Dandy-Walker malformation: analysis of 38 cases

Thirty-eight cases of Dandy-Walker malformation (DWM) are presented. A female predominance of 3:1 was found. Thirty-two cases (84%) were diagnosed within the 1st year of life. Of these, 17 cases (44.7%) were diagnosed at birth. Ten (26%) were delivered by cesarean section. Thirteen infants (34%) had a birth weight below 3000 g. Several associated malformations were observed, the most frequent being capillary angioma (6 case); cardiac malformations, ophthalmic anomalies, agenesis of the corpus callosum, malformed limbs, and occipital meningocele were also seen. These observations indicate that DWM represents a disorder of the midline central nervous system indicative of marked genetic and etiologic heterogeneity with the possibility of showing clinical and pathological alterations intra-and extracranially. Macrocephaly was the most frequent physical finding, appearing in 31 cases (82%). Seventeen (44.7%) patients died, 11 before 6 months of age, 3 between 6 and 12 months, and 3 after 1 year. Postmortem studies were performed in 13 patients. Three cases have been lost to follow-up. Mental retardation (IQ below 70) was found in 11 cases (58% of survivors), low intellect (IQ between 70 and 85) in 4, and only 2 patients showed normal intellectual development (IQ more than 85). The high incidence of malformations having several genetic and environmental origins, as well as the high early mortality of patients with DWM, indicate the complexity of this syndrome, which involves the midline developmental field structures. It is not an isolated malformation of the posterior fossa in most cases.     

Magnetic resonance imaging and histological studies of corpus callosal and hippocampal abnormalities linked to doublecortin deficiency

Mutated doublecortin (DCX) gives rise to severe abnormalities in human cortical development. Adult Dcx knockout mice show no major neocortical defects but do have a disorganized hippocampus. We report here the developmental basis of these hippocampal abnormalities. A heterotopic band of neurons was identified starting at E17.5 in the CA3 region and progressing throughout the CA1 region by E18.5. At neonatal stages, the CA1 heterotopic band was reduced, but the CA3 band remained unchanged, continuing into adulthood. Thus, in mouse, migration of CA3 neurons is arrested during development, whereas CA1 cell migration is retarded. On the Sv129Pas background, magnetic resonance imaging (MRI) also suggested abnormal dorsal hippocampal morphology, displaced laterally and sometimes rostrally and associated with medial brain structure abnormalities. MRI and cryosectioning showed agenesis of the corpus callosum in Dcx knockout mice on this background and an intermediate, partial agenesis in heterozygote mice. Wild-type littermates showed no callosal abnormalities. Hippocampal and corpus callosal abnormalities were also characterized in DCX-mutated human patients. Severe hippocampal hypoplasia was identified along with variable corpus callosal defects ranging from total agenesis to an abnormally thick or thin callosum. Our data in the mouse, identifying roles for Dcx in hippocampal and corpus callosal development, might suggest intrinsic roles for human DCX in the development of these structures.     

胼胝体发育不良合并罕见颅内多发对称脂肪瘤1例报告及文献复习

胼胝体发育不良是一种先天性颅脑畸形,包括胼胝体不发育或发育不全,发病率（0．5～70）例／万,但胼胝体发育不良合并颅内多发脂肪瘤报道很少,现将作者在工作中遇到的1例报告如下并结合文献对其发病机制、临床特点、诊断进行讨论。     

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.     

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.     

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.     

Novel movement disorder of the lower lip: Is it epilepsia partialis continua? Clues from a secondary case

A 28-year-old woman developed an acute-onset novel movement disorder of the lower lip mimicking focal dystonia. Investigations showed it to be a presentation of epilepsia partialis continua occurring in association with agenesis of the corpus callosum. It responded favorably to anti-epileptic drug therapy. Recently, Kleopa and Kyriakides reported on 4 patients who developed sudden-onset movement disorder characterized by a tonic sustained, lateral and outward protrusion of half of the lower lip. They failed to find any causative factors, despite extensive investigation. Treatment with anticholinergics, clonazepam, and botulinum toxin injection failed to improve the movement disorder. I present an additional case of similar focal movement disorder occurring in the presence of agenesis of the corpus callosum. A scalp electroencephalogram revealed focal epileptic activity, and the movement disorder responded favorably to treatment with antiepileptic drugs.     

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.     

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.