Quantitative magnetic resonance image analysis of the cerebellum in macrocephalic and normocephalic children and adults with autism.

A detailed morphometric analysis of the cerebellum in autism with and without macrocephaly. Four subject groups (N = 65; male; IQs > or = 65; age 7 to 26 years) were studied with quantitative MRI; normocephalic and macrocephalic individuals with autism without mental retardation were compared to normocephalic and benign macrocephalic typically developing individuals. Total cerebellum volumes and surface areas of four lobular midsagittal groups were measured. Independent t-tests between autism and control subjects matched for head size revealed no significant differences. Multivariate analyses of variance were also performed, using the diagnostic group as the fixed factor, cerebellar measures as the dependent variables and total intracranial volume, total brain volume, age, verbal IQ, and performance IQ as covariates. No significant differences were found; however, a trend was noted in which macrocephalic individuals with autism consistently exhibited slightly smaller cerebellar volume or surface area when compared to individuals with benign macrocephaly. In autism, with and without macrocephaly, cerebellar structures were found to be proportional to head size and did not differ from typically developing subjects.

Mesial temporal sclerosis after status epilepticus due to milk alkali syndrome.

Seizures induced by hypercalcemia are rare. A few case reports of seizures associated with hypercalcemia have been published, but none due to the milk alkali syndrome. This is the first report regarding seizures associated with calcium carbonate overuse. The two patients described in this article, who had no risk factors for developing epilepsy, suffered from status epilepticus probably induced by hypercalcemia. Subsequently, they both developed complex partial seizures, and were later found to have mesial temporal sclerosis on MRI. There are no reports linking hypercalcemia to mesial temporal sclerosis. While this may be a coincidence, there is reason to suspect that the development of persistent epilepsy, possibly due to mesial temporal sclerosis, was caused by prolonged seizures induced by hypercalcemia.

Cavum septum pellucidum in schizophrenia: clinical and neuropsychological correlates.

Increased frequency of cavum septum pellucidum (CSP) has been inconsistently observed in schizophrenia, and little is known about its functional implications. We investigated whether patients with schizophrenia were more likely than healthy controls to have CSP, and among patients assessed the relationship between CSP, psychiatric symptoms, and selected neuropsychological functions. Seventy-seven patients with diagnoses of DSM-IV schizophrenia spectrum disorders and 55 healthy controls were studied and completed a 1.5 T MRI scan. Two raters, blind to group membership, determined the presence, length and grade of the CSP. A subset of participants also underwent neuropsychological testing. A CSP of at least 1 mm in length was present in 68.8% of patients and 76.4% of controls, and the groups did not differ significantly with respect to presence or absence, length, overall size, or percent with an abnormally large CSP (> or =6 mm). Patients with an abnormally large CSP demonstrated poorer performance on measures of verbal learning and memory than patients with smaller CSP. Among patients, CSP length was significantly correlated with negative symptoms, verbal learning, and sentence comprehension. Among patients with abnormally large CSP, CSP length was correlated with reaction time on two conditions of a Continuous Performance Test. CSP, while prevalent, was not more frequent in our sample of patients with schizophrenia, and had few associations with symptom severity or neuropsychological deficits.

Frontal and temporal morphometric findings on MRI in children after moderate to severe traumatic brain injury.

In vivo MRI volumetric analysis enables investigators to evaluate the extent of tissue loss following traumatic brain injury (TBI). However, volumetric studies of pediatric TBI are sparse, and there have been no volumetric studies to date in children examining specific subregions of the prefrontal and temporal lobes. In this study, MRI volumetry was used to evaluate brain volume differences in the whole brain, and prefrontal, temporal, and posterior regions of children following moderate to severe TBI as compared to uninjured children of similar age and demographic characteristics. The TBI group had significantly reduced whole brain, and prefrontal and temporal regional tissue volumes as well as increased cerebrospinal fluid (CSF). Confidence interval testing further revealed group differences on gray matter (GM) and white matter (WM) in the superior medial and ventromedial prefrontal regions, WM in the lateral frontal region, and GM, WM, and CSF in the temporal region. Whole brain volume and total brain GM were reduced, and total ventricular volume, total CSF volume, and ventricle-to-brain ratio (VBR) were increased in the TBI group. Additional analyses comparing volumetric data from typically developing children and subgroups of TBI patients with and without regional focal lesions suggested that GM loss in the frontal areas was primarily attributable to focal injury, while WM loss in the frontal and temporal lobes was related to both diffuse and focal injury. Finally, volumetric measures of preserved frontotemporal tissue were related to functional recovery as measured by the Glasgow Outcome Scale (adapted for children) with greater tissue preservation predicting better recovery.

Macrocephaly, corpus callosum morphology, and autism.

Although the cause of autism is undetermined, a general consensus has been that some type of early aberrant neural development underlies the disorder. Given the increased prevalence of macrocephaly in autism, one theory of abnormal neural development implicates early brain growth resulting in larger brain and head size in autism. Surface area measurements of the midsagittal section of the corpus callosum can be used as an index of neural development and white-matter integrity because the corpus callosum is the major white-matter structure that interconnects the two cerebral hemispheres. The purpose of this study was to obtain corpus callosum surface area, shape, and contour in a sample of non-mentally retarded autistic subjects with macrocephaly (n = 12) and compare them with those of matched (n = 8), typically developing control subjects with benign macrocephaly. No significant differences were found in surface area, shape, or contour between groups, nor did corpus callosum surface area relate to measures of IQ or picture vocabulary. These findings suggest no unique difference in overall regional corpus callosum surface area in autism with macrocephaly.

Temporal lobe, autism, and macrocephaly.

BACKGROUND AND PURPOSE: Because of increased prevalence of macrocephaly in autism, head size must be controlled for in studies that examine volumetric findings of the temporal lobe in autistic subjects. We prospectively examined temporal lobe structures in individuals with autism who were normocephalic or macrocephalic (head circumference > 97th percentile) and in control subjects who were normocephalic or macrocephalic or who had a reading disorder (unselected for head size). The rationale for the reading disorder group was to have control subjects with potential temporal lobe anomalies, but who were not autistic. METHODS: In individuals aged 7-31 years, autism was diagnosed on the basis of standardized interview and diagnostic criteria. Control subjects ranged in age from 7 to 22 years. All subjects were male. MR morphometrics of the major temporal lobe structures were based on ANALYZE segmentation routines, in which total brain volume and total intracranial volume (TICV) were calculated. Both group comparisons and developmental analyses were performed. RESULTS: No distinct temporal lobe abnormalities of volume were observed once head size (TICV) was controlled for. In autistic and control subjects, robust growth patterns were observed in white and gray matter that differed little between the groups. Although subtle differences were observed in some structures (ie, less white matter volume in the region of the temporal stem and overall temporal lobe), none was statistically significant. CONCLUSION: No major volumetric anomalies of the temporal lobe were found in cases of autism when IQ, TICV, and age were controlled. Temporal lobe abnormalities that may be associated with autism are likely to be more related to functional organization within the temporal lobe than to any gross volumetric difference.

Hippocampal volume and shape analysis in an older adult population.

This report presents a manual segmentation protocol for the hippocampus that yields a reliable and comprehensive measure of volume, a goal that has proven difficult with prior methods. Key features of this method include alignment of the images in the long axis of the hippocampus and the use of a three-dimensional image visualization function to disambiguate anterior and posterior hippocampal boundaries. We describe procedures for hippocampal volumetry and shape analysis, provide inter- and intra-rater reliability data, and examine correlates of hippocampal volume in a sample of healthy older adults. Participants were 40 healthy older adults with no significant cognitive complaints, no evidence of mild cognitive impairment or dementia, and no other neurological or psychiatric disorder. Using a 1.5 T GE Signa scanner, three-dimensional spoiled gradient recalled acquisition in a steady state (SPGR) sequences were acquired for each participant. Images were resampled into 1 mm isotropic voxels, and realigned along the interhemispheric fissure in the axial and coronal planes, and the long axis of the hippocampus in the sagittal plane. Using the BRAINS program (Andreasen et al., 1993), the boundaries of the hippocampus were visualized in the three orthogonal views, and boundary demarcations were transferred to the coronal plane for tracing. Hippocampal volumes were calculated after adjusting for intracranial volume (ICV). Intra- and inter-rater reliabilities, measured using the intraclass correlation coefficient, exceeded .94 for both the left and right hippocampus. Total ICV-adjusted volumes were 3.48 (+/-0.43) cc for the left hippocampus and 3.68 (+/-0.42) for the right. There were no significant hippocampal volume differences between males and females (p > .05). In addition to providing a comprehensive volumetric measurement of the hippocampus, the refinements included in our tracing protocol permit analysis of changes in hippocampal shape. Shape analyses may yield novel information about structural brain changes in aging and dementia that are not reflected in volumetric measurements alone. These and other novel directions in research on hippocampal function and dysfunction will be facilitated by the use of reliable, comprehensive, and consistent segmentation and measurement methods.

Reduced hippocampal volume in alcohol and substance naïve Vietnam combat veterans with posttraumatic stress disorder.

OBJECTIVE: This pilot study was undertaken to exclude the effects of alcohol and other substances on brain morphology in posttraumatic stress disorder. BACKGROUND: Posttraumatic stress disorder and alcohol use are among the conditions associated with decreased hippocampal volume. The possible confounding contribution of alcohol and other substances of abuse to decreased hippocampal volume in posttraumatic stress disorder has not been previously explored directly. METHOD: In this pilot study, magnetic resonance imaging scans of 4 substance naive subjects with combat-related posttraumatic stress disorder and of 4 controls were quantified. RESULTS: Bilateral hippocampal volumes were significantly smaller in posttraumatic stress disorder subjects. No significant differences were found between posttraumatic stress disorder subjects and the comparison group for total brain, gray and white matter, and ventricular volumes. CONCLUSIONS: These findings suggest that posttraumatic stress disorder in the absence of alcohol and other substance abuse may be associated with reduced hippocampal volume. The significance of reduced hippocampal volume in posttraumatic stress disorder is discussed.

Cerebral volume loss, cognitive deficit and neuropsychological performance: comparative measures of brain atrophy: I. Dementia.

There are several magnetic resonance (MR) imaging methods to measure brain volume and cerebral atrophy; however, the best measure for examining potential relationships between such measures and neuropsychological performance has not been established. Relationships between seven measures of MR derived brain volume or indices of atrophy and neuropsychological performance in the elderly subjects of the population-based Cache County, Utah Study of Aging and Memory (n = 195) were evaluated. The seven MR measures included uncorrected total brain volume (TBV), TBV corrected by total intracranial volume (TICV), TBV corrected by the ratio of the individuals TICV by group TICV (TBVC), a ventricle-to-brain ratio (VBR), total ventricular volume (TVV), TVV corrected by TICV, and a measure of parenchymal volume loss. The cases from the Cache County Study were comprised of elderly individuals classified into one of four subject groups based on a consensus diagnostic process, independent of quantitative MR imaging findings. The groups included subjects with Alzheimer's disease (AD, n = 85), no dementia but mild/ambiguous (M/A) deficits (n = 30), a group of subjects with non-AD dementia or neuropsychiatric disorder including vascular dementia (n = 60), and control subjects (n = 20). Neuropsychological performance was based on the Mini-Mental Status Exam (MMSE) and an expanded neuropsychological test battery (consortium to establish a registry for Alzheimer's disease (CERAD). The results demonstrated that the various quantitative MR measures were highly interrelated and no single measure was statistically superior. However, TBVC, TBV/TICV and VBR consistently exhibited the more robust relationships with neuropsychological performance. These results suggest that a single corrected brain volume measure or index is sufficient in studies examining global MR indicators of cerebral atrophy in relation to cognitive function and recommends use of either TBVC, TBV/TICV, or VBR.