Sonographic spectrum and postnatal outcomes of early-onset versus late-onset fetal cerebral ventriculomegaly.

OBJECTIVES: To review the prenatal characteristics and postnatal outcomes of Early-onset and Late-onset cerebral ventriculomegaly (VM). METHODS: Single-center retrospective study 2013-2017; VM cases grouped into Early-onset VM (EVM; Diagnosis at/before 24 weeks) and Late-onset VM (LVM; Beyond 24 weeks). LVM cases had normal ventricle width measurement at mid-trimester scan. Infection serology, cytogenetics, MRI, sonographic follow-up, perinatal and neurodevelopmental outcomes were analyzed. RESULTS: During the 5-year period, 64,662 women underwent an anomaly screening scan and 302 fetuses were identified with ventriculomegaly; 183 (60.6%) classified as early-onset and 119 (39.4%) LVM. The mean ventricular width was significantly higher in LVM cohort (14.1 mm vs 11.6 mm; p < .01). EVM cases were more often associated with structural anomalies (p < .05). Possible etiologies for EVM were aneuploidy and cerebral malformations like Absent Corpus Callosum, spina bifida, Dandy-Walker malformation, etc., whereas LVM followed aqueductal stenosis, hemorrhage, porencephaly, cerebral tumors, etc. Pregnancy outcomes were available for 251 cases. The pregnancy resulted in more live births in LVM group (87.4% vs 65.6%, p = < .01). Multivariate regression analysis demonstrated additional malformations (p < .0001, OR11.5 [95%CI: 4-35.2]), progression of VM (p = .004, OR 10.2 [95% CI: 2.1-52.3]) and severity of VM (OR 5.3 [95%CI: 0.8-37.7]) were significant predictors of Neurodevelopmental Impairment (NDI). Late gestation at diagnosis was more often associated with NDI (p = .063, OR2.4 [95%CI: 0.9-6.2]), although statistically insignificant. CONCLUSIONS: EVM has a significantly different sonographic spectrum and outcomes compared to LVM. EVM is milder and associated with an increased risk of aneuploidy and structural malformations. LVM often occurs secondary to acquired brain lesions.

Obstructive Hydrocephalus in Newborn Due to Cerebral Atrium Diverticulum Formation: Complete Resolution After Subdural Hematoma Evacuation.

BACKGROUND: Cerebral atrium diverticula are focal enlargements of the ventricular system that may develop in the presence of persistent intracranial hypertension, but they are rarely described in cases of acute intracranial hypertension. Here we present a unique case of obstructive hydrocephalus in a newborn due to the formation of a cerebral atrium diverticulum compressing the ventricular system. CASE DISCUSSION: A preterm 38-week-old boy was born with urgent caesarian section due to severe hydrocephalus. Magnetic resonance imaging showed the presence of a subacute right subdural hematoma with secondary obstructive hydrocephalus. The cystic lesion was characterized as a right ventricular atrium diverticulum. The child underwent urgent burr-hole evacuation of the right subdural hematoma with complete regression of the obstructive hydrocephalus and right atrial diverticulum. CONCLUSION: Cerebral atrium diverticula are rare focal dilatations of the ventricular system, and their radiologic diagnosis may be challenging. Accurate diagnosis of atrial diverticula and understanding of the underlying physiopathology is mandatory to establish the appropriate operative strategy.

Single-Shot Version of FLAIR Sequence in the Detection of Intraventricular Anomalies: Preliminary Experience in Fetal MR Imaging.

OBJECTIVE: To evaluate single-shot (ss) FLAIR sequence in the detection of intraventricular anomalies in a series of fetuses showing mild-moderate ventriculomegaly at ultrasound. SUBJECTS AND METHODS: Fetuses with mild-moderate isolated ventriculomegaly, which underwent MR imaging between 2003 and 2014 were considered eligible. Fetuses were examined by standard MR protocol and ss-FLAIR sequence, tailored for snapshot imaging. Two paediatric neuroradiologists evaluated MR images. RESULTS: 542 cases were selected. MR imaging was performed at mean 26 weeks of gestation. ss-FLAIR sequence detected intraventricular findings, consistent with cysts in 10 cases. In 3/10 intraventricular cysts were also evident on ss-FSE T2 and FSE T1-weighted images. In no case diffusion weighted imaging was able to detect cyst. No cyst was highlighted on ss-FSE-T2 and FSE-T1-weighted images, without being visible also on ss-FLAIR. CONCLUSION: ss-FLAIR sequence may be useful to detect intraventricular anomalies especially when fetal position or maternal obesity prevents adequate visualization by ultrasound.

Risk factors for periventricular echodensities and outcomes in preterm infants.

OBJECTIVES: To determine the incidence, risk factors and outcomes associated with transient and/or persistent periventricular echodensities (PVED) among preterm infants. METHODS: Medical records of preterm infants born at ≤ 32 weeks gestational age (GA) with PVED and no other brain pathology were reviewed and compared to matched control infants in a case-controlled retrospective study. Neurodevelopmental outcomes at 8-24 months corrected age were documented. RESULTS: A 17.8% incidence of PVED was recorded, with the highest incidence of 30-40% recorded at 29-31 weeks GA. Study and control groups were similar for all maternal parameters and neonatal morbidities, except for a higher incidence of respiratory distress syndrome among the study group. PVED at one month of age was predicted by 5 min Apgar score < 7 [OR = 33.78 (CI 2.94-388.06, p = 0.005)]. PVED was not associated with long-term neurodevelopmental disability. CONCLUSIONS: No risk factors or specific associated morbidities were identified among preterm infants with transient PVED. PVED at one month of age was predicted by low 5 min Apgar scores, possibly suggesting different pathogenesis or timing between the groups. Long-term outcome studies are needed to determine PVED impact.

Surgery is associated with ventricular enlargement as well as cognitive and functional decline.

INTRODUCTION: In preclinical studies, surgery/anesthesia contribute to cognitive decline and enhance neuropathologic changes underlying Alzheimer's disease (AD). Nevertheless, the link between surgery, anesthesia, apolipoprotein E ε4 (APOE ε4), and AD remains unclear. METHODS: We performed a retrospective cohort analysis of two prospective longitudinal aging studies. Mixed-effects statistical models were used to assess the relationship between surgical/anesthetic exposure, the APOE genotype, and rate of change in measures of cognition, function, and brain volumes. RESULTS: The surgical group (n = 182) experienced a more rapid rate of deterioration compared with the nonsurgical group (n = 345) in several cognitive, functional, and brain magnetic resonance imaging measures. Furthermore, there was a significant synergistic effect of anesthesia/surgery exposure and presence of the APOE ε4 allele in the decline of multiple cognitive and functional measures. DISCUSSION: These data provide insight into the role of surgical exposure as a risk factor for cognitive and functional decline in older adults.

Prediction of Late Death or Disability at Age 5 Years Using a Count of 3 Neonatal Morbidities in Very Low Birth Weight Infants.

OBJECTIVE: To evaluate bronchopulmonary dysplasia (BPD), serious brain injury, and severe retinopathy of prematurity (ROP) as predictors of poor long-term outcome in very low birth weight infants. STUDY DESIGN: We examined the associations between counts of the 3 morbidities and long-term outcomes in 1514 of 1791 (85%) infants with birth weights of 500-1250 g who were enrolled in the Caffeine for Apnea of Prematurity trial from October 1999, to October 2004, had complete morbidity data, and were alive at 36 weeks postmenstrual age (PMA). BPD was defined as use of supplemental oxygen at 36 weeks PMA. Serious brain injury on cranial ultrasound included grade 3 and 4 hemorrhage, cystic periventricular leucomalacia, porencephalic cysts, or ventriculomegaly of any cause. Poor long-term outcome was death after 36 weeks PMA or survival to 5 years with 1 or more of the following disabilities: motor impairment, cognitive impairment, behavior problems, poor general health, deafness, and blindness. RESULTS: BPD, serious brain injury, and severe ROP occurred in 43%, 13%, and 6% of the infants, respectively. Each of the 3 morbidities was similarly and independently correlated with poor 5-year outcome. Rates of death or disability (95% CI) in children with none, any 1, any 2, and all 3 morbidities were 11.2% (9.0%-13.7%), 22.9% (19.6%-26.5%), 43.9% (35.5%-52.6%), and 61.5% (40.6%-79.8%), respectively. CONCLUSIONS: In very low birth weight infants who survive to 36 weeks PMA, a count of BPD, serious brain injury, and severe ROP predicts the risk of a late death or survival with disability at 5 years.

Enfoque perinatal de la ventriculomegalia / Perinatal approach of ventriculomegaly

La Ventriculomegalia Fetal es relevante dado que tiene una alta prevalencia e importante asociación con otras anomalías en el Sistema Nervioso Central. El enfoque perinatal está íntimamente ligado al desarrollo de la Medicina Materno Fetal e implica una evaluación precoz de la anatomía del SNC fetal, utilizando como herramienta de apoyo la ultrasonografía, se debe tener un claro conocimiento de la anatomía cerebral fetal, de los criterios diagnósticos y protocolos estandarizados de manejo clínico actual. Considerar el uso de Resonancia Nuclear Magnética Fetal como técnica complementaria, y proporcionar Consejo Médico a los padres apoyado en Equipos Multidisciplinarios. La presente Revisión tiene el propósito de ser una puesta al día, que sea útil para los profesionales clínicos.

The Fetal ventriculomegaly is relevant since it has a high prevalence and association with other anomalies in the Central Nervous System. The perinatal approach is closely linked to the development of Maternal-Fetal Medicine and involves an early assessment of the anatomy of fetal CNS, using as a support tool ultrasonography, one must have a clear understanding of the fetal brain anatomy, diagnostic criteria and standardized protocols current clinical management. Consider using Nuclear Magnetic Resonance Fetal as a complementary technique, and provide parents Medical Council supported by multidisciplinary teams. This review is an update that is useful for clinicians.

Characterization of samhd1 morphant zebrafish recapitulates features of the human type I interferonopathy Aicardi-Goutières syndrome.

In humans, loss of function mutations in the SAMHD1 (AGS5) gene cause a severe form of Aicardi-Goutières syndrome (AGS), an inherited inflammatory-mediated encephalopathy characterized by increased type I IFN activity and upregulation of IFN-stimulated genes (ISGs). In particular, SAMHD1-related AGS is associated with a distinctive cerebrovascular pathology that commonly leads to stroke. Although inflammatory responses are observed in immune cells cultured from Samhd1 null mouse models, these mice are physically healthy, specifically lacking a brain phenotype. We have investigated the use of zebrafish as an alternative system for generating a clinically relevant model of SAMHD1-related AGS. Using temporal gene knockdown of zebrafish samhd1, we observe hindbrain ventricular swelling and brain hemorrhage. Furthermore, loss of samhd1 or of another AGS-associated gene, adar, leads to a significant upregulation of innate immune-related genes and an increase in the number of cells expressing the zebrafish type I IFN ifnphi1. To our knowledge, this is the first example of an in vivo model of AGS that recapitulates features of both the innate immune and neurological characteristics of the disease. The phenotypes associated with loss of samhd1 and adar suggest a function of these genes in controlling innate immune processes conserved to zebrafish, thereby also contributing to our understanding of antiviral signaling in this model organism.

Incidental findings on preoperative computed tomography for nonsyndromic single suture craniosynostosis.

Although the diagnosis of nonsyndromic single suture craniosynostosis (NSSC) can usually be made by clinical examination, computed tomography (CT) is still commonly used in preoperative evaluation. This practice has been questioned in light of recent studies that document a small, but measurable, increased risk of malignancy from CT-associated radiation. The purpose of this study was to examine whether preoperative CT for patients with NSSC provided clinically important information beyond confirmation of craniosynostosis. We performed a retrospective analysis of all patients with NSSC undergoing cranial vault remodeling at our center from March 1999 to March 2011. Only patients with complete preoperative CT scans available for review were included. Staff pediatric neurosurgeons were blinded to patient diagnosis and official radiology report, analyzed the CT images, and documented the site of synostosis and any other findings. Of the 231 patients, 80 met the inclusion criteria. Sites of synostosis included sagittal (51 patients), coronal (17 patients), metopic (11 patients), and frontosphenoidal (1 patient). Clinical diagnosis correlated with radiographic site of fusion in all patients except the patient with frontosphenoidal synostosis. Incidental findings were documented in more than 50% of the patients including prominent extra-axial cerebrospinal fluid (n = 36, 45%), ventriculomegaly (n = 5, 6.25%), choroid fissure cyst (n = 2), cavum septum pellucidum (n = 2), Chiari malformation (n = 1), and prominent perivascular space (clinically nonsignificant finding, n = 1). Incidental findings required additional follow-up or management in 5 patients (6.25%). Our findings support the use of preoperative imaging in this population to identify intracranial anomalies that cannot be discerned by clinical examination. Whereas many findings were not clinically important, some required additional attention.

Correlation of brain ultrasonography scans to the neuromotor outcome of very-low-birth-weight infants during the first year of life.

To evaluate the consistency of the Hammersmith Infant Neurological Examination scores of very-low-birth-weight infants at 6 and 12 months of age and its correlation to cranial ultrasonography findings, we designed a prospective study between January 2005 and January 2008, in the tertiary Neonatal Unit of Aristotle University of Thessaloniki, Greece. All infants enrolled had a cranial ultrasonography performed at term. Preterm infants born at <32 weeks gestation with a birth weight <1500 g were eligible for the study. One hundred seventy-four infants were finally enrolled; out of those, 46 (26%) had an optimal score at 6 and 76 (44%) at 12 months of age. Mean global scores were 61 and 69 at 6 and 12 months, respectively. The Hammersmith Infant Neurological Examination score significantly increased between 6 and 12 months, equally in all ultrasonography groups. The presence of cystic periventricular leukomalacia was associated to lower scores and neurologic impairment.

[Anormalies of the fetal posterior fossa during second trimester--diagnosis and management].

Six cases of Dandy-Walker malformation are presented. Five of them, diagnosed in 18-20 gestation weeks, respectively ended up in intermission of the pregnancy in second trimester and one case, diagnosed in 29-30 gestation weeks ended up in giving birth to a hypotrophical foetus in a good general state. The opportunities for diagnosis by 2D/3D echography have been considered in accordance with the new classification of abnormality of the fetal posterior fossa fluid collections. This is a clinical approach and a possible way out for the pregnancy and the new-born baby.

[Congenital mydriasis as an initial sign of septo-optic dysplasia]. / Midriasis congénita como signo inicial de displasia septo-óptica.

Septo-optic dysplasia (SOD)[MIM182230] consisting of a heterogeneous and uncommon condition characterised by the classictriad: optic nerve hypoplasia, abnormalities of pituitary hormone, and defects of thebrain midline (including agenesis of the septum pellucidum and/or the corpus callosum; ithas also been described associated cortical malformations, it was referred to as SOD plus syndrome).We report the first known case in which the initial diagnostic sign of SOD was a bilateralmydriasis as a manifestation ofhypoplasia of both optic nerves, pituitary hypoplasia andcerebral dysgenesis with neuronal migration disorder.We discuss thedifferential diagnosis of congenital mydriasis.

Arl13b-regulated cilia activities are essential for polarized radial glial scaffold formation.

The construction of cerebral cortex begins with the formation of radial glia. Once formed, polarized radial glial cells divide either symmetrically or asymmetrically to balance appropriate production of progenitor cells and neurons. Following birth, neurons use the processes of radial glia as scaffolding for oriented migration. Radial glia therefore provide an instructive structural matrix to coordinate the generation and placement of distinct groups of cortical neurons in the developing cerebral cortex. We found that Arl13b, a cilia-enriched small GTPase that is mutated in Joubert syndrome, was critical for the initial formation of the polarized radial progenitor scaffold. Using developmental stage-specific deletion of Arl13b in mouse cortical progenitors, we found that early neuroepithelial deletion of ciliary Arl13b led to a reversal of the apical-basal polarity of radial progenitors and aberrant neuronal placement. Arl13b modulated ciliary signaling necessary for radial glial polarity. Our findings indicate that Arl13b signaling in primary cilia is crucial for the initial formation of a polarized radial glial scaffold and suggest that disruption of this process may contribute to aberrant neurodevelopment and brain abnormalities in Joubert syndrome-related ciliopathies.

Indication for endoscopic third ventriculostomy.

BACKGROUND: Endoscopic third ventriculostomy (ETV) is increasingly prevalent among pediatric neurosurgeons as the initial treatment for hydrocephalus. The combination of ETV and choroid plexus cauterization (ETV/CPC) has improved the success rate among infants with hydrocephalus for whom ETV alone is much less successful. In parts of the developing world where there are economic and human resource constraints, this mode of treatment may be more appropriate than the routine use of shunts, which are prone to failures that require urgent surgical treatment. Here we review indications for the use of ETV or ETV/CPC as the primary treatment for hydrocephalus. CONCLUSION: Primary treatment of hydrocephalus by ETV can avoid shunt-dependence and its complications for many patients. Optimal results depend upon proper patient selection and the use of combined ETV/CPC when treating infants.

Endoscopic management of complex hydrocephalus.

BACKGROUND: The management of complex hydrocephalus is challenging. There is no consensus of the best treatment for isolated fourth ventricles, arachnoid cysts, and multiloculated hydrocephalus, although the avoidance of multiple shunts is desirable. We reviewed our experience with the use of endoscopic techniques to simplify complex multicompartmental hydrocephalus to determine its efficacy and safety. METHODS: We performed a retrospective study of 114 consecutive adults and children undergoing endoscopic management of hydrocephalus by a single surgeon. The type of hydrocephalus and endoscopic procedure performed were recorded. The management algorithm for simplification of complex hydrocephalus is reviewed. All patients were followed up in the office or by telephone. RESULTS: A total of 143 endoscopic procedures were performed on 114 patients with a mean age of 4.4 years (4 weeks to 32 years). The endoscopic procedures performed included cyst fenestration, septum pellucidotomy, endoscopic third ventriculostomy, aqueductal plasty with and without stent, and removal of cystercicotic cysts. Twenty-two (19.3%) patients had planned staged endoscopic procedures. Mean follow up was 65 months (range 33-122 months). Eighty-two (72%) patients were reduced to 1 shunt, shunt independence was achieved in 32 (28%) patients, and only 8 (11%) patients required shunt revision in the follow-up period. CONCLUSIONS: Endoscopic simplification of complex hydrocephalus enables dependence on only a single shunt in the majority of patients, and a significant proportion achieve shunt independence. Endoscopic management should be considered before the placement of a second shunt, and some cases require staged endoscopic procedures to adequately communicate multicompartmental hydrocephalus.

Periventricular nodular heterotopia on prenatal ultrasound and magnetic resonance imaging.

OBJECTIVES: To describe the prenatal ultrasound and magnetic resonance imaging (MRI) findings suggestive of periventricular nodular heterotopia (PNH). METHODS: This retrospective case series included fetuses referred to our institution for brain MRI between 2007 and 2012, which were diagnosed with PNH and confirmed by postnatal MRI or autopsy. The type of PNH, associated ventriculomegaly and associated malformations are reported. RESULTS: We included 11 fetuses (nine female, two male) with a mean gestational age at diagnosis of 31 (range, 23-34) weeks. PNH lesions were small and diffuse (n = 7), large and multiple (n = 1) or single (n = 3). A targeted ultrasound examination performed before fetal MRI missed the diagnosis in four cases (one diffuse and three single); a further ultrasound examination performed after MRI diagnosed PNH in two of these four cases. Ventriculomegaly was present in six cases (four unilateral and two bilateral). PNH appeared in all cases as nodules of intermediate echogenicity protruding into the ventricular lumen. In all cases of diffuse PNH, the frontal horns and bodies of the lateral ventricles appeared square in shape on coronal view, with irregular borders on axial view. Associated cerebral malformations were observed in seven cases and included corpus callosal agenesis (n = 4, with additional malformations in two) and retrocerebellar cyst (n = 3). Extracerebral malformations were also present in two cases. Maternal MRI was performed in five of the six cases of isolated small and diffuse PNH in female fetuses, and demonstrated PNH in two of these. CONCLUSION: PNH is underdiagnosed at prenatal ultrasound, even on targeted scans. Irregular ventricular borders on axial view and irregular square-shaped lateral ventricles on coronal view are suggestive of PNH at prenatal ultrasound.

Diagnosis, treatment, and long-term outcomes of fetal hydrocephalus.

This study analyzed 156 cases of fetal hydrocephalus treated at Osaka National Hospital from 1992 to 2011 to review current methods for diagnosing and treating fetal hydrocephalus, and for estimating its clinical outcome. This was a retrospective study of a single institute (Osaka National Hospital). Of 156 cases in total, 37% were diagnosed as isolated ventriculomegaly, 50% as another type of malformation (36 cases of myelomeningocele, six of holoprosencephaly, three of Dandy-Walker syndrome, one case of Joubert syndrome, 12 of arachnoid cyst, nine of encephalocele, three of atresia of Monro and eight of corpus callosum agenesis, and 13% as secondary hydrocephalus. Diagnoses were made between 13 and 40 weeks of gestation (average 27 weeks). Diagnosis was made before 21 weeks of gestation in 24% of cases, from the first day of 22 weeks to the sixth day of 27 weeks in 27%, and after the first day of 28 weeks in 49%. With the exclusion of 17 aborted cases and 40 cases in which the patients were too young to evaluate or lost during follow-up, the final outcome was analyzed for 90 cases. Of these, 17% of the patients died, 21% showed severe retardation, 13% moderate retardation, 26% mild retardation, and 23% showed a good outcome. The long-term outcome was mostly influenced by the basic disease and accompanying anomaly. The time of diagnosis showed no correlation with outcome. Hydrocephalus associated with arachnoid cyst, atresia of Monro, and corpus callosum agenesis, and hydrocephalus due to fetal intracranial hemorrhage, resulted in good outcomes. By contrast, holoprosencephaly, hydrocephalus associated with encephalocele, syndromic hydrocephalus, and hydrocephalus due to fetal virus infection led to poor outcomes. For accurate diagnosis and proper counseling, established protocols are important for the diagnosis and treatment of fetal hydrocephalus, including not only fetal sonography, fetal magnetic resonance imaging, and TORCH (toxoplasma, rubella, cytomegalovirus, herpes simplex) screening test, but also chromosomal and gene testing.