Region-specific corpus callosum atrophy correlates with the regional pattern of cortical glucose metabolism in Alzheimer disease

BACKGROUND: Positron emission tomographic studies of patients with Alzheimer disease (AD) suggest a loss of metabolic functional interactions between different cortical regions. Atrophy of the corpus callosum as the major tract of intracortical connective fibers may reflect decreased cortical functional integration in AD. OBJECTIVES: To investigate whether regional atrophy of the corpus callosum is correlated with regional reductions of cortical glucose metabolism, as shown by positron emission tomography, and whether primary white matter degeneration is a possible cofactor of corpus callosum atrophy in AD. PATIENTS AND METHODS: We measured total and regional cross-sectional areas of the corpus callosum on midsagittal magnetic resonance imaging scans from 12 patients with AD and 15 age-matched control subjects. Regional cerebral metabolic rates for glucose in cortical lobes were measured by positron emission tomography using fludeoxyglucose F 18. White matter hyperintensities were rated in T2-weighted magnetic resonance imaging scans. RESULTS: The total cross-sectional area of corpus callosum was significantly reduced in patients with AD, with the most prominent changes in the rostrum and splenium and relative sparing of the body of the corpus callosum. Frontal and parietal lobe metabolism was correlated with the truncal area of the corpus callosum in AD. The ratios of frontal to parietal and of frontal to occipital metabolism were correlated with the ratio of anterior to posterior corpus callosum area in the group with AD. White matter hyperintensities did not correlate with corpus callosum atrophy in the patients with AD. CONCLUSION: The regional pattern of corpus callosum atrophy correlated with reduced regional glucose metabolism independently of primary white matter degeneration in the patients with AD.     

Regional pattern of increased water diffusivity in hippocampus and corpus callosum in mild cognitive impairment

BACKGROUND: Corpus callosum atrophy possibly indicates neuronal degeneration in association cortex in Alzheimer's disease (AD). Water diffusivity allows detecting physiological changes that probably occur earlier than structural shrinkage in cerebral regions during the development of AD. Objective: To simultaneously investigate the focal volumetric and early structural changes with apparent diffusion coefficient (ADC) of corpus callosum in mild cognitive impairment (MCI), and to explore the regional pattern of ADC increase in hippocampus and corpus callosum. METHODS: Thirteen subjects with MCI and 13 healthy age-matched control subjects were studied. With three-dimensional volumetric spoiled gradient recalled echo MRI images, we measured the volume of hippocampus and corpus callosum. Using MRI-guided diffusion-weighted imaging analysis, we calculated ADCs from hippocampus and corpus callosum. Within the receiver-operation curve (ROC) statistical framework, areas under ROC curves from hippocampal and callosal ADCs were compared in differentiating between MCI and controls. RESULTS: After normalization to intracranial volume, hippocampal, not callosal, volume was significantly reduced in MCI. ADC values were increased in hippocampus and corpus callosum in MCI. The extent of ADC increase was similar between hippocampus and corpus callosum. CONCLUSION: Alterations in water diffusivity may precede corpus callosum atrophy during the development of MCI. Diffusion changes might occur simultaneously in allocortex and neocortex in MCI.     

Quantitative structural changes in white and gray matter 1 year following traumatic brain injury in rats

There is evidence for chronic atrophy after human head trauma, which may be associated with long-term functional deficits. However, using established models of traumatic brain injury (TBI) only limited data are available for clarifying the extent of progressive gray and white matter atrophy. In the present study, male Sprague-Dawley rats underwent moderate (2.01-2.21 atm) parasagittal fluid percussion brain injury ( n=7) or sham ( n=3) surgery and were killed at 1 year post TBI. Semiserial sections were obtained through the neuraxis and double stained with hematoxylin and eosin to demarcate gray matter structures and Luxol fast blue for white matter visualization. Both ipsilateral and contralateral volume measurements were obtained for the following structures: cerebral cortex, hippocampus, dentate gyrus, thalamus, lateral ventricle, external capsule, internal capsule, cerebral peduncle and corpus callosum. Quantitative assessment of ipsilateral gray matter structures from TBI rats revealed significant reductions in cerebral cortical area measurements posterior from the trauma epicenter compared to sham animals. Importantly, several white matter tracts exhibited dramatic atrophy. A comparison of TBI and sham groups demonstrated a significant ( P<0.05) decrease in the external capsule and cerebral peduncle volumes ( P<0.007). In addition, there was a significant volume expansion (533% of control) of the ipsilateral lateral ventricle ( P<0.03). These novel data emphasize the need to clarify the pathophysiology of progressive white matter damage after TBI and the development of therapeutic strategies to target white matter pathology.     

Brain atrophy in relapsing-remitting multiple sclerosis: relationship with 'black holes', disease duration and clinical disability

Recent MRI studies in multiple sclerosis have highlighted the potential role of brain atrophy evaluation as a putative marker of disease progression. In the present study, we evaluated the supratentorial and infratentorial brain volume in patients with relapsing remitting multiple sclerosis (RR MS) and in healthy subjects. Moreover, we determined whether brain volumes of MS patients are associated with different aspects of brain MRI abnormalities and clinical findings. Two-dimensional acquired MRI was performed on 52 relapsing-remitting multiple sclerosis and 30 healthy subjects. The volume of supratentorial and infratentorial structures was measured in selected representative slices. Gd-enhancement, T2 hyperintense, T1 hypointense (i.e. 'black holes') total lesion load, as well as the area of corpus callosum was calculated in the MS group and related to brain volume measures. Correlations between MRI parameters and clinical features were also considered. MS patients had significantly lower supratentorial, infratentorial brain volume and corpus callosum area than healthy subjects (P<0.01). Supratentorial brain volume was significantly related to corpus callosum area (r=0.58; P<0.01) and T1 hypointense lesion load (r=0.48; P<0.01), but not with T2 hyperintense lesion load. Infratentorial/supratentorial ratio was significantly associated with disease duration and EDSS score (r=-0.34; P=0.02 and r=-0.49; P<0.01, respectively). This study documents that brain atrophy is an early MRI finding in RR MS and it is closely related to 'black holes' burden. The use of relative values (infratentorial/supratentorial ratio) may increase the conspicuity of correlation between clinical and MRI findings.     

Atrophy and magnetization transfer ratio of the corpus callosum in patients with Alzheimer's disease]

We compared atrophy and magnetization transfer ratio (MTR) in the corpus callosum in patients with Alzheimer's disease and age-matched normal subjects. Fifteen patients with Alzheimer's disease and fourteen normal subjects received MRI. The corpus callosum was divided into three parts (anterior, middle, and posterior portions) on midsagittal slice, and their areas on T2-weighted reversed images and MTR on magnetization transfer contrast images in each portion were measured. The area and MTR decreased significantly in the posterior portion in patients with Alzheimer's disease. In the anterior portion, MTR decreased significantly, but although the area showed no significant change. In the middle portion, the area and MTR showed no significant change. MTR and the area was correlated in each portion in patients with Alzheimer's disease. The score of Hasegawa dementia scale-revised (HDS-R) and the area of the middle, posterior and total of corpus callosum were significantly related. The score of HDS-R and MTR in the anterior portion of corpus callosum were significantly related. The present study revealed decreases in MTR in the anterior portion of the corpus callosum of patients with Alzheimer's disease although the area showed no significant change, and this change suggests the increase in free water and/or the decrease in bound water in tissues, probably due to demyelination and axonal degeneration.     

Morphologic alterations in the corpus callosum in abuse-related posttraumatic stress disorder: a preliminary study

Magnetic resonance imaging (MRI) studies in children with maltreatment-related posttraumatic stress disorder (PTSD) have demonstrated smaller corpus callosum area, with the greatest magnitude of change in posterior portions of the corpus callosum. The purpose of this study was to measure corpus callosum area in adult female patients with childhood abuse-related PTSD and comparison subjects. MRI was used to measure the midsagittal area of the corpus callosum as well as subregions of the corpus callosum in 9 female subjects with abuse-related PTSD and 9 healthy female subjects. No differences were found in total area of the corpus callosum or in individual subregions, but the subregion/total area ratio was significantly smaller in posterior midbody in PTSD compared with the healthy subjects. These results suggest that relatively smaller areas of the posterior midbody of the corpus callosum are associated with childhood abuse related PTSD in adults; these findings are consistent with findings in children with abuse-related PTSD.     

Comparison of Diffusion Tensor‐Based Tractography and Quantified Brain Atrophy for Analyzing Demyelination and Axonal Loss in MS

We combined diffusion tensor imaging (DTI) measures of the corpus callosum (CC) and the superior longitudinal fascicle (SLF) with calculation of brain atrophy in 53 patients with relapsing—remitting multiple sclerosis (MS) and 15 healthy controls, to analyze their interrelation and their correlation with disease duration and clinical impairment. The lateral ventricle volume in MS patients was increased; the fractional anisotropy in the CC was decreased as was the fiber volume. Perpendicular (in the literature also referred to as radial) diffusivity (ped), which reflects the diffusion perpendicular to the long axis of the axons within the fiber bundle, was increased in the SLF and the posterior CC, but contrary to our predictions, parallel (also called axial) diffusivity (pad) that refers to the amount of diffusion in the direction of the axon was increased, too. Brain atrophy and DTI‐derived parameters were highly intercorrelated and both correlated with disease duration. Discriminant analysis showed that DTI‐derived atrophy measures are superior to brain atrophy measures in classifying patients and controls. In light of our results, animal studies focusing on demyelination and axonal loss are reinterpreted.     

Brain structures in pediatric maltreatment-related posttraumatic stress disorder: a sociodemographically matched study.

BACKGROUND: Previous investigations suggest that maltreated children evidence alterations of chemical mediators of stress and adverse brain development. Previous anatomical magnetic resonance imaging (MRI) brain studies have not controlled for socioeconomic status. METHODS: In this study, 28 psychotropic na?ve children and adolescents with maltreatment-related posttraumatic stress disorder (PTSD) and 66 sociodemographically similar healthy control subjects underwent comprehensive clinical assessments and anatomical MRI brain scans. RESULTS: Compared with control subjects, subjects with PTSD had smaller intracranial, cerebral, and prefrontal cortex, prefrontal cortical white matter, and right temporal lobe volumes and areas of the corpus callosum and its subregions (2, 4, 5, 6, and 7), and larger frontal lobe cerebrospinal fluid (CSF) volumes than control subjects. The total midsagittal area of corpus callosum and middle and posterior regions remained smaller in subjects with PTSD, whereas right, left, and total lateral ventricles and frontal lobe CSF were proportionally larger than in control subjects, after adjustment for cerebral volume. Brain volumes positively correlated with age of onset of PTSD trauma and negatively correlated with duration of abuse. Significant gender x group effect demonstrated greater lateral ventricular volume increases in maltreated male subjects with PTSD than maltreated female subjects with PTSD. No hippocampal differences were seen. CONCLUSIONS: These data provide further evidence to suggest that maltreatment-related PTSD is associated with adverse brain development. These data also suggest that male children may be more vulnerable to these effects.     

The cholinergic system in mild cognitive impairment and Alzheimer's disease: An in vivo MRI and DTI study

Few studies have investigated in vivo changes of the cholinergic basal forebrain in Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI), an at risk stage of AD. Even less is known about alterations of cortical projecting fiber tracts associated with basal forebrain atrophy. In this study, we determined regional atrophy within the basal forebrain in 21 patients with AD and 16 subjects with MCI compared to 20 healthy elderly subjects using deformation‐based morphometry of MRI scans. We assessed effects of basal forebrain atrophy on fiber tracts derived from high‐resolution diffusion tensor imaging (DTI) using tract‐based spatial statistics. We localized significant effects relative to a map of cholinergic nuclei in MRI standard space as determined from a postmortem brain. Patients with AD and MCI subjects showed reduced volumes in basal forebrain areas corresponding to anterior medial and lateral, intermediate and posterior nuclei of the Nucleus basalis of Meynert (NbM) as well as in the diagonal band of Broca nuclei (P < 0.01). Effects in MCI subjects were spatially more restricted than in AD, but occurred at similar locations. The volume of the right antero‐lateral NbM nucleus was correlated with intracortical projecting fiber tract integrity such as the corpus callosum, cingulate, and the superior longitudinal, inferior longitudinal, inferior fronto‐occipital, and uncinate fasciculus (P < 0.05, corrected for multiple comparisons). Our findings suggest that a multimodal MRI‐DTI approach is supportive to determine atrophy of cholinergic nuclei and its effect on intracortical projecting fiber tracts in AD. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Social communication in young children with traumatic brain injury: Relations with corpus callosum morphometry

The purpose of the present investigation was to characterize the relations of specific social communication behaviors, including joint attention, gestures, and verbalization, with surface area of midsagittal corpus callosum (CC) subregions in children who sustained traumatic brain injury (TBI) before 7 years of age. Participants sustained mild (n = 10) or moderate–severe (n = 26) noninflicted TBI. The mean age at injury was 33.6 months; mean age at MRI was 44.4 months. The CC was divided into seven subregions. Relative to young children with mild TBI, those with moderate–severe TBI had smaller surface area of the isthmus. A semi-structured sequence of social interactions between the child and an examiner was videotaped and coded for specific social initiation and response behaviors. Social responses were similar across severity groups. Even though the complexity of their language was similar, children with moderate–severe TBI used more gestures than those with mild TBI to initiate social overtures; this may indicate a developmental lag or deficit as the use of gestural communication typically diminishes after age 2. After controlling for age at scan and for total brain volume, the correlation of social interaction response and initiation scores with the midsagittal surface area of the CC regions was examined. For the total group, responding to a social overture using joint attention was significantly and positively correlated with surface area of all regions, except the rostrum. Initiating joint attention was specifically and negatively correlated with surface area of the anterior midbody. Use of gestures to initiate a social interaction correlated significantly and positively with surface area of the anterior and posterior midbody. Social response and initiation behaviors were selectively related to regional callosal surface areas in young children with TBI. Specific brainbehavior relations indicate early regional specialization of anterior and posterior CC for social communication.     

A.E. Bennett Research Award. Developmental traumatology. Part II: Brain development.

BACKGROUND: Previous investigations suggest that maltreated children with a diagnosis of posttraumatic stress disorder (PTSD) evidence alterations of biological stress systems. Increased levels of catecholaminergic neurotransmitters and steroid hormones during traumatic experiences in childhood could conceivably adversely affect brain development. METHODS: In this study, 44 maltreated children and adolescents with PTSD and 61 matched controls underwent comprehensive psychiatric and neuropsychological assessments and an anatomical magnetic resonance imaging (MRI) brain scan. RESULTS: PTSD subjects had smaller intracranial and cerebral volumes than matched controls. The total midsagittal area of corpus callosum and middle and posterior regions remained smaller; while right, left, and total lateral ventricles were proportionally larger than controls, after adjustment for intracranial volume. Brain volume robustly and positively correlated with age of onset of PTSD trauma and negatively correlated with duration of abuse. Symptoms of intrusive thoughts, avoidance, hyperarousal or dissociation correlated positively with ventricular volume, and negatively with brain volume and total corpus callosum and regional measures. Significant gender by diagnosis effect revealed greater corpus callosum area reduction in maltreated males with PTSD and a trend for greater cerebral volume reduction than maltreated females with PTSD. The predicted decrease in hippocampal volume seen in adult PTSD was not seen in these subjects. CONCLUSIONS: These data suggest that the overwhelming stress of maltreatment experiences in childhood is associated with adverse brain development.     

Vulnerability of the anterior commissure in moderate to severe pediatric traumatic brain injury

In relation to the adult brain, the immature brain might be more vulnerable to damage during and following traumatic brain injury, particularly in white-matter tracts. Given well-established evidence of corpus callosum atrophy, we hypothesized that anterior commissure volume (using quantitative magnetic resonance imaging [MRI]) in this structure would be decreased in children with moderate to severe traumatic brain injury relative to typically developing children. Second, given the purported role of the anterior commissure in interhemispheric axon conveyance between temporal lobes, we hypothesized that temporal lobe white matter, temporal lesion volume, and injury severity (Glasgow Coma Scale score) would be predictive of decreased anterior commissure cross-sectional volume in patients with traumatic brain injury. Finally, we wished to establish the relationship between the anterior commissure and the temporal stem, a major white-matter tract into the temporal lobes, using diffusion tensor imaging fiber-tracking maps for each patient. We also hypothesized that children with traumatic brain injury would exhibit decreased fractional anisotropy in relation to typically developing children in a fiber system including the anterior commissure and the temporal lobes. Decreased anterior commissure cross-sectional volume was observed in patients with traumatic brain injury, and, as predicted, anterior commissure and temporal white-matter volumes were positively related to each other and to higher Glasgow Coma Scale scores. Lesion volume was not independently predictive of anterior commissure volume in the overall model. Diffusion tensor imaging fractional anisotropy values differed between the groups for the temporal stem-anterior commissure system, with the traumatic brain injury group exhibiting decreased fractional anisotropy. The anterior commissure, like the corpus callosum, appears to be highly vulnerable to white-matter degenerative changes resulting from mechanisms such as the direct impact of trauma, progressive axonal injury as tissue in other brain regions atrophies, or myelin degeneration. This is the first systematic examination of anterior commissure atrophy following traumatic brain injury using in vivo quantitative MRI and diffusion tensor imaging fiber tracking in pediatric subjects.     

In vivo imaging of region and cell type specific neocortical neurodegeneration in Alzheimer's disease. Perspectives of MRI derived corpus callosum measurement for mapping disease progression and effects of therapy. Evidence from studies with MRI,EEG and PET

Summary. Neuropathological studies in Alzheimer's disease (AD) indicate specific loss of layer III and V large pyramidal neurons in association cortex. These neurons give rise to long cortico-cortical connections, projecting through the corpus callosum, in an anterior-posterior topology. Based on these findings we hypothesized that regional corpus callosum atrophy may be a potential in vivo marker for neocortical neuronal loss in AD. To evaluate this hypothesis, we developed a method to measure cross-sectional area of the corpus callosum and of five corpus callosum subregions on midsagittal magnetic resonance imaging scans (MRI). In a subsequent series of six experimental studies using MRI, ¹⁸FDG-PET and EEG, we investigated the relation of white matter hyperintensities (WMH) to corpus callosum size and correlated regional pattern of corpus callosum atrophy with regional cortical metabolic decline as well as intracortical coherencies. Mean total corpus callosum area was reduced significantly in AD patients compared to healthy age-matched controls, with the greatest changes in the rostrum and the splenium and relative sparing of the truncus. The regional pattern of corpus callosum atrophy was independent of WMH load and correlated significantly with pattern of regional metabolic decline measured with ¹⁸FDG-PET, the degree of cognitive impairment and regional decline of bilateral intracortical-coherency in EEG in AD patients. We further found that hippocampus atrophy, as a marker of early allocortical degeneration, was more pronounced than total corpus callosum atrophy in mild stages of AD. Regional corpus callosum atrophy in mild disease, however, suggested early neocortical degeneration in AD. In a longitudinal study, AD patients showed significantly greater rates of corpus callosum atrophy than controls. Rates of atrophy correlated with progression of clinical dementia severity in AD. Our results indicate that regional corpus callosum atrophy in AD patients represents the loss of callosal efferent neurons in corresponding regions of the neocortex. As these neurons are a subset of cortico-cortical projecting neurons, region-specific corpus callosum atrophy may serve as a marker of progressive neocortical disconnection in AD. In combination with measurement of hippocampal atrophy, assessment of corpus callosum atrophy over time in individual patients is useful to evaluate effects on brain structure of currently developed drugs, thought to slow or modify AD progression. Received November 26, 2001; accepted January 8, 2002     

Corpus callosum atrophy is associated with mental slowing and executive deficits in subjects with age-related white matter hyperintensities: the LADIS Study

Background

Previous research has indicated that corpus callosum atrophy is associated with global cognitive decline in neurodegenerative diseases, but few studies have investigated specific cognitive functions.

Objective

To investigate the role of regional corpus callosum atrophy in mental speed, attention and executive functions in subjects with age‐related white matter hyperintensities (WMH).

Methods

In the Leukoaraiosis and Disability Study, 567 subjects with age‐related WMH were examined with a detailed neuropsychological assessment and quantitative magnetic resonance imaging. The relationships of the total corpus callosum area and its subregions with cognitive performance were analysed using multiple linear regression, controlling for volume of WMH and other confounding factors.

Results

Atrophy of the total corpus callosum area was associated with poor performance in tests assessing speed of mental processing—namely, trail making A and Stroop test parts I and II. Anterior, but not posterior, corpus callosum atrophy was associated with deficits of attention and executive functions as reflected by the symbol digit modalities and digit cancellation tests, as well as by the subtraction scores in the trail making and Stroop tests. Furthermore, semantic verbal fluency was related to the total corpus callosum area and the isthmus subregion.

Conclusions

Corpus callosum atrophy seems to contribute to cognitive decline independently of age, education, coexisting WMH and stroke. Anterior corpus callosum atrophy is related to the frontal‐lobe‐mediated executive functions and attention, whereas overall corpus callosum atrophy is associated with the slowing of processing speed.Corpus callosum is the largest commissural structure consisting of white matter tracts that connect the cerebral hemispheres according to an anterior–posterior topographical organisation. Recent research using diffusion tensor magnetic resonance imaging (MRI) has augmented earlier postmortem findings of corpus callosum topography and has shown that the anterior parts of corpus callosum (rostrum and genu) connect the orbitofrontal, lateral and medial frontal cortices, whereas the body and splenium connect parietal, temporal and occipital homotopic regions.¹ In neurodegenerative diseases, the corpus callosum area is markedly reduced, indicating marked axonal loss.^2,3,4,5 In Alzheimer''s disease, the severity and pattern of corpus callosum atrophy have been associated with cortical neuronal loss⁶ independently of white matter hyperintensities (WMH).⁷ In vascular dementia and other ischaemic conditions, however, corpus callosum atrophy is correlated with WMH and hence may result from subcortical ischaemic damage.^8,9Earlier studies have shown that corpus callosum atrophy is associated with global cognitive status,^5,6,10 but, to date, few studies have investigated the role of regional corpus callosum atrophy in specific cognitive processes. Based on the topographical organisation of corpus callosum, the integrity of its subregions may reflect distinct cognitive deficits. In particular, anterior corpus callosum atrophy may be related to the frontal‐lobe‐mediated executive deficits. Previous work of the Leukoaraiosis and Disability (LADIS) Study has shown that age‐related WMH are associated with cognitive impairment in elderly subjects without dementia.¹¹ Moreover, in these subjects, the corpus callosum area has been found to be inversely related to motor deficits and global cognitive decline.¹² This study examined the independent contribution of regional corpus callosum atrophy to deficits in mental speed, attention and executive functions in a large sample of elderly subjects with WMH by using quantitative MRI analysis and targeted neuropsychological test methods. The demographic and medical background variables, and coexisting WMH were controlled by using multivariate analysis.     

Callosal morphology and performance on intelligence tests

Abstract

Variation in the size of the human corpus callosum was examined in relation to variation in measured IQ. The midsagittal surface area of the corpus callosum, obtained by magnetic resonance imaging, was measured in 47 patients with epilepsy. Intellectual ability was positively related to a larger posterior callosal area. We suggest that the relationship between the posterior callosal region and measured intelligence is “non-functional” in itself, but rather, may reflect other anatomical-cognitive associations. That is, differences in splenial size may reflect differences in the number of cortical neurons and interconnections between areas of the brain that are important for processing the kind of information measured on intelligence tests. Our conclusions, however, must be tempered by a number of factors: in particular, the nature of our subjects and the relatively small sample size.     

A longitudinal study of brain atrophy in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG).

OBJECTIVE: To determine if progressive brain atrophy could be detected over 1- and 2-year intervals in relapsing MS, based on annual MR studies from the Multiple Sclerosis Collaborative Research Group (MSCRG) trial of interferon beta-1a (Avonex). METHODS: All subjects had mild to moderate disability, with baseline expanded disability status scores ranging from 1.0 to 3.5, and at least two relapses in the 3 years before study entry. Atrophy measures included third and lateral ventricle width, brain width, and corpus callosum area. RESULTS: Significant increases were detected in third ventricle width at year 2 and lateral ventricle width at 1 and 2 years. Significant decreases in corpus callosum area and brain width were also observed at 1 and 2 years. Multiple regression analyses suggested that the number of gadolinium-enhancing lesions at baseline was the single significant contributor to change in third ventricle width. Atrophy over 1 and 2 years as indicated by enlargement of the third and lateral ventricle and shrinkage of the corpus callosum was greater for patients entering the trial with enhancing lesions. Greater disability increments over 1 and 2 years were associated with more severe third ventricle enlargement. CONCLUSION: In patients with relapsing MS and only mild to moderate disability, significant cerebral atrophy is already developing that can be measured over periods of only 1 to 2 years. The course of cerebral atrophy in MS appears to be influenced by prior inflammatory disease activity as indicated by the presence of enhancing lesions. Brain atrophy measures are important markers of MS disease progression because they likely reflect destructive and irreversible pathologic processes.     

Grey and white matter abnormalities in temporal lobe epilepsy with and without mesial temporal sclerosis

Temporal lobe epilepsy with (TLE-mts) and without (TLE-no) mesial temporal sclerosis display different patterns of cortical neuronal loss, suggesting that the distribution of white matter damage may also differ between the sub-groups. The purpose of this study was to examine patterns of white matter damage in TLE-mts and TLE-no and to determine if identified changes are related to neuronal loss at the presumed seizure focus. The 4 T diffusion tensor imaging (DTI) and T1-weighted data were acquired for 22 TLE-mts, 21 TLE-no and 31 healthy controls. Tract-based spatial statistics (TBSS) was used to compare fractional anisotropy (FA) maps and voxel-based morphometry (VBM) was used to identify grey matter (GM) volume atrophy. Correlation analysis was conducted between the FA maps and neuronal loss at the presumed seizure focus. In TLE-mts, reduced FA was identified in the genu, body and splenium of the corpus callosum, bilateral corona radiata, cingulum, external capsule, ipsilateral internal capsule and uncinate fasciculus. In TLE-no, FA decreases were identified in the genu, the body of the corpus callosum and ipsilateral anterior corona radiata. The FA positively correlated with ipsilateral hippocampal volume. Widespread extra-focal GM atrophy was associated with both sub-groups. Despite widespread and extensive GM atrophy displaying different anatomical patterns in both sub-groups, TLE-mts demonstrated more extensive FA abnormalities than TLE-no. The microstructural organization in the corpus callosum was related to hippocampal volume in both patients and healthy subjects demonstrating the association of these distal regions.     

Corpus callosum area in children and adults with autism

Despite repeated findings of abnormal corpus callosum structure in autism, the developmental trajectories of corpus callosum growth in the disorder have not yet been reported. In this study, we examined corpus callosum size from a developmental perspective across a 30-year age range in a large cross-sectional sample of individuals with autism compared to a typically developing sample. Midsagittal corpus callosum area and the 7 Witelson subregions were examined in 68 males with autism (mean age 14.1 years; range 3–36 years) and 47 males with typical development (mean age 15.3 years; range 4–29 years). Controlling for total brain volume, increased variability in total corpus callosum area was found in autism. In autism, increased midsagittal areas were associated with reduced severity of autism behaviors, higher intelligence, and faster speed of processing (p = 0.003, p = 0.011, p = 0.013, respectively). A trend toward group differences in isthmus development was found (p = 0.029, uncorrected). These results suggest that individuals with autism benefit functionally from increased corpus callosum area. Our cross-sectional examination also shows potential maturational abnormalities in autism, a finding that should be examined further with longitudinal datasets.     

Atrophy of the corpus callosum associated with a decrease in cortical benzodiazepine receptor in large cerebral arterial occlusive diseases

OBJECTIVES: It remains controversial whether selective neuronal ischaemic change develops in patients with occlusion of the large cerebral arteries. Previous studies have shown atrophy of the corpus callosum with reduced cortical oxygen metabolism in large cerebral arterial occlusive diseases, which might be indirect evidence of loss of the neurons in cortical layer 3. Recent studies of patients with ischaemic cerebrovascular diseases have demonstrated reduced central benzodiazepine receptor (BZR) binding in the normal appearing cortical areas, which might be more direct evidence of changes of the neurons. Although pathophysiology of the decreased BZR is unclear, a decrease in the cortical BZR binding with neuronal loss would cause atrophy of the corpus callosum. The purpose of this study was to determine whether atrophy of the corpus callosum is associated with a decrease in cortical BZR binding in large cerebral arterial occlusive diseases. METHODS: Seven patients with occlusive diseases of the middle cerebral or internal carotid artery and only minor subcortical infarctions were studied. Single photon emission tomographic images of (123)I labelled iomazenil (IMZ) obtained 180 minutes after injection were analysed for BZR binding. The midsagittal corpus callosum area/skull area ratio (on T1 weighted magnetic resonance images) was compared with the cerebral IMZ uptake/cerebellar IMZ uptake ratio. RESULTS: Compared with 23 age and sex matched control subjects, the patients had significantly decreased callosal area/skull area ratio. The degree of corpus callosum atrophy was significantly and strongly (rho=0.99, p<0.02) correlated with that of the decreases in the mean cerebral cortical IMZ uptake ratio. CONCLUSION: Corpus callosum atrophy may occur in association with a decrease in cortical BZR binding in large cerebral arterial occlusive diseases. Corpus callosum atrophy with decreased cortical BZR binding might reflect cortical neuronal damage in large cerebral arterial occlusive diseases.     

Comparison of the pattern of atrophy of the corpus callosum in frontotemporal dementia, progressive supranuclear palsy, and Alzheimer's disease

OBJECTIVES: The loss of the neurons in layer 3, one of the groups of cortical neurons most vulnerable in various degenerative brain diseases, results in axonal degeneration leading to atrophy of the corpus callosum. Previous studies showed callosal atrophy in three degenerative dementias: frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), and Alzheimer's disease (AD). However, it is unclear whether a characteristic pattern of atrophy is present in each. The objective of this study was to investigate whether the pattern of the callosal atrophy was different among patients with FTD, PSP, or early onset AD. METHODS: Eleven patients with FTD, nine patients with PSP, 16 patients with early onset AD, and 23 normal controls, all age and sex matched, were studied using MRI. The ratios of midsagittal corpus callosum areas to the midline internal skull surface area on T1 weighted images were analyzed. The corpus callosum was divided into quarters: the anterior, middle-anterior, middle-posterior, and posterior portions. RESULTS: Compared with controls, all three patient groups had significantly decreased total callosal/skull area ratio. An analysis of covariance adjusted for the total callosal area/skull area ratio showed that the anterior quarter callosal/skull area ratio in FTD, the middle-anterior quarter area ratio in PSP, and the posterior quarter area ratio in AD were significantly smaller than those in the other three groups. CONCLUSION: Although atrophy of the corpus callosum is not specific to any degenerative dementia, the patterns of the atrophy are different among patients with FTD, PSP, or early onset AD. Differential patterns of callosal atrophy might reflect characteristic patterns of neocortical involvement in each degenerative dementia.