Two Different Manifestations of Neonatal Vascular Injury: Dyke-Davidoff-Masson Syndrome and Crossed Cerebellar Atrophy.

Dyke-Davidoff-Masson syndrome (DDMS) was first described in 1933 as a clinical condition characterized by hemiatrophy, hyperpneumatization of paranasal sinuses, contralateral hemiparesis, facial asymmetry, seizures, and mental retardation.1 DDMS can be of 2 types: congenital and acquired. The congenital type can be caused by various conditions experienced during fetal or early childhood development, including ischemia, infarction, trauma, infections, and hemorrhage. The acquired type is mostly associated with hemorrhage, trauma, and infections experienced after 1 month of age. DDMS can manifest alone or can be accompanied by crossed cerebellar atrophy (CCA) which is a newly discovered radiological marker characterized by prominent cortical sulci and loss of cerebellar parenchyma. The congenital type of DDMS is known to be accompanied by ipsilateral cerebellar atrophy and the acquired type is known to be accompanied by contralateral cerebellar atrophy.2,3 Supratentorial events may lead to destruction in the cortico-ponto-cerebellar pathways, mostly in the contralateral side of the body (80%) due to decussation.4 In this report, we present 2 cases of DDMS accompanied by CCA to emphasize the possibility that the DDMS cases with severe intrauterine hemorrhage can be accompanied by contralateral CCA and migratory abnormalities rather than ipsilateral CCA and clinical survey.

Virtual Reality Social Prediction Improvement and Rehabilitation Intensive Training (VR-SPIRIT) for paediatric patients with congenital cerebellar diseases: study protocol of a randomised controlled trial.

BACKGROUND: Patients with cerebellar malformations exhibit not only movement problems, but also important deficits in social cognition. Thus, rehabilitation approaches should not only involve the recovery of motor function but also of higher-order abilities such as processing of social stimuli. In keeping with the general role of the cerebellum in anticipating and predicting events, we used a VR-based rehabilitation system to implement a social cognition intensive training specifically tailored to improve predictive abilities in social scenarios (VR-Spirit). METHODS/DESIGN: The study is an interventional randomised controlled trial that aims to recruit 42 children, adolescents and young adults with congenital cerebellar malformations, randomly allocated to the experimental group or the active control group. The experimental group is administered the VR-Spirit, requiring the participants to compete with different avatars in the reaching of recreational equipment and implicitly prompting them to form expectations about their playing preference. The active control group participates in a VR-training with standard games currently adopted for motor rehabilitation. Both trainings are composed by eight 45-min sessions and are administered in the GRAIL VR laboratory (Motekforce Link, Netherlands), an integrated platform that allows patients to move in natural and attractive VR environments. An evaluation session in VR with the same paradigm used in the VR-Spirit but implemented in a different scenario is administered at the beginning (T0) of the two trainings (T1) and at the end (T2). Moreover, a battery of neurocognitive tests spanning different domains is administered to all participants at T0, T2 and in a follow-up session after 2 months from the end of the two trainings (T3). DISCUSSION: This study offers a novel approach for rehabilitation based on specific neural mechanisms of the cerebellum. We aim to investigate the feasibility and efficacy of a new, intensive, social cognition training in a sample of Italian patients aged 7-25 years with congenital cerebellar malformations. We expect that VR-Spirit could enhance social prediction ability and indirectly improve cognitive performance in diverse domains. Moreover, through the comparison with a VR-active control training we aim to verify the specificity of VR-Spirit in improving social perception skills. TRIAL REGISTRATION: ISRCTN, ID: ISRCTN 22332873. Retrospectively registered on 12 March 2018.

Novel EXOSC3 pathogenic variant results in a mild course of neurologic disease with cerebellum involvement.

EXOSC3-related autosomal recessive neurodevelopmental disorders are rare entities with variable clinical course and prognosis. They are characterized by hypoplasia of cerebellar structures and pons, degeneration of the anterior horn cells and motor as well as neurocognitive impairment. Phenotypic expression is variable with an overall poor outcome. Current research suggests clear genotype-phenotype correlations among EXOSC3-pathogenic-variants carriers. Homozygosity for the EXOSC3 variant c.395A > C, p.(Asp132Ala) is proposed to lead to a rather mild phenotype compared to compound-heterozygous EXOSC3-pathogenic-variants carriers with lethal neurological disease in very early childhood. In this study, we report two siblings (21- and 8-year-old) affected by PCH1B with an unusual presentation. We identified compound heterozygosity for the well-established EXOSC3 variant c.395A > C, p.(Asp132Ala) and the novel variant c.572G > A, p.(Gly191Asp), expanding the genetic spectrum. Phenotypic presentation of the siblings was strikingly different from that of literature reports with a surprisingly mild disease manifestation and an unexpected intrafamilial variability. This study demonstrates the extensive clinical heterogeneity and the broad phenotypic spectrum associated with EXOSC3-associated disorders. Enlargement of sample sizes and reports of novel cases will be essential for the delineation of associated phenotypes.

Cerebellar hypoplasia of prematurity: Causes and consequences.

As magnetic resonance imaging has been increasingly used to study brain injury and brain development in premature newborns, the prevalence of cerebellar abnormalities is increasingly recognized. The preterm cerebellum is highly vulnerable to a number of insults during its critical phase of growth and development throughout the period of prematurity and beyond. Direct cerebellar injury and additional factors such as supratentorial brain injury and glucocorticoid exposure adversely impact cerebellar growth and, consequently, increase the risk of neurodevelopmental disabilities. In this chapter the causes and consequences of cerebellar hypoplasia of prematurity are reviewed.

Cerebellar contributions to self-motion perception: evidence from patients with congenital cerebellar agenesis.

The cerebellum was historically considered a brain region dedicated to motor control, but it has become clear that it also contributes to sensory processing, particularly when sensory discrimination is required. Prior work, for example, has demonstrated a cerebellar contribution to sensory discrimination in the visual and auditory systems. The cerebellum also receives extensive inputs from the motion and gravity sensors in the vestibular labyrinth, but its role in the perception of head motion and orientation has received little attention. Drawing on the lesion-deficit approach to understanding brain function, we evaluated the contributions of the cerebellum to head motion perception by measuring perceptual thresholds in two subjects with congenital agenesis of the cerebellum. We used a set of passive motion paradigms that activated the semicircular canals or otolith organs in isolation or combination, and compared results of the agenesis patients with healthy control subjects. Perceptual thresholds for head motion were elevated in the agenesis subjects for all motion protocols, most prominently for paradigms that only activated otolith inputs. These results demonstrate that the cerebellum increases the sensitivity of the brain to the motion and orientation signals provided by the labyrinth during passive head movements.

Congenital basis of posterior fossa anomalies.

The classification of posterior fossa congenital anomalies has been a controversial topic. Advances in genetics and imaging have allowed a better understanding of the embryologic development of these abnormalities. A new classification schema correlates the embryologic, morphologic, and genetic bases of these anomalies in order to better distinguish and describe them. Although they provide a better understanding of the clinical aspects and genetics of these disorders, it is crucial for the radiologist to be able to diagnose the congenital posterior fossa anomalies based on their morphology, since neuroimaging is usually the initial step when these disorders are suspected. We divide the most common posterior fossa congenital anomalies into two groups: 1) hindbrain malformations, including diseases with cerebellar or vermian agenesis, aplasia or hypoplasia and cystic posterior fossa anomalies; and 2) cranial vault malformations. In addition, we will review the embryologic development of the posterior fossa and, from the perspective of embryonic development, will describe the imaging appearance of congenital posterior fossa anomalies. Knowledge of the developmental bases of these malformations facilitates detection of the morphological changes identified on imaging, allowing accurate differentiation and diagnosis of congenital posterior fossa anomalies.

Congenital cerebellar dysplasia in White Leghorn chickens (Gallus gallus domesticus).

Congenital cerebellar anomalies have been rarely reported in birds. We examined cerebellums with disorganized folia from seven specific-pathogen-free White Leghorn chickens (Gallus gallus domesticus). Islands of heterotopic cortex were distributed from the deeper cortices to the medulla in the cerebellum. The characteristic lesions were composed of randomly admixed components of the cerebellar cortex, including Purkinje cells, a molecular layer and granular cells. Immunofluorescent analysis revealed Purkinje cells with haphazardly extended dendrites and a lack of Bergmann's glial fibres in the foci. Chicken parvovirus, Aino virus and avian retrovirus were not detected in the affected birds by polymerase chain reaction. This is the first report of cerebellar dysplasia in chickens possibly caused by a genetic abnormality.

Síndrome PHACES (Pascual Castroviejo tipo II): resonancia magnética pre y posnatal / PHACES syndrome (Pascual Castroviejo type II): prenatal and postnatal magnetic resonance imaging

El síndrome neurocutáneo descrito con el acrónimo PHACE describe la presencia de un hemangioma facial segmentario que asocia, entre otras, anomalías de la fosa posterior, anomalías arteriales cerebrovasculares, afectación cardiaca/coartación de aorta y alteración ocular. La presencia añadida de defectos del desarrollo ventral se denomina como PHACES. Nuestro propósito es describir un caso de síndrome PHACES con resonancia magnética cerebral pre y posnatal y afectación de la arteria cerebelosa posteroinferior derecha. El caso presentado es excepcional dado que se trata del primero publicado con iconografía pre y posnatal y debido a que presenta una alteración vascular única que amplía el espectro de anomalías arteriales intracraneales posibles en este síndrome (AU)

The neurocutaneous syndrome known by the acronym PHACE consists of the association of a segmental facial hemangioma with, among other entities, posterior fossa anomalies, cerebrovascular anomalies, cardiac involvement/aortic coarctation, and eye abnormalities. When ventral developmental defects are also present, the syndrome is referred to as PHACES. We report the prenatal and postnatal MRI findings in a case of PHACES with involvement of the right posteroinferior cerebellar artery. This case is exceptional because, to our knowledge, it is the first to report the findings at both prenatal and postnatal MRI and because of the unique vascular anomaly that widens the spectrum of possible intracranial arterial anomalies in this syndrome (AU)

Joubert syndrome: congenital cerebellar ataxia with the molar tooth.

Joubert syndrome is a congenital cerebellar ataxia with autosomal recessive or X-linked inheritance, the diagnostic hallmark of which is a unique cerebellar and brainstem malformation recognisable on brain imaging-the so-called molar tooth sign. Neurological signs are present from the neonatal period and include hypotonia progressing to ataxia, global developmental delay, ocular motor apraxia, and breathing dysregulation. These signs are variably associated with multiorgan involvement, mainly of the retina, kidneys, skeleton, and liver. 21 causative genes have been identified so far, all of which encode for proteins of the primary cilium or its apparatus. The primary cilium is a subcellular organelle that has key roles in development and in many cellular functions, making Joubert syndrome part of the expanding family of ciliopathies. Notable clinical and genetic overlap exists between distinct ciliopathies, which can co-occur even within families. Such variability is probably explained by an oligogenic model of inheritance, in which the interplay of mutations, rare variants, and polymorphisms at distinct loci modulate the expressivity of the ciliary phenotype.

A bilateral infratentorial neurenteric cyst.

We report a patient with a large infratentorial neurenteric (NE) cyst. Intracranial NE cysts, also known as enterogenous cysts, constitute a rare, generally benign entity of unknown aetiology. The presentation, imaging characteristics and management of the case is discussed, including illustrative peri-operative images.

The shrunken, bright cerebellum: a characteristic MRI finding in congenital disorders of glycosylation type 1a.

SUMMARY: CDG-1a is an early-onset neurodegenerative disease with selective hindbrain involvement and highly variable clinical presentation. We retrospectively reviewed the clinical records and MR imaging studies of 5 children (3 boys and 2 girls aged 12 days to 2 years at presentation) with molecularly confirmed CDG-1a. The cerebellum was hypoplastic at presentation in 4 cases, progressive bulk loss involved the cerebellum and the pons in all cases, and the cerebellar cortex and subcortical white matter were hyperintense on T2-weighted and FLAIR images in all. We conclude that CDG-1a likely results from a combination of cerebellar hypoplasia and atrophy. Cerebellar volume loss with diffuse T2/FLAIR hyperintensity seems to be a peculiar association in the field of cerebellar atrophies, and may be useful to address the differential diagnosis.

Síndrome de Joubert: hallazgos en resonancia magnética convencional y tensor de difusión / Joubert syndrome: findings at conventional magnetic resonance image and at diffusion tensor imaging

Presentamos el caso de un paciente de 20 años con diagnóstico previo de parálisis cerebral infantil y que a la exploración física presentaba un trastorno del desarrollo. Se le realizó una tomografía computarizada (TC) craneal y una resonancia magnética (RM) craneal convencional con lo que se diagnosticó de síndrome de Joubert. Se completó el estudio con un tensor de difusión y una tractografía. En este artículo se revisan los hallazgos en las técnicas de imagen en este síndrome y la bibliografía (AU)

We present the case of a 20-year-old man previously diagnosed with cerebral palsy in whom a developmental disorder was detected at physical examination. After cranial CT and conventional cranial MRI, we diagnosed Joubert syndrome. We completed the study with diffusion tensor imaging and tractography. This article reviews the imaging findings for Joubert syndrome and the relevant literature (AU)

Ultrasound detection of posterior fossa abnormalities in full-term neonates.

Routine cranial ultrasonography, using the anterior fontanelle as acoustic window enables visualization of the supratentorial brain structures in neonates and young infants. The mastoid fontanelle enables a better view of the infratentorial structures, especially cerebellar hemorrhage in preterm infants. Reports on the usefulness and reliability of cranial ultrasonography using the mastoid fontanelle approach for the detection of posterior fossa abnormalities, focusing only on full-term neonates are limited. This article describes the technique of mastoid fontanelle ultrasonography in full-term neonates and the features of posterior fossa abnormalities that may be encountered in various neonatal disorders and conditions, combined with subsequent MRI in the same patients. Cranial ultrasound through the mastoid fontanelle plays a pivotal role in the early detection of posterior fossa pathology and selection of neonates with an indication for MRI.

Modifier genes and non-genetic factors reshape anatomical deficits in Zfp423-deficient mice.

Development of neural circuitry depends on the integration of signaling pathways to coordinate specification, proliferation and differentiation of cell types in the right number, in the right place, at the right time. Zinc finger protein 423 (Zfp423), a 30-zinc finger transcription factor, forms alternate complexes with components of several developmental signaling pathways, suggesting it as a point of signal integration during brain development. We previously showed that mice lacking Zfp423 have reduced proliferation of cerebellar precursor cells, resulting in complete loss of vermis and variable hypoplasia of cerebellar hemispheres. Here, we show that Zfp423(-/-) hemisphere malformations are shaped by both genetic and non-genetic factors, producing distinct phenotype distributions in different inbred genetic backgrounds. In genetic mapping studies, we identify four additive modifier loci (Amzn1-4) and seven synthetically interacting loci (Smzn1.1-3.1) that together explain approximately one-third of the phenotypic variance. Strain-specific sequence polymorphism and expression data provide a reduced list of functional variant candidate genes at each modifier locus. Environmental covariates add only modest explanatory power, suggesting an additional stochastic component. These results provide a comprehensive analysis of sources of phenotype variation in a model of hindbrain malformation.

X-linked disorders with cerebellar dysgenesis.

X-linked disorders with cerebellar dysgenesis (XLCD) are a genetically heterogeneous and clinically variable group of disorders in which the hallmark is a cerebellar defect (hypoplasia, atrophy or dysplasia) visible on brain imaging, caused by gene mutations or genomic imbalances on the X-chromosome. The neurological features of XLCD include hypotonia, developmental delay, intellectual disability, ataxia and/or other cerebellar signs. Normal cognitive development has also been reported. Cerebellar dysgenesis may be isolated or associated with other brain malformations or multiorgan involvement. There are at least 15 genes on the X-chromosome that have been constantly or occasionally associated with a pathological cerebellar phenotype. 8 XLCD loci have been mapped and several families with X-linked inheritance have been reported. Recently, two recurrent duplication syndromes in Xq28 have been associated with cerebellar hypoplasia. Given the report of several forms of XLCD and the excess of males with ataxia, this group of conditions is probably underestimated and families of patients with neuroradiological and clinical evidence of a cerebellar disorder should be counseled for high risk of X-linked inheritance.

Role of MR imaging in prenatal diagnosis of pregnancies at risk for Joubert syndrome and related cerebellar disorders.

BACKGROUND AND PURPOSE: JSRD are rare autosomal recessive brain malformations. We hypothesized that MR imaging can assess fetuses at risk for JSRD and might influence their diagnoses. MATERIALS AND METHODS: We prospectively performed cranial MR imaging for 12 fetuses (mean GA, 23 weeks; SD, 3.7) at 25% recurrence risk for JSRD. We correlated prenatal MR imaging findings with postnatal MR imaging and clinical outcome. Retrospectively, we compared posterior fossa measurements of the cases with those of 24 age-matched fetuses with proved normal brain MR imaging. Institutional review board approval and consents were obtained. Statistical methods included a t test and ANCOVA tests. RESULTS: Fetal MR imaging correctly diagnosed 3 cases at 22, 28, and 29 weeks of gestation as JSRD, and 9 cases as normal. In JSRD-affected fetuses, prenatal MR imaging detected narrow pontomesencephalic junction (isthmus) with deepening of the interpeduncular fossa and thick horizontally placed superior cerebellar peduncles (MTS), deformed anteriorly convex floor of the fourth ventricle, and midline cerebellar cleft in place of the hypoplastic vermis. Measurements on axial fetal MR imaging at pontomesencephalic junction, ratio of AP diameters of interpeduncular fossa to midbrain/isthmus, and ratio of the AP to transverse diameters of the fourth ventricle were significantly higher in JSRD-affected fetuses than in nonaffected cases and the control group. CONCLUSIONS: MR imaging can diagnose JSRD in at-risk pregnancies by detecting posterior fossa signs. Measurements at the pontomesencephalic junction may enhance fetal MR imaging accuracy in diagnosing JSRD.

Development and dysmorphism in Joubert syndrome--short case series from India.

Five children with Joubert syndrome (JS), who fulfilled the criteria and had molar tooth sign (MTS) on magnetic resonance imaging were included in the study. Prominent forehead, open mouth and low set ears were consistent facial features. Severe developmental delay was seen in three children (66%). A differential developmental delay was noticed in all children and was independent of the radiological features. The children who had complications in the neonatal period were found to have more developmental delay on follow-up. The optimal control of sleep disturbances and hyperkinesis in one child resulted in a better cognitive performance. A regular neuro-developmental follow-up and interventions can optimize the potential of children with JS. In addition to the regular screening for retinal, renal and hepatic functions in JS, there is a need to monitor cognitive functions, sleep and behavior.