Neurodevelopmental outcomes in children with prenatally diagnosed corpus callosal abnormalities

Objective

Although corpus callosal abnormalities are among the most common brain malformations detected prenatally, few previous studies have described the neurodevelopmental outcomes of children with this condition. The aim of our study was to evaluate the neurodevelopmental outcomes and associated clinical features of children with corpus callosal abnormalities diagnosed by prenatal ultrasonography.

Meta-analysis of magnetic resonance imaging studies of the corpus callosum in bipolar disorder

Objective: The corpus callosum (CC) plays a pivotal role in inter‐hemispheric transfer and integration of information and is a relatively understudied structure in bipolar disorder (BD). Magnetic resonance imaging (MRI) studies have reported callosal abnormalities in this condition but findings have been inconsistent. Structural changes affecting the CC may underlie functional abnormalities in BD and could contribute to, or explain the pathophysiology of, the condition. Method: A systematic review was carried out to identify, appraise and summarize MRI studies which compared callosal areas in BD with an unrelated control group. The findings were then synthesized using random effects meta‐analysis. Consideration was given to a number of variables to explain heterogeneity. Results: Five case–control studies were identified. Bipolar patients showed reduced callosal areas in comparison with healthy volunteers with no evidence of heterogeneity or publication bias. Conclusion: Findings from this study indicate that callosal areas are reduced in BD and suggest that a failure to integrate information across the hemispheres may contribute to the pathophysiology of the disorder. Further research is necessary to clarify the underlying cellular changes leading to these morphometric differences.     

A disconnection syndrome due to agenesis of the corpus callosum: disturbance of unilateral synchronization

Recently, interhemispheric disconnection syndromes have been noted in patients with agenesis of the corpus callosum (ACC) during the performance of certain tasks. However, few studies have demonstrated an asymmetric disconnection syndrome. In this report, we present just such a syndrome in a patient with ACC, who manifested ambidexterity (but with a left-hand tendency) and had high intelligence, no neurological deficits, and no associated malformations. In a comparison with similar subjects (amateur musician), we studied her asymmetric deficits using four tasks: (1) simple reaction time for visual stimuli, (2) paced finger tapping in synchrony with visual or auditory stimuli, (3) paced finger tapping without an external reference, and (4) rhythmical finger tapping in synchrony with visual or auditory stimuli. While the comparable subjects displayed no significant difference between hands, and the patient showed no significant difference between hands in the auditory paradigm, her tapping performance deteriorated significantly when asked to synchronize the left hand with timed visual stimuli, irrespective of whether finger tapping was paced or rhythmical. We believe that this phenomenon constitutes a novel asymmetrical disconnection syndrome in an ACC subject; these results suggest that synchronization of multimodal temporal information was lateralized in the left hemisphere (in this case), which is something that the ACC patient could not compensate for.     

Agenesis of the corpus callosum: symptoms consistent with developmental disability in two siblings

Agenesis of the corpus callosum (AgCC) is a congenital disorder that disrupts the development of neurological structures connecting the right and left hemispheres of the brain. In addition to neurological symptoms, many individuals with AgCC demonstrate marked deficits in social, communication, and adaptive skills. This paper presents two case studies of congenital AgCC in siblings with socioemotional and behavioral symptoms consistent with developmental disability, but with notably different symptom presentations and clinical needs. Conclusions from these cases suggest that unique symptom profiles of individuals with AgCC warrant careful consideration for referral to appropriate academic and habilitative services.     

Single forebrain ventricle without prosencephaly: agenesis of the corpus callosum with dehiscent fornices

Coalescence of the cerebral ventricles with formation of a single forebrain ventricle is described in an unusual case of agenesis of the corpus callosum with dehiscent fornices and severe hydrocephalus. The cerebral hemispheres were fully cleaved. The detached fornices were widely separated from the thalami. The membrana tectoria was retroverted over the midbrain and cerebellum, where it joined the fornices and merged with a curved membranous ependymal dome which, at a great distance, circumvented the thalami as it extended toward the anterior commissure. Other anomalies included arhinencephaly, multiple subependymal heterotopias, and Dandy-Walker malformation. Similar malformations have been described as interhemispheric cysts, as (holo)prosencephaly, or as midline telencephalic dysgenesis. The basic features of prosencephaly and agenesis of the corpus callosum are reviewed and compared to the present case.     

The corpus callosum modulates spindle-burst activity within homotopic regions of somatosensory cortex in newborn rats

The corpus callosum, a major interhemispheric fiber tract, mediates communication between homotopic regions within the primary somatosensory cortex (S1). Recently, in 1- to 6-day-old rats, brief bursts of oscillatory activity - called spindle-bursts (SBs) - were described in cortical somatosensory areas following sensory feedback from sleep-related myoclonic twitches or specific peripheral stimulation. To determine whether interhemispheric communication via the corpus callosum modulates the expression of SBs during this early period of development, we investigated the spontaneous expression of SBs in unanesthetized 1- to 6-day-old rats as well as SBs evoked by plantar surface stimulation of the forepaw. We hypothesized that surgically disrupting transcallosal communication (i.e. with callosotomy) or unilateral pharmacological manipulation of S1 activity (e.g. by blocking muscarinic receptors) would alter S1 activity in one or both hemispheres. First, callosotomy doubled the rate of spontaneous, twitch-related SBs in left and right S1s by reducing the interval between successive SBs. Second, unilateral infusion into the left S1 of the muscarinic receptor antagonist, scopolamine, inhibited SBs in response to right forepaw stimulation; importantly, SBs were now disinhibited in the right S1 to right forepaw stimulation, thus 'unmasking' an ipsilateral representation. Subsequent callosotomy reinstated contralateral SB responses in the left S1. Finally, tactile and proprioceptive stimulation produced dissociable neurophysiological S1 responses; specifically, SBs were produced in response to proprioceptive, but not tactile, stimulation. We conclude that the corpus callosum modulates functionally inhibitory interactions between homotopic regions in left and right S1s during the early developmental period when organized neurophysiological activity is first detected in the neocortex.     

Aicardi syndrome. Report of 6 cases and a review of Japanese literature

This report presents 6 cases of Aicardi syndrome (infantile spasms, agenesis of the corpus callosum, chorioretinopathy), and a review of Japanese literature. Two patients developed Lennox-Gastaut syndrome following infantile spasms. Visual evoked potential was examined in every case with binocular and monocular flash stimulations. Normal response was obtained in 5 cases, and no response in 1. Auditory brainstem response was examined in 2 cases. Central conduction time was prolonged in 1 case.     

Degeneration of corpus callosum and recovery of motor function after stroke: A multimodal magnetic resonance imaging study

Animal models of stroke demonstrated that white matter ischemia may cause both axonal damage and myelin degradation distant from the core lesion, thereby impacting on behavior and functional outcome after stroke. We here used parameters derived from diffusion magnetic resonance imaging (MRI) to investigate the effect of focal white matter ischemia on functional reorganization within the motor system. Patients (n = 18) suffering from hand motor deficits in the subacute or chronic stage after subcortical stroke and healthy controls (n = 12) were scanned with both diffusion MRI and functional MRI while performing a motor task with the left or right hand. A laterality index was employed on activated voxels to assess functional reorganization across hemispheres. Regression analyses revealed that diffusion MRI parameters of both the ipsilesional corticospinal tract (CST) and corpus callosum (CC) predicted increased activation of the unaffected hemisphere during movements of the stroke‐affected hand. Changes in diffusion MRI parameters possibly reflecting axonal damage and/or destruction of myelin sheath correlated with a stronger bilateral recruitment of motor areas and poorer motor performance. Probabilistic fiber tracking analyses revealed that the region in the CC correlating with the fMRI laterality index and motor deficits connected to sensorimotor cortex, supplementary motor area, ventral premotor cortex, superior parietal lobule, and temporoparietal junction. The results suggest that degeneration of transcallosal fibers connecting higher order sensorimotor regions constitute a relevant factor influencing cortical reorganization and motor outcome after subcortical stroke. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

胼胝体压部可逆性病变的MRI诊断与临床分析

目的探讨胼胝体压部(splenium of the corpus callosum,SCC)可逆性病变的MRI表现及临床特点。方法回顾性分析8例脑MRI表现为单纯胼胝体压部可逆性病变患者的临床和影像学资料。结果 8例患者的SCC可逆性病变均为继发性,原发病分别为脑内感染5例,肝豆状核变性、低血糖脑病及脑外伤各1例。8例患者均急性起病,临床表现为发热、头痛5例,急性意识障碍2例,肌张力增高2例,颈强2例,均符合原发病的临床表现。8例均行脑MRI检查,均表现为T1低或等信号,T2及FLAIR序列高信号,DWI高信号(提示细胞源性水肿),其中4例行增强扫描未见强化。8例患者均于临床症状好转或消失后复查MRI提示病灶消失。结论 SCC可逆性病变在多种疾病中均可出现,无该病变相关的特异性临床表现,MRI表现提示病灶为细胞源性水肿可能。     

Comprehension of humor in primary agenesis of the corpus callosum

Individuals with agenesis of the corpus callosum (ACC) can, in some cases, perform normally on standardized intelligence tests. Nevertheless, recent studies suggest that individuals with ACC and normal IQ scores have deficits in domains of fluid and social intelligence. Anecdotal reports from families suggest diminished appreciation of the subtleties of social interactions, and deficits in the comprehension of jokes and stories. In this research, both the cartoon and narrative joke subtests of a humor test (developed by Brownell et al. [Brownell, H., Michel, D., Powelson, J., & Gardner, H. (1983). Surprise but not coherence: sensitivity to verbal humor in right-hemisphere patients. Brain and language, 18(1), 20-27] and Bihrle et al. [Bihrle, A. M., Brownell, H. H., Powelson, J. A., & Gardner, H. (1986). Comprehension of humorous and non-humorous materials by left and right brain-damaged patients. Brain and Cognition, 5(4), 399-411]) were given to 16 adults with complete ACC (all with IQs>80) and 31 controls of similar age and IQ. Individuals with ACC performed worse than controls on the narrative joke subtest (p<.025) when VIQ was controlled. However, on the cartoon subtest the two groups were not significantly different. Covarying age, forms of IQ, narrative memory, set-switching, and literal language comprehension did not substantially alter the group difference. However, covarying comprehension of nonliteral language and proverbs eliminated the difference, suggesting a common origin for the comprehension of jokes, nonliteral language, and proverbs, most likely related to capacity for understanding second-order meanings.     

A new template to study callosal growth shows specific growth in anterior and posterior regions of the corpus callosum in early childhood

Most of the studies conducted on the development of the corpus callosum (CC) have been limited to a relatively simple assessment of callosal area, providing an estimation of the size of the CC in two dimensions rather than its actual measurement. The goal of this study was to revisit callosal development in childhood and adolescence by using a three‐dimensional (3D) magnetic resonance imaging template of the CC that considers the horizontal width of the CC and compares this with the two‐dimensional (2D) callosal area. We mapped callosal growth in a large sample of youths followed longitudinally (N = 370 at T1; N = 304 at T2; and N = 246 at T3). Both techniques were based on a five‐section subdivision of the CC. The results obtained with the 3D method revealed that the rate of CC growth over a 4‐year period in the rostrum, the genu, the anterior body and the splenium was significantly higher in the youngest age group (< 7 years) than in older groups, indicating an intense period of development in early childhood for the anterior and posterior parts of the CC. Similar results were obtained when 2D callosal area was used for the anterior and posterior parts of the CC. However, divergent results were found in the mid‐body and the caudal body of the CC. As shown by differences between 2D estimations and actual 3D measurements of callosal growth, our study highlights the importance of considering the horizontal width in measuring developmental changes in the CC.     

Timing and origin of the first cortical axons to project through the corpus callosum and the subsequent emergence of callosal projection cells in mouse

A precise knowledge of the timing and origin of the first cortical axons to project through the corpus callosum (CC) and of the subsequent emergence of callosal projection cells is essential for understanding the early ontogeny of this commissure. By using a series of mouse embryos and fetuses of the hybrid cross B6D2F₂/J weighing from 0.36 g to 1.0 g (embryonic day E15.75–E17.25), we examined the spatial and temporal distribution of callosal projection cells by inserting crystals of the lipophilic dye (DiI: 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl-indocarbocyanine perchlorate) into the contralateral white matter just lateral to the midsagittal plane. Around 0.4 g or E15.8, retrogradely labeled cells were found restricted to a discrete cluster continuously distributed from the most ventral part of presumptive cingulate cortex to the hippocampus. During subsequent development, however, the tangential distribution of these labeled cells in ventromedial cortex did not extend further dorsally, and in fetuses where the CC became distinct from the hippocampal commissure (HC), labeled axons of cells in the ventral cingulate cortex were observed to intersect the callosal pathway and merge with labeled axons of the HC derived from cells in the hippocampus. The first cortical axons through the CC crossed the midline at about 0.64 g or E16.4, and these axons originated from a scattered neuronal population in the dorsal to lateral part of the presumptive frontal cortex. The earliest callosal cells were consistently located in the cortical plate and showed an immature bipolar appearance, displaying an ovoid- or pearl-shaped perikaryon with an apical dendrite coursing in a zig-zagging manner toward the pial surface and a slender axon directed toward the underlying white matter. Callosal projection cells spread progressively with development across the tangential extent of the cerebral cortex in both lateral-to-medial and rostral-to-caudal directions. In any cortical region, the first labeled cells appeared in the cortical plate and their number in the subplate was insignificant compared to that in the cortical plate. Thus, these results clarify that the CC is pioneered by frontal cortical plate cells, and the subsequent ontogeny of callosal projection cells proceeds according to the gradient of cortical maturation. J. Comp. Neurol. 400:197–206, 1998. © 1998 Wiley-Liss, Inc.     

A study of the septum pellucidum and corpus callosum in schizophrenia with MR imaging

Surface areas of the septum pellucidum, corpus callosum and the brain were measured from mid-saggital slices obtained with magnetic resonance imaging in 18 patients with schizophrenia and an equal number of normal volunteers. The patients showed larger septa and septo-brain ratios. These indices correlated with age in both patients and controls. In the patients, septal area also correlated with duration of illness. Changes in the septum pellucidum were unrelated to the intensity of positive and negative symptoms of schizophrenia. The patients had significantly longer corpora callosa, but the two groups did not differ on its size or the ratio between the latter and the mid-saggital slice area. Dimensions of the corpus callosum did not correlate with age, duration of the illness or positive and negative symptoms of schizophrenia. The anteroposterior elongation of the structure seemed to accompany enlargement of the septum pellucidum.     

Postnatal lesion evidence against a primary role for the corpus callosum in mouse sociability

The BTBR T+tf/J (BTBR) strain is an inbred strain of mice that displays prominent social deficits and repetitive behaviors analogous to the defining symptoms of autism, along with complete congenital agenesis of the corpus callosum (CC). The BTBR strain is genetically distant from the widely used C57BL/6J (B6) strain, which exhibits high levels of sociability, a low level of repetitive behaviors, and an intact CC. Emerging evidence implicates compromised interhemispherical connectivity in some cases of autism. We investigated the hypothesis that the disconnection of CC fiber tracts contributes to behavioral traits in mice that are relevant to the behavioral symptoms of autism. Surgical lesion of the CC in B6 mice at postnatal day 7 had no effect on juvenile play and adult social approaches, and did not elevate repetitive self-grooming. In addition, LP/J, the strain that is genetically closest to the BTBR strain but has an intact CC, displayed juvenile play deficits and repetitive self-grooming similar to those seen in BTBR mice. These corroborative results offer evidence against the hypothesis that the CC disconnection is a primary cause of low sociability and a high level of repetitive behaviors in inbred mice. Our findings indicate that genes mediating other aspects of neurodevelopment, including those whose mutations underlie more subtle disruptions in white matter pathways and connectivity, are more likely to contribute to the aberrant behavioral phenotypes in the BTBR mouse model of autism.     

Social cognition in individuals with agenesis of the corpus callosum

Past research has revealed that individuals with agenesis of the corpus callosum (ACC) have deficits in interhemispheric transfer, complex novel problem-solving, and the comprehension of paralinguistic aspects of language. Case studies and family reports also suggest problems in social cognition. The performance of 11 individuals with complete ACC and with normal intelligence was compared to that of 13 IQ- and age-matched controls on three measures of social cognition. Individuals with ACC were indistinguishable from controls on the Happé Theory of Mind Stories and the Adult Faux Pas Test, but performed significantly worse on various portions of the Thames Awareness of Social Inference Test (TASIT) involving interpretations of videotaped social vignettes. Further analysis of the TASIT indicated that individuals with ACC showed deficiency in the recognition of emotion, weakness in understanding paradoxical sarcasm, and particular difficulty interpreting textual versus visual social cues. These results suggest that the tendency for deficient social cognition in individuals with ACC stems from a combination of difficulty integrating information from multiple sources, using paralinguistic cues for emotion, and understanding nonliteral speech. Together, these deficits would contribute to a less robust theory of mind.     

Primary intracranial arachnoidal cysts

Sixty-seven cases (41 males and 26 females) of arachnoidal cysts in children under 11 years are reported. About 53% of cases were diagnosed before 1 year of life. Thirty-one (42.2%) were supratentorial (interhemispheric 9, temporal fossa 10, convexity 5, sylvian fissure 3, supra- and/or retrosellar 4); 31 (46.2%) infratentorial (supra- and/or retrocerebellar 22, foramen of Magendie 3, quadrigeminal cistern 5, pontocerebellar 1); 5 (7.5%) supra-and infratentorial. Macrocephaly was the presenting symptom in 48 cases (71.5%). Associated features were frequent: cranial asymmetry in 24; aqueductal stenosis in 10; agenesis of corpus callosum in 8; deficient cerebellar lobullation in 4; Chiari I malformation in 2; neurofibromatosis type 1 with dysgenetic zones of the brain in 1; arteriovenous malformation in 1. Diagnosis was made at autopsy in six cases in the days before computed tomography and magnetic resonance: three patients had a cyst in the supra-and retrocerebellar midline; two had a cyst in the quadrigeminal cistern and the sixth was a rare case with the cyst passing from the posterior fossa to the left lateral ventricle through a hole in the basal surface of the brain. Small and some middle-sized cysts were not treated. Big and some middle-sized cysts were usually treated by cysto- and/or ventriculoperitoneal shunts. Arachnoidal cysts of the quadrigeminal cistern usually present with aqueductal stenosis and have to be treated with ventriculoperitoneal shunt. Craniotomy and fenestration of the cysts were performed in some cases with good results. The average mental level of these children is usually moderately low.     

A familial Sonic Hedgehog (SHH) stop-gain mutation associated with agenesis of the corpus callosum,mild intellectual disability and facial dysmorphism

BackgroundAgenesis of the corpus callosum (ACC) is a relatively common brain malformation in children with developmental disabilities, caused by mutations in many genes. These genetic causes are characterized by their extreme heterogeneity with more than 300 causative genes identified to date.Case reportWe describe two new cases from a three-generation family with ACC and a de novo mutation of the sonic hedgehog (SHH) gene. The affected family members had mild intellectual disability, broad forehead, and widely spaced eyes. A next-generation sequencing (NGS) approach revealed a stop-gain mutation (NM_000193.2:c.1300_1301insA p.Trp434Ter) of the SHH gene; it is the first family to report ACC associated with a single SHH gene mutation.ConclusionACC with mild intellectual disability and facial dysmorphism may be caused by a mutation in SHH, but further research investigating the genotype-phenotype correlation of SHH mutations is required.     

Unlayered polymicrogyria and agenesis of the corpus callosum: a relevant association?

Summary Three anatomical cases of unlayered polymicrogyria associated with agenesis of the corpus callosum and heterotopias are presented. The cortical dysplasia includes: (1) thin unlayered cortical mantle with radial disposition but no horizontal organisation of the neurons; (2) microgyria with fused molecular layers; and (3) persisting transitory cells in the molecular layer (Cajal-Retzius cells, subpial granular layer). A Golgi study of the cortex in one case shows abnormal orientation of the neuronal dendritic tree in the superficial area along the fused molecular layers. Heterotopias are of two types: scattered neurons in the subcortical region and in layer I; and nodular heterotopias in the paraventricular region and in centrum semi ovale. This type of cortical dysplasia differs from the classical four-layered microgyria and is similar to the cortical anomalies described in Aicardi syndrome. One case presented here has Aicardi syndrome, while the two others, one girl and one boy, do not meet the criteria for Aicardi syndrome; in particular, they do not display chorioretinal lacunae. Nevertheless, this neuropathological association is responsible for severe mental retardation and epilepsy, and incites the search for a genetic origin like that in Aicardi syndrome.