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Long-term neurodevelopmental outcome and brain volume after treatment for hydrops fetalis by in utero intravascular transfusion.

OBJECTIVE: We tested the hypothesis that long-term neurodevelopmental outcomes of successfully treated fetuses with immune hydrops are similar to their unaffected siblings according to a protocol that addresses the underlying pathophysiologic condition. STUDY DESIGN: Sixteen of 18 consecutive hydropic fetuses (89%) who were treated in a dedicated fetal medicine unit between July 1985 and October 1995 survived. The transfusion protocol used a 2-step correction over a 2 to 4 day interval, combined with umbilical venous pressure measurements to avoid over transfusion and bicarbonate administration to assure a posttransfusion UV pH of >7.30. Survivors were evaluated at a mean age of 10 years. Statistical analyses included t-test, Wilcoxon rank-sum test, Fisher's exact test, and Pearson coefficients. RESULTS: Overall, death or major neurologic morbidity occurred in 4 of 18 of the fetuses (22%) who were treated (2/16 of survivors [12.5%]). Among the survivors, the children with immune hydrops had physical, neurologic, and cognitive outcomes statistically similar to their siblings, except for a measure of visual attention. Two of the children (12%) had major neurologic sequelae. Brain volumes were statistically smaller than unrelated control subjects by 8.8%, but these control subjects were not matched for height at testing or gestational age at birth. Both groups had brain volumes within the normal range. CONCLUSION: Intravascular transfusion of fetuses with profoundly anemic immune hydrops results in high survival rates and favorable long-term neuropsychological outcomes.

Blood Transfusion, Intrauterine↗

Loss of brain volume in endogenous Cushing's syndrome and its reversibility after correction of hypercortisolism.

Chronic exposure to excess glucocorticoids results in cognitive and psychological impairment. A few studies have indicated that cerebral atrophy can be found in patients with Cushing's syndrome (CS), but its evolution after cure has not been studied extensively. We report the presence of apparent cerebral atrophy in CS and its reversibility after the correction of hypercortisolism. Thirty-eight patients with CS, including 21 with Cushing's disease and 17 with adrenal CS were studied. The control groups consisted of 18 patients with other non-ACTH-secreting sellar tumors and 20 normal controls. Twenty-two patients with CS were reevaluated after cure. Subjective loss of brain volume was present in 86% of patients with Cushing's disease and 100% of patients with adrenal CS. The values for third ventricle diameter, bicaudate diameter, and subjective evaluation were significantly increased in CS groups in comparison with the control group (P < or = 0.001). Imaging reevaluated at 39.7 +/- 34.1 months after achieving eucortisolism showed an improvement of the third ventricle diameter (P = 0.001), bicaudate diameter (P < 0.0005), and subjective evaluation (P = 0.05). We conclude that brain volume loss is highly prevalent in CS and is at least partially reversible following correction of hypercortisolism.

Adult↗

Insight and regional brain volumes in schizophrenia.

We have investigated the relationship between insight impairment and regional brain volumes (gray and white matter) in schizophrenia using voxel-based morphometry (VBM). Fifty patients with schizophrenia were evaluated using the Scale for Unawareness of Mental Disorders. Magnetic resonance images were acquired, segmented and spatially normalized using optimized VBM routines. No significant inverse correlations were detected between insight impairment and gray or white matter volumes in the prefrontal region (where significant findings had been predicted a priori), or in any other brain areas. Our results do not support previous hypotheses suggesting a relationship between frontal lobe atrophy and impaired insight in patients with schizophrenia.

Adolescent↗

Adolescents who were born very preterm have decreased brain volumes.

Infants born very preterm have an increased risk of brain injury. Given the great increase in the number of such infants that are surviving, it is important to establish whether any resultant brain abnormalities persist into adolescence and adult life. We therefore examined in vivo whole brain, grey matter, white matter and hippocampal volumes, ventricular size and grey/white matter ratios in a series of adolescents who had been born very preterm, and an age-matched full-term control group. Structural MRI was carried out on a cohort of 72 adolescents (mean age 15 years) who were born before 33 weeks, and 48 age-matched full-term controls. Brain measurements were made blind to group affiliation using stereological principles. After controlling for gender and height, the very preterm subjects showed a 6.0% decrease in whole brain volume, and an 11.8% decrease in cortical grey matter volume, as well as a 15.6% decrease in right and a 12.1% decrease in left hippocampal volumes; they also had a 42.0% increase in the size of the lateral ventricles. Therefore, individuals who were born very preterm continue to show noticeable decrements in brain volumes and striking increases in lateral ventricular volume into adolescence. The functional significance of these abnormalities merits further investigation.

Adolescent↗

Application of dynamic computed tomography scan and computed tomography densitometry in the evaluation of brain volume enlargement.

Cats with brain cold injury and epidural balloon compression with sudden decompression were used as models of vasogenic or ischemic edema and vasoparalysis of the brain vessels. Dynamic CT scan and CT densitometric studies were performed to diagnose and differentiate between brain edema and vasoparalytic changes. The CT methods were found to be useful in CBF and edema zone estimation. The correlation of CT scan and CT densitometry enabled us to evaluate the degree of autoregulation disorders and can be also applied in clinical investigations.

Blood-Brain Barrier↗

The assessment of changes in brain volume using combined linear measurements. A CT-scan study.

All linear measurements employed for evaluation of brain atrophy, were performed on 148 computed tomograms of patients aged 28 to 84 without evidence of any nervous system disorder. These included size of lateral, third and fourth ventricles, width of the Sylvian and frontal interhemispheric fissures and cortical sulci and size of the pre-pontine cistern. Various parameters indicated decrease in brain mass with age. Since the atrophic process is a diffuse phenomenon, integration of several measurements evaluating separate brain regions was made. The bicaudate ratio and the Sylvian fissure ratio (representing both central and cortical atrophy) were combined arithmetically, resulting in a correlation of 0.6390 with age (P less than 0.0005). With a computed canonical correlation analysis; a formula was obtained which combined measurements of the lateral and third ventricles, the Sylvian fissure and the pre-pontine cistern. This formula yielded a correlation of 0.67795 (P less than 0.0005). These linear measurements will allow simple and reliable assessement of reduction in brain volume during the normal aging process and in disorders accompanied by brain atrophy.

Adult↗

Asynchronous regional brain volume losses in presymptomatic to moderate AD.

To determine if rates and locations of brain volume loss associated with AD are phase-specific, occurring prior to clinical onset and at later stages, we performed longitudinal volumetric MRI analysis on 155 subjects enrolled in a prospective study of aging and dementia. Subjects were divided by Clinical Dementia Rating (CDR) scale into stages of Normal (CDR 0 --> 0), Very Mild (CDR 0 --> 0.5 and 0.5 --> 0.5), Mild (CDR 0.5 --> 1.0 and 1.0 --> 1.0) and Moderate (CDR 1.0 --> 2.0 and 2.0 --> 2.0) dementia. Rates of volume change in CSF spaces, lobar and medial temporal lobe regions were analyzed for group differences across stages. Annual rates of ventricular volume change differed between non-demented and very mild group (p<0.01). In later severity stages, ventricular, temporal, basal ganglia-thalamic region and total volumes show change. Rates of volume loss increase as dementia progresses, but not uniformly in all regions. These regional and phase-specific volume changes form targets for monitoring disease-modifying therapies at clinically relevant, defined stages of dementia.

Aged↗

Improved outcome after severe head injury with a new therapy based on principles for brain volume regulation and preserved microcirculation.

OBJECTIVE: To assess the new "Lund therapy" of posttraumatic brain edema, based on principles for brain-volume regulation and improved microcirculation. DESIGN: A prospective, nonrandomized outcome study over a 5-yr period on severely head-injured patients with increased intracranial pressure, comparing the results with a historical control group with the same selection criteria for patients who were treated according to conventional principles. SETTING: General intensive care unit of a university hospital. PATIENTS: Fifty-three consecutive head-injured patients with a Glasgow Coma Score of <8, and with increased intracranial pressure (>25 mm Hg), despite conventional treatment. INTERVENTIONS: Interstitial fluid resorption was obtained by lowering intracapillary hydrostatic pressure, by preserving normal colloid osmotic pressure, and by maintaining a normovolemic (normal albumin/serum and hemoglobin/serum), not overtransfused patient. Intracapillary pressure was reduced by the combination of precapillary vasoconstriction (low-dose thiopental, dihydroergotamine) and reduction of mean arterial pressure, the latter attained with a beta1-antagonist (metoprolol 0.2 to 0.3 mg/kg/24 hrs iv) and an alpha2-agonist (clonidine 0.4 to 0.8 microg/kg x 4 to 6 iv). Clonidine, in combination with normovolemia, also improves microcirculation by reducing catecholamines in plasma. Intracranial blood volume was reduced by arterial (low-dose thiopental sodium and dihydroergotamine) and large-vein (dihydroergotamine) vasoconstriction. The start dose of dihydroergotamine (maximum 0.9 microg/kg/hr) was successively reduced toward discontinuation within 4 to 5 days. MEASUREMENTS AND MAIN RESULTS: There were 8% of patients who died and the neurologic conditions of 13% remained severely damaged, compared with 47% and 11%, respectively, for the control group. CONCLUSIONS: The low mortality compared with previous outcome studies strongly indicates that this therapy improves outcome for severe head injuries. However, a randomized, controlled study is needed to reach general acceptance of this new therapy.

Acute Disease↗

Age-related changes in regional cerebral blood flow and brain volume in healthy subjects.

Using the xenon-133 inhalation method, we studied the age-related decline in regional cerebral blood flow, calculated as the initial slope index (ISI), in neurologically normal subjects without any risk factors for cerebral arteriosclerosis (154 men and 123 women), ranging in age from 19 to 88 years. The decline in the ISI was rapid in younger age groups and gradual in older age groups. The ISI was higher in women than in men older than 40 years. Using computed tomography, we studied the age-related decline in brain volume index (BVI; 100% X brain volume/cranial cavity volume) in neurologically normal subjects without any risk factors for cerebral arteriosclerosis (92 men and 49 women), ranging in age from 37 to 86 years. The decline in the BVI was gradual in younger age groups and rapid in older age groups. The BVI was higher in women than in men older than 60 years.

Adult↗

A preliminary morphometric magnetic resonance imaging study of regional brain volumes in body dysmorphic disorder.

Morphometric magnetic resonance imaging (MRI) was used to compare regional brain volumes in eight women with body dysmorphic disorder (BDD) and eight healthy comparison subjects. The BDD group exhibited a relative leftward shift in caudate asymmetry and greater total white matter vs. the comparison group. Findings with respect to the caudate nucleus are consistent with both the conceptualization of BDD as an obsessive-compulsive spectrum disorder, and the 'striatal topography model' of obsessive-compulsive disorders.

Brain↗

Cognitive deficits in Huntington's disease are predicted by dopaminergic PET markers and brain volumes.

The main aim of this study was to investigate the relationship between dopaminergic markers and brain volumes for striatal and cortical structures, and cognitive performance in patients with Huntington's disease and control subjects. We used PET and MRI data as predictors of performance in tasks assessing executive function, visuospatial ability, episodic memory, verbal fluency, perceptual speed and reasoning. The dopamine neurotransmission parameters (D1 and D2 receptor density and dopamine transporter density) and the volumetric measurements for caudate and putamen accounted for substantial portions of the variance across the majority of cognitive tasks. In addition, frontal volume showed a strong relationship with all cognitive tasks. D1 binding and volume measurements for the temporal cortex and thalamic volume showed associations with a select number of cognitive tasks. The overall data pattern is consistent with the view that Huntington's disease may be characterized as a frontostriatal dementia, in which cognitive deficits may result from pathological changes at multiple sites in the frontostriatal circuitry.

Benzazepines↗

Brain volume in children with neurofibromatosis type 1: relation to neuropsychological status.

OBJECTIVE: To determine characteristics of brain morphology in children and adolescents with neurofibromatosis type 1 and relate these characteristics to neuropsychological functioning. BACKGROUND: Neurofibromatosis type 1 is associated with numerous CNS abnormalities and cognitive impairment. Abnormal high signal intensity visible on brain MRI, brain tumors, and macrocephaly are common. Research into links between neuroanatomic and cognitive features has been inconclusive. METHODS: Fifty-two children and adolescents with neurofibromatosis type 1 were compared with 19 control subjects on several quantitative neuroanatomic and neuropsychological measures. RESULTS: Total brain volume, especially gray matter, was significantly greater for neurofibromatosis type 1 subjects than the control subjects. Group differences in the ratio of gray matter to white matter were more prominent in younger than in older subjects. Volume of gray matter in the subjects with neurofibromatosis type 1 was related to their degree of learning disability. Corpus callosum size was significantly larger for subjects in the neurofibromatosis type 1 group, and diminished performance on measures of academic achievement and visual-spatial and motor skills were associated with greater regional corpus callosum size. CONCLUSIONS: Neuroanatomic morphology and the developmental pattern of gray matter and white matter in subjects with neurofibromatosis type 1 differed from in control subjects. Some of these differences are related to the neuropsychological status of the neurofibromatosis type 1 group. We propose that delayed developmental apoptosis results in macrocephaly and a delay in the development of appropriate neuronal connections in children with neurofibromatosis type 1. We further propose that these morphologic delays are related to the cognitive profile of neurofibromatosis type 1.

Adolescent↗

Brain volume changes on longitudinal magnetic resonance imaging in normal older people.

BACKGROUND AND PURPOSE: The purpose of this study is to investigate the longitudinal age-related changes in human brain volume using stereological methods. METHODS: Sixty-six older participants (34 men, 32 women, age [mean +/- SD] 78.9 +/- 3.3 years, range 74-87 years) with normal baseline and follow-up examinations underwent 2 MRIs (magnetic resonance imaging) of the brain on average 4.4 years apart. The volumes of the cerebrum (defined as cortex, basal ganglia, thalamus, and white matter), lateral ventricles, and cerebellum were estimated on the 2 MRIs using an unbiased stereological method (Cavalieri principle). RESULTS: The annual decrease (mean +/- SD) of the cerebral volume was 2.1% +/- 1.6% (P < .001). The average volume of the lateral ventricles on the second MRI was increased by 5.6% +/- 3.6% per year (P < .001). The average volume of the cerebellum on the second MRI was decreased by 1.2% +/- 2.2% per year (P < .001). Even though the average cerebral volume was significantly different between men and women on initial MRI and second MRI, the percentage change of the age-related cerebral volume decrease in male and female brains between initial MRI and second MRI were identical. CONCLUSIONS: The findings showed that there was age-related atrophy of cerebrum and cerebellum and age-related disproportional enlargement of lateral ventricles in normal older men and women.

Aged↗

Abnormal cognition and behavior in preterm neonates linked to smaller brain volumes.

Volumetric measurements of the brain regions in eight-year-old children indicate that the poor cognitive and behavioral outcomes noted in ex-preterm neonates are associated with reduced volumes of specific regions in the brain. Recent literature suggests that this reduction might result from enhanced apoptosis or excitotoxic damage to highly susceptible immature neurons.

Adult↗

Automatic segmentation of left and right cerebral hemispheres from MRI brain volumes using the graph cuts algorithm.

An automated algorithm has been developed to segment stripped (non-brain tissue excluded) T1-weighted MRI brain volumes into left and right cerebral hemispheres and cerebellum+brainstem. The algorithm, which uses the Graph Cuts technique, performs a fully automated segmentation in approximately 30 s following pre-processing. It is robust and accurate and has been tested on datasets from two scanners using different field strengths and pulse sequences. We describe the Graph Cuts algorithm and compare the results of Graph Cuts segmentations against "gold standard" manual segmentations and segmentations produced by three popular software packages used by neuroimagers: BrainVisa, CLASP, and SurfRelax.

Adult↗

The relationship of clozapine and haloperidol treatment response to prefrontal, hippocampal, and caudate brain volumes.

OBJECTIVE: The study was designed to assess the predictive relationship between brain structure volume and positive and negative symptom response to clozapine and haloperidol. METHOD: Partially responsive outpatients with schizophrenia who participated in a 10-week, parallel-group, double-blind comparison of clozapine and haloperidol and who had an available magnetic resonance imaging scan were included in the current study. Prefrontal gray and white matter, hippocampal, and caudate volumes were manually measured. The Scale for the Assessment of Negative Symptoms (SANS) and the Brief Psychiatric Rating Scale (BPRS) were used to assess symptom changes. The Simpson-Angus Rating Scale was used to assess extrapyramidal symptoms. RESULTS: Twenty-two patients randomly assigned to clozapine and 23 patients assigned to haloperidol met study entry criteria. There were significant interactions between treatment and right prefrontal gray matter volume for BPRS total score and SANS total score. There were no significant treatment-by-brain structure interactions for BPRS positive symptom items. Right prefrontal gray matter volume was also related to differential treatment effects for the BPRS subscales of anxiety/depression and hostility and the Simpson-Angus Rating Scale akathisia item. CONCLUSIONS: These results suggest that there is a differential interaction among clozapine and haloperidol, brain structure, and treatment response. Partially responsive patients with larger brain volumes may be more likely to experience the benefits of clozapine treatment, but they may be more vulnerable to side effects and experience a subsequent worsening of their symptoms when treated with haloperidol.

Adult↗

Meta-analysis of regional brain volumes in schizophrenia.

OBJECTIVE: The authors' goal was to determine whether patients with schizophrenia differ from comparison subjects in regional brain volumes and whether these differences are similar in male and female subjects. METHOD: They conducted a systematic search for structural magnetic resonance imaging (MRI) studies of patients with schizophrenia that reported volume measurements of selected cortical, subcortical, and ventricular regions in relation to comparison groups. They carried out a meta-analysis of the volumes of these regions in the patients with schizophrenia and the comparison subjects using a random effects model; they also used random effects regression analysis to examine the influence of gender on effect sizes. RESULTS: Fifty-eight studies were identified as suitable for analysis; these studies included 1,588 independent patients with schizophrenia. Assuming a volume of 100% in the comparison group, they found that the mean cerebral volume of the subjects with schizophrenia was smaller (98%), but the mean total ventricular volume of the subjects with schizophrenia was greater (126%). Relative to the cerebral volume differences, the regional volumes of the subjects with schizophrenia were 94% in the left and right amygdala, 94% in the left and 95% in the right hippocampus/amygdala, and 93% in the left and 95% in the right parahippocampus. Relative to the global ventricular system differences, the largest differences in ventricular subdivisions were in the right and left body of the lateral ventricle, where the volumes of schizophrenic subjects were 116% and 116%, respectively. For most regions, effect size was not significantly related to gender. CONCLUSIONS: Regional structural differences in patients with schizophrenia include bilaterally reduced volume of medial temporal lobe structures. There is a need for greater integration of results from structural MRI studies to avoid redundant research activity.

Adult↗

Relationship of cognitive functioning, whole brain volumes, and T2-weighted hyperintensities in neurofibromatosis-1.

Using quantitative magnetic resonance imaging morphometry, we report that the whole brain volumes of patients with neurofibromatosis-1 are significantly larger than normal, confirm the prevalence of macrocephaly as about 50%, and report that macrocephaly in patients with neurofibromatosis-1 does not appear to be related to the familial or sporadic origin of the neurofibromatosis-1 or to the presence or absence of T2-weighted hyperintensities. No strong relationship emerged between the extent of neurofibromatosis-1-associated impairment of cognitive functions and degree of macrocephaly; however, the macrocephalic neurofibromatosis-1 group did have a significant verbal impairment relative to the nonmacrocephalic neurofibromatosis-1 group in vocabulary (P < .009).

Adolescent↗