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Acute infarct of the corpus callosum: appearance on diffusion-weighted MR imaging and MR spectroscopy.

Few reports of corpus callosum infarction are published in the radiologic literature. We present a case of an atypical infarction of the corpus callosum and adjacent gyri involving both anterior cerebral artery territories. Standard magnetic resonance (MR) imaging was performed including diffusion weighted imaging. In addition, perfusion-weighted imaging and MR spectroscopy were employed to further characterize the patient's corpus callosal lesion. On MR imaging and spectroscopic examination, the lesion demonstrated T2 hyper-intensity, restricted diffusion, and the metabolite lactate. While the MR imaging appearance of this bilateral infarction has some characteristics that mimic tumor, employment of the full range of MR techniques can obviate the need for biopsy in acute infarcts of the corpus callosum.

Acute Disease↗

Multislice T1 relaxation time measurements in the brain using IR-EPI: reproducibility, normal values, and histogram analysis in patients with multiple sclerosis.

PURPOSE: To perform T(1) measurements using inversion recovery (IR) echoplanar imaging (EPI) to evaluate reproducibility, normal values, and T(1) histogram analysis as a measure of disease progression in multiple sclerosis (MS) patients. MATERIALS AND METHODS: Multislice IR-EPI was performed in 10 controls and 36 MS patients. Region-of-interest (ROI) and T(1) histogram analysis were performed on T(1) maps and compared to hypointense T(1) lesions and brain atrophy in MS patients. RESULTS: Coefficient of variation (COV) varied from 1.6% to 4.9%. Callosal normal (appearing) white matter (N(A)WM) showed the lowest and cortical gray matter the highest T(1) values. T(1) histogram analysis in controls showed a sharp WM peak centered on a T(1) value of 729 msec (range = 679-765) with extension into a shoulder of higher T(1) values. In MS patients, a shift toward higher T(1) values (mean = 788 msec, range = 700-957) with a lower relative peak amplitude was present, predominantly resulting from T(1) prolongation in NAWM. T(1) histogram parameters strongly related to hypointense T(1) lesion volume and brain atrophy in MS patients. CONCLUSIONS: IR-EPI provides a reproducible method to obtain T(1) values in the brain. Regional variation in T(1) values is present in N(A)WM of volunteers and MS patients. Since T(1) histogram parameters reflect changes in NAWM and correlate with conventional measures of disease burden in MS patients, T(1) histogram analysis may provide a global measure of disease progression in MS.

Adult↗

Long-term survival of mouse corpus callosum grafts in neonatal rat recipients, and the effect of host sensitization.

Previous studies have suggested that the incidence of spontaneous rejection among immunogenetically mismatched neural transplants in neonatal recipients varies significantly depending on the cellular composition of the graft material. For example, neuron-rich grafts of embryonic mouse retina generally survive for extended periods without showing signs of rejection after implantation into neonatal rats, whereas cortical xenografts, which contain abundant glial and endothelial cells as well as neurons, typically undergo rejection 4-6 weeks after implantation. To determine whether the presence of donor glia is responsible for this high incidence of spontaneous rejection, we examined the fate of a non-neuronal graft material composed predominantly of xenogeneic glial cells (post-natal day 3, PD3, CD-1 mouse corpus callosum) implanted into the mesencephalon of PD1 Sprague-Dawley rats. The distribution and survival of donor astrocytes were assessed using a monoclonal antibody specific for a mouse astrocyte surface antigen, M2. Thirteen of 16 animals sacrificed within 2 months of implantation had detectable transplants. In these animals, M2-positive cells frequently migrated well away from body of the graft, clustering in large numbers in several characteristic regions of the host brain. Unlike cortical grafts of similar age, the vast majority (93%) of callosal transplants showed no histological signs of rejection or major histocompatibility complex antigen expression in and around the transplant-derived cells. As previously noted in the neonatal retinal transplant paradigm, however, well-integrated 1-month-old corpus callosum grafts could be induced to reject by appropriate sensitization of the host immune system, implying that the host was not immunologically tolerant to the foreign neural graft. With longer survival times in unsensitized hosts, a progressively smaller percentage of animals had detectable donor astrocytes (5 of 10 animals at 3 months postimplantation and 4 of 16 animals at 4 months); in those 9 animals with surviving grafts, only small numbers of M2-positive cells were seen within the graft bed and surrounding host brain. However, only 2 of the 26 "long-term" animals showed evidence of graft rejection. These results indicate that mouse astrocytes show characteristic patterns of migration into the host brain when implanted into neonatal rats; however, these xenogeneic cells have a limited duration of survival. The infrequency with which even subtle signs of spontaneous rejection were detected in animals that had received corpus callosum xenografts suggests that an immune-mediated process is unlikely to be responsible for the time-dependent elimination of the donor astrocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Measurements of transcallosally mediated cortical inhibition for differentiating parkinsonian syndromes.

Clinicopathologic evidence suggests differential involvement of cortex and corpus callosum (CC) in various disorders presenting with a parkinsonian syndrome. We tested the hypothesis of whether neurophysiologic and morphometric assessments of CC as surrogate parameters of cortical involvement could be helpful in differential diagnosis of parkinsonian disorders. The integrity of CC was assessed neurophysiologically by measuring the ipsilateral silent period (iSP) evoked by transcranial magnetic stimulation (TMS) in a total of 25 patients with idiopathic parkinsonian syndromes (IPS), corticobasal ganglionic degeneration (CBD), progressive supranuclear palsy (PSP), or multiple system atrophy (MSA). Additionally, morphometric analyses of magnetic resonance imaging (MRI) measurements of CC was carried out in all patients. iSP was abnormal in all 5 CBD and all 5 PSP patients, whereas it was intact in all 10 IPS patients and all 5 MSA patients. Among various MRI parameters of CC, testing between different groups revealed a significant difference only for measurements of the middle part of the truncus. CBD and PSP patients exhibited a significant atrophy as compared with control subjects. These data suggest impairment of callosal integrity in patients with CBD and PSP. iSP measurements may be a useful clinical neurophysiologic test in differential diagnosis of patients with parkinsonian syndromes.

Aged↗

Alien limb syndrome and moya-moya disease.

We present the case of a 29-year-old woman with an alien limb and callosal disconnection syndrome who was diagnosed with moya-moya disease. We discuss the potential mechanisms responsible for the alien limb syndrome.

Adult↗

Differences of the ipsilateral silent period in small hand muscles.

The ipsilateral silent period (iSP) is thought to depend on activity transmitted by the corpus callosum but ipsilateral corticospinal pathways may also contribute. Because the presence of ipsilateral corticospinal pathways differs between small hand muscles, we compared the iSP in the first dorsal interosseous (FDI) and abductor pollicis brevis (APB) muscles. The iSP was elicited in 20 healthy subjects by focal transcranial magnetic stimulation of one primary motor cortex during maximal voluntary contraction of the ipsilateral target muscle. The iSP duration was significantly longer in the FDI than APB because of an irregularly occurring second phase of inhibition in the FDI that was absent in the APB. Although the first phase of inhibition is transmitted by the corpus callosum, we provide evidence that the second phase is mediated through ipsilateral corticospinal pathways. Therefore, for specific assessment of callosal conduction, the iSP should be measured in the APB rather than FDI.

Adolescent↗

Aspects of early postnatal development of cortical neurons that proceed independently of normally present extrinsic influences.

To examine the contribution of local versus extrinsic influences on postnatal development of cortical neurons, we compared the maturation of deep (infragranular) layer neurons in isolated slices of neocortex grown in organotypic culture to a similar population of neurons developing in vivo. All slice cultures were prepared from sensorimotor cortices of newborn mice (P0) and neurons in these cultures were examined at daily intervals during the first 9 days in vitro (DIV). The maturational state of neurons developing in vivo over this same time period was assessed in acute slices prepared from animals of equivalent postnatal age, P1-P9. Electrophysiological recordings were obtained from neurons in both cultured and acute slices, using Lucifer yellow filled whole-cell recording electrodes, enabling subsequent morphometric analysis of the labeled cells. We report significant changes in both cellular morphology and electrical membrane properties of these deep layer cortical neurons during the first week in culture. Morphological maturation over this time period was characterized by a two- to three-fold increase in cell body size and total process length, and an increase in dendritic complexity. In this same population of cells a three-fold decrease in input resistance and changes in the action potential waveform, including a two-fold decrease in the AP duration, also occur. The degree of morphological and electrophysiological differentiation of individual neurons was highly correlated across developmental ages, suggesting that the maturational state of a cell is reflected in both cellular morphology and intrinsic membrane properties. A remarkably similar pattern of neuronal maturation was observed in neurons in layers V, VI/SP examined in acute slices prepared from animals between P1-P9. Because our culture system preserves many aspects of the local cortical environment while eliminating normal extrinsic influences (including thalamic, brainstem, and callosal connections), our findings argue that this early phase of neuronal differentiation, including the rate and extent of dendritic growth and development of AP waveform, results from instructive and/or permissive local influences, and appears to proceed independently of the many normally present extrinsic factors.

Action Potentials↗

Proteomic analysis of pathogen-responsive proteins from rice leaves induced by rice blast fungus, Magnaporthe grisea.

Proteomic approaches using two-dimensional gel electrophoresis (2-DE) were adopted to identify proteins from rice leaf that are differentially expressed in response to the rice blast fungus, Magnaporthe grisea. Microscopic observation of inoculated leaf with M. grisea revealed that callose deposition and hypersensitive response was clearly visible in incompatible interactions but excessive invading hypha with branches were evident in compatible interactions. Proteins were extracted from leaves 24, 48, and 72 hours after rice blast fungus inoculation. Eight proteins resolved on the 2-DE gels were induced or increased in the inoculated leaf. Matrix-assisted laser desorption/ionization-time of flight analysis of these differentially displayed proteins showed them to be two receptor-like protein kinases (RLK), two beta-1.3-glucanases (Glu1, Glu2), thaumatin-like protein (TLP), peroxidase (POX 22.3), probenazole-inducible protein (PBZ1), and rice pathogenesis-related 10 (OsPR-10). Of these proteins, RLK, TLP, PBZ, and OsPR-10 proteins were induced more in the incompatible interactions than in compatible ones. A phytohormone, jasmonic acid also induced all eight proteins in leaves. To confirm whether the expression profile is equal to the 2-DE data, seven cDNA clones were used as probes in Northern hybridization experiments using total RNA from leaf tissues inoculated with incompatible and compatible rice blast fungal races. The genes encoding POX22.3, Glu1, Glu2, TLP, OsRLK, PBZ1, and OsPR-10 were activated in inoculated leaves, with TLP, OsRLK, PBZ1, and OsPR-10 being expressed earlier and more in incompatible than in compatible interactions. These results suggest that early and high induction of these genes may provide host plants with leading edges to defend themselves. The localization of two rice PR-10 proteins, PBZ1 and OsPR-10, was further examined by immunohistochemical analysis. PBZ1 accumulated highly in mesophyll cells under the attachment site of the appressorium. In contrast, OsPR-10 expression was mainly localized to vascular tissue.

Blotting, Northern↗

Neocortical kindling is associated with opposing alterations in dendritic morphology in neocortical layer V and striatum from neocortical layer III.

Previous research has shown that seizures kindled in the corpus callosum result in a persistent enhancement of the callosal-neocortical evoked response but only a transient reduction in layer III pyramidal cell morphology. To date, there are no reports on the direct effects of repeated seizures on dendritic morphology in layer V, the pyramidal layer thought to mediate the kindling-induced enhanced evoked response. This experiment examined the effect of repeated seizures elicited from the corpus callosum, at the level of the frontal neocortex, on the morphology of sensorimotor frontal (Fr1) and occipital (OC1) neocortical layer V, as well as striatal and neuronal dendrites, in male rats. After 25 days of electrically elicited seizures or handling control, rats were sacrificed either 2 days or 3 weeks following the last seizure and processed for Golgi-Cox staining. Analysis of the impregnated pyramidal cell dendrites indicated a significant increase in the amount of dendritic length and branching in rats 2 days, but a decrease 3 weeks, following the last seizure. There was no effect at the distant occipital site. The differential effect between layer V pyramidal neurons and layer III pyramidal neurons suggests that these areas play different roles in the expression of seizures and the adaptation of the brain to the persistent effect of kindling.

Animals↗

Differential diagnosis in fetuses with absent septum pellucidum.

OBJECTIVE: To elucidate the characteristic morphological features that may help in the prenatal differential diagnosis of absent septum pellucidum as demonstrated by ultrasound. METHODS: Twenty-six fetuses were referred to the fetal neurology clinic due to mild to severe ventriculomegaly and a connection between the lateral ventricles. The following ultrasonographic features were evaluated: place and extent of the ventricular communication, non-cleavage of the hemispheres and deep gray nuclei, callosal anomalies, position of the choroid plexus, and other central nervous system and facial or body anomalies. A flowchart was created in order to facilitate the final diagnosis. RESULTS: The presence of non-cleavage and/or characteristic facial anomalies prompted the diagnosis of holoprosencephaly (HPE) in 14 fetuses, including two fetuses with the middle interhemispheric variant. Ten fetuses were diagnosed as having hydrocephalus based on the lack of the same features and the observation that the communication between the lateral ventricles was at the level of the third ventricle with almost normal anterior and posterior segments. In two fetuses the diagnosis of septo-optic dysplasia vs. isolated agenesis of the cavum septi pellucidi was contemplated. CONCLUSIONS: The use of the proposed flowchart enabled differentiation between hydrocephalus and HPE. The communication between the ventricles in hydrocephalic fetuses may be due to a disruption of the septum pellucidum or to a pathological enlargement of the foramen of Monro. Published by John Wiley & Sons, Ltd.

Diagnosis, Differential↗

Characteristics, associations and outcome of partial agenesis of the corpus callosum in the fetus.

OBJECTIVES: To report, in a population of fetuses diagnosed with partial agenesis of the corpus callosum (PACC), the sonographic characterization, incidence of cerebral, extracerebral and chromosomal anomalies, and outcome. In addition, in some of our cases a comparison was made between findings on ultrasound and fetal magnetic resonance imaging (MRI). METHODS: This was a retrospective study of all cases of PACC seen at two referral centers for prenatal diagnosis of congenital anomalies over a 10-year period. The following variables were assessed: indication for referral, additional cerebral and extracerebral malformations, chromosomal abnormalities, and pregnancy and fetal/neonatal outcome. RESULTS: Among 54 cases of fetal agenesis of the corpus callosum detected in the referral centers during the observation period, PACC was diagnosed at prenatal sonography in 20 cases and confirmed at pre/postnatal MRI and necropsy examinations in 19 cases (35%). These 19 constituted the study group. The diagnosis was made in the sagittal planes and in 12 cases it was made prior to 24 weeks. In most cases the indication for referral was the presence of indirect signs of callosal anomalies, such as colpocephaly. In 10 cases PACC occurred in association with other anomalies and in nine it was isolated. MRI was particularly useful for demonstrating some additional cerebral anomalies such as late sulcation, migrational pathological conditions and heterotopia. Regarding pregnancy outcome, of those diagnosed before 24 weeks which had associated anomalies, all except two were terminated. Of the nine cases with isolated PACC, all were liveborn. Follow-up was available in eight, and two of these (25%) showed evidence of significant developmental delay. In our series the outcome of isolated PACC was not better than that of complete agenesis of the corpus callosum reported in other series. CONCLUSIONS: PACC can be diagnosed reliably and characterized in prenatal life. The sonographic sign present in most cases is colpocephaly. Prenatal MRI can be performed to confirm the diagnosis. It is particularly useful to demonstrate some additional cerebral anomalies such as late sulcation, migrational pathological conditions and heterotopia. The relatively poor survival rate is due to the high rate of terminations and associated major anomalies.

Abnormalities, Multiple↗

Spatial frequency and right hemisphere: an electrophysiological investigation.

The influence of the spatial frequency of visual stimuli on hemispheric asymmetry has been studied with visual evoked potentials (VEP). Nineteen different sinusoidal gratings (19 SF from 1 to 10 cpd) were presented in an ON-OFF mode to five right-handed subjects. The amplitude of the VEPs and the latency of the first positive component (C1) were analyzed. The results show that in the low range of spatial frequencies, the latency and the amplitude of C1 are similar in both hemispheres. At medium to high spatial frequencies, the VEPs on the right hemisphere (RH) present shorter latencies and larger amplitudes than those on the left hemisphere (LH). These results, discussed in relation to the directional differences in the time of callosal interhemispheric transfer, strengthen the idea that the RH is relatively more sensitive than the LH to the spatial component of the visual stimuli.

Brain↗

Individual differences in stroop and local-global processing: a possible role of interhemispheric interaction.

Two experiments are reported examining individual differences in the processing of centrally presented stimuli containing two dimensions of information lateralized to opposite cerebral hemispheres. Left-handers, arising from (a) their lesser degree of functional lateralization and (b) their greater degree of callosal connectivity, were hypothesized to exhibit greater interdimensional (and presumably interhemispheric) interaction. Experiment 1 utilized local-global stimuli, and left-handers were found to be impaired at keeping the two dimensions independent and superior at integrating the two dimensions. Experiment 2 used Stroop stimuli, and left-handers again were impaired at keeping the two dimensions independent (i.e., showed greater Stroop interference). Correlational analyses indicated that the mechanisms of interdimensional integration versus independence are at least partially independent from one another. Results suggest that aspects of interhemispheric interaction can be addressed via the use of nonlateralized input.

Attention↗

Bimanual coordination in chronic schizophrenia.

Anomalies of movement are observed both clinically and experimentally in schizophrenia. While the basal ganglia have been implicated in its pathogenesis, the nature of such involvement is equivocal. The basal ganglia may be involved in bimanual coordination through their input to the supplementary motor area (SMA). While a neglected area of study in schizophrenia, a bimanual movement task may provide a means of assessing the functional integrity of the motor circuit. Twelve patients with chronic schizophrenia and 12 matched control participants performed a bimanual movement task on a set of vertically mounted cranks at different speeds (1 and 2 Hz) and phase relationships. Participants performed in-phase movements (hands separated by 0 degrees ) and out-of-phase movements (hands separated by 180 degrees ) at both speeds with an external cue on or off. All participants performed the in-phase movements well, irrespective of speed or cueing conditions. Patients with schizophrenia were unable to perform the out-of-phase movements, particularly at the faster speed, reverting instead to the in-phase movement. There was no effect of external cueing on any of the movement conditions. These results suggest a specific problem of bimanual coordination indicative of SMA dysfunction per se and/or faulty callosal integration. A disturbance in the ability to switch attention during the out-of-phase task may also be involved.

Adult↗

The relation of planum temporale asymmetry and morphology of the corpus callosum to handedness, gender, and dyslexia: a review of the evidence.

Asymmetry of the planum temporale in relation to handedness, gender, and dyslexia is reviewed. The frequency of rightward asymmetry is rather higher than are estimates of the proportion of right hemisphere speech representation in the general population. Conversely, the frequency of leftward asymmetry is lower than the proportion of the population with left hemisphere speech. Neuro-anatomic asymmetry may relate more to handedness than to language lateralization. There are suggestions that neuroanatomic asymmetry is reduced in females compared to males but the data are inconclusive. Reports concerning handedness and gender differences in callosal structure are conflicting but, as with planum asymmetry, any effect of handedness is as likely to relate to degree as to direction of handedness. It has been reported that the plana are more often symmetrical in size or larger on the right side among dyslexics than controls but this has not always been found. However, greater frequency of atypical (a)symmetry of the planum in dyslexia would be consistent with the absence of a factor which, when present, biases the distribution of planum asymmetry toward the left (and handedness towards the right) as hypothesized by Annett (1985). Studies of the size of the corpus callosum in dyslexia have produced conflicting findings.

Adolescent↗

Interhemispheric effects of simulated lesions in a neural model of single-word reading.

A neural model consisting of paired cerebral hemispheric regions interacting via homotopic callosal connections was trained to generate pronunciations for 50 monosyllabic words. Lateralization of this task occurred readily when different underlying cortical asymmetries were present. Following simulated focal cortical lesions of systematically varied sizes, acute changes in the distribution of cortical activation were found to be most consistent with experimental data when interhemispheric interactions were assumed to be excitatory. During subsequent recovery, the contribution of the unlesioned hemispheric region to performance improvement was a function of both the amount of preexisting lateralization and the side and size of the lesion. These results are discussed in the context of unresolved issues concerning the mechanisms underlying language lateralization, the nature of interhemispheric interactions, and the role of the nondominant hemisphere in recovery from adult aphasia.

Functional Laterality↗

Noninvasively induced degeneration of neocortical pyramidal neurons in vivo: selective targeting by laser activation of retrogradely transported photolytic chromophore.

Interactions among neuronal subpopulations determine brain development and function. The present study illustrates the ability to noninvasively and selectively lesion targeted subpopulations of neurons in a highly specific, temporally defined, and geographically localized manner. This method provides a fundamental advance toward rigorous investigation of the importance of identified neuronal subtypes. Projecting pyramidal neurons of rats and mice were targeted by retrograde transport of latex nanospheres from contralateral motor cortex containing a nontoxic chromophore (chlorin e6) that produces cytotoxic singlet oxygen during photoactivation by deeply penetrating 670-nm light. Geographically defined regions of cortex were exposed to laser illumination at 670 nm to activate singlet oxygen production by the intracellular chromophore, and animals were sacrificed from 4 h to 7 days following laser exposure. Brains were processed to display degenerating neurons using sensitive silver-staining procedures. Selective damage occurred to pyramidal neurons with known callosal projections, solely within layers II/III and V of the illuminated region. Such subpopulation specificity provides models for neural transplantation and analysis of anatomically distributed neuronal networks.

Animals↗

Mature astrocytes transform into transitional radial glia within adult mouse neocortex that supports directed migration of transplanted immature neurons.

Neuronal migration is an essential step in normal mammalian neocortical development, and the expression of defined cellular and molecular signals within the developing cortical microenvironment is likely crucial to this process. Therapy via transplanted or manipulated endogenous precursors for diseases which involve neuronal loss may depend critically on whether newly incorporated cells can actively migrate to repopulate areas of neuronal loss within the adult brain. Previous studies demonstrated that embryonic neurons and multipotent precursors transplanted into the neocortex of adult mice undergoing targeted apoptosis of pyramidal neurons migrate long distances into neuron-deficient regions, undergo directed differentiation, accept afferent synaptic input, and make appropriate long-distance projections. The experiments presented here: (1) use time-lapse digital confocal imaging of neuronal migration in living slice cultures to assess cellular mechanisms utilized by immature neurons during such long distance migration, and (2) identify changes within the host cortical astroglial population that may contribute to this migration. Prelabeled embryonic day 17 mouse neocortical neurons were transplanted into adult mouse primary somatosensory cortex undergoing targeted apoptotic degeneration of callosal projection neurons. Four to 7 days following transplantation, living slice cultures containing the region of transplanted cells were prepared and observed. Sequential time-lapse images were recorded using a video-based digital confocal microscope. Transplanted cells displayed bipolar morphologies characteristic of migrating neuroblasts and moved in a saltatory manner with mean rates of up to 14 microm/h. To investigate whether a permissive glial phenotype may provide a potential substrate for this directed form of neuronal migration, slice cultures were immunostained with the RC2 monoclonal antibody, which identifies radial glia that act as a substrate for neuronal migration during corticogenesis. RC2 does not label mature stellate astrocytes, which express glial fibrillary acidic protein (GFAP). RC2 expression was observed in glial cells closely apposed to migrating donor neurons within the slice cultures. The timing and specificity of RC2 expression was examined immunocytochemically at various times following transplantation. RC2 immunostaining within regions of neuronal degeneration was transient, with peak staining between 3 and 7 days following transplantation. Strongly RC2-immunoreactive cells that did not express GFAP were found within these regions, but not in distant cortical regions or within control brains. RC2-positive cells were identified in recipient transgenic mice which express beta-galactosidase under a glial specific promoter. Coexpression of RC2 and beta-galactosidase identified these cells as host astroglia. These results demonstrate that adult cortical astrocytes retain the capacity to reexpress an earlier developmental phenotype that may partially underlie the observed active migration of transplanted neurons and neural precursors. Further understanding of these processes could allow directed migration of transplanted or endogenous precursors toward therapeutic cellular repopulation and complex circuit reconstruction in neocortex and other CNS regions.

Animals↗