Blaine L. Hart

Reduced hippocampal volume and total white matter volume in posttraumatic stress disorder

BACKGROUND Reduced hippocampal volumes in posttraumatic stress disorder (PTSD) patients are thought to reflect specific changes of this structure. Previous magnetic resonance imaging (MRI) studies have not consistently examined indices of overall brain atrophy, therefore it cannot be completely ruled out that hippocampal changes are explained by whole-brain atrophy. The purpose of this study was to assess hippocampal and whole-brain volume in civilian PTSD. METHODS Twelve subjects with PTSD and 10 control subjects underwent brain MRI. Hippocampal volumes were visually quantified using a computerized volumetric program. Whole-brain volumes were obtained with automated k-means-based segmentation. RESULTS No differences were found in intracranial volumes (ICV). Subjects with PTSD had higher cerebrospinal fluid (CSF)/ICV ratios and lower white matter/ICV ratios, consistent with generalized white matter (WM) atrophy. The effect of age on CSF/ICV was more pronounced in the PTSD group. Subjects with PTSD had smaller absolute and normalized bilateral hippocampal volumes. These differences persisted after adjusting for lifetime weeks of alcohol intoxication. Posttraumatic stress disorder and depression scores correlated negatively with left hippocampal volume, but PTSD scores were a better predictor of hippocampal volumes. CONCLUSIONS Our results replicate previous findings of reduced hippocampal volume in PTSD but also suggest independent, generalized, white matter atrophy.

Magnetic resonance imaging correlates of attention-deficit/hyperactivity disorder in children.

This study compared magnetic resonance imaging size differences in several brain regions and neurocognitive function in a group of male and female children with attention-deficit/hyperactivity disorder (ADHD) with no comorbid learning disorders with a normal control group of children. The ADHD group demonstrated smaller total brain, superior prefrontal, and right superior prefrontal volumes, as well as significantly smaller areas for cerebellar lobules I-V and VIII-X, total corpus callosum area, and splenium. No group differences were observed for the inferior prefrontal, caudate, or cerebellar volumes, or for the area of cerebellar lobules VI-VII. In the ADHD group but not in the control group, greater right superior prefrontal volume predicted poorer performance on a test of sustained attention. Patterns of brain abnormality did not differ in male and female children with ADHD.

Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1).

Congenital fibrosis of the extraocular muscles type 1 (CFEOM1; OMIM #135700) is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. We show that individuals with CFEOM1 harbor heterozygous missense mutations in a kinesin motor protein encoded by KIF21A. We identified six different mutations in 44 of 45 probands. The primary mutational hotspots are in the stalk domain, highlighting an important new role for KIF21A and its stalk in the formation of the oculomotor axis.

Quantitative proton MRS predicts outcome after traumatic brain injury

Objective: To determine whether proton MRS (1H-MRS) neurochemical measurements predict neuropsychological outcome of patients with traumatic brain injury (TBI). Background: Although clinical indices and conventional imaging techniques provide critical information for TBI patient triage and acute care, none accurately predicts individual patient outcome. Methods: The authors studied 14 patients with TBI soon after injury (45 ± 21 days postinjury) and again at 6 months (172 ± 43 days) and 14 age-, sex-, and education-matched control subjects. N-acetylaspartate (NAA), creatine, and choline were measured in normal-appearing occipitoparietal white and gray matter using quantitative 1H-MRS. Outcome was assessed with the Glasgow Outcome Scale (GOS) and a battery of neuropsychological tests. A composite measure of neuropsychological function was calculated from individual test z-scores probing the major functional domains commonly impaired after head trauma. Results: Early NAA concentrations in gray matter predicted overall neuropsychological performance (r = 0.74, p = 0.01) and GOS (F = 11.93, p = 0.007). Other metabolite measures were not related to behavioral function at outcome. Conclusion: 1H-MRS provides a rapid, noninvasive tool to assess the extent of diffuse injury after head trauma, a component of injury that may be the most critical factor in evaluating resultant neuropsychological dysfunction. 1H-MRS can be added to conventional MR examinations with minimal additional time, and may prove useful in assessing injury severity, guiding patient care, and predicting patient outcome.

Cerebellar hypoplasia and frontal lobe cognitive deficits in disorders of early childhood.

A developmental chronometry hypothesis of early brain damage is suggested in which regions of the brain with a protracted course of postnatal development will be more vulnerable than earlier maturing areas to deleterious effects of early insult and, therefore, may become common sites of abnormality across many disorders originating in early childhood. Initial investigations of the cerebellum and frontal lobes are presented using MRI and neuropsychological measures. Planimetric measures of the cerebellar vermis (lobuli I-V and VI-VII) and pons, and neuropsychological frontal lobe measures were obtained from high functioning individuals with autism (A), survivors of acute lymphoblastic leukemia (ALL) with brain sequelae following radiation and chemotherapy, and from rigorously selected healthy controls (C). The neuropsychological results were clustered according to functions commonly related to frontal brain, posterior brain, and left and right hemispheres. The A and ALL groups, as compared to C, yielded modest but consistently reduced MRI measures for vermal lobuli I-V and VI-VII. Hypoplasia of lobuli VI-VII was more marked than I-V. Performance on neuropsychological tests for frontal lobe functions was generally depressed in both groups, with more severe deficits in A. Between-group differences in verbal, visual-spatial, and emotional-social skills are discussed. The cerebellar and frontal brain deficits that are present in both clinical groups (A and ALL) may be common to other developmental and acquired disorders of early childhood. Such joint manifestation of cerebellar and frontal lobe abnormalities is in agreement with the concept of cerebellar significance for the development of higher cognitive functions.

Magnetic Resonance Imaging And Brain Histopathology In Neuropsychiatric Systemic Lupus Erythematosus

OBJECTIVE Magnetic resonance imaging (MRI) often demonstrates brain lesions in neuropsychiatric systemic lupus erythematosus (NPSLE). The present study compared postmortem histopathology with premortem MRI in NPSLE. METHODS Two hundred subjects with NPSLE were studied prospectively with MRI over a 10-year period during which 22 subjects died. In 14 subjects, a brain autopsy with histopathology, that permitted direct comparison with premortem MRI, was successfully obtained. Surface anatomy was used to determine the approximate location of individual lesions. RESULTS Premortem MRI findings in fatal NPSLE were small focal white matter lesions (100%), cortical atrophy (64%), ventricular dilation (57%), cerebral edema (50%), diffuse white matter abnormalities (43%), focal atrophy (36%), cerebral infarction (29%), acute leukoencephalopathy (25%), intracranial hemorrhage (21%), and calcifications (7%). Microscopic findings in fatal NPSLE included global ischemic changes (57%), parenchymal edema (50%), microhemorrhages (43%), glial hyperplasia (43%), diffuse neuronal/axonal loss (36%), resolved cerebral infarction (33%), microthomboemboli (29%), blood vessel remodeling (29%), acute cerebral infarction (14%), acute macrohemorrhages (14%), and resolved intracranial hemorrhages (7%). Cortical atrophy and ventricular dilation seen by MRI accurately predicted brain mass at autopsy (r = -0.72, P = 0.01, and r = -0.77, P = 0.01, respectively). Cerebral autopsy findings, including infarction, cerebral edema, intracranial hemorrhage, calcifications, cysts, and focal atrophy, were also predicted accurately by premortem MRI. CONCLUSION Brain lesions in NPSLE detected by MRI accurately represent serious underlying cerebrovascular and parenchymal brain injury on pathology.

Familial Cerebral Cavernous Angiomas: Clinical and Radiologic Studies

Article abstract-Cavernous angiomas are well-circumscribed cerebrovascular malformations whose natural history is poorly understood. We reviewed 5,000 cranial MRI reports of studies performed between 1986 and 1993 and retrospectively evaluated the histories and imaging studies of 29 patients whose lesions were suggestive of cavernous angiomas. Patients ranged from 3 to 66 years and 27 were of Hispanic origin. The number of malformations per patient ranged from one to 30, and 24 patients had more than one lesion. In our series, the number of lesions per patient increased at a rate of one lesion per decade of age, but the mean size of the lesions was smaller with advancing decade (p < 0.05). All patients had MRI evidence of old or recent hemorrhage confined only to the malformation and adjacent brain. In only one patient was it deemed necessary to remove the malformation. Two excluded patients with typical lesions on MRI had small arteriovenous malformations found at surgery. Thus, MRI or CT cannot identify cavernous angiomas with certainty. This study supports studies that propose that cavernous angioma-like lesions, as identified by MRI or CT, are more common in Hispanics. It is possible that patients may not be born with MRI-identifiable malformations, but with advancing age the malformations become MRI-visible through malformation growth, hemorrhage, or both. The declining size by decade favors hemorrhage rather than growth. Cavernous angiomas may be more benign than previously thought. NEUROLOGY 1995;45: 492-497

Biochemical markers of cognition: a proton MR spectroscopy study of normal human brain.

In the current study we explored the relationship between neurometabolites measured by proton magnetic resonance spectroscopy (1H-MRS) and cognitive ability assessed with a battery of neuropsychological tests. Forty-five participants were recruited from the local college community, and examined utilizing neuropsychological testing and 1H-MRS. Our central finding was that N-acetylaspartate (NAA) was associated with overall neuropsychological performance (F(1,42) = 23.16, p < 0.0001], r2 = 0.35. We found an even stronger association between timed neuropsychological measures and NAA (F(1,42) = 31.15, p < 0.0001], r = 0.43. These results reveal the specific relationship of NAA to neuropsychological functioning in normal human brain. The current observations in healthy individuals are consistent with the hypothesis that variability in NAA levels and neuropsychological performance may be related to mitochondrial function.

Effect of lordosis on the position of the nucleus pulposus in supine subjects: A study using magnetic resonance imaging

Study Design Healthy young women (N =20) underwent magnetic resonance imaging while supine with their hips and knees fiexed (fiexed position) and supine with a lumbar roll under the low back (extended position). The posterior and anterior margins of the nucleus pulposus (NP) relative to posterior and anterior margins of the adjacent vertebral bodies were calculated from mid-sagittal T2-weighted images to determine the position change of the NP as a function of two supine postures. Objectives This study describes the effect of two commonly used supine postures on the position of the NP. Summary of Background Data Management of patients with low back pain is often based on theorized positional changes of the NP during spinal extension and flexion. Data describing NP positional changes have not been reported for noninvasive measurements. Results The distance of the posterior margin of the NP to the posterior margins of the adjacent vertebral bodies was greater in the extended compared with the fiexed position. There was no difference in the anterior distance. Eight of the 20 subjects had at least one degenerative disc in the lower lumbar spine. The NPs of the degenerative discs did not move the same as normal discs. Conclusions The use of a lumbar roll under the low back when supine causes an increase in the distance from the posterior margin of the NP to the posterior portions of the vertebral bodies in normal discs of healthy young females. Degenerative discs deform differently from nondegenerative discs.

Longitudinal follow-up of neurochemical changes during the first year of antipsychotic treatment in schizophrenia patients with minimal previous medication exposure

Reduced frontal N-acetylaspartate (NAA) has been repeatedly found in chronic schizophrenia and suggests neuronal loss or dysfunction. However, the potential confounding effect of antipsychotic drugs on NAA has not been resolved. The few studies of antipsychotic-nai;ve patients are inconclusive. A recent report suggests that antipsychotic drugs may increase NAA in the dorsolateral prefrontal cortex (DLPFC). We studied 10 minimally treated (less than 3 weeks lifetime exposure) schizophrenia patients and 10 normal controls with single-voxel proton magnetic resonance spectroscopy (1H-MRS) of the left frontal and occipital lobes. Concentrations of NAA, Cho, and Cre were determined and corrected for the proportion of cerebrospinal fluid (CSF) in the voxel. Patients were treated in a randomized-controlled double-blind design with either haloperidol or quetiapine. 1H-MRS was repeated within a year. There were no differences in frontal or occipital NAA between patients and controls at baseline. However, frontal NAA was reduced in the schizophrenia group within the first year of treatment. Patients had a clear clinical response to treatment but changes in frontal NAA were not correlated with symptom improvement. The well-described reduced frontal NAA in schizophrenia may not be a trait of the illness but may represent medication effect or progression of the disease.