Poor school and cognitive functioning with silent cerebral infarcts and sickle cell disease

The authors evaluated education attainment and neuropsychological deficits in children with sickle cell disease (SCD) and silent cerebral infarcts. Children with silent infarcts had twice the rate of school difficulties as children without infarcts. Eighty percent of silent infarct cases had clinically significant cognitive deficits, whereas 35% had deficits in academic skills. Children with silent cerebral infarcts show high rates of poor educational attainment, cognitive deficits, and frontal lobe injury. Poor school performance in SCD is one indicator of silent infarcts.     

Silent infarcts in children with sickle cell anemia and abnormal cerebral artery velocity.

BACKGROUND: A substantial minority of neurologically normal children with sickle cell disease have lesions consistent with cerebral infarction as seen on magnetic resonance imaging (MRI). OBJECTIVES: To determine if transfusion therapy affects the rate at which silent infarcts develop and to evaluate the contribution of MRI of the brain to stroke prediction by transcranial Doppler (TCD) ultrasonography. STUDY DESIGN: Children with elevated TCD ultrasonographic velocity were randomized to receive long-term transfusion therapy or standard care. Magnetic resonance imaging of the brain was obtained at randomization, annually, and with clinical neurologic events. The risk for new silent lesions and/or stroke was compared for each treatment arm. RESULTS: Among the 37% of subjects with silent infarcts, those receiving standard care were significantly more likely to develop new silent lesions or stroke than were those who received transfusion therapy. For subjects receiving standard care, those with lesions at baseline were significantly more likely to develop stroke or new silent lesions than those whose MRI studies showed no abnormality. CONCLUSIONS: Transfusion therapy lowers the risk for new silent infarct or stroke for children having both abnormal TCD ultrasonographic velocity and silent infarct. However, those with both abnormalities who are not provided transfusion therapy are at higher risk for developing a new silent infarct or stroke than are those whose initial MRI showed no abnormality. The finding of a silent infarct reinforces the need for TCD ultrasonographic screening and consideration of transfusion therapy if the abnormalities are seen. Similarly, elevated TCD ultrasonographic velocity warrants MRI of the brain because children with both abnormalities seem to be at increased risk for developing new silent infarct or stroke.     

Meta-analysis of corpus callosum size in schizophrenia.

Studies with MRI have shown differences in corpus callosum size between schizophrenic patients and controls. Most have found that the corpus callosum is smaller in schizophrenic patients, but in only a minority was this finding statistically significant, perhaps due to small sample sizes. Therefore a meta-analysis of 11 published studies of corpus callosum morphology in schizophrenia was conducted to ascertain whether there was a significant difference in corpus callosum size between schizophrenic patients and normal controls. These studies combined comprised 313 patients and 281 controls. Measures of corpus callosum midsagittal area, length, and corpus callosum area:brain area ratio were used in the meta-analysis. There was overall a statistically significant reduction in corpus callosum area in schizophrenic patients compared with controls (P < 0.02). Differences between patients and controls in measures of corpus callosum: brain area and corpus callosum length were not statistically significant. Age and corpus callosum area were related in both patients and controls. The influences on the corpus callosum of overall alterations of brain size, sex, handedness, and psychiatric illness in general remains to be determined.     

Differential rearing affects corpus callosum size and cognitive function of rhesus monkeys

This study investigated the effects of different rearing conditions on neural and cognitive development of male rhesus monkeys (Macaca mulatta). Infants raised individually in a nursery from 2 to 12 months of age (NURSERY, n=9) were compared to age-matched infants raised in a semi-naturalistic, social environment (CONTROL, n=11). Various brain regions were measured by MRI. Although overall brain volumes did not differ between NURSERY and CONTROL animals, corpus callosum (CC) size, measured in mid-sagittal sections, was significantly decreased in the NURSERY group. Group differences were most evident in the posterior aspects of the corpus callosum and appeared to result from changes in the number of cross-hemispheric projections rather than from a decrease in cortical gray matter volume. The decrease in corpus callosum size in the NURSERY animals persisted after 6 months of social housing in a peer-group. Rearing group differences were not found in other structures analyzed, including the hippocampus, cerebellum and anterior commissure. In cognitive testing, NURSERY animals had more difficulty acquiring the delayed non-matching to sample (DNMS) task, but showed no deficits in subsequent memory performance when a 2 or 10 min delay was imposed. The NURSERY infant monkeys were also impaired in object, but not in spatial, reversal learning, although there were no differences in a simple object discrimination task. The cognitive deficits exhibited by the NURSERY animals were significantly correlated with the alterations found in the CC. In summary, rearing environment was associated with sustained differences in cross-hemispheric projections, white matter volume and cognitive performance.     

Corpus callosum size in children with spastic cerebral palsy: relationship to clinical outcome

This study examines corpus callosum pathology in children with spastic cerebral palsy aged 7 to 15 years and to investigates the relation between corpus callosum areas and clinical picture. Magnetic resonance images of 46 patients were reviewed prospectively. Twenty-two patients with cerebral palsy were age and gender matched with the control patients. The cerebral palsy group had a significantly smaller mean corpus callosum surface area than did the control group. The cerebral palsy group also had a significantly smaller mean internal skull surface area measurement than did the control group. The corpus callosum/internal skull surface area ratio was also smaller for those with cerebral palsy. Wechsler Intelligence Scale Verbal IQ scores were associated with the surface area of the corpus callosum in cerebral palsy patients. A significant relationship between corpus callosum surface area and IQ scores in children with cerebral palsy was found. A positive correlation between internal skull surface area and IQ scores in children with cerebral palsy was noted. A significant correlation between Apgar score and corpus callosum surface area in the cerebral palsy group was found. A negative correlation between corpus callosum surface area and the Gross Motor Function Classification System in patients with cerebral palsy was noted.     

Structural changes of the corpus callosum in mild cognitive impairment and Alzheimer's disease

BACKGROUND: Although previous studies demonstrate significant atrophy of the corpus callosum (CC) in patients with Alzheimer's disease (AD), CC alterations in mild cognitive impairment have not been investigated yet. METHODS: 21 subjects with mild cognitive impairment, 10 with AD and 21 healthy controls were investigated using magnetic resonance imaging. In the mid-sagittal slice the CC was traced manually. Additionally, voxel-based morphometry (VBM) was performed. RESULTS: The CC was significantly smaller in patients with AD compared to healthy controls in both manual tracing and VBM. The atrophy was prominent in rostral parts of the CC. In subjects with mild cognitive impairment, the two rostral CC segments were smaller compared to controls when manually traced. In contrast, VBM revealed no significant difference between subjects with mild cognitive impairment and controls. CONCLUSION: Manual tracing was more sensitive in detecting discrete structural CC changes than VBM. Alterations of the CC in mild cognitive impairment rank in between normal aging and AD, supporting the hypothesis that mild cognitive impairment most often represents a preclinical stage of AD.     

The corpus callosum in nonhuman primates. Determinants of size

The relationships between brain weight, sex and various callosal parameters including cross-sectional surface area and maximum splenial width in nonhuman primates are delineated. Overall, brain weight is a good predictor of quantitative aspects of the corpus callosum. However, both pongids and strepsirhines evince sex differences on certain callosal measures. No sex differences were found for either the ceboids or cercopithecoids. We speculate that one aspect of primate brain evolution has involved the modulation of interhemispheric connectivity along the lines of sex.     

Transcranial Doppler correlation with cerebral angiography in sickle cell disease.

BACKGROUND AND PURPOSE: Cerebral infarction in sickle cell disease is associated with arterial narrowing or occlusions of intracranial arteries. Primary stroke prevention would be feasible if a noninvasive screening test could be developed to detect intracranial disease in patients before symptoms develop. METHODS: To determine the sensitivity and specificity of transcranial Doppler in detecting significant (greater than or equal to 50% lumen diameter reduction) intracranial arterial lesions, we compared transcranial Doppler and cerebral angiography in a primarily young, symptomatic group of 33 patients (18 males and 15 females) with sickle cell disease. RESULTS: From a total of 34 examinations, transcranial Doppler detected significant abnormalities in 26 of 29 (sensitivity 90%, specificity 100%). Five were normal by both techniques. The transorbital examination detected abnormalities in two patients whose studies were otherwise unremarkable. CONCLUSIONS: Transcranial Doppler is sensitive and specific for the detection of arterial vasculopathy of sickle cell disease. Screening should include a transorbital examination of the distal internal carotid artery as well as examination using the transtemporal approach.     

Large cerebral vessel disease in sickle cell anaemia.

An 18 year old male with documented sickle cell disease was admitted to the hospital for the final time in coma. Cerebral angiography revealed multiple stenotic lesions of the large cerebral vessels. The pathology of this large vessel involvement is demonstrated and the potential contribution of large as opposed to small cerebral vessel disease in the neurological manifestations of sickle cell anaemia is discussed.     

Lesion burden and cognitive morbidity in children with sickle cell disease

The effect of increased tissue injury in children with sickle cell disease and silent cerebral infarcts is not known. We determined the relationship between the extent of injury and IQ scores in children with silent cerebral infarcts. Participants were 27 children with sickle cell disease who had received magnetic resonance imaging (MRI). Children were divided into three groups: group 1, small lesion volume (n = 9, < 6.8 cm3); group 2, large lesion volume (n = 9; > 6.8 cm3); and group 3, no cerebral infarcts (n = 9). The Wechsler Full-Scale IQ was significantly lower for group 2 (mean = 76.1) when compared with group 1 (mean = 87.7) or group 3 (mean = 89.9). In children with silent cerebral infarcts, large tissue loss is associated with lower Wechsler Full-Scale IQ and small tissue loss is associated with no apparent change in IQ compared with children with no cerebral infarcts. The progressive accumulation of silent infarcts may lead to poorer intellectual functioning.     

Corpus callosum structural characteristics in very preterm children and adolescents: Developmental trajectory and relationship to cognitive functioning

Previous studies suggest that structural alteration of the corpus callosum, i.e., the largest white matter commissural pathway, occurs after a preterm birth in the neonatal period and lasts across development. The present study aims to unravel corpus callosum structural characteristics across childhood and adolescence in very preterm (VPT) individuals, and their associations with general intellectual, executive and socio-emotional functioning. Neuropsychological assessments, T1-weighted and multi-shell diffusion MRI were collected in 79 VPT and 46 full term controls aged 6–14 years. Volumetric, diffusion tensor and neurite orientation dispersion and density imaging (NODDI) measures were extracted on 7 callosal portions using TractSeg. A multivariate data-driven approach (partial least squares correlation) and a cohort-based age normative modelling approach were used to explore associations between callosal characteristics and neuropsychological outcomes. The VPT and a full-term control groups showed similar trends of white-matter maturation over time, i.e., increase FA and reduced ODI, in all callosal segments, that was associated with increase in general intellectual functioning. However, using a cohort-based age-related normative modelling, findings show atypical pattern of callosal development in the VPT group, with reduced callosal maturation over time that was associated with poorer general intellectual and working memory functioning, as well as with lower gestational age.     

高功能孤独障碍患儿胼胝体和额叶纤维的对照研究

目的 对照分析高功能孤独障碍患儿与正常儿童胼胝体及额叶纤维结构的差异.方法 选取18例高功能孤独障碍患儿(病例组)和16名年龄、性别、智商、身高、体质量与之相匹配的正常儿童(对照组),进行头部弥散张量成像(diffusion tensor imaging,DTI)扫描.使用DTIStudio软件进行图像处理,计算并比较2组胼胝体各亚区及左、右额叶的各向异性分数(fractional anisotropy,FA)、表面扩散分数(apparent diffusion coefficient,ADC)、纤维数目及平均长度的差异.结果 与对照组相比,病例组胼胝体前1/3部的纤维数目显著下降[(839±193)条vs(630±203)条;F=9.419,P=0.004];纤维的平均长度、FA值的差异无统计学意义(P＞0.05);病例组胼胝体前1/3部纤维的ADC值显著增大[(0.88±8.56)×10-3 mm2/s vs(0.94±6.98)×10-3 mm2/s;F=5.739,P=0.023].左、右大脑额叶长、短纤维的FA值均较对照组显著减小(F=10.109,P=0.003;F=9.186,P=0.005),长程纤维的ADC值显著增加(F=6.154,P=0.019;F=6.814,P=0.014).结论 高功能孤独障碍儿童胼胝体前1/3部纤维减少最明显,额叶与其他脑区之间呈现低连通性.     

Alzheimer's disease with and without cerebral infarcts

OBJECTIVE: To compare the clinical and pathological features of Alzheimer's disease (AD) patients with and without associated cerebral infarcts (CI). METHODS: The consecutive records of 57 prospectively studied demented patients fulfilling the CERAD criteria for the pathological diagnosis of AD were reviewed. Cases with cortical Lewy bodies were excluded. CI were found in 22 cases (39%) (AD+CI group): large infarcts (5), lacunes (13) and/or hippocampal sclerosis (4), and were absent in 35 cases (AD group). Microscopic infarcts, cribiform change, amyloid angiopathy, and white matter rarefaction were not considered in this classification, but were quantified. Cortical atrophy, neurofibrillary tangle and senile plaque (diffuse and neuritic) load were also measured. Pathological evaluation was independent of clinical information. Clinical and pathological data were compared between both groups. RESULTS: AD+CI cases were significantly older, more commonly female, less educated, and more often had blue collar occupations, sleep disturbances, frontal release signs, and EEG spikes than AD cases. Other differences found (acute/subacute onset, behavioral disturbances, and leukoaraiosis on CT scan) disappeared after controlling for age. The frequency of known vascular risk factors and focal motor and sensory signs did not differ between the groups, which showed remarkable clinical similarity overall. The only significant differences on pathological exam were hippocampal microinfarcts and white matter lesions, although there was a trend for lower neurodegenerative lesion load in the AD+CI group. The ischemic lesions were located in temporal lobe in 50% of AD+CI patients; these cases had a significantly lower neocortical neurodegenerative lesion load than those with CI in other sites. CONCLUSIONS: The presence of CI in AD increases significantly with age, but has scarce influence on the clinical features, and cannot be predicted from common vascular risk factors. In spite of a trend, there are no major differences in neurodegenerative lesion load between AD and AD+CI groups, except when CI are located in the temporal lobe (including hippocampus), suggesting that this location may be important in the physiopathology of mixed vascular and AD dementia.     

Relationship between corpus callosum atrophy and cerebral metabolic asymmetries in multiple sclerosis.

Corpus callosum (CC) atrophy by magnetic resonance imaging (MRI) is a common finding in multiple sclerosis (MS). In order to examine the relationship between CC atrophy and cortical brain metabolism, we compared the cerebral metabolic rates for glucose (CMRglc), measured by positron emission tomography (PET), of 8 MS patients with evidence of CC atrophy on midsagittal MRI, 8 MS patients without CC atrophy and 10 healthy controls. Results showed no significant differences in supratentorial CMRglc absolute values between the three groups, although a slight metabolic reduction was observed in both MS groups compared with normal controls. By contrast, only patients with CC atrophy showed greater directional metabolic asymmetry than normals, the left frontal, temporal and parietal association cortices being significantly lower than the right. Predominant left hemispheric metabolic reductions were not accompanied by a corresponding left-sided predominance in the extent of MRI-detected demyelinating lesions. Therefore our data suggest that CC atrophy interfers more with left than with right metabolic function.     

Parallel interhemispheric processing in aging and alcoholism: relation to corpus callosum size

We tested parallel processing of visual information using the redundant targets effect (RTE) in 12 alcoholics and 13 matched controls. The paradigm was a simple reaction time (RT) task with targets presented in the same (uncrossed), opposite (crossed), or both (redundant) visual-fields. In older alcoholics (>50 years) the RT gain invoked by redundant targets did not exceed probability measures, suggesting compromised interhemispheric processing of parallel information in this subgroup compared with controls or younger alcoholics. The difference between crossed and uncrossed reaction times (CUD), an index of interhemispheric transfer time (ITT), was greater in older than younger subjects. Moreover, the CUD was negatively correlated with the corpus callosum (CC) total area and body in controls, supporting the concept of a structure-function relationship of interhemispheric transfer. This relationship was not found in alcoholics, although the midsagittal area of the CC, genu, and body but not intracranial volume (ICV), was significantly smaller in alcoholics than controls. These results suggest that chronic alcohol abuse together with advancing age exert subtle disruption on parallel interhemispheric processing reliant on callosal connections.     

Marchiafava-Bignami disease: diffusion-weighted MRI in corpus callosum and cortical lesions

The clinical diagnosis of Marchiafava-Bignami disease (MBD) can be difficult. Acute demyelination of the corpus callosum is characteristic of the disease. The authors report the use of MR diffusion-weighted imaging (DWI) in six cases of acute MBD. They show that apparent diffusion coefficient restriction of the corpus callosum and cortical lesions were associated with a higher mortality rate and more severe cognitive sequelae.     

Diffuse cerebral hypomyelination with cerebellar atrophy and hypoplasia of the corpus callosum

Three unrelated Japanese patients who presented with ataxia and mild mental retardation were examined in this study. Early development was normal in two patients and slightly delayed in one. All could walk independently, but were unstable due to cerebellar ataxia. They had mild intellectual retardation and displayed slow, progressive, and mild clinical courses. Two patients lost the ability to walk at 12 and 25 years of age. Brain MRI of the three patients revealed diffuse cerebral hypomyelination, moderate cerebellar cortical atrophy, and hypoplasia of the corpus callosum, which were seen in other diffuse hypomyelination syndrome. No known abnormalities were found in biochemical and genetic studies. Auditory brainstem responses and nerve conduction studies were normal. A definite diagnosis could not be made because of the lack of hypodontia, hypogonadism, cataracts, or basal ganglia atrophy. Based on common MRI findings and the relatively mild clinical courses, we believe that these patients may have another subset form of diffuse hypomyelination syndrome involving the cerebral white matter and cerebellum.