Degeneration Of Corpus Callosum Research Articles

Multivariate white matter differences links to cognition in individuals with family history of Alzheimer’s disease and APOE4 genetic risk

AbstractBackgroundGrowing evidence suggests Alzheimer’s disease (AD) develops from a complex cascade of events that vary between individuals. Multivariate approaches have the potential to capture the complexity and heterogeneity of pathologies underlying AD in a more holistic manner compared to univariate approaches.MethodThe MRI data of 105 older adults with a family history of AD from the PREVENT‐AD dataset were analysed. Forty six of these individuals had the APOE4‐3 genotype (greater risk of developing AD), while 59 subjects had the APOE3‐3 genotype (normal risk). Diffusion‐weighted imaging and multi‐echo magnetization transfer, proton density and T1‐weighted data were used to compute several WM metrics (Fig1 b‐c). We computed the voxel‐wise Mahalanobis distance (D2) in WM between APOE4‐3 individuals and a reference group (APOE3‐3) (Fig1). D2 is a multivariate measure that combines several MRI metrics, accounting for their covariance, and yielding a score indicative of the degree of abnormality at each WM voxel (Fig2). Associations between WM D2 and cognitive performance were then investigated (Fig3). Independent component analysis (ICA) was performed on spatial dimensions and linear regression analyses were conducted between D2 in ICA components and scores on items of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We then extracted the contribution of each MRI feature to D2 in the regions where significant associations were found.ResultA significant negative association (R = ‐0.36, p = 0.014) was found between D2 in a component corresponding to the splenium of the corpus callosum (CC) and scores on RBANS‐immediate memory (Fig3), indicating a link between a greater degree of WM abnormality and poorer performance. Proton density (MPM_PD) and longitudinal relaxation rate (MPM_R1), potentially indicative of WM loss, contributed most to D2 in this region.ConclusionOur findings suggest that microstructural alterations in the posterior part of the CC may play a role in memory deficit in older adults who are at greater risk of developing AD. This is in line with other studies that showed a link between CC degeneration and memory impairments in early AD stages.1 1. Qiu et al. (2016). Inter‐hemispheric dysconnectivity in AD and aMCI. Sci.Rep.

Multivariate white matter differences links to cognition in individuals with family history of Alzheimer’s disease and APOE4 genetic risk

AbstractBackgroundGrowing evidence suggests Alzheimer’s disease (AD) develops from a complex cascade of events that vary between individuals. Multivariate approaches have the potential to capture the complexity and heterogeneity of pathologies underlying AD in a more holistic manner compared to univariate approaches.MethodThe MRI data of 105 older adults with a family history of AD from the PREVENT‐AD dataset were analysed. Forty six of these individuals had the APOE4‐3 genotype (greater risk of developing AD), while 59 subjects had the APOE3‐3 genotype (normal risk). Diffusion‐weighted imaging and multi‐echo magnetization transfer, proton density and T1‐weighted data were used to compute several WM metrics (Fig1 b‐c). We computed the voxel‐wise Mahalanobis distance (D2) in WM between APOE4‐3 individuals and a reference group (APOE3‐3) (Fig1). D2 is a multivariate measure that combines several MRI metrics, accounting for their covariance, and yielding a score indicative of the degree of abnormality at each WM voxel (Fig2). Associations between WM D2 and cognitive performance were then investigated (Fig3). Independent component analysis (ICA) was performed on spatial dimensions and linear regression analyses were conducted between D2 in ICA components and scores on items of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We then extracted the contribution of each MRI feature to D2 in the regions where significant associations were found.ResultA significant negative association (R = ‐0.36, p = 0.014) was found between D2 in a component corresponding to the splenium of the corpus callosum (CC) and scores on RBANS‐immediate memory (Fig3), indicating a link between a greater degree of WM abnormality and poorer performance. Proton density (MPM_PD) and longitudinal relaxation rate (MPM_R1), potentially indicative of WM loss, contributed most to D2 in this region.ConclusionOur findings suggest that microstructural alterations in the posterior part of the CC may play a role in memory deficit in older adults who are at greater risk of developing AD. This is in line with other studies that showed a link between CC degeneration and memory impairments in early AD stages.1 1. Qiu et al. (2016). Inter‐hemispheric dysconnectivity in AD and aMCI. Sci.Rep.

Altered Callosal Morphology and Connectivity in Asymptomatic Carotid Stenosis.

Carotid stenosis, even in the clinically asymptomatic stage, causes cognitive impairment, silent lesions, and hemispheric changes. The corpus callosum (CC) is crucial for hemispheric cortical integration and specialization. To examine if CC morphology and connectivity relate to cognitive decline and lesion burden in asymptomatic carotid stenosis (ACS). Retrospective, cross-sectional. 33 patients with unilaterally severe (70%) ACS and 28 demographically and comorbidity-matched controls. A publicly available healthy adult lifespan (ages between 18 and 80; n = 483) MRI dataset was also included. A 3.0 T; T1 MPRAGE and diffusion weighted gradient echo-planar imaging sequences. Structural MRI and multidomain cognitive data were obtained. Midsagittal CC area, circularity, thickness, integrity, and probabilistic tractography were calculated and correlated with cognitive tests and white matter hyperintensity. Fractional anisotropy, mean diffusivity (MD), and radial diffusivity were determined from DTI. Independent two-sample t-tests, χ2 tests, Mann-Whitney U, locally weighted scatterplot smoothing (LOWESS) curve fit, and Pearson correlation. A P value < 0.05 was considered statistically significant. Patients with ACS demonstrated significant reductions in callosal area, circularity, and thickness compared to controls. The callosal atrophy was significantly correlated with white matter hyperintensity size (r = -0.629, P < 0.001). Voxel-wise analysis of diffusion measures in the volumetric CC showed that ACS patients exhibited significantly lower fractional anisotropy and higher MD and radial diffusivity in the genu and splenium of the CC than controls. Further lifespan trajectory analysis showed that although the midsagittal callosal area, circularity, and thickness exhibited age-related decreases, the values in the ACS patients were significantly lower in all age groups. Midsagittal callosal atrophy and connectivity reflect the load of silent lesions and the severity of cognitive decline, respectively, suggesting that CC degeneration has potential to serve as an early marker in ACS. 3 TECHNICAL EFFICACY STAGE: 2.

Neurological chikungunya virus infection induces corpus callosum degeneration associated with resident immune cell activation and peripheral immune cell infiltration

Abstract Chikungunya virus (CHIKV) is an Old World alphavirus that typically induces arthralgia and rash. However, CHIKV is also capable of infecting the central nervous system (CNS), resulting in encephalitis, myelitis, and peripheral neuropathy. Patients who survive acute infection typically have long lasting neurological effects. To date, an immunocompetent small animal model that recapitulates CHIKV CNS disease has not been established. To develop a mouse model of CNS CHIKV infection, we intracranially inoculated 4–6 week old C57BL/6J mice with 1 of 3 clinical CHIKV isolates: Asian lineage strains SM2013 and AF15561, and ECSA lineage strain SL15649. CHIKV CNS disease is most commonly reported in regions where ECSA lineage strains circulate; in agreement with observations in humans, SL15649 was associated with more severe neurological disease, while SM2013 induced minimal to no disease, and AF15561 induced an intermediate clinical phenotype. At 7dpi when mice demonstrated signs of CNS disease but infectious virus was cleared from the brain, significant corpus callosum degeneration was observed in mice infected with SL15649, and to a lesser extent AF15561. Recruited CD4+ T cells and B cells were significantly elevated in the corpus callosum of mice infected with SL15649 compared to mice infected with SM2013. SL1549 infected mice also had significant micro- and astrogliosis in this area. At 3dpi, prior to neurological signs, the corpus callosum in SL1549 infected mice did not show significant degeneration but did have an influx of peripheral immune cells and increased gliosis. These results suggest that the CNS manifestations of CHIKV are associated with corpus callosum degeneration driven by both peripheral and CNS resident immune cells. Supported by the following grants: K01 OD026529 (VKB) T32AI0075151 (ACK) AAI Careers in Immunology Fellowship (VKB, ACK) UNC SOM Junior Investigator Development Award (VKB) UNC Department of Pathology and Laboratory Medicine (VKB)

Increased functional homotopy of the prefrontal cortex is associated with corpus callosum degeneration and working memory decline

Functional homotopy reflects the link between spontaneous activity in a voxel and its counterpart in the opposite hemisphere. Alterations in homotopic functional connectivity (FC) are seen in normal aging, with highest and lowest homotopy being present in sensory-motor and higher-order regions, respectively. Homotopic FC relates to underlying structural connections, but its neurobiological underpinnings remain unclear. The genu of the corpus callosum joins symmetrical parts of the prefrontal cortex (PFC) and is susceptible to age-related degeneration, suggesting that PFC homotopic connectivity is linked to changes in white-matter integrity. We investigated homotopic connectivity changes and whether these were associated with white-matter integrity in 338 individuals. In addition, we examined whether PFC homotopic FC was related to changes in the genu over 10 years and working memory over 5 years. There were increases and decreases in functional homotopy, with the former being prevalent in subcortical and frontal regions. Increased PFC homotopic FC was partially driven by structural degeneration and negatively associated with working memory, suggesting that it reflects detrimental age-related changes.

Aberrant inter-hemispheric coordination characterizes the progression of minimal hepatic encephalopathy in patients with HBV-related cirrhosis.

Patients with hepatitis B virus (HBV)-related cirrhosis (HBV-RC) and minimal hepatic encephalopathy (MHE) exhibit alterations in homotopic inter-hemispheric functional connectivity (FC) and corpus callosum (CC) degeneration. However, the progression of inter-hemispheric dysconnectivity in cirrhotic patients from no MHE (NMHE) to MHE and its association with the progression of diseased-related cognitive impairment remain uncharacterized. We hypothesized that inter-hemispheric dysconnectivity exists in NMHE patients and further deteriorates at the MHE stage, which is associated with performance measured by psychometric hepatic encephalopathy scores (PHES) that can characterize cirrhotic patients with NMHE and MHE. Using inter-hemispheric homotopic FC and CC (and its subfields) volumetric measurements in 31 patients with HBV-RC (17 with NMHE and 14 with MHE) and 37 healthy controls, we verified that MHE patients had significant attenuated inter-hemispheric homotopic FC in the bilateral cuneus, post-central gyrus, inferior parietal lobule, and superior temporal gyms, as well as CC degeneration in total CC, CC2, CC3, and CC4 (each comparison had a corrected P < 0.05). In contrast, NMHE patients had relatively less severe inter-hemispheric homotopic FC and no CC degeneration. In addition, the degeneration of the CC and inter-hemispheric homotopic functional disconnections correlated with poor PHES performances in all cirrhotic patients (NMHE and MHE). Furthermore, impairment of inter-hemispheric homotopic FC partially mediated the association between CC degeneration and worse PHES performance. Notably, a combination of inter-hemispheric homotopic FC and CC volumes had higher discriminative values according to the area under the curve (AUC) score (AUC=0.908, P < 0.001) to classify patients into MHE or NMHE groups when compared with either alone. Our findings shed light on the progression of inter-hemispheric dysconnectivity in relation to the progression of disease-related cognitive impairment in patients with HBV-RC.

The Effects of P-Hydroxycinnamic Acid in Ameliorating Spatial Learning and Flexibility Deficits in Rats with Chronic Cerebral Hypoperfusion

Cerebral blood reduction resulting in oligemic energy failure and metabolic insufficiency initiates gradual neurodegeneration and cognitive impairments. We investigated the neuroprotective effects of p-hydroxycinnamic acid (pHCA) on neurodegeneration in association with cognitive impairments in rats with chronic cerebral hypoperfusion (CCH). Forty male Sprague-Dawley rats were randomly divided into 4 groups: Sham-veh, 2VO-veh, 2VO-pHCA50 and 2VO-pHCA100. We used modified 2-vessel occlusion (2VO) to induce CCH, and the 2 latter groups were given 50 mg/kg and 100 mg/kg of pHCA after the 2VO operation, respectively, which continued for 3 weeks. The behavioral tests consisted of anxiety-like behavior tested in an elevated plus maze (EPM) and hippocampal-dependent spatial learning and flexibility tested in a Morris water maze (MWM). Brain oxidative status, infarction, vulnerable hippocampus and corpus callosum (CC) white matter degeneration were evaluated. The results showed that modified 2VO induced reversible short-term anxiolytic-like behavior in the EPM (p 0.05) with significance infarction, vulnerable hippocampal CA1, CA3, DG and CC degeneration (p < 0.05). These were found along with significant spatial learning and flexibility deficits (p < 0.05). Additionally, 100 mg/kg of pHCA significantly ameliorated the spatial learning and flexibility deficits, which coincided with the significant decreases of infarction volume, CA1, CA3 and CC degeneration (p < 0.05). We conclude that pHCA’s improving effects on spatial learning and flexibility deficits are neuroprotective against oligemic energy failure-induced vulnerable neuronal and white matter degeneration in CCH rats.

Conventional Structural Magnetic Resonance Imaging in Differentiating Chronic Disorders of Consciousness.

Differential diagnosis of unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) is one of the most challenging problems for specialists who deal with chronic disorders of consciousness (DOC). The aim of the current study was to develop a conventional MRI-based scale and to evaluate its role in distinguishing chronic disorders of consciousness (Disorders of Consciousness MRI-based Distinguishing Scale, DOC-MRIDS). Data were acquired from 30 patients with clinically diagnosed chronic disorders of consciousness. All patients underwent conventional MRI using a Siemens Verio 3.0 T scanner, which included T2 and T1 sequences for patient assessment. Diffuse cortical atrophy, ventricular enlargement, sulcal widening, leukoaraiosis, brainstem and/or thalamus degeneration, corpus callosum degeneration, and corpus callosum lesions were assessed according to DOC-MRIDS criteria, with a total score calculation. The ROC-analysis showed that a reasonable threshold DOC-MRIDS total score was 5.5, that is, patients with DOC-MRIDS total score of 6 and above were classified as UWS and 5 and below as MCS, with sensitivity of 82.4% and specificity of 92.3%. The novel structural MRI-based scale for the assessment of typical brain lesions in patients with chronic DOC is relatively easy to apply, and provides good specificity and sensitivity values for discrimination between UWS and MCS.

Abnormal corpus callosum induced by diabetes impairs sensorimotor connectivity in patients after acute stroke.

To test the hypothesis that abnormal corpus callosum (CC) induced by diabetes may impair inter-hemispheric sensorimotor functional connectivity (FC) that is associated with poor clinical outcome after stroke. Forty-five patients with acute ischaemic stroke in the middle cerebral artery territory and 14 normal controls participated in the study. CC was divided into five subregions on three-dimensional T1-weighted image. The microstructural integrity of each subregion of CC was analysed by DTI and the inter-hemispheric FCs in primary motor cortex (M1-M1 FC) and primary sensory cortex (S1-S1 FC) were examined by resting-state functional magnetic resonance imaging. Diabetic patients (n = 26) had significantly lower fractional anisotropy (FA) in the isthmus of CC (CCisthmus) when compared with non-diabetic patients (n = 19) and normal controls (p < 0.0001). In addition, diabetic patients had the lowest M1-M1 FC (p = 0.015) and S1-S1 FC (p = 0.001). In diabetic patients, reduced FA of CCisthmus correlated with decreased M1-M1 FC (r = 0.549, p = 0.004) and S1-S1 FC (r = 0.507, p = 0.008). Decreased M1-M1 FC was independently associated with poor outcome after stroke in patients with diabetes (odds ratio = 0.448, p = 0.017). CC degeneration induced by diabetes impairs sensorimotor connectivity and dysfunction of motor connectivity can contribute to poor recovery after stroke in patients with diabetes. • Abnormal isthmus of corpus callosum in stroke patients with diabetes. • Abnormal isthmus of corpus callosum correlated with decreased inter-hemispheric sensorimotor connectivity. • Decreased motor connectivity correlated with poor stroke outcome in diabetic patients.

Inter-hemispheric functional dysconnectivity mediates the association of corpus callosum degeneration with memory impairment in AD and amnestic MCI.

Evidences suggested that both corpus callosum (CC) degeneration and alternations of homotopic inter-hemispheric functional connectivity (FC) are present in Alzheimer’s disease (AD). However, the associations between region-specific CC degeneration and homotopic inter-hemispheric FC and their relationships with memory deficits in AD remain uncharacterized. We hypothesized that selective CC degeneration is associated with memory impairment in AD and amnestic mild cognitive impairment (aMCI), which is mediated by homotopic inter-hemispheric functional dysconnectivity. Using structural magnetic resonance imaging (MRI) and task-free functional MRI, we assessed the CC volume and inter-hemispheric FC in 66 healthy controls, 41 aMCI and 41 AD. As expected, AD had CC degeneration and attenuated inter-hemispheric homotopic FC. Nevertheless, aMCI had relatively less severe CC degeneration (mainly in mid-anterior, central, and mid-posterior) and no reduction in inter-hemispheric homotopic FC. The degeneration of each CC sub-region was associated with specific inter-hemispheric homotopic functional disconnections in AD and aMCI. More importantly, impairment of inter-hemispheric homotopic FC partially mediated the association between CC (particularly the central and posterior parts) degeneration and memory deficit. Notably, these results remained after controlling for hippocampal volume. Our findings shed light on how CC degeneration and the related inter-hemispheric FC impact memory impairment in early stage of AD.

Callosal degeneration topographically correlated with cognitive function in amnestic mild cognitive impairment and alzheimer's disease dementia

Degeneration of the corpus callosum (CC) is evident in the pathogenesis of Alzheimer's disease (AD). However, the correlation of microstructural damage in the CC on the cognitive performance of patients with amnestic mild cognitive impairment (aMCI) and AD dementia is undetermined. We enrolled 26 normal controls, 24 patients with AD dementia, and 40 single-domain aMCI patients with at least grade 1 hippocampal atrophy and isolated memory impairment. Diffusion tensor imaging (DTI) with fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (DA), and radial diffusivity (DR) were measured. The entire CC was parcellated based on fiber trajectories to specific cortical Brodmann areas using a probabilistic tractography method. The relationship between the DTI measures in the subregions of the CC and cognitive performance was examined. Although the callosal degeneration in the patients with aMCI was less extended than in the patients with AD dementia, degeneration was already exhibited in several subregions of the CC at the aMCI stage. Scores of various neuropsychological tests were correlated to the severity of microstructural changes in the subregional CC connecting to functionally corresponding cortical regions. Our results confirm that CC degeneration is noticeable as early as the aMCI stage of AD and the disconnection of the CC subregional fibers to the corresponding Brodmann areas has an apparent impact on the related cognitive performance.

Corpus callosal atrophy in premanifest and early Huntington's disease.

Volumetric MRI studies have highlighted the pronounced loss of white matter in premanifest and early Huntington's Disease (HD). The current study focussed on the corpus callosum (CC) since it provides interhemispheric connections to vulnerable cortical areas. To investigate cross-sectional and longitudinal group differences in CC volume and hypothesis-driven associations with three cognitive tasks. Baseline and 24-month 3T MRI were analysed from 106 premanifest (PreHD), (59 preHD-A ≥10.8 and 47 preHD-B <10.8 years from predicted onset), 84 early HD (53 Stage 1 (HD1) and 31 Stage 2 (HD2)) and 101 control subjects from the TRACK-HD study, using a semi-automated technique for CC delineation. Between-group differences in volume and 24-month atrophy rates, and correlations with cognitive performance were investigated using regression models, adjusting for potential confounders. PreHD-B, HD1 and HD2 had statistically significantly smaller baseline CC volumes (p < 0.001) and all groups had elevated 24-month atrophy rates compared with controls (p < 0.001). Smaller baseline CC volume was associated with impaired performance in the Circle Tracing Indirect task in early HD (p < 0.05). Positive, non-statistically significant relationships with Stroop Word Reading were shown in both gene-positive groups. There was no evidence of an association with the Trail Making B task. We found reduced CC volume and elevated 24-month atrophy rates, even in individuals far from disease onset. Structural degeneration of interhemispheric connections may contribute to cognitive deficits, such as performance in the Circle Tracing Indirect task in HD. Examination of different image acquisitions may provide more specific information about underlying CC degeneration.

Age-related degeneration of corpus callosum in the 90+ years measured with stereology

The present study is aimed to assess age-related structural changes in corpus callosum with stereology in 21 postmortem human brains without neuropathology, of age 65–75 (Group A, n = 7), 80–85 (Group B, n = 7), and 94–105 (Group C, n = 7) years. Cross-sectional area, fiber number and density decrease in Group B compared with Group A, then remain unchanged in Group C. Mean fiber diameter increases with age. Cross-sectional area shows strong positive correlation to fiber numbers and negative correlation to mean fiber thickness. With age, modest but significant change in fiber size including a decrease in the percentage of 1–2-μm fibers and an increase in 2–3-μm fibers was observed. Fiber density shows a steeper decline with age in the anterior compared with posterior segments. Neurodegeneration is an ongoing process where the anterior corpus callosum is more susceptible to age-related degeneration. Corpus callosum cross-sectional area atrophy is mostly related to decline in fiber number and density rather than demyelination, with preferential disruption of small caliber fibers.

Degeneration of corpus callosum and recovery of motor function after stroke: A multimodal magnetic resonance imaging study

Animal models of stroke demonstrated that white matter ischemia may cause both axonal damage and myelin degradation distant from the core lesion, thereby impacting on behavior and functional outcome after stroke. We here used parameters derived from diffusion magnetic resonance imaging (MRI) to investigate the effect of focal white matter ischemia on functional reorganization within the motor system. Patients (n = 18) suffering from hand motor deficits in the subacute or chronic stage after subcortical stroke and healthy controls (n = 12) were scanned with both diffusion MRI and functional MRI while performing a motor task with the left or right hand. A laterality index was employed on activated voxels to assess functional reorganization across hemispheres. Regression analyses revealed that diffusion MRI parameters of both the ipsilesional corticospinal tract (CST) and corpus callosum (CC) predicted increased activation of the unaffected hemisphere during movements of the stroke-affected hand. Changes in diffusion MRI parameters possibly reflecting axonal damage and/or destruction of myelin sheath correlated with a stronger bilateral recruitment of motor areas and poorer motor performance. Probabilistic fiber tracking analyses revealed that the region in the CC correlating with the fMRI laterality index and motor deficits connected to sensorimotor cortex, supplementary motor area, ventral premotor cortex, superior parietal lobule, and temporoparietal junction. The results suggest that degeneration of transcallosal fibers connecting higher order sensorimotor regions constitute a relevant factor influencing cortical reorganization and motor outcome after subcortical stroke.

The VPAC 2 agonist peptide histidine isoleucine (PHI) up‐regulates glutamate transport in the corpus callosum of a rat model of amyotrophic lateral sclerosis (hSOD1 G93A ) by inhibiting caspase‐3 mediated inactivation of GLT‐1a

Degeneration of corpus callosum appears in patients with amyotrophic lateral sclerosis (ALS) before clinical signs of upper motor neuron death. Considering the ALS-associated impairment of astrocytic glutamate uptake, we have characterized the expression and activity of the glutamate transporter isoforms GLT-1a and GLT-1b in the corpus callosum of transgenic rats expressing a mutated form of the human superoxide dismutase 1 (hSOD1(G93A)). We have also studied the effect of peptide histidine isoleucine (PHI), a vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating polypeptide (PACAP) receptor 2 (VPAC(2)) agonist on glutamate transporters both in vivo and in callosal astrocytes. Before the onset of motor symptoms, the expression of both transporter isoforms was correlated with a constitutive activity of caspase-3. This enzyme participates in the down-regulation of GLT-1 in ALS, and here we demonstrated its involvement in the selective degradation of GLT-1a in the white matter. A single stereotactic injection of PHI into the corpus callosum of symptomatic rats decreased caspase-3 activity and promoted GLT-1a expression and uptake activity. Together, with evidence for a reduced expression of prepro-VIP/PHI mRNA in the corpus callosum of transgenic animals, these data shed light on the modulatory role of the VIP/PHI system on the glutamatergic transmission in ALS.

Relationship between Microstructural Degeneration of the Corpus Callosum, White Matter Hyperintensities, and Motor Function in Cognitively Intact Elderly

Age-related changes in cerebral white matter, such as decreased corpus callosum (CC) volume and the presence of periventricular white matter hyperintensities (PVWMH) on fluid attenuated inversion recovery (FLAIR) MRI sequences have been demonstrated in nondemented elderly and are associated with motor impairment. Diffusion tensor imaging (DTI) can potentially detect microstructural white matter changes prior to macrostructural volume change. Examination of the relationship of microstructual CC degeneration detected by DTI, PVWMH's and motor function in cognitively intact elderly may suggest a structural-functional connection to this pathology. 14 cognitive intact (CDR = 0, mean MMSE 29.5) elderly men and women (mean age 80.2, range 70 - 92) underwent 3T MRI and detailed neurological evaluation, including fine motor and balance testing. WMH volumes were obtained with FLAIR sequences and were adjusted for intracranial volume. CC microstructural integrity was assessed using fractional anisotrophy (FA) from DTI (TR = 9500 ms; TE = 95 ms; slice thickness 2.0 mm; 20 non-collinear directions). For each subject, a 24 mm2 region of interest was placed in the CC genu (figure) . Relationships between WMHs, CC integrity, and motor function were examined using multivariate analyses adjusted for age. Greater age was associated with decreased CC genu FA (R2 = 0.41, p = 0.01) and total CC volume (R2 = 0.37, p = 0.02). Neither total nor anterior CC volume was associated with motor test performance. %PVWMH volume was associated with slower finger tapping (R2 = 0.23, p = 0.08), but was not associated with one leg standing (OLS). After adjusting for age and %PVWMH, decreased CC genu FA was associated with slower finger tapping (p = 0.02). After adjusting for age, decreased CC genu FA was associated with OLS with eyes open (p = 0.03 left; p = 0.02 right), and OLS with eyes closed (p = 0.07). Advanced age is associated with microstructural degeneration of the anterior corpus callous that disrupts fine motor skills and balance function in cognitively intact elderly, independent of WMH's or CC atrophy. Identification of risk factors to prevent such white matter change is needed to preserve motor abilities in our elderly population

Callosal dysfunction in amyotrophic lateral sclerosis correlates with diffusion tensor imaging of the central motor system

We investigated the frequency and functional relevance of corpus callosum degeneration in amyotrophic lateral sclerosis (ALS). A total of 22 ALS patients and 29 healthy controls performed the newly developed Contralateral Co-Movement Test as indicator of callosal dysfunction. Diffusion tensor imaging was applied to determine fractional anisotropy values in the callosal area containing the crossing motor fibers and in the pyramidal tracts in 13 subjects of each group. ALS patients had more than twice the amount of co-movements as compared to healthy subjects. Contralateral co-movements correlated with fractional anisotropy values of the corpus callosum motor region as did ALS Functional Rating Scale as measure of disease progression. In both groups, contralateral co-movements correlated with the central motor index (ratio of the mean of fractional anisotropy values of both pyramidal tracts and corpus callosum motor region). Neuropsychological test results failed to show correlations with functional or morphological parameters. Combining Contralateral Co-Movement Test and diffusion tensor imaging in ALS revealed the close relation between functional and morphological impairment in the degenerating central motor-neuronal network. The Contralateral Co-Movement Test delivers simple means of symptom quantification, independent of ALS Functional Rating Scale, for future neuroprotective trials.

Age-related degeneration of corpus callosum measured with diffusion tensor imaging

The corpus callosum is the major commissure connecting the cerebral hemispheres, and there is evidence of its change with aging. The sub-regions of the corpus callosum (genu, rostral body, anterior midbody, posterior midbody, isthmus, splenium) respectively comprise fibers connecting heteromodal- and unimodal-associated cortical regions, and it is known that abnormalities of the corpus callosum are correlated with abnormalities in cognition and behavior. Yet, little is known about changes in the tissue characteristics of its sub-regions. We assessed age-related changes in fractional anisotropy and mean diffusivity in the sub-regions of the corpus callosum using diffusion tensor imaging. We studied 42 healthy right-handed individuals aged 21–73 years. There were no significant interactions of sex × region. Age has significant negative correlation with fractional anisotropy in the genu ( P < 0.001), rostral body ( P < 0.001), and isthmus ( P = 0.005). Fractional anisotropy of the anterior midbody was correlated negatively with age at a trend level ( P = 0.022). Age was significantly positively correlated with mean diffusivity in the genu ( P = 0.001), rostral body ( P = 0.002), anterior midbody ( P = 0.001), and isthmus ( P = 0.001). Age-related changes were detected in the sub-regions where their projection areas are thought to be vulnerable to normal aging. This suggested that fractional anisotropy and mean diffusivity values of the corpus callosum sub-regions could serve as markers of disturbance across the respective projection areas.

MR imaging of white matter lesions in uncomplicated chronic alcoholism.

Chronic alcoholics may have CNS lesions, such as microvasculitis or glial, neural, and myelin degeneration, as documented in postmortem studies on subjects who had Wernicke encephalopathy, corpus callosum degeneration, or central pontine myelinolysis. One may also expect the presence of early white matter disease in patients who do not have neurologic complications of alcoholism. Thirty-five chronic alcoholics (Diagnostic and Statistical Manual III criteria) and 35 normal control subjects were studied by means of magnetic resonance (MR) imaging. Subjects greater than 60 years old, or those with CNS involvement, or clinically evident systemic disorders were excluded. Of the remaining asymptomatic alcoholics, MR detected multiple round hyperintense areas in the white matter of 14 patients, in addition to aspecific corticosubcortical and cerebellar atrophies. None of the normal control subjects showed such a finding. These results suggest an early involvement of the brain in asymptomatic alcoholic patients.

Autopsy Findings in the Prader-Willi Syndrome

Autopsy findings in two cases of Prader-Willi syndrome were described. Case 1. was a 4–3/12 year-old boy who had hypotonia in the neonatal period, hypogonadism, mental retardation and obesity. Autopsy revealed edema, congestion and focal bleeding in the lung, cardiac hypertrophy, localized degeneration of corpus callosum, nesidioblastosis, fatty liver and absence of testicular tissue. Case 2. was a3–11/12 year-old boy who had hypotonia in the neonatal period, hypogonadism, mental retardation, obesity and recurrent respiratory tract infections. Autopsy revealed multiple thrombosis, pulmonary changes including edema, congestion, focal bleeding and infarcts, cardiac hypertrophy, fatty liver and absence of testicular tissue. These findings were thought to be summarized in the following three categories; 1) terminal changes characterized by pulmonary edema and congestion and cardiomegaly probably due to respiratory failure, 2) aquired changes due to metabolic abnormalities in this syndrome including fatty liver, nesidioblastosis and focal degeneration of the central nervous system; and 3) congenital abnormalities characterizing hypogonadism. (Acta Paediatr Jpn 23(3):289–293 1981)