lung lavage (WLL) and in autoimmune PAP, granulocyte-macrophage colony stimulating factor (GM-CSF) administration. Nevertheless, GM-CSF therapy in LPI-associated PAP has not been scientifically justified. CASE PRESENTATION: We describe the case of an 8-month-old infant presenting with respiratory failure due to LPI associated with PAP, who was twice treated with WLL; firstly, while on veno-venous ECMO assistance and then by the use of a selective bronchial blocker. After the two treatments with WLL, she was weaned from daytime respiratory support while on initially subcutaneous, then on inhaled GM-CSF therapy. CONCLUSIONS: This case supports the notion that GM-CSF therapy might be of benefit in patients with LPI-associated PAP. Further studies are needed to clarify the exact mechanism of GM-CSF in patients with LPI-associated PAP.

Perinatal stroke: management guideline / Perinatalis stroke: Vizsgálati irányelv

A perinatalis stroke egy heterogen neurologiai szindroma, mely agyi erserules kovetkezteben alakul ki, es hosszu tavon altalaban kronikus neurologiai kimenetellel jar. Az akut stroke-ok koze a perinatalis arterias ischaemias stroke, a sinusthrombosis es a perinatalis verzeses stroke tartozik. A kes??bb, altalaban 4-8 honapos kor kozott motoros aszimmetriat okozo korkepeket feltetelezetten perinatalis eredet?? stroke-nak nevezzuk. A magneses rezonancias perinatalis stroke-ot. Az ujabb adatok szerint a perinatalis stroke incidenciaja 1 korul van 1100 elveszuletesb??l (1/1100). Bar a stroke-os ujszulottek 40%-a kes??bb tunetmentesen fejl??dik, a tobbiek hosszu tavu neurologiai kimenetele koros, es a karosodas spektrumahoz cerebralparesis, epilepszia, kognitiv karosodas, magatartaszavar, beszedzavar es/vagy valamilyen erzekszervi karosodas tartozik. Az utobbi id??ben tobb tanulmany vizsgalta a rizikotenyez??k, az MR-kepek es a kimenetel osszefuggeset. A jelen osszefoglalo kozlemenyben a perinatalis stroke perinatalis stroke vizsgalatanak meneter??l es terapiajarol iranyelvet keszitettunk.

The role of brain territorial involvement and infection/inflammation in the long-term outcome of neonates with arterial ischemic stroke: A population-based cohort study.

BACKGROUND: Neonatal arterial ischemic stroke (NAIS) carries the risk of significant long-term neurodevelopmental burden on survivors. AIMS: To assess the long-term neurodevelopmental outcome of term neonates diagnosed with NAIS and investigate the associations among brain territorial involvement on MRI, clinical risk factors and neurodevelopmental outcomes. STUDY DESIGN: Population-based cohort study. SUBJECTS: Seventy-nine term neonates with NAIS confirmed by MRI born between 2007 and 2017. OUTCOME MEASURES: Long-term neurodevelopmental outcome assessed using the Bayley Scales of Infant Development-II, the Brunet-Lézine test and the Binet Intelligence scales-V. RESULTS: Follow-up was available in 70 (89%) of the subjects enrolled, at a median age of 60 months [IQR: 35-84]. Normal neurodevelopmental outcome was found in 43% of the patients. In a multivariable model, infants with main MCA stroke had an increased risk for overall adverse outcome (OR: 9.1, 95% CI: 1.7-48.0) and a particularly high risk for cerebral palsy (OR: 55.9, 95% CI: 7.8-399.2). The involvement of the corticospinal tract without extensive stroke also increased the risk for cerebral palsy/fine motor impairment (OR: 13.5, 95% CI: 2.4-76.3). Multiple strokes were associated with epilepsy (OR: 9.5, 95% CI: 1.0-88.9) and behavioral problems (OR: 4.4, 95% CI: 1.1-17.5) and inflammation/infection was associated with cerebral palsy (OR: 9.8, 95% CI: 1.4-66.9), cognitive impairment (OR: 9.2, 95% CI: 1.8-47.8) and epilepsy (OR: 10.3, 95% CI: 1.6-67.9). CONCLUSIONS: Main MCA stroke, involvement of the corticospinal tract, multiple strokes and inflammation/infection were independent predictors of adverse outcome, suggesting that the interplay of stroke territorial involvement and clinical risk factors influence the outcome of NAIS.