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Axonal pathfinding mechanisms at the cortical midline and in the development of the corpus callosum.

The corpus callosum is a large fiber tract that connects neurons in the right and left cerebral hemispheres. Agenesis of the corpus callosum (ACC) is associated with a large number of human syndromes but little is known about why ACC occurs. In most cases of ACC, callosal axons are able to grow toward the midline but are unable to cross it, continuing to grow into large swirls of axons known as Probst bundles. This phenotype suggests that in some cases ACC may be due to defects in axonal guidance at the midline. General guidance mechanisms that influence the development of axons include chemoattraction and chemorepulsion, presented by either membrane-bound or diffusible molecules. These molecules are not only expressed by the final target but by intermediate targets along the pathway, and by pioneering axons that act as guides for later arriving axons. Midline glial populations are important intermediate targets for commissural axons in the spinal cord and brain, including the corpus callosum. The role of midline glial populations and pioneering axons in the formation of the corpus callosum are discussed. Finally the differential guidance of the ipsilaterally projecting perforating pathway and the contralaterally projecting corpus callosum is addressed. Development of the corpus callosum involves the coordination of a number of different guidance mechanisms and the probable involvement of a large number of molecules.

Agenesis of Corpus Callosum↗

[Histogenesis of the corpus callosum].

The corpus callosum results from neocortical commissural axon fasciculation. Its development reflects the interhemispheric circuitry and then follows the successive steps of synaptogenesis. The first stage consists of callosal neuron differentiation, which allows the extention of the future callosal axon; this is an early event that occurs while neuronal migration to the cortical plate is still ongoing. Callosal axon guidance towards its specific target is the second step which includes reaching and crossing the midline and further target recognition with formation of initial synapses. This period extends from 12 to 22 post-conceptional weeks and corresponds to the following histological features: i) progressive invasion by callosal growth cones of the dorsal part of lamina reuniens through a preformed glial pathway; ii) appearence of the three parts of corpus callosum, namely truncus, rostrum and lastly the splenium. Both these stages are genetically controlled either directly by developmental gene expression (neurogenesis genes) or indirectly by the establishment of cue maps (spatial expression of extra-cellular matrix proteins). The third step is that of synapse remodeling by synaptic activity, giving rise to axonal elimination, macroscopically revealed by a transitory thinning of corpus callosum. This perinatal event contributes to the corpus callosum acquiring a mature topography. Finally, analysis of corpus callosum ontogenesis appears as a striking model of synaptogenesis study and provides physiopathological assumptions for a understanding of the corpus callosum agenesis.

Animals↗

[Development of the corpus callosum (CC)].

Corpus callosum embryology can be divided into three parts: during "commissuration", a cellular mass develops between the two telencephalic vesicles. The primitive lamina terminalis corresponds to the closing point of the anterior neuropore. Its dorsal part grows and forms the lamina reunions (6-8 intra uterine weeks, IUW). From ventral to dorsal, this lamina reunions gives rise to the area praecommissuralis (origin of the anterior commissure), to the primordium hippocampi (10 I.U.W., fornix), and to the massa commissuralis (10 S.I.U., corpus callosum). Fibers arising from the developing hemispheres run through this primitive corpus callosum. The growth of the corpus callosum follows the expansion of the hemispheres, in a rostro-caudal and then dorso-ventral circular movement. The last part of the corpus callosum to form is the rostrum. Maturation occurs postnatally, and corresponds to axonal elimination, and myelination, progressively changing the callosal connection pattern of the newborn and infant into the adult pattern.

Animals↗

MR imaging of the corpus callosum.

The corpus callosum is the major axonal commissure of the brain, connecting the two cerebral hemispheres and providing communication between the cortical and subcortical neurons. With MR imaging in the sagittal plane, the corpus callosum can be depicted in great detail. We review the normal anatomy, development, and process of myelination of the corpus callosum. The MR features of various pathologic conditions involving the corpus callosum are described. Finally, we discuss the evolving role of MR imaging in neuropsychiatric diseases with respect to the corpus callosum.

AIDS Dementia Complex↗

[Morphologic anatomy of the corpus callosum].

The corpus callosum is a neopallial commissure. In inferior vertebrates, the pallial commissures are essentially represented by the anterior commissure. The corpus callosum appears in mammals only. Eutherians alone have a corpus callosum, the other mammals have an anterior commissure and hipocampal commissure. In humans, the different portions of the corps callosum are described on a median sagittal slice: rostrum, genu, body, isthmus, splenium. Klingler method allows to dissect fibers of each of these portions and their relationship with the corona radiata and optic radiations. These latter are separated from the ventricular ependyme by callosal radiations. Finally, each part of the corpus callosum participates in lateral ventricle wall formation.

Animals↗

[Clinical features in subjects with congenital anomalies of the corpus callosum].

The corpus callosum is a connecting structure between the two cerebral hemispheres. Its development occurs between 8th and 20th week of gestation. Anomalies of the corpus callosum are divided into malformative or acquired anomalies and may be isolated or associated with other cerebral malformations. The diagnosis of an alteration of the corpus callosum is fundamentally based on neuroradiological examinations. In our study we evaluate the major clinical findings, the psychomotor development, the electroencephalographic and neuroradiological features in a group of 14 children with congenital callosal anomalies, trying to single out how the associated cerebral malformations interfered with the clinical manifestations and especially the prognosis. It was not possible to highlight a distinctive symptom indicative of the presence of a corpus callosum anomaly; nevertheless in 11/14 children there was a psychomotor delay of varying degree. 42% of our subjects presented epilepsy, with a typical West syndrome in 5/6. Children affected by isolated callosum anomalies did not present any significant clinical manifestations. Finally, we conclude that the determinating factors in the severity of the clinical-electroencephalographic picture as a whole, and especially in the prognosis of our patients are the cerebral malformations associated to the callosum anomalies.

Agenesis of Corpus Callosum↗

[Corpus callosum disconnection syndromes and functional organization or the corpus callosum in adults].

Knowledge concerning the role of the corpus callosum derives from the study of patients with lesions of spontaneous or surgical origin. Three major aspects are defined: interhemispheric elementary transfer of symmetrically organized messages, complex transfer of asymmetrically organized information, interhemispheric transfer and complex behaviors. Symptoms are both complex and rather limited; they can be missed if they are not specifically searched for.

Agenesis of Corpus Callosum↗

Ictal EEG changes with corpus callosum section.

Corpus callosum section diminishes but does not completely abolish secondary bilaterally synchronous interictal EEG discharges, yet often causes cessation of generalized seizures. The effects of corpus callosum section on ictal EEG patterns have not been described. We contrasted ictal EEG patterns before and after anterior callosotomy in 18 patients and before and after total callosotomy in 10 patients. Bilaterally synchronous seizure onset was disrupted in 5 of 11 anterior section patients and 5 of 5 total section patients. Seven of 18 anterior section patients and 5 of 10 total section patients had more localized seizure onset after the procedure; localization to the frontal lobe was observed after anterior or total section, but only total section patients had newly demonstrated posterior locations of seizure onset. These data suggest that the mechanisms by which bilaterally synchronous interictal and ictal discharges are generated differ. Although brainstem or diencephalic structures may contribute to formation of interictal bilateral synchrony, the corpus callosum may be the only pathway used in producing apparent bilateral synchronous seizure onset in patients with secondarily generalized seizures.

Brain Stem↗

[Lipoma of the corpus callosum associated with the hypertrophy of the corpus callosum: case report].

Despite the lipomas are the tumors that more commonly occur in the corpus callosum (CC), its incidence in the population is not common. We report on a 5-year old boy, with history of retardation in the psychomotor development and disturbs in the gait, secondary to generalized hypotony. Magnetic resonance imaging showed a curvilinear lipoma of the CC related to its hypertrophy. In the literature patients with CC lipoma usually have agenesis or hypotrophy of the CC, but in the reported case we have seen, by the first time, a hypertrophy of the CC. We made embryologic, genetic, clinical, radiographic and therapeutic considerations about the patients that have CC lipoma comparing to findings in the case we report.

Brain Neoplasms↗

Sexual dimorphism of the human corpus callosum from three independent samples: relative size of the corpus callosum.

Three independent autopsy samples of brains without apparent neuropathology were studied to ascertain whether there was sexual dimorphism in the human corpus callosum (CC). Using planimetric measurements on midsagittal brain sections, several morphometric features of the CC were studied: total callosal area, maximum dorsoventral splenial width, the posterior one fifth of the total area of the CC (mostly splenium), and brain weight. Ratio data correcting for brain size were also studied. In all samples, absolute brain size was larger in males, and significantly so. Measurements of splenial dorsoventral width were higher in females than males, but not significantly, except in the Australian sample. Total callosal area was absolutely higher in the Australian female sample than in males, and almost equal in the two American samples, without statistically significant differences. The posterior one-fifth area (splenium) was larger for females in each of the samples. The variables which were corrected for brain size were usually significantly larger in females, although this pattern varied in each sample. The statistical pattern of sexual dimorphism for the human CC differs from that found in most other neural structures, such as the amygdaloid nucleus, cerebellum, hippocampus, and thalamus. The absolute sizes of these structures are always significantly larger in males. When corrected for brain size, the relative sizes are not significantly larger. The CC is the only structure to show a larger set of relative measures in females.

Adolescent↗

Source activity in the human secondary somatosensory cortex depends on the size of corpus callosum.

If corpus callosum (CC) mediates the activation of the secondary somatosensory area (SII) ipsilateral to the side of stimulation, then the peak latencies of the contra- and ipsilateral SII activity as well as the amplitude of the ipsilateral SII activity should correlate with the size of CC. Innocuous electrical stimuli of five different intensities were applied to the ventral surface of the right index finger in 15 right-handed men. EEG was recorded using 82 closely spaced electrodes. The size of CC and of seven callosal regions was measured from the mid-sagittal slice of a high-resolution anatomical MRI. The activation in the contralateral and ipsilateral SII was evaluated using spatio-temporal source analysis. At the strongest stimulus intensity, the size of the intermediate part of the callosal truncus correlated negatively with the interpeak latency of the sources in ipsi- and contralateral SII (r = -0.83, P < 0.01). Stepwise regression analysis showed that the large size of the intermediate truncus of CC was paralleled by a latency reduction of peak activity of the ipsilateral SII, whereas both contra- and ipsilateral peak latencies were positively correlated. The peak amplitude of the ipsilateral SII source correlated positively with the size of the intermediate truncus of CC, and with the peak amplitudes of sources in the primary somatosensory cortex (SI) and in the mesial frontal cortex. The results suggest that in right-handed neurologically normal men, the size of the intermediate callosal truncus contributes to the timing and amplitude of ipsilateral SII source activity.

Adult↗

[Neurosurgical Embryology. Part 3: Molecular control of corpus callosum development].

The corpus callosum is the most important cerebral commissure allowing axonal fibres to cross the midline. Corpus callosum agenesis is an important condition in man that can reveal numerous genetic syndromes. The corpus callosum develops from the commissural plate, a dorsal region of the telencephalon. Then, axons growing from pyramidal neurons of cortical layer III extend and cross the midline. In experimental models, it is possible to decipher two conditions in which the development of the corpus callosum is impaired. The first condition is characterized by an impairment of the formation of the roof of the telencephalon (the primordium of the commissural plate). This condition can be explained by an abortive induction of this region by an impairment of BMP signaling. This can generate all the forms of holoprosencephaly. Other forms are due to a defective gene coding Hesx1, a transcription factor involved in the control of telencephalic morphogenesis. Such a genetic defect can be observed in human dominant forms of septo-optic dysplasia. The second condition is explained by an impairment of the molecular control of axon growth: such is the case for the couple netrin 1 and DCC or for the adhesion molecule L1.

Agenesis of Corpus Callosum↗