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The increasing pace of gene discovery in the last decade has brought a major change in the way the genetic causes of brain malformations are being diagnosed. Unbiased genomic screening has gained the first place in the diagnostic protocol of a child with congenital (brain) anomalies and the detected variants are matched with the phenotypic presentation afterwards. This process is defined as "reverse phenotyping". Screening of DNA, through copy number variant analysis of microarrays and analysis of exome data on different platforms, obtained from the index patient and both parents has become a routine approach in many centers worldwide. Clinicians are used to multidisciplinary team interaction in patient care and disease management and this explains why the majority of research that has led to the discovery of new genetic disorders nowadays proceeds from clinical observations to genomic analysis and to data exchange facilitated by open access sharing databases. However, the relevance of multidisciplinary team interaction has not been object of systematic research in the field of brain malformations. This review will illustrate some examples of how diagnostically driven questions through multidisciplinary interaction, among clinical and preclinical disciplines, can be successful in the discovery of new genes related to brain malformations. The first example illustrates the setting of interaction among neurologists, geneticists and neuro-radiologists. The second illustrates the importance of interaction among clinical dysmorphologists for pattern recognition of syndromes with multiple congenital anomalies. The third example shows how fruitful it can be to step out of the "clinical comfort zone", and interact with basic scientists in applying emerging technologies to solve the diagnostic puzzles., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Brain abnormalities in cerebral palsy (CP) are known to relate to motor outcome; however, their association with cognitive functioning is less clear., Aim of the Study: 1) To investigate the prognostic value of brain abnormalities for cognitive functioning; 2) To explore the added value of prognostic variables across ICF domains: motor function, epilepsy, gestational age, birthweight and educational level of the parents., Methods: We retrospectively analyzed brain MRI scans of 75 children with CP (GMFCS level I-V, 36% born preterm), as part of a longitudinal study. MRI classification: qualitative classification of brain abnormality pattern and semi-quantitative grading of the extent of damage. Cognitive functioning, measured as non-verbal intelligent quotient (IQ), was dichotomized into 'impaired cognition' (IQ ≤ 70) and 'normal' (IQ > 70). Multivariable logistic regression produced odds ratios (OR) with 95% confidence interval (C.I.) of risk factors for impaired cognition., Results: Overall, 27% of the tested participants had a non-verbal IQ below 70 and 36% of the participants was classified as 'having impaired cognition'. At a young age, a higher degree of white matter damage (OR 1.6, 95% C.I. 0.97-2.67) and a more severe GMFCS level (OR 3.2, 95% C.I. 1.70-5.98) are risk factors for impaired cognition at school-age (4-7 years of age). This model correctly predicts 89% of the cases. Brain damage alone predicts the presence of impaired cognition in 71% of the cases., Interpretation: Brain MRI characteristics and GMFCS level at a young age can each help identify children with CP at risk for impaired cognition at school age and together have a strong predictive value., Competing Interests: Declaration of competing interest None of the authors has any competing interest to declare., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Children with syndromic craniosynostosis (sCS) have a higher incidence of cerebellar tonsillar herniation (TH) than the general population. In the general population, TH ≥ 5 mm below the foramen magnum is associated with typical neurological deficits but, in sCS, we do not know whether this degree of TH is required before such deficits occur., Objective: This prospective cohort study aimed to determine the association between findings on neurological assessment and cerebellar tonsillar position., Methods: Magnetic resonance imaging (MRI) was used to determine TH ≥ 5 mm and the presence of syringomyelia. In regard to the outcome of neurological deficits, these were categorized according to: A, cerebellar function; B, cranial nerve abnormalities; and C, sensory or motor dysfunction., Results: Twenty of 63 patients with sCS (32% [95% confidence interval 21-45%]) had TH ≥ 5 mm and/or syringomyelia. There was no significant difference in proportion between individual forms of sCS: 16/34 Crouzon, 2/11 Muenke, 2/12 Apert, and 0/7 Saethre-Chotzen patients. Neurological deficits were prevalent (73% [95% confidence interval 60-83%]), and as frequent in patients with TH ≥ 5 mm and/or syringomyelia as those without. Surgery occurred in 3 patients overall, and only in Crouzon patients., Conclusion: Determining the effect of TH ≥ 5 mm on neurologic functioning in sCS patients is used to better determine when surgical intervention is warranted. However, we have found that neurological deficits are prevalent in sCS patients, irrespective of cerebellar tonsillar position, suggesting that such findings are developmental and, in part, syndrome-specific central nervous system features., Competing Interests: Declaration of competing interest None., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: The aim was to establish any differences in the predictive value of EEG and MRI for outcome in infants treated and not-treated with therapeutic hypothermia (HT) for perinatal asphyxia. We hypothesize that they are equally predictive and that combining both has the highest predictive value., Study Design: We retrospectively compared data of infants with hypoxic-ischemic encephalopathy (HIE) who received HT (n = 45) between September 2009 and December 2013 with those of infants with HIE born between January 2004 and August 2009, before HT was available (NT, n = 37). All received conventional and/or amplitude-integrated EEG during the first days and early MRI (day 4-5). Associations of EEG, MRI and severe neurodevelopmental outcome (death or Bayley's -2SD below mean), were tested with a multivariable logistic regression analysis, corrected for HT., Results: Forty-eight hours' EEG background pattern had a PPV of 92% and a NPV of 81% in HT, versus 100% and 58% in NT. MRI had a PPV of 71% and a NPV of 93% in HT, versus 82% and 75% in NT. The adjusted OR for adverse outcome was 0.013 (95% CI 0.002-0.154, p < 0.001) for EEG background normalization within 48 h and 32.19 (95% CI 4.84-214.25, p < 0.001) for abnormal MRI., Conclusion: The predictive value of EEG and MRI is equal in cooled and non-cooled infants with HIE. Our data show a higher predictive value (death and severe outcome) for EEG compared to MRI. In HIE, persistent abnormal EEG background pattern until 48 h, combined with abnormal early MRI is strongly predictive for poor neurodevelopment., (Copyright © 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Iodinated and gadolinium-based contrast materials have excellent safety profiles for use in pediatric computed tomography and MR imaging. The rate of acute adverse reactions and contrast-induced nephropathy is lower than in adults. The relationship between nephrogenic systemic fibrosis and gadolinium administration is well established and only a small number of children suffer from this debilitating disorder. The recent finding of gadolinium deposition in the brain of patients with normal renal function has renewed concerns regarding its long-term toxicity. The necessity of gadolinium-based contrast agent use in children should be considered carefully for each examination, and more stable macrocyclic agents should be the primary choice., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Neuropsychological deficits after treatment of paediatric brain tumour are well known, but not the role of hydrocephalus in these deficits., Aims: To study long-term neurological, cognitive, and behavioural deficits in children with a low grade tectal tumour and acquired obstructive hydrocephalus., Methods: In a consecutive series of 12 children with low-grade tectal tumour diagnosed in our hospital between 1994 and 2008, neurologic, neuropsychological, and radiologic data were prospectively collected. Intelligence, memory, attention, language, visual-spatial, and executive functions were assessed. Median follow-up was 2 years and 9 months., Results: At follow-up, most frequent neurologic disability was fatigue in children with a low-grade tectal tumour. They scored lower on sustained attention, long-term memory and had more behavioural problems. Factor influencing cognition was persisting severe hydrocephalus at time of assessment. The cognitive problems resulted in 60% of children needing assistances of special services at school., Conclusions: At long-term, children with a low-grade tectal tumour display invalidating neuropsychological impairments resulting in educational problems. Adequate treatment of hydrocephalus may result in better cognitive functioning. Our findings suggest that part of the symptoms of the cerebellar cognitive affective syndrome may not have resulted from a cerebellar lesion itself but rather from a cerebral dysfunction or compression of supratentorial structures in the cerebello-cortical circuitry due to the obstructive hydrocephalus., (Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Postmortem imaging has become an increasingly important part in the examination of deceased fetuses and neonates. This article discusses how to perform magnetic resonance (MR) imaging autopsy, including such technical determinators as field strength, and factors influencing image quality. Also included is a discussion on the indications for MR autopsy, including stillborns and terminations of pregnancy, and natural and unexplained death., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Six term newborns presented with apnoea and temporal lobe haemorrhage., Aim: In this observational study, we described involvement of the limbic system in apnoeic term newborns with temporal lobe injury., Methods: Six term newborns presented to the neonatal care unit with apnoea within the first 2 days of life. Ultrasound (US) and MRI of the brain were obtained in the first week of life., Results: Apnoea was related to temporal lobe haemorrhage in all. During apnoeic periods four had focal epileptic activity on EEG. All lesions were detected first with US. On MRI, haemorrhages were located in the parenchyma, the subdural and/or subarachnoid space. Three haemorrhages were surrounded by infarction in the temporal lobe. In three infants hippocampus and mesial temporal cortex were affected. In two basal temporal cortex only was involved. Vascular anomalies were excluded by MRA, serial MRI or serial US with Doppler imaging., Conclusion: Term infants with seizure associated apnoea may present with haemorrhage and/or infarction to hippocampus, mesial and basal temporal cortex. This study supports the existence and possible disruption of descending influences from the temporal cortex and/or amygdala on brainstem breathing centres in the term newborn.

Introduction: Incontinentia pigmenti (IP) is a rare X-linked dominant neuroectodermal multisystem disorder characterized by skin lesions following Blaschko lines. In almost all patients the skin is involved and in 30-50% the central nervous system (CNS) is. Vascular occlusive phenomena probably play a role in CNS involvement. Whether these vascular changes are based on macro- or microvascular disease in the neonatal presentation is not fully understood., Patients and Methods: We describe two patients with IP with neonatal seizures related to cerebral infarction. In comparison, we reviewed reports of ischaemic cerebrovascular injury in neonatal IP., Results: No descriptions of documented large artery occlusion in neonatal IP was found in the literature. One of our patients showed striatal arteriopathy, never described before in IP. Extensive injury in one of our cases was heterogeneous, mixing healthy with diseased areas within large arterial fields., Conclusions: We postulate that neonatal cerebral infarction in IP is a macrovascular disorder of medium sized or small arteries. The pattern of arterial involvement might follow hypothetical brain Blaschko lines. The extent of cerebral involvement probably results from genetic mosaicism in which Lyonisation leads to endothelial apoptosis, similar to the process in the skin.

The authors describe a case of split notochord syndrome with a neuroenteric fistula in a newborn presenting with meningitis. Associated anomalies included agenesis of the corpus callosum, short colon, malrotation, epispadias, and an abnormally high bifurcation of the abdominal aorta and inferior vena cava. The embryological mechanisms and etiologic theories are discussed in short.

Familial porencephaly is a rare disorder causing motor impairment, hemiplegia, mental retardation and epilepsy in variable degrees. Two families with porencephaly and apparently dominant inheritance are reported. Brain MRI findings are reviewed and described in seven affected individuals. Most patients also show white matter abnormalities in the cerebral hemisphere, also contralateral to the cystic lesion. In the first family an obligate carrier was identified who did not have a cystic lesion but clear abnormalities of the white matter. Although a predisposition for thrombophilia has previously been reported, we did not observe any genetic, environmental or epigenetic predisposition for the porencephaly. The lesions are most compatible with a deep venous thrombosis/ischemic event occurring in a late stage of pregnancy, not necessarily aggravated by perinatal asphyxia.

Background/purpose: The aim of this study was to add to the experience of slide tracheoplasty in infants with congenital tracheal stenosis (CTS), to review the recent literature on this subject, and to evaluate the diagnostic workup in infants with CTS., Methods: A retrospective review of 3 infants with CTS treated with slide tracheoplasty was conducted at our institution. They all underwent bronchoscopy, tracheobronchography, and echocardiography. Therapy consisted of slide tracheoplasty and simultaneous correction of associated vascular malformations., Results: A pulmonary artery sling was missed initially on esophagography in 2 patients. Stridor became worse in 2 patients after tracheobronchography. After surgical therapy, 2 patients survived and were discharged 12 days after surgery. Both are without symptoms at follow-up of 12 and 20 months. One patient had inoperable restenosis and died 27 days after the operation., Conclusions: Esophagography is not a reliable tool to depict associated vascular anomalies for patients with CTS. According to the literature, computer tomography has become more reliable to depict the tracheobronchial tree and is useful to elucidate associated vascular anomalies as well. Compared with other surgical techniques for infants with CTS reported in the literature, slide tracheoplasty has fewer postoperative complications and comparable survival rates.

Arterial stroke in a neonate caused by carotid artery dissection is rare. We report two cases, one with dissection at the level of the skull base, one just distal to the carotid bulb. Non-invasive techniques like MR angiography and sonography demonstrated the dissection accurately. MR imaging, especially the diffusion-weighted images, showed the extension and site of the cerebral infarction. In one case dissection could be suspected following vacuum and forceps extraction. In the other no obvious birth trauma was reported. In conclusion, in a neonate with clinical signs suggestive of cerebral infarction, dissection of the carotid artery should be considered.