Search

Objective This long‐term retrospective follow‐up study aimed to address the knowledge gap between prenatal diagnosis of complete isolated Agenesis of Corpus Callosum (cACC) at fetal MRI and postnatal neurodevelopmental outcome to improve prenatal counseling for parents. Methods Data on fetuses with isolated cACC from a single‐center MRI database built up in two decades were considered. Detailed postnatal clinical, neuropsychological evaluations were performed and descriptions of available neuroradiological and genetic data were provided. Results Following a detailed neuropsychological evaluation and a long‐term follow‐up, the subsequent results emerged: 38 school‐aged children (older than 6 years) of 50 (aged 2.5‐15 years) showed normal intellectual functions (50%), intellectual disability (21%), and borderline intelligence quotient (29%). Deficits in motor functions (58%), executive functions (37%), language (61%), memory abilities (58%), and academic performances (53%) were found. Twenty‐one percent of participants showed behavioral difficulties. Almost half of the participants underwent rehabilitation. Additional findings (21%) were detected at postnatal brain MRI, and a significant association between additional findings at postnatal imaging and abnormal neurodevelopmental outcome was observed. Interpretations This study supports the view that children with prenatal diagnosis of isolated cACC may present with several degrees of neurologic and neuropsychological impairment which become more evident only in their second decade of life. Postnatal MRI and detailed genetic analysis may add crucial information to prenatal data and substantially influence final judgment on the outcome and orient clinical management and counseling.

Data about the neurological prognosis of isolated cerebellar hypoplasia in utero are scant and inconsistent. In this monocentric retrospective study, we describe the neurodevelopmental outcomes in a series of children with isolated cerebellar hypoplasia of presumably hemorrhagic origin prenatally detected with fetal magnetic resonance imaging (fMRI). We retrospectively reviewed the charts of all the pregnant women who were referred for a neurological consultation, diagnosed with fetal encephalic malformation/disruption between 2010 and 2020 in the Fetal Therapy Unit of our institution. Fetal MRI (fMRI) was performed in all the pregnancies. Fetuses with cerebellar hypoplasia presumably of hemorrhagic origin were selected for the study. Fetuses exposed to alcohol or with additional malformations in other cerebral or body areas were excluded. All the infants received the postpartum follow-up care adopted in our center, including post-natal MRI, serial neurological examinations, standardized neurodevelopmental tests, and regular parental interviews. Cognitive functions were tested with GRIFFITHS II, WPPSI-III, and WISC-IV according to the child's age. A total of 14 pregnant women out of 479 fetal consultations were eligible and included in the study group. In 57% of cases, the etiology of the hemorrhage was unknown. In 21% of cases, it was attributed to a blood transfusion, while in the remaining ones, it was attributed to maternal predisposing factors. Among the survivors, two infants were excluded for prematurity, and two were lost to follow-up. Ten patients were thus included in the study. Six patients had normal neurodevelopment and cognition, and three presented mild-moderate neurological signs, i.e., mild dyspraxia and visuoperceptual impairment. Only one child had a severe outcome, i.e., autism spectrum disorder. The cerebellum is particularly vulnerable to disruptions throughout its prolonged development. Extreme caution must be used in prenatal counseling considering that in the acute phase, lesion extension and vermis involvement can be overestimated with fMRI. In cases of uncertainty, performing an additional fMRI could be advisable after 4-8 weeks. However, in our series, infants with isolated cerebellar hypoplasia tended to have a favorable prognosis. Nevertheless, a long-term follow-up is needed and should include a postnatal brain MRI, serial neurological examinations, and neurodevelopmental tests at least up to school age.

Objective To the best of our knowledge, there have not been studies to address the issue of long-term follow-up of patients with prenatal diagnosis of isolated complete septum pellucidum agenesis (SPA). The aim of this study was to acquire information about the school-age outcome of such patients as a resource for counseling parents receiving this prenatal finding. Methods From a large fetal magnetic resonance (MR) database, we selected only those cases with isolated complete SPA as confirmed by two senior pediatric neuroradiologists in consensus; we then gathered information from the parents of those children who had reached the school age. Results None among the 12 cases (mean age at follow-up: 8.7 years, range: 6–13 year) of the resulting final cohort presented visual or stature deficits; only one required special teaching assistance in school. All other 11 children resulted without any notable academic issue. Conclusion Our report may provide information of practical value about the school-age outcome of fetuses detected by prenatal MR imaging to carry isolated complete SPA.

To describe the correlation between fetal imaging (in vivo and ex vivo) and neuropathology in two fetuses at early gestational age (GA) with isolated thick corpus callosum (CC), a rare finding whose pathological significance and neuropathology data are scarce. Two fetuses at 21-week GA underwent fetal MRI (fMRI) for suspected callosal anomalies at ultrasound (US). After fMRI results, termination of pregnancy (TOP) was carried out and post-mortem MRI (pmMRI) was performed. Neuropathology correlation consisted in macro and microscopic evaluation with sections prepared for hematoxylin-eosin and immunohistochemistry staining. Fetal imaging confirmed in both cases the presence of a shorter and thicker CC with respect to the reference standard at the same GA, without a clear distinction between its different parts. Moreover, on pmMRI, an abnormal slightly T2-weighted hyperintense layer along the superior and inferior surface of CC was noted in both cases. At histopathology, these findings corresponded to an increased amount of white matter tracts but also to an abnormal representation of embryological structures that contribute to CC development, naming induseum griseum (IG) and the glioepithelial layer (GL) of the “callosal sling.” After reviewing the literature data, we confirmed the recent embryological theory regarding the CC development and provide new insights into the pathophysiology of the abnormal cases. An abnormally thick CC at the early fetal period could be associated to an abnormal representation of the midline glia structures, so to result in potential disturbance of the axon guidance mechanism of callosal formation and eventually in CC dysgenesis.

Cerebral folate transporter deficiency syndrome, caused by FOLR-1 mutations is characterized by late infantile onset, severe developmental regression, epilepsy, and leukodystrophy. An extremely low concentration of 5-methyltetrahydrofolate in the cerebrospinal fluid provides a crucial clue to its diagnosis and is a treatment target. Oral or intravenous folinic acid (5-formyltetrahydrofolate) administration improves clinical symptoms and brain magnetic resonance imaging (MRI) findings. We describe three siblings carrying a novel homozygous FOLR1 nonsense mutation, that were referred due to intractable epilepsy and progressive neurological decline. Brain MRI showed hypomyelination and cerebellar atrophy. Folinic acid (oral and intravenous) supplementation, initiated after over 15 years illness, has failed to result in any sizeable clinical or neurophysiological improvement. Cerebral folate transport deficiency bears overlapping clinical features with many severe developmental encephalopathies. It is crucial to recognize FOLR1 signs and establish an early clinical and molecular diagnosis in order to provide timely folinic acid treatment and improve outcome.

Aicardi-Goutieres Syndrome (AGS) is a monogenic leukodystrophy with pediatric onset, clinically characterized by a variable degree of neurologic impairment. It belongs to a group of condition called type I interferonopathies that are characterized by abnormal overproduction of interferon alpha, an inflammatory cytokine which action is mediated by the activation of two of the four human Janus Kinases. Thanks to an ever-increasing knowledge of the molecular basis and pathogenetic mechanisms of the disease, Janus Kinase inhibitors (JAKIs) have been proposed as a treatment option for selected interferonopathies. Here we reported the 24 months follow-up of the fifth AGS patient treated with ruxolitinib described so far in literature. The treatment was globally well tolerated; clinical examinations and radiological images demonstrated a progressively improving course. It is however to note that patients presenting with mild and spontaneously improving course have been reported. Large natural history studies on AGS spectrum are strongly required in order to get a better understanding of the results emerging from ongoing therapeutic trials on such rare disease.

BACKGROUND AND PURPOSE: The ganglionic eminences are transient fetal brain structures that produce a range of neuron types. Ganglionic eminence anomalies have been recognized on fetal MR imaging and anecdotally found in association with a number of neurodevelopmental anomalies. The aim of this exploratory study was to describe and analyze the associations between ganglionic eminence anomalies and coexisting neurodevelopmental anomalies. MATERIALS AND METHODS: This retrospective study includes cases of ganglionic eminence anomalies diagnosed on fetal MR imaging during a 20-year period from 7 centers in Italy and England. Inclusion criteria were cavitation or increased volume of ganglionic eminences on fetal MR imaging. The studies were analyzed for associated cerebral developmental anomalies: abnormal head size and ventriculomegaly, reduced opercularization or gyration, and abnormal transient layering of the developing brain mantle. The results were analyzed using χ(2) and Fisher exact tests. RESULTS: Sixty fetuses met the inclusion criteria (21 females, 24 males, 15 sex unknown). Thirty-four had ganglionic eminence cavitations (29 bilateral and 5 unilateral), and 26 had increased volume of the ganglionic eminences (19 bilateral, 7 unilateral). Bilateral ganglionic eminence cavitations were associated with microcephaly (P = .01), reduced opercularization, (P < .001), reduced gyration (P < .001), and cerebellar anomalies (P = .01). Unilateral ganglionic eminence cavitations were not significantly associated with any particular feature. Bilateral increased volume of the ganglionic eminences showed an association with macrocephaly (P = .03). Unilateral increased volume was associated with macrocephaly (P = .002), abnormal transient layering (P = .001), unilateral polymicrogyria (P = .001), and hemimegalencephaly (P < .001). CONCLUSIONS: Ganglionic eminence anomalies are associated with specific neurodevelopmental anomalies with ganglionic eminence cavitations and increased ganglionic eminence volume apparently having different associated abnormalities.

We describe 64 foetuses with cortical formation abnormalities (CFA) who had two in utero magnetic resonance (iuMR) exams, paying particular detail to those in which the original classification of CFA category changed between the two studies. The goal was to attempt to quantify the value of third-trimester follow-up studies in CFA foetuses on second-trimester iuMR imaging. The 64 foetuses reviewed came from a CFA cohort of 374 foetuses reported in an earlier publication, which detailed a classification for foetal CFA. A consensus panel of senior paediatric neuroradiologists reviewed both studies, described any change in the category of CFA between them, and attempted to predict the possible clinical significance of any differences based on the combined clinical experience of the panel. In 40/64 (62%) foetuses, the CFA description was the same on both studies. In 24/64 (38%) cases, there was a category change which included three foetuses without CFA on first examination, six foetuses where the difference involved change in laterality/symmetry, and in 15 cases the re-classification involved categorical change within the same group. Brain abnormalities other than CFA were present in 30/64 (47%) foetuses on the first study and in 33/64 (52%) on the second. We predicted that prognosis would have changed on the basis of the second study in 8% of cases, all indicating worse prognosis. We have shown that the extra diagnostic and predicted prognostic yield justifies follow-up studies in the third trimester if a CFA is shown on the second-trimester iuMR imaging. • Sixty-four foetuses with cortical formation abnormalities had two iuMR studies, for the vast majority the baseline in the second trimester and the sequential in the third. • In three foetuses, the cortical formation abnormality (CFA) was not visible on the first study. In a further 21 foetuses, the categorical description of the CFA changed between the two studies. Prognosis changed in 8% of the cases following the second iuMR study, and in all cases, the prognosis was worse. • Multiple iuMR studies provide information about the natural history of CFA; the extra diagnostic and predicted prognostic yield justifies follow-up studies.

To formulate a classification system for foetal cortical formation abnormalities (CFAs) based on in utero magnetic resonance (iuMR) appearances and trial it in 356 cases. This retrospective study included all cases of foetal CFA diagnosed between 2000 and 2017 from seven centres in Italy and UK. All of the studies were reviewed by a panel of paediatric neuroradiologists experienced in iuMR with the aid of an algorithm designed to categorise the abnormalities. Consensus expert review confirmed 356 foetuses with CFA and the first level of classification distinguished bilateral CFA (229/356–64%) from unilateral CFA (127/356–36%) cases with sub-classification of the bilateral cases into asymmetric (65/356–18%) and symmetric (164/356–46%) involvement. There was a statistically significant excess of foetuses with small head size, e.g. 17% of the cohort had a bi-parietal diameter

We investigated whether prenatal magnetic resonance imaging (MRI) within 26 weeks of gestation (GW) may predict the fate of isolated upward rotation of the cerebellar vermis (URCV). This retrospective multicentre observational study included foetuses diagnosed with isolated URCV in prenatal MRI performed within 26 GW. Isolated URCV was defined by a brainstem-vermis angle (BVA) ≥ 12° in the MR midline sagittal view without abnormalities of the supratentorial structures, brainstem, or cerebellum hemispheres. The assessments included the BVA, clival-supraoccipital angle, transverse diameter of the posterior cranial fossa, tentorial angle, width of the cisterna magna (WCM), ventricular width, vermian diameters, hypointense stripes, and cerebellar tail sign. Late prenatal or postnatal MRI was used as a reference standard to assess the final vermian fate (rotated/de-rotated). Forty-five foetuses (mean GW at prenatal MRI = 21.5 ± 1.4 weeks) were included. In the reference standard, the vermis was de-rotated in 26 cases (57.7%). At least two of the following criteria were used to predict the persistence of URCV at imaging follow-up: BVA ≥ 23°, WCM ≥ 9 mm, and the cerebellar tail sign. The results were a sensitivity of 84.21% (95% CI, 60.4–96.6%), specificity of 80.8% (95% CI, 60.6–93.4%), positive predictive value of 76% (95% CI, 58.7–87.8%), and negative predictive value of 87.5% (95% CI, 70.9–95.2%). MRI within 26 GW on foetuses diagnosed with isolated URCV may predict delayed cerebellar vermis de-rotation, which is associated with good neurodevelopmental outcome in most cases. • Foetal MRI is a valuable tool in predicting the fate of isolated upward-rotated cerebellar vermis. • A wider angle between the brainstem and vermis is associated with higher risk of persistence of vermian rotation. • The presence of ≥ 2 factors among a brainstem-to-vermis angle ≥ 23°, width of the cisterna magna ≥ 9 mm, and the presence of the “cerebellar tail sign” has a sensitivity of 84.21% (95% CI, 60.4–96.6%) and specificity of 80.8% (95% CI, 60.6–93.4%) in predicting the persistence of the vermian rotation at imaging follow-up.

AIM To improve the genetic, clinical, and neuroradiological characterization of cerebellar involvement in tuberous sclerosis complex (TSC) and determine whether cerebellar lesions could be a reliable biomarker of neurological impairment. METHOD This retrospective cohort study, held at two tertiary paediatric university centres, was conducted on patients with a confirmed diagnosis of TSC who underwent brain magnetic resonance imaging between October 2009 and May 2016. The study population consisted of 112 patients with TSC (median age 10y; range 5mo-38y; 61 females, 51 males). RESULTS The results from multivariable statistical analysis indicated that cerebellar involvement (34 out of 112 patients, none carrying a TSC1 mutation) was the most powerful predictor of supratentorial cortical tuber load; however, cerebellar involvement was not the best predictor of clinical phenotype when supratentorial tuber load and TSC2 mutations were taken into consideration. The association between cerebellar lesions and a more severe clinical and neuroradiological phenotype was statistically significant and may be due to its strong association with TSC2 mutations and higher cortical tuber load. INTERPRETATION Cerebellar involvement is not the best predictor of neurobehavioural outcome, including TSC-related autism, after adjusting for TSC2 and the number of cortical tubers. Its role in the TSC clinical phenotype needs to be investigated further. WHAT THIS PAPER ADDS Cerebellar involvement is a powerful predictor of supratentorial cortical involvement and a potential biomarker of disease severity. Cerebellar lesions significantly correlate with a more severe clinical and neuroradiological phenotype. Cerebellar involvement is not the best predictor of neurobehavioural outcome.

Intracranial calcification (ICC) is an important diagnostic clue in pediatric neurology. Considering the radiation-induced cancer risk associated with computed tomography (CT), we aim to define the diagnostic value of magnetic resonance imaging (MRI) sequences sensitive to paramagnetic/diamagnetic substances in the detection of ICC, comparing with CT scanning. We selected MRI and CT scans performed in children affected by neurological conditions associated with ICC referred to the participating centers between 2005 and 2018. Inclusion criteria were age at neuroradiological investigation

Monoallelic mutations on TMEM63A have been recently reported as cause of a previously unrecognized disorder named "infantile-onset transient hypomyelination". Clinical and neuroradiological presentation is described as highly similar to Pelizaeus-Merzbacher Disease but evolution over time was surprisingly benign with a progressive spontaneous improving course. We report on a new TMEM63A-mutated girl. The clinical picture was similar to the one already described except for the presence of recurrent episodes of unilateral eyelid twitching, and for the evidence of spinal cord involvement on MRI. These are interesting findings helping in distinguishing this condition from classic PMD since early disease stages. However, additional observations are needed to confirm if these are common features of this condition.

Objective: The aim of this study was to report the rate of additional anomalies detected exclusively at prenatal magnetic resonance imaging (MRI) in fetuses with isolated severe ventriculomegaly undergoing neurosonography. Method: Multicenter, retrospective, cohort study involving 20 referral fetal medicine centers in Italy, United Kingdom, Spain and Denmark. Inclusion criteria were fetuses affected by isolated severe ventriculomegaly (≥15 mm), defined as ventriculomegaly with normal karyotype and no other additional central nervous system (CNS) and extra-CNS anomalies on ultrasound. In all cases, a multiplanar assessment of fetal brain as suggested by ISUOG guidelines on fetal neurosonography had been performed. The primary outcome was the rate of additional CNS anomalies detected exclusively at fetal MRI within two weeks from neurosonography. Subgroup analyses according to gestational age at MRI (

Data on fetal MRI in L1 syndrome are scarce with relevant implications for parental counseling and surgical planning. We identified two fetal MR imaging patterns in 10 fetuses harboring L1CAM mutations: the first, observed in 9 fetuses was characterized by callosal anomalies, diencephalosynapsis, and a distinct brainstem malformation with diencephalic–mesencephalic junction dysplasia and brainstem kinking. Cerebellar vermis hypoplasia, aqueductal stenosis, obstructive hydrocephalus, and pontine hypoplasia were variably associated. The second pattern observed in one fetus was characterized by callosal dysgenesis, reduced white matter, and pontine hypoplasia. The identification of these features should alert clinicians to offer a prenatal L1CAM testing.

Although epileptic seizures occur in approximately a quarter of patients with Aicardi-Goutières syndrome (AGS), their phenotypic and electrophysiological characterization remains elusive. The aim of our study was to characterize epilepsy phenotypes and electroencephalographic (EEG) patterns in AGS and look for possible correlations with clinical, genetic and neuroradiological features.We selected patients with an established AGS diagnosis followed at three Italian reference centers. Medical records, EEGs and MRI/CT findings were reviewed. EEGs were independently and blindly reviewed by three board-certified pediatric epileptologists. Chi square and Fisher's exact tests were used to test associations between epilepsy and EEG feature categories and clinical, radiological and genetic variables.Twenty-seven patients were enrolled. We reviewed 63 EEGs and at least one brain MRI scan per patient. Epilepsy, mainly in the form of epileptic spasms and focal seizures, was present in 37 % of the cohort; mean age at epilepsy onset was 9.5 months (range 1-36). The presence of epilepsy was associated with calcification severity (p = 0.016) and startle reactions (p = 0.05). Organization of EEG electrical activity appeared to be disrupted or markedly disrupted in 73 % of cases. Severe EEG disorganization correlated with microcephaly (p 0.001) and highly abnormal MRI T2-weighted signal intensity in white matter (p = 0.022). Physiological organization of the EEG was found to be better preserved during sleep (87 %) than wakefulness (38 %). Focal slow activity was recorded in more than one third of cases. Fast activity, either diffuse or with frontal location, was more frequent in the awake state (78 %) than in sleep (50 %). Interictal epileptiform discharges (IEDs) were present in 33 % of awake and 45 % of sleep recordings. IEDs during sleep were associated with a higher risk of a epileptic seizures (p = 0.008).The hallmarks of EEG recordings in AGS were found to be: disruption of electrical organization, the presence of focal slow and fast activity, and the presence of IEDs, both in patients with and in those without epilepsy. The associations between epilepsy and calcification and between EEG pattern and the finding of a highly abnormal white matter T2 signal intensity suggest a common anatomical correlate. However, the complex anatomical-electroclinical basis of AGS-related epilepsy still requires further elucidation.

Introduction ECHS1 encodes for short-chain enoyl-CoA hydratase, a key component in b-oxidation. This enzyme is also involved in the isoleucine and valine catabolic pathways. The literature contains reports of scattered cases of ECHS1 mutation, which show a wide clinical spectrum of presentation. Despite that the clinical spectrum of the disease has not been defined so far due to the absence of previous systematic reviews and descriptions of large series of patients. Methods We performed a systematic literature review of so far reported ECHS1 mutated patients and we reported two additional cases. We pointed out clinical and neuroradiological features of all patients. Results 45 patients were included in the analysis. Based on clinical and neuroradiological feature we were able to distinguish four main phenotypes of ECHS1deficiency: a severe neonatal presentation with a rapid and fatal course and significant white matter abnormalities; a severe infantile variant with slower neurological deterioration, developmental delay, pyramidal and extrapyramidal signs, optic atrophy, feeding difficulties, and degeneration of the deep gray nuclei; a slowly progressive infantile form, qualitatively similar to the previous phenotype, but less severe with mainly basal ganglia involvement; and a final phenotype, present in only few cases, characterized by paroxysmal exercise-induced dystonic attacks, normal neurological examination between these episodes, and isolated pallidal degeneration on MRI. Interpretation ECHS1 mutations cause metabolic encephalopathy with a wide range of clinical presentations that can be grouped into four main phenotypes, each with a distinct profile in terms of severity on clinical presentation, disease course and MRI involvement.

The term PROS (PIK3CA-Related Overgrowth Spectrum) indicates a wide spectrum of overgrowth disorders related to somatic mutations in PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) pathway. We present three cases with PIK3CA mutation and clinical characteristics encompassing MCAP (megalencephaly-capillary malformation) condition but lacking all criteria to a certain diagnosis, most of all showing prevalent and peculiar involvement of cerebellar structures at MRI (magnetic resonance imaging) mainly consisting in cortical rim thickening and abnormal orientation of folia axis. These cases expand the spectrum of intracranial MRI features in PIK3CA disorders.

Objective The aim of our study was to determine the outcome of fetuses with isolated mild ventriculomegaly, with prenatal imaging work-up, prenatal consultation, delivery and clinical follow-up performed in a single tertiary referring center. Methods Fetuses with isolated and non-progressive mild ventriculomegaly (10–15 mm) were included in the study. Inclusion criteria were as follows: singleton pregnancies, normal chromosomal analysis, normal serological evaluation of TORCH, fetal ultrasound and MRI excluding additional CNS or extra-CNS malformations. The prenatal consultation consisted in discussing the prognosis of ventriculomegaly, according to the literature. The postnatal follow-up protocol included a neuroradiological investigation (cranial ultrasound or MRI), neurological and pediatric examinations. The Griffiths Scales were used to assess the neurodevelopmental outcome. Results Thirty newborns were included in follow-up. The postnatal neuroradiological investigations confirmed the ventriculomegaly as an isolated finding in all cases except one. Nineteen children were available for formal neurodevelopmental testing. In our case series, 93.3% of the children had a favorable outcome or mild anomalies. Two children (6.6%) with mild ventriculomegaly were diagnosed as having rare genetic conditions. The Griffiths developmental quotients were normal (mean General Quotient 98.3) at the latest assessment (mean age 20.8 months) in all but one case. Discussion Most children in our case series had a favorable outcome, as described in the literature. Even though a large quantity of data is now available on ventriculomegaly, fetal consultation remains challenging and requires caution. The diagnostic work-up of pregnancies diagnosed with mild ventriculomegaly must be very meticulous and include TORCH evaluation, microarray, serial ultrasounds to exclude progression, and a fetal MRI. However, despite accurate screening, there are more complex conditions in which ventriculomegaly can be the only non-specific finding in fetal life, making postnatal follow up mandatory.

Monochorionic twins, resulting from a single fertilized egg giving rise to two separate embryos, are monozygotic and considered genetically identical. However, discordant phenotypes have been reported in monozygotic twins. We analyzed a retrospective cohort of 155 monochorionic pregnancies (312 twins) with major discordant structural anomalies coded by the ICD-10 system in order to describe the spectrum of anomalies, the management of the pregnancies, and the perinatal outcome. Treatment options included conservative management, selective feticide with bipolar cord coagulation, or complete termination. All survivors underwent at least 24 months of postnatal follow-up. Discordancy was complicated by twin-to-twin transfusion syndrome in eight pregnancies (5%) and by selective intrauterine growth restriction in 41 (26%). Major structural anomalies affected one system in 139 cases (90%) and multiple systems in 16 (10%). Median gestational age at diagnosis was 19.1 weeks (IQR 16.4–21.3). The most frequent single-system anomalies involved the nervous and circulatory systems. In total, 72 anomalous twins (46%) and 116 normal co-twins (74%) were delivered at a median gestational age of 34.6 weeks (IQR 31.0–36.3). Neonatal/infant death of the anomalous twin occurred in 22 cases (14%), with an overall survival rate of 32% (50/155). Surviving anomalous twins underwent major surgery in 22/50 cases (44%), four of whom (8%) now suffer from severe neurologic morbidity. This study shows that a wide spectrum of major discordant structural anomalies can be found in monochorionic pregnancies. The outcome for the anomalous twin is poor, while the survival rate for the normal co-twin was 71%, with a favorable overall prognosis.

Background Mutations occurring in the orthodenticle homeobox 2 gene (OTX2) are responsible for a rare genetic syndrome, characterized mainly by microphthalmia/anophthalmia associated with extra-ocular defects such as brain malformations, pituitary abnormalities, short stature and intellectual disability. To date, the spectrum of radiological features observed in patients with OTX2 mutations has never been summarized. Case presentation In this report, we describe a case of large microdeletion encompassing OTX2 but not BMP4 presenting with a syndromic anophthalmia with corpus callosum hypoplasia, pituitary gland hypoplasia and vermian hypoplasia. Conclusion Our case report provides an illustration of the neuroradiological spectrum in a case of OTX2-related syndrome and the first radiological evidence of 14q22.2q23.1 deletion associated posterior cranial fossa anomalies.

BACKGROUND AND PURPOSE: Evaluation of biometry is a fundamental step in prenatal brain MR imaging. While different studies have reported reference centiles for MR imaging biometric data of fetuses in the late second and third trimesters of gestation, no one has reported them in fetuses in the early second trimester. We report centiles of normal MR imaging linear biometric data of a large cohort of fetal brains within 24 weeks of gestation. MATERIALS AND METHODS: From the data bases of 2 referral centers of fetal medicine, accounting for 3850 examinations, we retrospectively collected 169 prenatal brain MR imaging examinations of singleton pregnancies, between 20 and 24 weeks of gestational age, with normal brain anatomy at MR imaging and normal postnatal neurologic development. To trace the reference centiles, we used the CG-LMS method. RESULTS: Reference biometric centiles for the developing structures of the cerebrum, cerebellum, brain stem, and theca were obtained. The overall interassessor agreement was adequate for all measurements. CONCLUSIONS: Reference biometric centiles of the brain structures in fetuses between 20 and 24 weeks of gestational age may be a reliable tool in assessing fetal brain development.

Introduction The clinical manifestation of a stretched low-lying cone (LLC) is represented by the tethered cord syndrome (TCS) with cutaneous, urologic, neurologic, and orthopaedic dysfunctions. TC is frequently found in patients with anorectal malformations (ARMs). The aim of our article is to report a series of patients affected by LLC and ARMs and evaluate their management and long-term follow-up results. Materials and Methods We performed a retrospective analysis over a period of 15 years including patients with ARM and TC and excluding those with severe polymalformations. We collected information related to the types of malformations and demographic data. We analyzed their management (perinatal protocol, radiological investigations, surgery, and multidisciplinary follow-up). QOL was assessed through the International Classification of Functioning, Disability, and Health for Children and Youth (ICF-CY). Results Thirty-three patients among 210 ARM cases had TC (16%). Eleven of them underwent neurosurgery. One patient had retethering; out of 11 patients, 4 remained stable and 6 improved after surgery (UDS normalization and resolution of symptoms). At a mean follow-up of 10 years, four patients were on clean intermittent catheterization and five on the Peristeen transanal irrigation. The majority of patients were defined as 3 (from 1-bad to 5-excellent) for their physical and mental state. Conclusion The use of MRI is considered to complete the ARM screening in detecting TC. The multidisciplinary approach is crucial and helps in defining the management of patients. In fact, it is not clear how the features of ARM and TC affect each other. The selection of cases for surgery should take into account the critical elements.

The FARS2 gene encodes the mitochondrial phenylalanyl-tRNA synthetase and is implicated in autosomal recessive combined oxidative phosphorylation deficiency 14, a clinical condition characterized by infantile onset epilepsy and encephalopathy. Mutations in FARS2 have been reported in only few patients, but a detailed description of seizures, electroencephalographic patterns, magnetic resonance imaging findings, and long-term follow-up is still needed. We provide a clinical report of a child with FARS2-related disease manifesting drug-resistant infantile spasms associated with focal seizures. By comparative genomic hybridization analysis we identified a heterozygous microdeletion in the short arm of chromosome 6, inherited from the mother, that encompasses the first coding exon of FARS2. By sequencing of the FARS2 gene we identified a variant c.1156C>G; p.(R386G), inherited from the father. By using standard spectrophotometric techniques in skin fibroblasts, we found a combined abnormality of complexes I and IV of the mitochondrial respiratory chain. The main clinical features of the patient included axial hypotonia, mild distal hypertonia, and psychomotor delay. The magnetic resonance imaging showed microcephaly, frontal cerebral atrophy, and signal changes of dentate nuclei. At the age of 3 years and 6 months, the patient was still under treatment with vigabatrin and he has been seizure free for the last 23 months. © 2016 Wiley Periodicals, Inc.

In this paper, we extend the one-class Support Vector Machine (SVM) and the regularized discriminative direction analysis to the Multiple Kernel (MK) framework, providing an effective analysis pipeline for the detection and characterization of brain malformations, in particular those affecting the corpus callosum. The detection of the brain malformations is currently performed by visual inspection of MRI images, making the diagnostic process sensible to the operator experience and subjectiveness. The method we propose addresses these problems by automatically reproducing the neuroradiologist's approach. One-class SVMs are appropriate to cope with heterogeneous brain abnormalities that are considered outliers. The MK framework allows to efficiently combine the different geometric features that can be used to describe brain structures. Moreover, the regularized discriminative direction analysis is exploited to highlight the specific malformative patterns for each patient. We performed two different experiments. Firstly, we tested the proposed method to detect the malformations of the corpus callosum on a 104 subject dataset. Results showed that the proposed pipeline can classify the subjects with an accuracy larger than 90% and that the discriminative direction analysis can highlight a wide range of malformative patterns (e.g., local, diffuse, and complex abnormalities). Secondly, we compared the diagnosis of four neuroradiologists on a dataset of 128 subjects. The diagnosis was performed both in blind condition and using the classifier and the discriminative direction outputs. Results showed that the use of the proposed pipeline as an assisted diagnosis tool improves the inter-subject variability of the diagnosis. Finally, a graphical representation of the discriminative direction analysis was proposed to enhance the interpretability of the results and provide the neuroradiologist with a tool to fully and clearly characterize the patient malformations at single-subject level.

Fetal postmortem MR Imaging (pmMRI) has been recently used as an adjuvant tool to conventional brain autopsy after termination of pregnancy (TOP). Our purpose was to compare the diagnostic performance of intrauterine MRI (iuMRI) and pmMRI in the detection of brain anomalies in fetuses at early gestational age (GA). We retrospectively collected 53 fetuses who had undergone iuMRI and pmMRI for suspected brain anomalies. Two pediatric neuroradiologists reviewed iuMRI and pmMRI examinations separately and then together. We used Cohen’s K to assess the agreement between pmMRI and iuMRI. Using the combined evaluation iuMRI+pMRI as the reference standard, we calculated the “correctness ratio.” We used Somers’ D to assess the cograduation between postmortem image quality and time elapsed after fetus expulsion. Our data showed high agreement between iuMRI and pmMRI considering all the categories together, for both observers (K1 0.84; K2 0.86). The correctness ratio of iuMRI and pmMRI was 79% and 45% respectively. The major disagreements between iuMRI and pmMRI were related to postmortem changes as the collapse of liquoral structures and distorting phenomena. We also found a significant cograduation between the time elapsed from expulsion and pmMRI contrast resolution and distortive phenomena (both p

Purpose To describe and classify the range of brain injuries present at prenatal, in-utero magnetic resonance (MR) imaging in co-twin survivors of monochorionic (MC) twin pregnancies complicated by single intrauterine death (SIUD). Materials and Methods This retrospective, observational study from six tertiary fetal medicine centers that perform tertiary-level prenatal in-utero MR studies reviewed cases in which prenatal in-utero MR imaging had shown a brain injury in a surviving co-twin of a twin pregnancy with a MC component complicated by SIUD. Results Forty-two surviving MC twins were described. The primary distinction of brain abnormalities was into nonfocal and focal lesions. The nonfocal lesions included periventricular leukomalacia (group 1; two fetuses), generalized encephalomalacia (group 2; nine fetuses), posterior encephalomalacia (group 3; seven fetuses), and bilateral parasagittal and perisylvian injury (group 4; three fetuses). The focal lesions included nonhemorrhagic lesions (group 5; 14 fetuses) and hemorrhagic lesions (group 6; seven fetuses). Focal brain lesions were more likely to be found in the surviving MC pregnancies complicated by twin-twin transfusion syndrome (TTTS) (odds ratio, 2.4; 95% confidence interval: 1.3, 18.5; P = .01) and in fetuses that underwent an obstetric intervention (odds ratio, 2.8; 95% confidence interval: 1.8, 23.6; P = .006). Conclusion Brain injury of the surviving co-twin after SIUD in MC pregnancies is usually of ischemic origin and spares the brainstem and cerebellum. Focal brain lesions are more frequent in pregnancies complicated by TTTS or in those where an intervention has been performed.

Despite complex olfactory bulb embryogenesis, its development abnormalities in tuberous sclerosis complex (TSC) have been poorly investigated. Brain MRIs of 110 TSC patients (mean age 11.5 years; age range 0.5–38 years; 52 female; 26 TSC1, 68 TSC2, 8 without mutation identified in TSC1 or TSC2, 8 not tested) were retrospectively evaluated. Signal and morphological abnormalities consistent with olfactory bulb hypo/aplasia or with olfactory bulb hamartomas were recorded. Cortical tuber number was visually assessed and a neurological severity score was obtained. Patients with and without rhinencephalon abnormalities were compared using appropriate parametric and non-parametric tests. Eight of110 (7.2%) TSC patients presented rhinencephalon MRI changes encompassing olfactory bulb bilateral aplasia (2/110), bilateral hypoplasia (2/110), unilateral hypoplasia (1/110), unilateral hamartoma (2/110), and bilateral hamartomas (1/110); olfactory bulb hypo/aplasia always displayed ipsilateral olfactory sulcus hypoplasia, while no TSC patient harboring rhinencephalon hamartomas had concomitant forebrain sulcation abnormalities. None of the patients showed overt olfactory deficits or hypogonadism, though young age and poor compliance hampered a proper evaluation in most cases. TSC patients with rhinencephalon changes had more cortical tubers (47 ± 29.1 vs 26.2 ± 19.6; p = 0.006) but did not differ for clinical severity (p = 0.45) compared to the other patients of the sample. Olfactory bulb and/or forebrain changes are not rare among TSC subjects. Future studies investigating clinical consequences in older subjects (anosmia, gonadic development etc.) will define whether rhinencephalon changes are simply an imaging feature among the constellation of TSC-related brain changes or a feature to be searched for possible implications in the management of TSC subjects.

To describe the MRI and structural features of a peculiar malformation of the corpus callosum (CC) in a group of young patients with intellectual disability. We studied with conventional MRI and DTI a group of subjects showing an aberrant supracallosal bundle, characterized by the presence of a triangle-shaped bulging above the dorsal surface of CC on the midline. Clinical evaluations, CGH-array and instrumental analysis were also collected. Among 85 patients with malformed CC, we identified 15 subjects that showed the supracallosal bundle. The CC was thickened in five cases, long and thinned in three cases, short and thinned in three cases and it had a “ribbon-like” appearance in four subjects. Additional brain anomalies were present in eight cases. DTI colour maps and tractography showed that the bundle had an antero-posterior longitudinal orientation and that the tract bifurcated posteriorly, ending in the posterior hippocampi. Patients had different combinations of neurological symptoms, but all showed mild or severe intellectual disability. Combining radiological and genetic data with embryological knowledge of the development of cerebral commissures, we hypothesize that the supracallosal bundle represents a vestigial structure, the dorsal fornix, present during fetal life. Its persistence is associated with intellectual disability. • An aberrant longitudinal bundle can be detected above corpus callosum. • The presence of the supracallosal bundle is associated with intellectual disability. • The supracallosal bundle may represent a persistent dorsal fornix.

BACKGROUND AND PURPOSE: Agenesis of the corpus callosum, even when isolated, may be characterized by anatomic variability. The aim of this study was to describe the types of other forebrain commissures in a large cohort of randomly enrolled fetuses with apparently isolated agenesis of the corpus callosum at prenatal MR imaging. MATERIALS AND METHODS: All fetuses with apparent isolated agenesis of the corpus callosum undergoing prenatal MR imaging from 2004 to 2014, were evaluated for the presence of the anterior or a vestigial hippocampal commissure assessed in consensus by 2 pediatric neuroradiologists. RESULTS: Overall, 62 cases of agenesis of the corpus callosum were retrieved from our data base. In 3/62 fetuses (4.8%), no forebrain commissure was visible at prenatal MR imaging, 23/62 fetuses (37.1%) presented with only the anterior commissure, and 20/62 fetuses (32.3%) showed both the anterior commissure and a residual vestigial hippocampal commissure, whereas in the remaining 16/62 fetuses (25.8%), a hybrid structure merging a residual vestigial hippocampal commissure and a rudiment of the corpus callosum body was detectable. Postnatal MR imaging, when available, confirmed prenatal forebrain commissure findings. CONCLUSIONS: Most fetuses with apparent isolated agenesis of the corpus callosum showed at least 1 forebrain commissure at prenatal MR imaging, and approximately half of fetuses also had a second commissure: a vestigial hippocampal commissure or a hybrid made of a hippocampal commissure and a rudimentary corpus callosum body. Whether such variability is the result of different genotypes and whether it may have any impact on the long-term neurodevelopmental outcome remains to be assessed. AC : anterior commissure ACC : agenesis of the corpus callosum CC : corpus callosum GA : gestational age HC : hippocampal commissure HS : hybrid structure

Rhombencephalosynapsis is a hindbrain malformation characterized by complete or partial absence of the cerebellar vermis, with varying degrees of midline continuity of cerebellar hemispheres, dentate nuclei, and in some patients of the superior cerebellar peduncles. Partial rhombencephalosynapsis usually consists of a segmental deficiency of posterior vermis. Although prenatal diagnosis of rhombencephalosynapsis is feasible by ultrasound and magnetic resonance imaging both, partial rhombencephalosynapsis might be difficult to detect, especially at an early gestational age. We report two fetal cases of atypical partial rhombencephalosynapsis, with deficiency of anterior vermis, detected by prenatal magnetic resonance imaging at 21st and 23rd week of gestation, respectively.

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.

Several extraorbital findings have been described in morning glory disc anomaly (MGDA), including optic pathway abnormalities. We want to emphasize the importance of looking for ipsilateral optic nerve and chiasm thickening in MGDA-affected patients because we think that it may be a relevant common associated finding to date not stressed by anyone. We report three cases of clinically diagnosed unilateral MGDA in which magnetic resonance imaging revealed enlargement of the ipsilateral optic nerve and chiasm. A literature analysis was made and previously reported MGDA cases, and case series were checked, looking for described, or misunderstood similar magnetic resonance imaging findings. Three other cases with very similar prechiasmatic optic nerve and chiasm findings were identified from the literature. Two further cases are discussed as possibly characterized by similar misinterpreted magnetic resonance features. Our study broadens the constellation of intra- and extraorbital findings of MGDA. Though magnetic resonance imaging is not sufficient to determine the neuropathological substrate of this finding, clinicians and radiologists should be aware of the possible association of MGDA with ipsilateral thickening of the optic nerve and chiasm, to properly plan the clinical and imaging follow-up.

In Joubert syndrome, the “molar tooth” sign can be associated to several additional supra and infratentorial malformations. Here we report on three subjects (two siblings, age: 8-14 years) with Joubert syndrome, showing an abnormal thick bulging of the anterior profile of the mesencephalon causing a complete obliteration of the interpeduncular fossa. DTI revealed that the abnormal tissue consists of an ectopic white matter tract with a latero-lateral transverse orientation. Tractographic reconstructions support the hypothesis of impaired axonal guidance mechanisms as responsible for the malformation. The two siblings were compound heterozygous for two missense variants in the TMEM67 gene, while no mutations in a panel of 120 ciliary genes were detected in the third patient. The name “anterior mesencephalic cap dysplasia”, referring to the peculiar aspect of the mesencephalon on sagittal MRI, is proposed for this new malformative feature.

SUMMARY: Diencephalic-mesencephalic junction dysplasia is a rare malformation characterized by a poorly defined junction between the diencephalon and the mesencephalon, associated with a characteristic butterfly-like contour of the midbrain (butterfly sign). This condition may be variably associated with other brain malformations, including callosal abnormalities and supratentorial ventricular dilation, and is a potential cause of developmental hydrocephalus. Here, we have reported 13 fetuses with second-trimester obstructive ventriculomegaly and MR features of diencephalic-mesencephalic junction dysplasia, correlating the fetal imaging with available pathology and/or postnatal data. The butterfly sign can be clearly detected on axial images on fetal MR imaging, thus allowing for the prenatal diagnosis of diencephalic-mesencephalic junction dysplasia, with possible implications for the surgical management of hydrocephalus and parental counseling.

Hereditary and sporadic cerebellar ataxias represent a vast and still growing group of diseases whose diagnosis and differentiation cannot only rely on clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear medicine techniques allows for characterization of structural and functional abnormalities underlying symptomatic ataxias. These methods thus constitute a potential source of radiological biomarkers, which could be used to identify these diseases and differentiate subgroups of them, and to assess their severity and their evolution. Such biomarkers mainly comprise qualitative and quantitative data obtained from MR including proton spectroscopy, diffusion imaging, tractography, voxel-based morphometry, functional imaging during task execution or in a resting state, and from SPETC and PET with several radiotracers. In the current article, we aim to illustrate briefly some applications of these neuroimaging tools to evaluation of cerebellar disorders such as inherited cerebellar ataxia, fetal developmental malformations, and immune-mediated cerebellar diseases and of neurodegenerative or early-developing diseases, such as dementia and autism in which cerebellar involvement is an emerging feature. Although these radiological biomarkers appear promising and helpful to better understand ataxia-related anatomical and physiological impairments, to date, very few of them have turned out to be specific for a given ataxia with atrophy of the cerebellar system being the main and the most usual alteration being observed. Consequently, much remains to be done to establish sensitivity, specificity, and reproducibility of available MR and nuclear medicine features as diagnostic, progression and surrogate biomarkers in clinical routine.

Aicardi-Goutières syndrome (AGS) is a genetically determined early onset encephalopathy characterized by cerebral calcification, leukodystrophy, and increased expression of interferon-stimulated genes (ISGs). Up to now, seven genes (TREX1, RNASEH2B, RNASEH2C, RNASEH2A, ADAR1, SAMHD1, IFIH1) have been associated with an AGS phenotype. Next Generation Sequencing (NGS) analysis was performed on 51 AGS patients and interferon signature (IS) was investigated in 18 AGS patients and 31 healthy controls. NGS identified mutations in 48 of 51 subjects, with three patients demonstrating a typical AGS phenotype but not carrying mutations in known AGS-related genes. Five mutations, in RNASEH2B, SAMHD1 and IFIH1 gene, were not previously reported. Eleven patients were positive and seven negatives for the upregulation of interferon signaling (IS > 2.216). This work presents, for the first time, the genetic data of an Italian cohort of AGS patients, with a higher percentage of mutations in RNASEH2B and a lower frequency of mutations in TREX1 than those seen in international series. RNASEH2B mutated patients showed a prevalence of negative IS consistent with data reported in the literature. We also identified five novel pathogenic mutations that warrant further functional investigation. Exome/genome sequencing will be performed in future studies in patients without a mutation in AGS-related genes.

Cervical abortive myelocistocele is a very rare congenital malformation. In this case report, we describe the prenatal magnetic resonance imaging (MRI) of such entity in a 20-week gestational age fetus, whose imaging features showed to be different from the only other previous prenatal report. We underscored the value of fetal MR for counseling and prognosis, especially when assessing the integrity of the spinal cord.

The development of the human cerebral cortex is a complex and precisely programmed process by which alterations may lead to morphological and functional neurological abnormalities. We report familial cases of prenatally diagnosed abnormal brain, characterized by aberrant symmetrical mesial oversulcation of the parietooccipital lobes, in fetuses affected by abnormal skeletal features. Fetal brain anomalies were characterized by prenatal magnetic resonance imaging at 21 weeks of gestation and histologically evaluated at 22 weeks. Histological examination added relevant information showing some focal cortical areas of micropoligyria and heterotopic extension of the cortical plate into the marginal zone beneath the cortical surface. Genetic analysis of the fetuses excluded FGFR3 mutations known to be related to skeletal dysplasia and aberrant symmetrical oversulcation in other brain areas (temporal lobes). Hence, the present report suggests the existence of a class of rare syndromes of skeleton and brain development abnormality unrelated to FGFR3 mutations or related to other not described FGFR3 gene defects. Using magnetic resonance imaging, histopathology and molecular characterization we provide an example of a translational study of a rare and unreported brain congenital malformation.

Objective: To report the incidence of fetal and maternal complications after selective fetoscopic laser surgery for twin-to-twin transfusion syndrome (TTTS). Methods: A total of 150 cases of TTTS were treated from January 2004 to June 2009 (period 1, 2004–2006, 62 cases; period 2, 2007 to June 2009, 88 cases). Fetal complications (double and single intrauterine fetal death, recurrence of TTTS, twin anemia-polycythemia sequence (TAPS), reversal of TTTS, cerebral lesions in one twin) and maternal complications were recorded, and retrospectively analyzed. Results: Nineteen (12.6%), 58 (38.7%), 61 (40.7%) and 12 cases (8.0%) were classified preoperatively as Quintero stage I, II, III and IV, respectively. The anterior placenta was described in 73 cases (48.6%). Double and single fetal death occurred overall in 7.3 and 36.0% of cases, respectively. The rate of recurrence was 11.3%, of TAPS 3.3%, and of reversal of TTTS 1.3%. Cerebral lesions were diagnosed in 3 donors (2.0%). Eighteen cases (12.0%) of fetal complications had a second procedure (6 repeat laser, 4 serial amnioreduction, 8 bipolar cord coagulation). Pregnancies undergoing a second procedure delivered at a median gestational age of 30.2 weeks compared to 32.1 weeks for those not repeating (p = 0.04). Perinatal survival of at least one twin improved from 66.1 to 79.5% (p = 0.06) in the two consecutive periods. For every 10 laser surgeries performed, there was an average improvement of 1.5% in the predicted percentage of survival of at least one twin (OR 1.09, 95% CI 1.00–1.19). Major maternal complications occurred in 9 cases (6.0%), 3 of which required admission to intensive care unit. Conclusions: Fetal complications are common after fetoscopic laser surgery. In this experience, an increasing number of procedures improved the performance of a new fetoscopic laser center.

BACKGROUND AND PURPOSE: Different and specific MR imaging patterns of lesions involving WM are widely defined in neonatal encephalopathy. The aim of this study was to describe a novel MR imaging pattern of damage characterized by the abnormal prominence of DMVs in premature and full-term neonates. MATERIALS AND METHODS: Twenty-one (11 premature and 10 full-term) neonates with MR imaging evidence of linear radially oriented fan-shaped lesions in the periventricular WM and without dural venous thrombosis were enrolled in this retrospective study. A total of 37 MR imaging examinations were performed at ages ranging from day 0 to 24 months. RESULTS: According to the appearance of linear anomalies on T2-weighted images, we identified 2 main patterns: T2 hypointense lesions without WM cavitations and T2 hypointense lesions associated with linear cysts. The first pattern was found in 17 examinations performed between 0 and 44 days of life; the second pattern was found in another 14 examinations performed between 6 days and 4 months of life. Five examinations performed between 9 and 24 months of life showed a reduction in volume and hyperintense signal intensity of the periventricular WM on T2-weighted and FLAIR images. CONCLUSIONS: Subtle linear WM lesions with the same anatomic distribution of DMVs may be evident in premature and full-term neonates without signs of major venous thrombosis, both in the acute and subacute phases. Their appearance and evolution suggest that transient DMV engorgement/thrombosis may be responsible for WM damage that can lead to a PVL-like pattern.

Neuroimaging plays an important and growing role in the diagnosis and therapeutic management of pediatric brain infections. This article describes the spectrum of imaging findings associated with major pediatric viral and bacterial brain infections, outlining the role of current imaging technology in the differential diagnoses of brain injury, detection of complications and therapy monitoring. MRI is the tool of choice in the evaluation of brain infections and particular attention is devoted to the role of diffusion-weighted imaging and magnetic resonance spectroscopy. This article considers viral and bacterial infection in their different modalities of presentation as congenital, acute and subacute/chronic disease. With regard to congenital infections, the growing role of fetal MRI as a valuable complement to ultrasound in the prenatal assessment of brain damage is emphasized.

Hypochondroplasia (HCH) is a genetic skeletal dysplasia, inherited in an autosomal dominant fashion. About 50–70% of HCH patients have a mutation in FGFR3 gene and in the majority of cases it is a de novo mutation. Recent magnetic resonance imaging studies on relative large cohorts of HCH patients have showed a central nervous system involvement with a high incidence of characteristic temporal lobe and hippocampal abnormalities. To the best of our knowledge, this report shows the first magnetic resonance imaging prenatal detection of characteristic brain anomalies in a case of HCH, molecularly confirmed through postnatal FGFR3 analysis. © 2014 John Wiley & Sons, Ltd.

UNLABELLED Neuropathological and Magnetic Resonance Imaging (MRI) studies showed a high frequency of posterior fossa abnormalities in preterms. To assess whether cerebellar haemorrhages (CH) diagnosed with ultrasound and/or MRI affect pons development in ELBW infants. The anteroposterior diameter of the pons was measured manually on the midline sagittal T1 MR image in 75 ELBW babies consecutively scanned at term postmenstrual age. Subjects with CH were identified and compared to babies with no posterior fossa bleeding. Nine ELBW infants with CH (CH-Group: median gestational age -GA- 26 wks, range 23-27; birth weight -BW- 680 g, 425-980) were compared with 66 babies with normal cerebellum (Control-Group: GA 28 wks, 23-33; BW 815 g, 430-1000). The two groups were comparable for BW (p=0.088) while GA was significantly shorter in CH babies (p=0.005). The pontine diameter was significantly lower in CH-Group compared to Control-Group (12.8 +/- 2.2 vs 14.8 +/- 1.2 mm; p

Background/purpose Neuroimaging plays a fundamental role in the diagnosis of Dandy Walker malformation (DWM), a posterior fossa anomaly that is usually associated with genetic abnormalities, but may rarely be ascribed to acquired causes. Here, we report the clinical history and neuroimaging studies of a child with a complex cardiac malformation, developmental delay, and oculomotor anomalies whose neuroimaging findings were consistent with an acquired form of DWM. Methods/results Fetal MRI at gestational weeks 27 and 31 showed cerebellar and vermis hypoplasia and fourth ventricle enlargement, together with hemosiderin deposits on the cerebellar hemispheric surface, but without significant vermian rotation. Postnatal MRIs at 5 days and 13 months revealed progressive counter-clockwise rotation of the hypoplastic cerebellar vermis with cystic dilation of the fourth ventricle, eventually leading to a full-blown DWM. Conclusion This case strengthens the opinion that DWM is a heterogeneous condition, and may support the hypothesis that acquired meningeal abnormalities in the form of cortico-pial hemosiderosis may play a role in the development of DWM. This case also demonstrates that serial neuroimaging plays a key role in the correct diagnosis of posterior fossa malformations, whose prognosis is difficult to establish on second trimester fetal MRI and requires longer clinical follow-up.