Delineating the neurological phenotype in children with defects in the ECHS1 or HIBCH gene.

The neurological phenotype of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) and short-chain enoyl-CoA hydratase (SCEH) defects is expanding and natural history studies are necessary to improve clinical management. From 42 patients with Leigh syndrome studied by massive parallel sequencing, we identified five patients with SCEH and HIBCH deficiency. Fourteen additional patients were recruited through collaborations with other centres. In total, we analysed the neurological features and mutation spectrum in 19 new SCEH/HIBCH patients. For natural history studies and phenotype to genotype associations we also included 70 previously reported patients. The 19 newly identified cases presented with Leigh syndrome (SCEH, n = 11; HIBCH, n = 6) and paroxysmal dystonia (SCEH, n = 2). Basal ganglia lesions (18 patients) were associated with small cysts in the putamen/pallidum in half of the cases, a characteristic hallmark for diagnosis. Eighteen pathogenic variants were identified, 11 were novel. Among all 89 cases, we observed a longer survival in HIBCH compared to SCEH patients, and in HIBCH patients carrying homozygous mutations on the protein surface compared to those with variants inside/near the catalytic region. The SCEH p.(Ala173Val) change was associated with a milder form of paroxysmal dystonia triggered by increased energy demands. In a child harbouring SCEH p.(Ala173Val) and the novel p.(Leu123Phe) change, an 83.6% reduction of the protein was observed in fibroblasts. The SCEH and HIBCH defects in the catabolic valine pathway were a frequent cause of Leigh syndrome in our cohort. We identified phenotype and genotype associations that may help predict outcome and improve clinical management.

Perinatal outcomes and central nervous system abnormalities following intrauterine fetal transfusion: 17 years' experience in a tertiary center.

BACKGROUND: This study aimed to describe the perinatal outcome and central nervous system (CNS) anomalies in fetuses undergoing red blood cell (RBC) intrauterine transfusion (IUT). METHODS AND MATERIALS: This was an observational single-cohort study carried out at Vall d'Hebron University Hospital in Barcelona, Spain, between 2002 and 2018 in women undergoing RBC IUT for suspected fetal anemia. Primary outcomes were adverse perinatal outcome (intrauterine or neonatal death and termination of pregnancy [TOP]), prenatal or postnatal CNS anomalies, and significant neurological impairment. RESULTS: A total of 145 RBC transfusions were performed in 68 pregnancies of 60 women. The median gestational age for the first transfusion was 26 weeks (range, 18-32). Twenty-two (32%) fetuses were hydropic at the first transfusion. Fifty-eight pregnancies (85.3%) resulted in live births and 10 (14.7%) in adverse perinatal outcomes. Adverse perinatal outcomes were associated with hydrops (odds ratio [OR], 6.69; 95% confidence interval [CI], 1.53-29.23; P = .012) and gestational age at first transfusion (OR, 0.69; 95% CI, 0.54-0.89; P = .04). Four (5.9%) cases of cerebellar hemorrhage were diagnosed prenatally. In 14 (35%) of the 41 neonates undergoing brain ultrasound and/or magnetic resonance imaging (MRI) abnormalities were reported. The median follow-up was 6.5 years (range, 3 months to 19 years). Significant neurological impairment was reported in two cases (4.2%). CONCLUSION: In fetuses undergoing intrauterine RBC transfusion, the survival rate is high, particularly in the absence of hydrops and if the gestational age at first transfusion is above 22 weeks. Significant neurological impairment is uncommon, despite the fact that postnatal CNS anomalies at ultrasound or MRI are frequent.

Pediatric minor head injury imaging practices: results from an ESPR survey.

PURPOSE: Computed tomography (CT) for minor head injury exposes a large number of children to ionizing radiation, with an associated increased lifetime risk of malignancy. To study imaging practices for children with minor head injury and the level of awareness of radiologists of the current clinical decision rules for minor traumatic brain injury (TBI). METHODS: A questionnaire consisting of 17 questions was distributed electronically to 472 ESPR members. The questionnaire covered demographic information, employment status, years of experience and the current practice setting of the participants, the number of CTs performed for pediatric head trauma, awareness of clinical decision rules and use of shielding, pediatric CT protocol and MRI. RESULTS: The response rate was 18.4%. The majority of participants was aged over 50 years and was full-time consultants. Regarding decision rules, 73.8% of respondents cited the NICE head injury guidelines, and 79% reported that the decision to perform CT was agreed between specialists. Shielding was used by 58.3% and 67.4% applied a specific pediatric protocol. MRI was not used for pediatric head trauma by 70.6% of respondents, although always available in 68.6% of cases. The reported obstacles to MRI use were machine availability (42.7%), the long acquisition time (39%) and patients' intolerance (18.3%), and less frequently the cost and the need for sedation. CONCLUSION: There is room for decreasing the use of CT for pediatric minor TBI. The use of shielding and application of pediatric CT protocols constitute areas for improvement.

Mutations in the mitochondrial complex I assembly factor NDUFAF6 cause isolated bilateral striatal necrosis and progressive dystonia in childhood.

AIM: To perform a deep phenotype characterisation in a pedigree of 3 siblings with Leigh syndrome and compound heterozygous NDUFAF6 mutations. METHOD: A multi-gene panel of childhood-onset basal ganglia neurodegeneration inherited conditions was analysed followed by functional studies in fibroblasts. RESULTS: Three siblings developed gait dystonia in infancy followed by rapid progression to generalised dystonia and psychomotor regression. Brain magnetic resonance showed symmetric and bilateral cytotoxic lesions in the putamen and proliferation of the lenticular-striate arteries, latter spreading to the caudate and progressing to cavitation and volume loss. We identified a frameshift novel change (c.554_558delTTCTT; p.Tyr187AsnfsTer65) and a pathogenic missense change (c.371T>C; p.Ile124Thr) in the NDUFAF6 gene, which segregated with an autosomal recessive inheritance within the family. Patient mutations were associated with the absence of the NDUFAF6 protein and reduced activity and assembly of mature complex I in fibroblasts. By functional complementation assay, the mutant phenotype was rescued by the canonical version of the NDUFAF6. A literature review of 14 NDUFAF6 patients showed a consistent phenotype of an early childhood insidious onset neurological regression with prominent dystonia associated with basal ganglia degeneration and long survival. INTERPRETATION: NDUFAF6-related Leigh syndrome is a relevant cause of childhood onset dystonia and isolated bilateral striatal necrosis. By genetic complementation, we could demonstrate the pathogenicity of novel genetic variants in NDUFAF6.

Whole-brain structural connectivity in dyskinetic cerebral palsy and its association with motor and cognitive function.

Dyskinetic cerebral palsy (CP) has long been associated with basal ganglia and thalamus lesions. Recent evidence further points at white matter (WM) damage. This study aims to identify altered WM pathways in dyskinetic CP from a standardized, connectome-based approach, and to assess structure-function relationship in WM pathways for clinical outcomes. Individual connectome maps of 25 subjects with dyskinetic CP and 24 healthy controls were obtained combining a structural parcellation scheme with whole-brain deterministic tractography. Graph theoretical metrics and the network-based statistic were applied to compare groups and to correlate WM state with motor and cognitive performance. Results showed a widespread reduction of WM volume in CP subjects compared to controls and a more localized decrease in degree (number of links per node) and fractional anisotropy (FA), comprising parieto-occipital regions and the hippocampus. However, supramarginal gyrus showed a significantly higher degree. At the network level, CP subjects showed a bilateral pathway with reduced FA, comprising sensorimotor, intraparietal and fronto-parietal connections. Gross and fine motor functions correlated with FA in a pathway comprising the sensorimotor system, but gross motor also correlated with prefrontal, temporal and occipital connections. Intelligence correlated with FA in a network with fronto-striatal and parieto-frontal connections, and visuoperception was related to right occipital connections. These findings demonstrate a disruption in structural brain connectivity in dyskinetic CP, revealing general involvement of posterior brain regions with relative preservation of prefrontal areas. We identified pathways in which WM integrity is related to clinical features, including but not limited to the sensorimotor system. Hum Brain Mapp 38:4594-4612, 2017. © 2017 Wiley Periodicals, Inc.

Recommendations for the radiological diagnosis and follow-up of neuropathological abnormalities associated with tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a genetic condition with multisystem involvement, characterized by the development of tumors and other abnormalities in organs such as the brain, retina, skin, heart, kidneys, and lungs. Most patients have neuropathological abnormalities such as cortical tubers, white matter radial migration lines, subependymal nodules, and subependymal giant cell astrocytomas (SEGAs). These lesions are associated with different neurological manifestations that are frequently associated with TSC. These manifestations consist of epilepsy, intellectual disability, and neurobehavioral and psychiatric problems, including autism spectrum disorder. Hydrocephalus may also develop in patients with SEGAs due to ventricular obstruction, when this usually slow-growing tumor reaches sufficient size. Surgery has been the classical approach to treat SEGAs, although this treatment is associated with substantial morbidity and does not completely prevent tumor recurrence. Recently, the mammalian target of rapamycin (mTOR) inhibitor, everolimus, has been approved by the Food and Drug Administration and the European Medicines Agency for the treatment of patients with SEGAs associated with TSC. However, the treatment of SEGAs with these agents requires the development of guidelines that establish a differential diagnosis between SENs and SEGAs, in which neuroradiological examinations play an essential role. With the aim of improving the neuroradiological diagnosis and follow-up of the neuropathological abnormalities associated with TSC, a group of experts in this field has reviewed different aspects related to these issues and put together, a series of statements and recommendations intended to provide guidance to specialists involved in the management of TSC.

Imaging abusive head trauma: why use both computed tomography and magnetic resonance imaging?

Abusive head trauma is the leading cause of death in child abuse cases. The majority of victims are infants younger than 1 year old, with the average age between 3 and 8 months, although these injuries can be seen in children up to 5 years old. Many victims have a history of previous abuse and the diagnosis is frequently delayed. Neuroimaging is often crucial for establishing the diagnosis of abusive head trauma as it detects occult injury in 37% of cases. Several imaging patterns are considered to be particularly associated with abusive head trauma. The presence of subdural hematoma, especially in multiple locations, such as the interhemispheric region, over the convexity and in the posterior fossa, is significantly associated with abusive head trauma. Although CT is the recommended first-line imaging modality for suspected abusive head trauma, early MRI is increasingly used alongside CT because it provides a better estimation of shear injuries, hypoxic-ischemic insult and the timing of lesions. This article presents a review of the use and clinical indications of the most pertinent neuroimaging modalities for the diagnosis of abusive head trauma, emphasizing the newer and more sensitive techniques that may be useful to better characterize the nature and evolution of the injury.

At-risk brain tissue identified with arterial spin labeling in neurotuberculosis.

A 13-year-old immunocompromised girl developed neurotuberculosis. Arterial spin labeling technique indicated areas of hypoperfusion in the vascular territories of the left posterior cerebral artery and superior cerebellar artery without restricted diffusion, suggesting early tuberculous arteritis. MR angiography confirmed vascular involvement, so adjunctive anticoagulant therapy was initiated. Complete resolution of arterial spin labeling findings was observed 1 month later. This documents early tuberculous vasculopathy revealed by arterial spin labeling in a child with neurotuberculosis. Since there may be a paucity of clinical symptoms in the evolution of arteritis in neurotuberculosis, arterial spin labeling may help indicate early hypoperfusion and alert for modification of treatment before irreversible vascular damage occurs.

Brainstem dysgenesis during the neonatal period: diagnosis and management.

AIMS: To report our neonatal management experience in patients who received a diagnosis of brainstem dysgenesis (BSD). PATIENTS AND METHODS: This study retrospectively reviewed the medical records of 15 neonates with BSD diagnosed between 1984 and 2011. Data on the perinatal period, physical examination, laboratory findings, and management by systems were systematically analyzed. RESULTS: All cases were sporadic. Cocaine abuse and misoprostol use were recorded in two pregnancies. The reason for admission was prematurity (2 of 15), respiratory distress (8 of 15), gastroschisis (1 of 15), and abnormal neurological examination (4 of 15). Clinically, the most commonly affected cranial nerves were the 7th (13 of 15), 9th (11 of 15), 10th (8 of 15), 5th (7 of 15), 12th (7 of 15), 6th (3 of 15), 4th (1 of 15), and 3rd (1 of 15). Five patients required positive pressure ventilation during delivery room resuscitation, three had difficult airways, and two needed tracheostomy during admission. Most patients required nasogastric tube feeding shortly after birth, and four patients had a gastrostomy on discharge. Two patients died of respiratory and cardiac failure. Electromyography and nerve conduction velocity were used to exclude generalized neuromuscular disorders, and in conjunction with other neurophysiological and gastrointestinal tract studies, helped uncover the extent of brainstem involvement in most cases. Cranial magnetic resonance imaging supported the diagnosis in more than half of the patients. CONCLUSIONS: Early diagnosis of BSD is mainly clinical, difficult to establish unless suspected, and crucial to prevent complications. Neonatal care of patients with BSD requires a comprehensive approach that must take into consideration the etiological, anatomical, and pathogenic aspects contributing to the clinical manifestations of this disorder. Care should be provided by multidisciplinary teams, in which neonatologists, pediatric neurologists, nutritionists, physical therapists, and other professionals participate, depending on the associated morbidity in order to improve its management and prognosis.

Evolution of fetal subependymal cysts throughout gestation.

Subependymal cysts are secondary to brain germinal matrix hemorrhage or infarction and are associated with fetal chromosomal and metabolic conditions, as well as infections. They are found in 1-3% of neonates in the first days of life and have been described in fetuses, although much less frequently. We report the prenatal diagnosis of a case of subependymal cysts first visualized at 12 weeks' gestation and its evolution throughout pregnancy and after birth. As far as we know, this is the first time that such a condition is described before 16 weeks' gestation as well as its longitudinal evolution. Knowledge that subependymal cysts can be seen as early as 12 weeks' gestation and their natural evolution is important to avoid equivocal diagnoses. The prognosis of isolated subependymal cysts remains uncertain.

Pituitary macroadenomas in childhood and adolescence: a clinical analysis of 7 patients.

BACKGROUND: Pituitary adenomas (PPAs) are uncommon in childhood and adolescence, accounting for 2-6% of all intracranial neoplasms. Delayed puberty, growth retardation, galactorrhea and weight gain are common features at presentation in pediatric patients. Functional tumors constitute a vast majority (90%) of PPAs, with the most frequent being prolactinomas. CASE PRESENTATION: A retrospective review of the clinical features and outcomes of 7 pediatric patients with pituitary macroadenomas was conducted. We included PPAs in patients under 18 years at diagnosis with diameters larger than 10 mm by magnetic resonance (MRI). Six patients were males (85%), with age at diagnosis ranging from 8 to 15 (median 14 ± 2.8SDS). The primary symptoms that led to medical attention were growth retardation, gigantism and secondary amenorrhea. The visual field was reduced in three cases (42%). Suprasellar extension was present in 3 subjects, and one had a giant adenoma. Adenomas were clinically functioning in 6 patients (85%) (three prolactinomas, two somatropinomas, one secreting FSH and one no-producer). The prolactinomas responded to treatment with cabergoline. For the rest, one required transsphenoidal surgery and the other three both surgery and radiotherapy. All patients undergoing radiotherapy had secondary panhypopituitarism. In relation to the genetic studies, two patients presented a pathogenic mutation of the AIP gene and one of the MEN1. DISCUSION AND CONCLUSION: Pediatric pituitary macroadenomas are a distinct entity, mostly found in males and with a predominance of functional tumors leading to detrimental effects on growth and puberty in addition to neuro-ophthalmological manifestations. It is important to perform genetic studies in patients with macroadenomas appearing under the age of 18 years as genetic and syndromic associations are more frequent in this age group.

Myocardial tissue characterization by cardiovascular magnetic resonance T1 mapping and pericardial fat quantification in adolescents with morbid obesity. Cardiac dimorphism by gender.

PURPOSE: Changes in the myocardial extracellular matrix (ECM) identified using T1 mapping cardiovascular magnetic resonance (CMR) have been only reported in obese adults, but with opposite conclusions. The objectives are to assess the composition of the myocardial ECM in an obese pediatric population without type 2 diabetes by quantifying native T1 time, and to quantify the pericardial fat index (PFI) and their relationship with cardiovascular risk factors. METHODS: Observational case-control research of 25 morbidly obese adolescents and 13 normal-weight adolescents. Native T1 and T2 times (ms), left ventricular (LV) geometry and function, PFI (g/ht3) and hepatic fat fraction (HFF, %) were calculated by 1.5-T CMR. RESULTS: No differences were noticed in native T1 between obese and non-obese adolescents (1000.0 vs. 990.5 ms, p0.73), despite showing higher LV mass values (28.3 vs. 22.9 g/ht3, p0.01). However, the T1 mapping values were significantly higher in females (1012.7 vs. 980.7 ms, p < 0.01) while in males, native T1 was better correlated with obesity parameters, particularly with triponderal mass index (TMI) (r = 0.51), and inflammatory cells. Similarly, the PFI was correlated with insulin resistance (r = 0.56), highly sensitive C-reactive protein (r = 0.54) and TMI (r = 0.77). CONCLUSION: Female adolescents possess myocardium peculiarities associated with higher mapping values. In males, who are commonly more exposed to future non-communicable diseases, TMI may serve as a useful predictor of native T1 and pericardial fat increases. Furthermore, HFF and PFI appear to be markers of adipose tissue infiltration closely related with hypertension, insulin resistance and inflammation.

Diagnosis of Genetic White Matter Disorders by Singleton Whole-Exome and Genome Sequencing Using Interactome-Driven Prioritization.

BACKGROUND AND OBJECTIVES: Genetic white matter disorders (GWMD) are of heterogeneous origin, with >100 causal genes identified to date. Classic targeted approaches achieve a molecular diagnosis in only half of all patients. We aimed to determine the clinical utility of singleton whole-exome sequencing and whole-genome sequencing (sWES-WGS) interpreted with a phenotype- and interactome-driven prioritization algorithm to diagnose GWMD while identifying novel phenotypes and candidate genes. METHODS: A case series of patients of all ages with undiagnosed GWMD despite extensive standard-of-care paraclinical studies were recruited between April 2017 and December 2019 in a collaborative study at the Bellvitge Biomedical Research Institute (IDIBELL) and neurology units of tertiary Spanish hospitals. We ran sWES and WGS and applied our interactome-prioritization algorithm based on the network expansion of a seed group of GWMD-related genes derived from the Human Phenotype Ontology terms of each patient. RESULTS: We evaluated 126 patients (101 children and 25 adults) with ages ranging from 1 month to 74 years. We obtained a first molecular diagnosis by singleton WES in 59% of cases, which increased to 68% after annual reanalysis, and reached 72% after WGS was performed in 16 of the remaining negative cases. We identified variants in 57 different genes among 91 diagnosed cases, with the most frequent being RNASEH2B, EIF2B5, POLR3A, and PLP1, and a dual diagnosis underlying complex phenotypes in 6 families, underscoring the importance of genomic analysis to solve these cases. We discovered 9 candidate genes causing novel diseases and propose additional putative novel candidate genes for yet-to-be discovered GWMD. DISCUSSION: Our strategy enables a high diagnostic yield and is a good alternative to trio WES/WGS for GWMD. It shortens the time to diagnosis compared to the classical targeted approach, thus optimizing appropriate management. Furthermore, the interactome-driven prioritization pipeline enables the discovery of novel disease-causing genes and phenotypes, and predicts novel putative candidate genes, shedding light on etiopathogenic mechanisms that are pivotal for myelin generation and maintenance.

Side effects of oncologic therapies in the pediatric central nervous system: update on neuroimaging findings.

The need for early, accurate diagnosis of central nervous system (CNS) complications occurring during and after pediatric cancer treatment is growing because of the improvement in overall survival rates related to innovative and aggressive oncologic therapies. An elevated degree of suspicion is needed to recognize the radiologic features of these CNS complications. Radiologists need familiarity with the early and late side effects of cancer therapy in the pediatric CNS (eg, toxic effects, infection, endocrine or sensory dysfunction, neuropsychologic impairment, second malignancies), in order to accelerate the imaging diagnosis and minimize as much as possible the associated morbidity. Acquisition of knowledge about these complications will enable the development of more appropriate therapeutic trials and more effective patient surveillance and will lead to an improved quality of life by decreasing the long-term sequelae in survivors.

Accuracy of prenatal ultrasound in the diagnosis of corpus callosum anomalies.

Objectives: The main objective of this study was to evaluate the accuracy of prenatal ultrasound to diagnose corpus callosum alterations, compared to prenatal magnetic resonance imaging (MRI), postnatal image techniques (ultrasound and/or MRI), and post-mortem examination in terminated pregnancies.Methods: Retrospective review of 86 cases of prenatal ultrasound diagnosis of corpus callosum anomalies between January 2007 and December 2015 at a third level Maternal Fetal Medicine center. The study reviewed the findings of prenatal ultrasound and MRI, post-mortem examination in cases of termination of pregnancy (TOP) or stillbirths and postnatal ultrasound, and MRI in neonates. The anomalies of corpus callosum (CC) were classified as complete agenesis of the corpus callosum (ACC), partial ACC, or dysgenesis of CC.Results: Fifty-eight (67.4%) cases resulted in TOP, 26 (30.2%) cases opted to continue with the pregnancy and two (2.3%) cases were lost to follow up. Among the 26 cases that continued with the pregnancy, 24 (92.3%) were live births and two (7.7%) were stillborn. All cases in which a third trimester MRI was performed (n = 46) confirmed the prenatal ultrasound diagnosis of CC anomaly. In seven (15.2%) of them, the MRI found additional intracranial findings and in three cases (6.5%) the type of CC anomaly (complete, partial, or dysgenesis) was reclassified (Kappa index: 0.86, 95% CI: 0.71-1.00). CC anomalies were confirmed in 46 (95.8%) of the 48 cases in which a post-mortem examination was available, the type of anomaly being reclassified in three cases (6.3%) (Kappa index: 0.88, 95% CI: 0.75-1.00). Among the 10 cases in which a postnatal ultrasound was performed, the CC anomaly was confirmed in all and the type of anomaly was reclassified in 1 (10%) of them (Kappa index: 0.75, 95% CI: 0.32-1.00).Conclusion: Corpus callosum agenesis can be detected on the routine mid-trimester ultrasound scan. Prenatal ultrasound and MRI can accurately classify the type of CC abnormality. Moreover, third trimester MRI can detect additional intracranial anomalies in 15% of cases.

Reduced hippocampal subfield volumes and memory performance in preterm children with and without germinal matrix-intraventricular hemorrhage.

Preterm newborns with germinal matrix-intraventricular hemorrhage (GM-IVH) are at a higher risk of evidencing neurodevelopmental alterations. Present study aimed to explore the long-term effects that GM-IVH have on hippocampal subfields, and their correlates with memory. The sample consisted of 58 participants, including 36 preterm-born (16 with GM-IVH and 20 without neonatal brain injury), and 22 full-term children aged between 6 and 15 years old. All participants underwent a cognitive assessment and magnetic resonance imaging study. GM-IVH children evidenced lower scores in Full Intelligence Quotient and memory measures compared to their low-risk preterm and full-term peers. High-risk preterm children with GM-IVH evidenced significantly lower total hippocampal volumes bilaterally and hippocampal subfield volumes compared to both low-risk preterm and full-term groups. Finally, significant positive correlations between memory and hippocampal subfield volumes were only found in preterm participants together; memory and the right CA-field correlation remained significant after Bonferroni correction was applied (p = .002). In conclusion, memory alterations and both global and regional volumetric reductions in the hippocampus were found to be specifically related to a preterm sample with GM-IVH. Nevertheless, results also suggest that prematurity per se has a long-lasting impact on the association between the right CA-field volume and memory during childhood.

Enterovirus-A71 Rhombencephalitis Outbreak in Catalonia: Characteristics, Management and Outcome.

BACKGROUND: Between April and June 2016, an outbreak of rhombencephalitis (RE) caused by enterovirus (EV) A71 was detected in Catalonia, Spain-the first documented in Western Europe. The clinical characteristics and outcome of patients with this condition differed from those reported in outbreaks occurring in Southeast Asia. METHODS: Observational, multicenter study analyzing characteristics, treatment and outcome of patients with EV-A71 rhombencephalitis diagnosed in 6 publicly funded hospitals within the Catalonian Health Institute. A review of clinical characteristics, diagnosis, treatment and outcome of these patients was conducted. RESULTS: Sixty-four patients met the clinical and virologic criteria for rhombencephalitis caused by EV-A71. All patients had symptoms suggesting viral disease, mainly fever, lethargy, ataxia and tremor, with 30% of hand-foot-mouth disease. Intravenous immunoglobulin therapy was given to 44/64 (69%) patients and methylprednisolone to 27/64 (42%). Six patients (9%) required pediatric intensive care unit admission. Three patients had acute flaccid paralysis of 1 limb, and another had autonomic nervous system (ANS) dysfunction with cardiorespiratory arrest. Outcome in all patients (except the patient with hypoxic-ischemic encephalopathy) was good, with complete resolution of the symptoms. CONCLUSIONS: During the 2016 outbreak, rhombencephalitis without ANS symptoms was the predominant form of presentation and most patients showed no hand-foot-mouth disease. These findings contrast with those of other patient series reporting associated ANS dysfunction (10%-15%) and hand-foot-mouth disease (60%-80%). Complete recovery occurred in almost all cases. In light of the favorable outcome in untreated mild cases, therapies for this condition should be reserved for patients with moderate-severe infection. The main relevance of this study is to provide useful information for setting priorities, management approaches and adequate use of resources in future EV-A71 associated rhombencephalitis outbreaks.

Congenital tumours involving the head, neck and central nervous system.

Congenital intracranial tumours are uncommon and differ from those occurring in older children in clinical presentation, imaging characteristics and prognosis. These tumours are often detected incidentally on routine prenatal US and/or fetal MRI. Hence, the paediatric radiologist should be familiar with the features of those lesions that should be included in the differential diagnosis. In general, the prognosis of these conditions is poor owing to large tumour size and the limitations of adjuvant therapy at such a young age. Congenital lesions involving the head and neck region require a meticulous imaging approach using both US and MRI techniques to better guide prenatal planning and fetal or neonatal surgical procedures.