Partial development of the corpus callosum

PURPOSE: To determine whether the MR findings of callosal dysgenesis suggest that the partially formed corpus callosum in humans is the result of arrested growth or delayed continued development. METHODS: The MR scans of 25 patients with callosal dysgenesis were reviewed to determine whether the observed corpus callosum corresponded to the form and position of a portion of a normal corpus callosum, as suggested by a theory of arrested growth. RESULTS: In 10 of the 25 cases, the partially formed corpus callosum corresponded to a portion of a normal corpus callosum. In the remaining 15 cases, the partially formed corpus callosum was located posterior to the expected location of a normal genu and inferior to the expected location of a normal body. CONCLUSIONS: Corpus callosum dysgenesis in humans may be caused by arrested growth in some cases; in other cases it is most likely caused by delayed continued development that attempts to compensate for earlier abnormalities in the evolution of midline structures.     

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.     

Morphological changes of the corpus callosum in schizophrenia

Asthma and allergic disorders have been on the increase in recent decades, especially among children living in affluent countries; some aspects of the "Western" way of life may explain this trend. We evaluated the relation of aeroallergen skin test reactivity with socioeconomic status, number of siblings, and respiratory infections in early life. We examined a total of 2,226 schoolchildren, ages 7-11 years, in three areas of Lazio, Italy. Skin prick tests were performed to assess atopic status, and self-administered questionnaires were completed by the parents. The prevalence of prick test positivity was greater among children whose fathers were in the highest educational level than among those in the lowest [prevalence ratio (PR) = 1.58; 95% confidence interval (CI) = 1.21-2.06]. There was also a lower prevalence of atopy among larger sibships (PR = 0.38 for subjects with four or more siblings vs those without siblings; 95% CI = 0.14-0.99). A history of bronchitis or bronchiolitis before age 2 years was weakly associated with an increased risk of atopy, whereas a history of pertussis or pneumonia was not. Both the effect of father's education and the influence of larger sibship size remained when we adjusted for several potential confounding factors, including respiratory infections in early life. We infer that higher socioeconomic status and lower sibling number are determinants of atopy in this Italian population. Protection arising from early severe respiratory infections does not explain this association, although we cannot exclude a role for other viral infections.     

Transient axonal branching in the developing corpus callosum

During development, there is a transient overproduction of axons in the corpus callosum; this overproduction of axons is due, in part, to a transient excess of neurons that send an axon through the corpus callosum. However, transient axonal branching could also contribute to the developmental overproduction of callosal axons. To investigate this possibility, we filled developing callosal axons in the Syrian hamster with the carbocyanine dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil). Light microscopic analysis showed that, indeed, developing callosal axons branch transiently in the hamster: branching was robust on postnatal day 0 (P0) and P3 (P0 = the first 24 hr after birth), less prominent on P6 and P8, and absent by P11. Immature callosal axons branched before or after crossing the midline and at all rostral-caudal and medial-lateral levels within the corpus callosum. The majority of callosal axon collaterals that were contained within individual 100-micron-thick sections were relatively short (mean = 15.1 microns) but some collaterals extended up to approximately 135 microns from the main axon trunk before passing out of the section in which they were observed. Nearly all of the collaterals emanated from the main axon trunk; higher-order collaterals were rare. Some callosal axon trunks had multiple collaterals. Branching callosal axons originated from multiple cortical areas, including area 17. Electron microscopic observations indicated that the processes designated as axon collaterals by light microscopic criteria would have been included in electron microscopic counts of developing callosal axons. Some callosal axon trunks and branches had ultrastructural features that suggested they were degenerating. In cats, developing callosal axons branch on embryonic day 57 (E57; the first 24 hr after conception = E0) and P0. Thus, it is likely that transient branching of immature callosal axons is a generalized feature of mammalian cortical development and that it contributes to the overproduction of callosal axons, albeit perhaps to varying degrees, in multiple species.     

Agenesis of the corpus callosum in a mother and son

Most reported familial cases of agenesis of the corpus callosum have followed either an autosomal recessive or an X-linked recessive pattern of inheritance. To the best of our knowledge, there is only one previous report of a family showing clear-cut autosomal dominant inheritance. We present the second such family, among whom a mother and her son had moderately severe coordination problems and low-normal intelligence. We suggest that agenesis of the corpus callosum, when transmitted as an autosomal dominant trait, is clinically characterized by a relatively milder phenotype than that occurring when inheritance is either autosomal or X-linked recessive and may be more common than has been thought.     

Evolution of anisotropic diffusion in the developing rat corpus callosum

Changes in the ability of substances to diffuse in the intersticial space of the brain are important factors in the pathophysiology of cerebrovascular diseases. Extracellular space (ECS) volume fraction alpha (alpha = ECS volume/ total tissue volume), tortuosity lambda (lambda 2 = free diffusion coefficient/apparent diffusion coefficient), and nonspecific uptake (k')-three diffusion parameters of brain tissue were studied in cortex and subcortical white matter (WM) of the developing rat during anoxia. Changes were compared with the rise in extracellular potassium concentration ([K+]e), extracellular pH (pHe) shifts, and anoxic depolarization (AD). Diffusion parameters were determined from extracellular concentration-time profiles of tetramethylammonium (TMA+) or tetraethylammonium (TEA+), TMA+, TEA+, K+, and pH changes were measured using ion-selective microelectrodes. In the cortex and WM of animals at 4-12 postnatal days (P4-P12), the volume fraction, alpha, is larger than that of animals at > or = P21. Anoxia evoked by cardiac arrest brought about a typical rise in [K+]e to approximately 60-70 mM, AD of 25-30 mV, decrease in alpha, increase in lambda, and increase in k'. At P4-P6, alpha decreased from approximately 0.43 to 0.05 in cortical layer V and from approximately 0.45 to 0.5 in WM. Tortuosity, lambda, increased in the cortex from 1.50 to 2.12 and in WM from approximately 1.48 to 2.08. At P10-P12 and at P21-P23, when alpha in normoxic rats is lower than at P4-P6 by approximately 25 and 50%, respectively, the final changes in values of alpha and lambda evoked by anoxia were not significantly different from those in P4-P6. However, the younger the animal, the longer the time course of the changes. On P4-P6 final changes in alpha, lambda and k' in cortex and WM were reached after 37 +/- 3 min and 54 +/- 2 min; on P10-P12, after 24 +/- 2 and 27 +/- 3 min; and on P21-P23 at 15 +/- 1 and 17 +/- 3 min, respectively (mean +/- SE, n = 6). The time course of the changes was longer in WM than in gray matter (GM), particularly during the first postnatal week, i.e., in the period during which WM is largely unmyelinated. Changes in diffusion parameters occurred in three phases. The first slow and second fast changes occurred simultaneously with the rise in [K+]e and AD. Peaks in [K+]e and AD were reached simultaneously; the younger the animal, the longer the time course of the changes. The third phase outlasted the rise in [K+]e and AD by 10-15 min and correlated with the acid shift in pHe. Linear regression analysis revealed a positive correlation between the normoxic size of the ECS volume and the time course of the changes. Slower changes in ECS volume fraction and tortuosity in nervous tissue during development can contribute to slower impairment of signal transmission, e.g., due to lower accumulation of ions and neuroactive substances released from cells and their better diffusion from the hypoxic area in uncompacted ECS.     

Bimanual motor coordination in agenesis of the corpus callosum.

The nature and extent of deficiencies in bimanual motor coordination in individuals with agenesis of the corpus callosum (ACC) was studied using the computerized Bimanual Coordination Test (cBCT). Compared with previous bimanual tasks, the cBCT is more specifically reliant on interhemispheric interactions of lateralized motor control, allows more precise measurement, and permits examination of performance over a wider range of bimanual challenges. The cBCT performance of 13 high-functioning individuals with complete ACC was compared to 21 age- and IQ-matched controls. The groups did not differ in unimanual response speed. On trials involving angled paths that require bimanual coordination, the ACC group performed significantly slower and less accurately across all angles. The largest group differences in speed occurred on trials where the hands must respond symmetrically, while mirror-image (vs. parallel) responding produced the greatest deficits in accuracy. These data confirm previous findings of deficits in bimanual coordination in callosal absence, but using significantly improved measurement technology. Deficits in bimanual coordination in ACC are present across different demands for interhand interactions in the speed and direction of movement. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Atrophy of the corpus callosum in Alzheimer's disease versus healthy aging

OBJECTIVE: To investigate the specificity of atrophic changes in the corpus callosum (CC) compared with the cerebellum and pons in patients with Alzheimer Disease (AD), healthy elderly subjects (HE), and a sample of prospectively studied subjects who have developed cognitive decline or "incipient dementia" (ID). DESIGN: Cross-sectional comparison by age using quantitative MRI. SETTING: Ambulatory research unit. PARTICIPANTS: Sixty HE subjects (mean age 78.2 years; range 66-95), 20 ID subjects (mean age 88.1 years; range 78-98) and 39 AD subjects (mean age 72.2 years; range 52-91) were enrolled in longitudinal studies of healthy aging or AD. The population was selected for optimal health; all were examined to exclude medical, neurological and psychiatric illness. MEASUREMENTS: Brain atrophy by quantitative MRI. RESULTS: AD subjects had smaller CC than HE or ID subjects, who did not differ from each other. All three sectors of the CC were smaller in AD than in HE or ID subjects. The cross sectional area of the cerebellum and pons did not differ between groups. HE and ID subjects showed a significant decline in CC size with age. No age-related decline was found for AD subjects. The regional atrophy of the CC in AD subjects was significantly related to cognitive function but not to disease duration. CONCLUSIONS: Atrophy of the CC differentiates HE and ID from AD subjects and tracks the cognitive decline of this disease. In addition, optimally healthy subjects show an age-related decline in callosum size. The atrophy is specific to the CC, a cortical projection system, and does not occur in cerebellum or pons.     

Prenatal MR diagnosis of a thick corpus callosum

Fetal sonography revealed cerebral, facial, and genitourinary abnormalities, prompting MR at 33 weeks' gestational age. Cerebral MR confirmed a thickened corpus callosum and showed open sylvian fissures, abnormal gyri in the frontal lobes, and presumed neuronal heterotopias. An abortion was performed at 34 weeks' gestational age, and pathologic findings corresponded well to the MR manifestations.     

Clinical, urodynamic, and histologic effects of urethral intussusception in clinically normal dogs

OBJECTIVE: To evaluate clinical and histologic effects of surgically created urethral intussusception and determine whether it creates a high-pressure zone that resists passive urine flow in clinically normal dogs. ANIMALS: 8 healthy adult sexually intact female dogs. PROCEDURE: Urethral pressure profilometry was used to measure maximal urethral closure pressure (MUCP) and functional profile length (FPL) in dogs sedated with xylazine hydrochloride and atropine before and 2, 4, 7, 14, 28, 60, and 90 days after surgery. Cystourethral leak point pressure (CLPP) and cystourethral leak point volume (CLPV) were determined in anesthetized dogs immediately before and after surgery. Dogs were assigned to 4 groups of 2 dogs each; groups were euthanatized 4, 14, 28, and 90 days later, and representative tissues were examined. RESULTS: Dog 1 developed complete postoperative urethral obstruction. The procedure was altered, and all dogs recovered without complication. Mild inflammation attributable to surgical manipulation, but not ischemic damage or reduction of the intussusception, was evident. Comparison of preoperative MUCP and FPL with postoperative values did not yield significant differences. Immediate postoperative CLPP and CLPV were significantly higher than preoperative values, but were not significantly increased at euthanasia. A distinct but nonsignificant pressure spike was observed in postoperative urethral pressure profiles and persisted in 7 of 8 dogs. CONCLUSIONS: Urethral intussusception does not have deleterious effects when performed as described. Urodynamic data do not support the premise that urethral intussusception will create a high-pressure zone in the urethra that will resist passive urine flow long term in clinically normal dogs.     

Sex and handedness effects on corpus callosum morphology in chimpanzees (Pan troglodytes).

Findings suggest that in humans, sex and hand preference may be associated with the size of the corpus callosum (CC). The authors measured CC morphology from MRIs in 67 chimpanzees (Pan troglodytes) to see whether similar effects were present in this species. Hand preference was assessed by performance on 4 tasks, and chimpanzees were classified as left-handed, right-handed, or ambidextrous. In a subsequent analysis, the chimpanzees were reclassified into 2 groups: right-handed and left-handed. The results revealed no sex difference in CC area, but significant effects of hand preference were found for several CC regions (rostrum body, anterior midbody, posterior midbody, isthmus, and splenium) and for overall CC size, with left-handed chimpanzees exhibiting significantly smaller CC measurements than right-handed chimpanzees. The results indicate that lateralized hand use in chimpanzees, as in humans, is associated with variation in CC size. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interocular transfer in guinea pigs following section of the corpus callosum.

Measured interocular transfer of an active-avoidance habit, based on discriminations of shape discriminanda or of slant discriminanda, in 27 ocularly pigmented male American Brown guinea pigs, after section of the corpus callosum or a sham operation. Mastery of discriminations was not retarded by the section, but interocular transfer, while nearly perfect in sham-operated Ss, was significantly inferior in callosally sectioned Ss. (19 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long latency evoked potentials in a case of corpus callosum agenesia

Following monoaural stimulation, long latency auditory evoked potentials (LLAEPs) recorded from contralateral temporal areas have a shorter latency and larger amplitude than those recorded from the ipsilateral temporal areas. This observation agrees with the operational model drawn up in 1967 by Kimura, which assumes that only anatomically prevailing crossed auditory pathways are active during dichotic hearing, while direct pathways are inhibited. The inputs may then be conveyed to the contralateral cortex, from where they finally reach the ipsilateral temporal areas by means of interhemispheric commissures. It is this mechanism which may underline the right ear advantage for verbal stimuli and the left ear advantage for melodies observed when administering dichotic listening tasks. With the aim of verifying this hypothesis, we recorded temporal LLAEPs in a 21 year-old woman suffering from complex partial seizures, whose CT scan and MRI showed corpus callosum agenesia. Our data support the hypothesis that ipsilateral pathways are greatly inhibited by the contralateral pathways, and therefore auditory stimuli can be supposed to reach the contralateral auditory cortex from where they are transferred through the corpus callosum to the ipsilateral auditory cortex.     

Increased axon number in the anterior commissure of mice lacking a corpus callosum

Relatively few behavioral deficits are apparent in subjects with hereditary absence of the corpus callosum (CC). The anterior commissure (AC) has been suggested to provide an extracallosal route for the transfer of interhemispheric information in subjects with this congenital defect. Anterior commissure size, axon number, axon diameter, and neuronal distribution were compared between normal mice and those with complete CC absence. No difference in midsagittal AC area was found between normals and acallosals, nor were differences found in the numbers or diameters of myelinated axons. However, axon counts indicated an 17% increase or about 70,000 more unmyelinated axons in the AC of acallosal mice, and the mean diameter of unmyelinated axons was slightly less than in normal mice (0.24 vs 0.26 microm). This decrease in axon diameter enabled more axons to pass through the AC without increasing its midsagittal area. The topographical distribution of neurons sending axons through the AC, assessed with lipophilic dyes, was qualitatively similar for almost all the known regions of origin of the anterior commissure in normal and acallosal mice. There was a pronounced deficit of AC cells in the anterior piriform cortex of BALB/c mice, but this occurred whether or not the mouse suffered absent CC. Although the increase in AC axon number is far smaller than the number of CC axons that fail to reach the opposite hemisphere, the higher number of axons present in the AC of acallosal mice may contribute to the functional compensation for the loss of the CC.     

Topography of fibers in the human corpus callosum mediating interhemispheric inhibition between the motor cortices

We have previously shown, using human T-cell lymphocytotrophic virus-I (HTLV-I)-infected cell lines, that soluble interleukin-6 receptor (sIL-6R) is generated through an alternative splicing mechanism. In this study, we examined human sera for the presence of alternatively spliced soluble IL-6R (AS-sIL-6R). We produced a monoclonal antibody (mAb) recognizing the unique sequence of AS-sIL-6R peptide, generated by an altered reading frame. We also made recombinant AS-sIL-6R protein in Spodoptera frugiperda-9 (Sf-9) cells carrying baculovirus, which encoded altered sIL-6R or conventional IL-6R cDNA. mAbs specifically recognized AS-sIL-6R, but not conventional IL-6R, as demonstrated by Western blot analyses, fluorescence-activated cell sorter, immunofluorescence analyses and enzyme-linked immunosorbent assay (ELISA). We adapted an ELISA system and used it for detection of altered sIL-6R in sera from 23 healthy persons, 12 patients with adult T-cell leukaemia (ATL) and 13 patients with HTLV-I-associated myelopathy (HAM). Serum levels of AS-sIL-6R were 6.4 or 6.1 times greater in ATL (28.7+/-20.4 ng/ml, P<0.0001) and in HAM patients (27.5+/-12.1 ng/ml, P<0.0001) than in healthy individuals (4.5+/-2.1 ng/ml). High levels of AS-sIL-6R were also observed in plasma from rheumatoid arthritis patients and in persons with elevated levels of alanine aminotransferase (ALT), antinuclear antibody (ANA), or alpha-fetoprotein (AFP). However, in human immunodeficiency virus-1 (HIV-1), hepatitis B virus (HBV) or hepatitis C virus (HCV)-infected individuals, AS-sIL-6R levels were not elevated. In this study, we confirmed that AS-sIL-6R is indeed present in human sera. These observations suggest that alternative splicing of IL-6R mRNA is of consequence in ATL, HAM and in some autoimmune diseases. The HTLV-I-infected T cells appeared to play an important role in AS-sIL-6R production.