RESUMEN

Congenital Zika syndrome (CZS) is a set of birth defects caused by Zika virus (ZIKV) infection during pregnancy. Microcephaly is its main feature, but other brain abnormalities are found in CZS patients, such as ventriculomegaly, brain calcifications, and dysgenesis of the corpus callosum. Many studies have focused on microcephaly, but it remains unknown how ZIKV infection leads to callosal malformation. To tackle this issue, we infected mouse embryos in utero with a Brazilian ZIKV isolate and found that they were born with a reduction in callosal area and density of callosal neurons. ZIKV infection also causes a density reduction in PH3+ cells, intermediate progenitor cells, and SATB2+ neurons. Moreover, axonal tracing revealed that callosal axons are reduced and misrouted. Also, ZIKV-infected cultures show a reduction in callosal axon length. GFAP labeling showed that an in utero infection compromises glial cells responsible for midline axon guidance. In sum, we showed that ZIKV infection impairs critical steps of corpus callosum formation by disrupting not only neurogenesis, but also axon guidance and growth across the midline.

Asunto(s)

RESUMEN

The corpus callosum (CC), the largest brain commissure and the primary white matter pathway for interhemispheric cortical connectivity, was traditionally viewed as a predominantly homotopic structure, connecting mirror areas of the cortex. However, new studies verified that most callosal commissural fibers are heterotopic. Recently, we reported that ~75% of the callosal connections in the brains of mice, marmosets, and humans are heterotopic, having an essential role in determining the global properties of brain networks. In the present study, we leveraged high-resolution diffusion-weighted imaging and graph network modeling to investigate the relationship between heterotopic and homotopic callosal fibers in human subjects and in a spontaneous mouse model of Corpus Callosum Dysgenesis (CCD), a congenital developmental CC malformation that leads to widespread whole-brain reorganization. Our results show that the CCD brain is more heterotopic than the normotypical brain, with both mouse and human CCD subjects displaying highly variable heterotopicity maps. CCD mice have a clear heterotopicity cluster in the anterior CC, while hypoplasic humans have strongly variable patterns. Graph network-based connectivity profile showed a direct impact of heterotopic connections on CCD brains altering several network-based statistics. Our collective results show that CCD directly alters heterotopic connections and brain connectivity.

RESUMEN

BACKGROUND: Unilateral agenesis of a cervical pedicle is a known rare entity that has been well described over the past 70 years. It is usually an incidental or minimally symptomatic presentation with no significant clinical repercussion. No previous report has described concurrent non-osseous developmental abnormalities alongside this unique pathology. OBSERVATIONS: This case reported a cervical hemangioma with associated unilateral pedicle agenesis and an incidental finding of callosal dysgenesis and lipoma. The initial presentation consisted solely of persistent neck pain, with cervical radiography illustrating significant kyphotic deformity secondary to apparent anterolisthesis of C3-C4. The patient underwent a combined approach: anterior cervical corpectomy at C4-C5 with supplemental posterior fusion. The authors provided a review of the literature concerning developmental pedicle abnormalities and vertebral hemangioma. Pedicle agenesis is known to be associated with multiple pathologies, but the authors have not found evidence of a clinical paradigm consisting of a vertebral hemangioma in the presence of cervical pedicle agenesis, callosal dysgenesis, or callosal lipoma. LESSONS: Careful evaluation of radiographs with appropriate subsequent multimodal imaging is key to identifying unique pathologies in the spine that complement a patient's history and clinical findings. If multiple abnormalities are noted, a novel clinical etiology or syndrome must be considered.

RESUMEN

Pathogenic variants of collagen type IV alpha 1 and 2 (COL4A1/COL4A2) genes cause various phenotypic anomalies, including intracerebral hemorrhage and a wide spectrum of developmental anomalies. Only 20% of fetuses referred for COL4A1/COL4A2 molecular screening (fetuses with a suspected intracerebral hemorrhage) carry a pathogenic variant in these genes, raising questions regarding the causative anomaly in the remaining 80% of these fetuses. We examined, following termination of pregnancy or in-utero fetal death, a series of 113 unrelated fetuses referred for COL4A1/COL4A2 molecular screening, in which targeted sequencing was negative. Using exome sequencing data and a gene-based collapsing test, we searched for enrichment of rare qualifying variants in our fetal cohort in comparison to the Genome Aggregation Database (gnomAD) control cohort (n = 71 702). Qualifying variants in pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) were overrepresented in our cohort, reaching genome-wide significance (P = 2.11 × 10-7 ). Heterozygous PDHA1 loss-of-function variants were identified in three female fetuses. Among these three cases, we observed microcephaly, ventriculomegaly, germinolytic pseudocysts, agenesis/dysgenesis of the corpus callosum and white-matter anomalies that initially suggested cerebral hypoxic-ischemic and hemorrhagic lesions. However, a careful a-posteriori reanalysis of imaging and postmortem data showed that the observed lesions were also consistent with those observed in fetuses carrying PDHA1 pathogenic variants, strongly suggesting that these two phenotypes may overlap. Exome sequencing should therefore be performed in fetuses referred for COL4A1/COL4A2 molecular screening which are screen-negative, with particular attention paid to the PDHA1 gene. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Asunto(s)

RESUMEN

Dysgenesis of the corpus callosum is a rare developmental abnormality in brain structure that is associated with changes in physical appearance, as well as behavioral and cognitive consequences. A relatively commonly co-occurring structural abnormality with callosal dysgenesis is colpocephaly, characterized by enlargement of the posterior lateral ventricles and reductions in posterior brain volume. Although some case studies of individuals with this combination of structural malformations exist, they do not often report results of neuropsychological evaluation. Furthermore, those that do contain neuropsychological data may be of limited generalizability due to unique patient characteristics. The current manuscript overcomes these limitations by presenting the case of a 55-year-old male with callosal dysgenesis and colpocephaly identified in adulthood. The paper includes a full profile of his performance on a comprehensive neuropsychological test battery with discussion of differential diagnosis and treatment planning. Findings indicated low average intellectual abilities with deficits in processing speed, executive functions, and social cognition, consistent with expectations based on callosal dysgenesis. One surprising finding was that despite the significant posterior involvement of colpocephaly, visuospatial skills were a relative strength. The manuscript provides a clear characterization of callosal dysgenesis with colpocephaly to facilitate future clinical comparisons and set the stage for future research on this rare neuromorphological presentation.

Asunto(s)

RESUMEN

The corpus callosum is the largest white matter pathway connecting homologous structures of the two cerebral hemispheres. Remarkably, children and adults with developmental absence of the corpus callosum (callosal dysgenesis, CD) show typical interhemispheric integration, which is classically impaired in adult split-brain patients, for whom the corpus callosum is surgically severed. Tovar-Moll and colleagues (2014) proposed alternative neural pathways involved in the preservation of interhemispheric transfer. In a sample of six adults with CD, they revealed two homotopic bundles crossing the midline via the anterior and posterior commissures and connecting parietal cortices, and the microstructural properties of these aberrant bundles were associated with functional connectivity of these regions. The aberrant bundles were specific to CD and not visualised in healthy brains. We extended this study in a developmental cohort of 20 children with CD and 29 typically developing controls (TDC). The two anomalous white-matter bundles were visualised using tractography. Associations between structural properties of these bundles and their regional functional connectivity were explored. The proposed atypical bundles were observed in 30% of our CD cohort crossing via the anterior commissure, and in 30% crossing via the posterior commissure (also observed in 6.9% of TDC). However, the structural property measures of these bundles were not associated with parietal functional connectivity, bringing into question their role and implication for interhemispheric functional connectivity in CD. It is possible that very early disruption of embryological callosal development enhances neuroplasticity and facilitates the formation of these proposed alternative neural pathways, but further evidence is needed.

Asunto(s)

RESUMEN

The paradoxical absence of a split-brain syndrome in most cases of callosal dysgenesis has originated three main hypotheses, namely, (i) bilateral cortical representation of language, (ii) bilateral thalamocortical projections of somatosensory pathways conveyed by the spinothalamic-medial lemniscus system, and (iii) a variable combination of (i) and (ii). We used functional neuroimaging to investigate the cortical representation and lateralization of somatosensory information from the palm of each hand in six cases of callosal dysgenesis (hypothesis [ii]). Cortical regions of interest were contralateral and ipsilateral S1 (areas 3a and 3b, 1 and 2 in the central sulcus and postcentral gyrus) and S2 (parts of areas 40 and 43 in the parietal operculum). The degree of cortical asymmetry was expressed by a laterality index (LI), which may assume values from -1 (fully left-lateralized) to +1 (fully right-lateralized). In callosal dysgenesis, LI values for the right and the left hands were, respectively, -1 and + 1 for both S1 and S2, indicating absence of engagement of ipsilateral S1 and S2. In controls, LI values were - 0.70 (S1) and - 0.51 (S2) for right hand stimulation, and 0.82 (S1) and 0.36 (S2) for left hand stimulation, reflecting bilateral asymmetric activations, which were significantly higher in the hemisphere contralateral to the stimulated hand. Therefore, none of the main hypotheses so far entertained to account for the callosal dysgenesis-split-brain paradox have succeeded. We conclude that the preserved interhemispheric transfer of somatosensory tactile information in callosal dysgenesis must be mediated by a fourth alternative, such as aberrant interhemispheric bundles, reorganization of subcortical commissures, or both.

Asunto(s)

RESUMEN

Intracranial lipomas are rare incidental lesions. Rokitansky first described a corpus callosal lipoma on the posterior part of the corpus callosum in 1856. Since then many cases have been reported. We report the imaging findings of an interhemispheric lipoma extending into subcutaneous plane associated with spinal lipomeningocele and corpus callosal dysgenesis. Computed tomography and magnetic resonance imaging findings are characteristic. All cases have been reported in pediatric age group till now. Such a case in this age group has not been reported earlier.

RESUMEN

For general radiologists, congenital brain malformations pose substantial challenges in terms of recognition, description, and classification. This review describes a practical approach to imaging and classifying the most common supratentorial brain malformations. It begins with a discussion of embryology and optimal imaging technique and then summarizes distinguishing imaging features for several major categories of cerebral malformation, including holoprosencephaly, gray matter heterotopia, lissencephaly/pachygyria, focal cortical dysplasia, polymicrogyria, and cobblestone malformation. The importance of identifying abnormalities in the corpus callosum and basal ganglia is also discussed, both for detection and characterization of cerebral malformations.

Asunto(s)

RESUMEN

OBJECTIVES: The purpose of this study was to determine whether routine direct visualization of the corpus callosum is achievable during second-trimester sonography when performed by a large group of sonographers in a general second-trimester sonographic screening program. The secondary aim was to determine the time taken to obtain a sagittal corpus callosum image. METHODS: We conducted a retrospective cohort study of visualization of the corpus callosum before and after intensive training. Images from 150 consecutive second-trimester scans were reviewed before and after training to evaluate the image quality of the corpus callosum. RESULTS: A total of 300 cases were evaluated before and after training. There was a significant increase in the rate of complete visualization of the corpus callosum after intensive training (P < .0001). Before training 35 of 150 cases (23%) had complete visualization of the corpus callosum versus 107 of 150 (71%) after training. The mean time to perform the corpus callosum views was 53.4 seconds before training compared to 56.2 seconds after training. CONCLUSIONS: Assessing the corpus callosum in the sagittal view is difficult and requires appropriate training and patience; however, this view is feasible without adding substantial time to the examination and provides additional information during a routine second-trimester morphologic scan.

Asunto(s)

RESUMEN

The corpus callosum connects the two cortical hemispheres of the mammalian brain and is susceptible to structural defects during development, which often result in significant neuropsychological dysfunction. To date, such individuals have been studied primarily with regards to the integrity of the callosal tract at the midline. However, the mechanisms regulating the contralateral targeting of the corpus callosum, after midline crossing has occurred, are less well understood. Recent evidence suggests that defects in contralateral targeting can occur in isolation from midline-tract malformations, and may have significant functional implications. We propose that contralateral targeting is a crucially important and relatively under-investigated event in callosal development, and that defects in this process may constitute an undiagnosed phenotype in several neurological disorders.

Asunto(s)