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PubMed1988

White matter disease in AIDS: findings at MR imaging.

A review of the magnetic resonance (MR) images of 365 patients with acquired immunodeficiency syndrome (AIDS) revealed that 112 (31%) had signal abnormalities confined to the white matter. Four patterns were observed: (a) diffuse: widespread involvement of a large area; (b) patchy: localized involvement with ill-defined margins; (c) focal: well-defined areas of involvement; and (d) punctate: small foci less than 1 cm in diameter. Clinical or pathologic findings were available in 60 of the 112 patients and were correlated with the white matter patterns seen on MR images. The diffuse pattern correlated with AIDS dementia complex (ADC), which was the most common clinical diagnosis. Patchy or punctate lesions may be seen with ADC but are less common. Focal white matter lesions were not seen in patients with ADC but were seen in all six patients with progressive multifocal leukoencephalopathy, in both patients with lymphoma, and in one patient with toxoplasmosis. The authors conclude that white matter lesions are are common in AIDS and are often secondary to direct infection of the brain with human immunodeficiency virus, which causes the ADC and usually produces a diffuse white matter pattern. Biopsy is probably not indicated in these patients. Focal white matter lesions suggest a focal infection or tumor, and biopsy may be warranted.

Acquired Immunodeficiency Syndrome↗
PubMed1989

White matter lesions: role of spin density in MR imaging.

To study the effect of hydrogen spin density (N[H]) on magnetic resonance (MR) image contrast in white matter disease of the brain, T1, T2, and N[H] values were determined for normal white matter and idiopathic white matter lesions (IWMLs) in 21 patients by using multiple spin-echo (SE) sequences. T1 values of IWMLs were significantly greater than those of normal white matter in all patients studied, and T2 values of IWMLs were significantly greater in 20 of 21 patients. N[H] values of IWMLs were greater in 20 of 21 patients, with statistically significant differences from those of normal white matter in 17 of those 20 patients. Averaged over all 21 patients studied, N[H] values of IWMLs were 20% higher than N[H] values of normal white matter. The effect of unequal N[H] values on contrast between IWMLs and normal tissues is to reduce contrast on short SE sequences with a short repetition time (TR) and a short echo time (TE), while enhancing contrast between IWMLs and normal tissues on long TR/TE SE sequences. Elevated N[H] values in IWMLs have a minimal effect on contrast in conventional inversion-recovery (IR) sequences but substantially enhance contrast between IWMLs and normal brain tissues in short inversion time IR sequences.

Brain↗
PubMed2003

Diffusion tensor magnetic resonance imaging of disruption of regional white matter in schizophrenia.

Diffusion tensor imaging provides a new approach for quantifying anisotropic diffusion of white matter in vivo. We used this technique to investigate subtle disruption of regional white matter in schizophrenia. Twelve patients with schizophrenia were compared with 11 healthy controls. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale. A significant fractional anisotropy (FA) reduction was found in all white matter regions bilaterally in schizophrenic patients. Higher FA of left frontal white matter correlated significantly with higher dosage of antipsychotic medication. These findings support the view that the pathological process is a distortion of the central nervous system myelination affecting the whole white matter. Our findings also show the effects of antipsychotics on the white matter in the left frontal region in schizophrenia.

Adult↗
PubMedDate not supplied

Do white matter changes have clinical significance in Alzheimer's disease?

BACKGROUND: Although white matter changes visible with MRI are generally considered to result from ischemia, it has become clear that these changes also appear in patients with Alzheimer's disease (AD). However, their significance in AD is unknown. OBJECTIVE: We evaluated the clinical significance of white matter changes in AD. METHODS: Ninety-six AD patients (79.4 +/- 5.92 years old) and 48 age-matched control subjects (80.0 +/- 7.03 years old) participated in the study. Three neuroradiologists assessed the degree of periventricular hyperintensities (PVH) and deep white matter hyperintensities (DWMH) using a modified Fazekas' rating scale. We examined whether there was a difference in the severity and the histogram pattern of the white matter changes, or in vascular factors (hypertension, diabetes mellitus, and ischemic heart disease) between the two groups. We also analyzed the association between the severity of the white matter changes and the degree of dementia (MMSE score and disease duration). RESULTS: There were no differences in the vascular factors between AD and control subjects. The degree of PVH in AD was severe compared with that in the control subjects. In histograms of the number of subjects with each degree of PVH severity, the distribution of AD patients had peaks at both the low and intermediate degrees of PVH, while most of the controls had a low degree of PVH. There was no difference in the degree or the histogram pattern of DWMH between the two groups. The severity of white matter changes was not associated with severity of dementia in AD. CONCLUSIONS: Although PVH might have several causative factors, and may have some clinical significance, the change itself does not contribute to the progression of AD.

Aged↗
PubMed2006

Lobar brain hemorrhages and white matter changes: Clinical, radiological and laboratorial profiles.

BACKGROUND: White matter changes have several histopathologic correlates including cerebral amyloid angiopathy (CAA). The aim of this study was to characterize the clinical, laboratorial and neuroradiological profile of a CAA-related lobar hemorrhages case series. METHODS: A cohort of 50 consecutive patients with cerebral lobar hemorrhages was studied and clinical, radiological data and ApoE polymorphisms were analyzed. White matter changes were graded and microbleeds were characterized according to number and location using T2* MRI. RESULTS: A statistically significant association was found between the prestroke cognitive performance and poststroke dementia and between hemorrhage volume and mortality. More severe white matter changes were found in probable CAA when comparing to possible CAA. The most prominent white matter lesions are associated with the presence and the number of microbleeds. The frequency of APOE epsilon 2 and epsilon 4 alleles was higher in this cohort when compared to a Northern Portuguese population. CONCLUSION: White matter changes are frequent in lobar hemorrhage patients and are associated with cortical microbleeds, the radiological hallmark of CAA. Therefore, white matter changes may be the sole phenotype of CAA and, potentially, involved in the pre-stroke cognitive impairment presented by the patients, which are genetically distinct from the population in general.

Aged↗
PubMed2003

Silent brain infarcts and white matter lesions increase stroke risk in the general population: the Rotterdam Scan Study.

BACKGROUND AND PURPOSE: Silent brain infarcts and white matter lesions are associated with an increased risk of subsequent stroke in minor stroke patients. In healthy elderly people, silent brain infarcts and white matter lesions are common, but little is known about their relevance. We examined the risk of stroke associated with these lesions in the general population. METHODS: The Rotterdam Scan Study is a population-based prospective cohort study among 1077 elderly people. The presence of silent brain infarcts and white matter lesions was scored on cerebral MRI scans obtained from 1995 to 1996. Participants were followed for stroke for on average 4.2 years. We estimated the risk of stroke in relation to presence of brain lesions with Cox proportional hazards regression analysis. RESULTS: Fifty-seven participants (6%) experienced a stroke during follow-up. Participants with silent brain infarcts had a 5 times higher stroke incidence than those without. The presence of silent brain infarcts increased the risk of stroke >3-fold, independently of other stroke risk factors (adjusted hazard ratio 3.9, 95% CI 2.3 to 6.8). People in the upper tertile of the white matter lesion distribution had an increased stroke risk compared with those in the lowest tertile (adjusted hazard ratio for periventricular lesions 4.7, 95% CI 2.0 to 11.2 and for subcortical lesions 3.6, 95% CI 1.4 to 9.2). Silent brain infarcts and severe white matter lesions increased the stroke risk independently of each other. CONCLUSIONS: Elderly people with silent brain infarcts and white matter lesions are at a strongly increased risk of stroke, which could not be explained by the major stroke risk factors.

Aged↗
PubMed1988

Nuclear magnetic resonance image white matter lesions and risk factors for stroke in normal individuals.

The incidence, average number, and localization of lesions of the white matter detected by the T2-weighted nuclear magnetic resonance images among volunteers without cerebrovascular symptoms have been correlated with the number of risk factors for stroke. Accepted risk factors were arterial hypertension, diabetes mellitus, smoking, hypercholesterolemia, and cardiac disease. The 42 subjects examined were divided into Group A (0-1 risk factor, mean age 59.36 +/- 5.73 years), Group B (2 risk factors, mean age 61.54 +/- 8.33 years), and Group C (greater than or equal to 3 risk factors, mean age 62.57 +/- 9.83 years). Multiple risk factors among the age-matched groups was accompanied by a highly significant increase (p less than 0.001, Group A versus Group B; p less than 0.01, Group A versus Group C) of the incidence of white matter lesions. The average number of white matter lesions was increased (p less than 0.001) when Group A was compared with Groups B and C. Ninety-two percent of the white matter lesions were localized in watershed zones. Only 11 of the 155 abnormalities of the white matter detected by nuclear magnetic resonance imaging could be detected by computed tomography. White matter lesions in T2-weighted images appear to be an early stage of cerebrovascular disease.

Brain↗
PubMed1989

Cerebral cortical and white matter reactivity to carbon dioxide.

We measured cerebrovascular reactivity to carbon dioxide in the cerebral cortex and the subcortical white matter of 12 healthy adult volunteers (four young subjects aged 21-24, four middle-aged subjects aged 34-40, and four elderly subjects aged 62-85 years). Blood flow was computed from the concentration history of xenon-133 in the volume of interest measured with an ultrapure germanium detector array. End-tidal PaCO2 ranged from 35.4 to 42.6 mm Hg. The mean +/- SD baseline blood flows in the cerebral cortex were 60 +/- 7, 51 +/- 9, and 33 +/- 4 ml/100 cm3/min in the young, the middle-aged, and the elderly subjects, respectively; the corresponding subcortical white matter baseline blood flows were 21 +/- 1, 22 +/- 3, and 16 +/- 5 ml/100 cm3/min. Mean +/- SD cerebrovascular reactivities to carbon dioxide in the cerebral cortex were 2.03 +/- 0.58, 1.36 +/- 0.41, and 0.72 +/- 0.19 ml/100 cm3/min/mm Hg PaCO2 for the young, the middle-aged, and the elderly subjects, respectively; the corresponding reactivities in the subcortical white matter were 0.69 +/- 0.11, 0.59 +/- 0.17, and 0.36 +/- 0.41 ml/100 cm3/min/mm Hg PaCO2. Blood flow and cerebrovascular reactivity in the cerebral cortex of the young subjects were significantly higher than those for white matter and significantly higher than those in the elderly subjects (p less than 0.001). Age vs. blood flow (for the cortex) and age vs. cerebrovascular reactivity (for both cortical gray and subcortical white matter) also showed significant linear correlation (p less than 0.05). However, the age-related changes in white matter blood flow and cerebrovascular reactivity were slow, and the differences among the age groups were not statistically significant.

Adult↗
PubMed1993

Lacunar infarcts and white matter attenuation. Ophthalmologic and microcirculatory aspects of the pathophysiology.

BACKGROUND AND PURPOSE: By means of neurological and ophthalmologic examinations we considered whether there is a microcirculatory disorder not related to hypertension and diabetes in patients with lacunar infarcts and whether there are microcirculatory differences in patients with lacunar infarcts compared with those with white matter attenuation. METHODS: Eighty neurological patients with a lacunar infarct underwent computed tomography and, based on the results, were prospectively assigned to subgroups as follows: (1) patients without changes; (2) patients with white matter attenuation but without lacunar infarcts; (3) patients with lacunar infarcts alone; and (4) patients with both lacunar infarcts and white matter attenuation. Clinical and ophthalmologic parameters were monitored. The retinal microcirculation was studied by videofluorescence angiography. These neurological patients were compared with control ophthalmologic patients matched for age, sex, hypertensive and diabetic ocular fundus changes, and smoking habits. RESULTS: On average, the 80 patients with lacunar infarcts had a significantly (P = .0001) slower arteriovenous passage time (2.6 +/- 0.7 seconds) than the ophthalmologic control subjects (1.6 +/- 0.6 seconds). Arteriovenous dye passage time through the retinal microcirculation was nearly normal (2.2 +/- 0.8 seconds) in patients with white matter attenuation alone, but was significantly prolonged in patients with lacunar infarcts (2.9 +/- 0.8 seconds, P = .00085) or both white matter attenuation and lacunar infarcts (2.8 +/- 0.4 seconds, P = .008). CONCLUSIONS: Patients with lacunar infarcts are characterized by an additional disorder of retinal microcirculation independent of arterial hypertension and diabetes. Our data suggested that white matter attenuation and lacunar infarcts may be phenomena with only weak interdependence.

Aged↗
PubMed1994

Cognitive correlates of ventricular enlargement and cerebral white matter lesions on magnetic resonance imaging. The Rotterdam Study.

BACKGROUND AND PURPOSE: Ventricular enlargement and white matter lesions are frequent findings on cerebral magnetic resonance imaging scans of elderly subjects. In demented subjects they seem related to the severity of the dementia, but in nondemented subjects their clinical significance is less clear. We investigated the relation of size of the lateral ventricles and white matter lesions with cognitive function in a population-based random sample of nondemented elderly persons. METHODS: The study population consisted of 90 subjects, aged 65 to 84 years, who were randomly selected from the cohort of the Rotterdam Study, and who were not demented. The presence of white matter lesions and the ventricle-to-brain ratio were assessed on magnetic resonance scans. Participants were tested with a neuropsychological battery that covered a broad range of cognitive functions. RESULTS: Ventricular enlargement and white matter lesions were both and independently associated with poorer performance on all tests. After adjustment for age and sex, ventricular enlargement was significantly associated with worse scores on tests assessing global cognitive function (Mini-Mental State Examination, P = .02; Groninger Intelligence Test, P = .01), memory (Word List Learning delayed recall, P = .03), and executive control functions (Stroop part II, P = .02; Trial Making Test B, P < .01); for white matter lesions the differences were significant for tests measuring executive control functions and mental speed (Trail Making Test A and B, P = .01 and P < .01, respectively; verbal fluency, P = .01), and memory (Word List Learning delayed recall, P = .04). CONCLUSIONS: This study suggests that white matter lesions are primarily related to impairment of subcorticofrontal functions, whereas enlargement of the lateral ventricles is associated with disturbances of cortical functions as well.

Age Factors↗
PubMed1999

Clinical severity in CADASIL related to ultrastructural damage in white matter: in vivo study with diffusion tensor MRI.

BACKGROUND AND PURPOSE: CADASIL is a newly recognized cause of subcortical ischemic strokes that progressively leads to dementia associated with pseudobulbar palsy and severe motor disability. This deleterious progression and the severity of clinical presentation are widely variable among affected subjects. The exact role played by MRI white-matter abnormalities, a hallmark of the disease, in the severity of the clinical phenotype remains poorly understood. METHODS: To address this issue, we used diffusion tensor imaging (DTI), a new MRI technique highly sensitive to white-matter microstructural changes, in 16 symptomatic patients and 10 age-matched controls. Mean diffusivity and anisotropy of diffusion were measured within hyperintensities identified on T2-weighted images (T2WI) and outside these lesions on 4 slices at the level of centrum semiovale. RESULTS: We found a 60% increase of water mean diffusivity and a parallel loss of diffusion anisotropy in hyperintensities identified on T2WI. The same pattern of diffusion changes, but of lesser intensity, was found in the normal-appearing white matter on T2WI. Mean diffusivity in regions with increased signal on T2WI was higher in patients with severe clinical disability compared with those with no or mild deficit (1.33+/-0.11 versus 1.13+/-0.11 10(-3) mm(2)/s, P<0.01). Furthermore, diffusion measured within T2 hyperintensities correlated with both the Mini-Mental State Examination and Rankin scale scores. In patients with a severe clinical status, the increase of water diffusion in these regions exceeded 70% in comparison with values obtained in the normal white matter in control subjects. CONCLUSIONS: These results indicate that DTI is able to detect important ultrastructural changes in regions with increased signal on T2WI and within the normal-appearing white matter in CADASIL. The diffusion changes might be related to both neuronal loss and demyelination. The degree of the underlying ultrastructural alterations is related to the severity of the clinical status with a possible threshold level of white-matter damage above which severe neurological impairment may occur in this disease. DTI appears to be a promising technique for monitoring disease progression in CADASIL.

Adult↗
PubMed2001

Nociceptin/orphanin FQ exacerbates excitotoxic white-matter lesions in the murine neonatal brain.

Intracerebral administration of the excitotoxin ibotenate to newborn mice induces white-matter lesions, mimicking brain lesions that occur in human preterm infants. Nociceptin (NC), also called orphanin FQ, is the endogenous ligand of the opioid receptor-like 1 (ORL1) receptor and does not bind classical high-affinity opioid receptors. In the present study, administration of NC exacerbated ibotenate-induced white-matter lesions while coadministration of ibotenate with either of two NC antagonists reduced excitotoxic white-matter lesions by up to 64%. Neither ibotenate plus endomorphin I (a selective mu receptor agonist), nor ibotenate plus naloxone (a classical opioid receptor antagonist) modulated the excitotoxic lesion. Pretreatment with antisense oligonucleotides targeting the NC precursor peptide mRNA significantly reduced ibotenate-induced white-matter damage. Finally, high doses of fentanyl, which stimulates both classical mu-opioid receptors and ORL1, exacerbated excitotoxic white-matter lesion. This toxic effect was blocked by inhibiting ORL1 but not classical opioid receptors. Together, these findings show that endogenous or exogenous stimulation of the ORL1 receptor can be neurotoxic and that blocking NC signaling protects the white matter against excitotoxic challenge. These data point to potential new avenues for neuroprotection in human preterm infants at high risk of brain lesions.

Animals↗
PubMed1992

White matter hyperintensity signals in psychiatric and nonpsychiatric subjects.

OBJECTIVE: As part of an ongoing study investigating the relationship between brain morphology/function and neuropsychological performance in psychopathology, the authors conducted brain magnetic resonance imaging (MRI) studies to investigate the prevalence and psychiatric significance of white matter hyperintensity signals. METHOD: Brain MRI acquisition was done with 0.5 and 1.5 Tesla Philips scanners. Psychiatric subjects (N = 229) and normal volunteers (N = 154) were recruited by newspaper and local advertising and by physician referral. DSM-III-R criteria were used. White matter hyperintensity signals were rated on a 4-point scale of severity. Prevalence rates and risk ratios were calculated. RESULTS: Prevalence rates of hyperintensity signals in all psychiatric subjects (mean age = 34 years, SD = 9) and normal volunteers (mean age = 34, SD = 10) were 6.6% and 9.1%, respectively (a nonsignificant difference). When all psychiatric subjects, subjects under age 45, and subjects age 45 and over in a diagnostic category were considered, there were no statistically significant differences between them and normal volunteers in the same age groups in prevalence of schizophrenia, schizoaffective disorder, bipolar disorder, major depression, and obsessive-compulsive disorder. A significant difference existed between the severity of deep white matter hyperintensity signals in subjects with major depression and normal volunteers. Older age was correlated as a risk factor for white matter hyperintensity signals for psychiatric subjects. CONCLUSIONS: These results do not support previous findings of greater prevalence of hyperintensity signals in bipolar disorder. Significantly higher prevalence rates of hyperintensity signals were seen in subjects with major depression only when severity of the deep white matter hyperintensity signals was considered. Older age is an indirect risk factor for the presence of white matter hypertensity signals, probably as a result of vascular changes associated with concurrent medical illnesses.

Adult↗
PubMed2001

Structural abnormalities in frontal, temporal, and limbic regions and interconnecting white matter tracts in schizophrenic patients with prominent negative symptoms.

OBJECTIVE: Imaging studies of schizophrenia have repeatedly demonstrated global abnormalities of cerebral and ventricular volumes. However, pathological changes at more local levels of brain organization have not yet been so clearly characterized because of the few brain regions of interest heretofore included in morphometric analyses as well as heterogeneity of patient samples. METHOD: Dual echo magnetic resonance imaging (MRI) data were acquired at 1.5 T from 27 right-handed patients who met DSM-IV criteria for schizophrenia with enduring negative symptoms and from 27 healthy comparison subjects. Between-group differences in gray and white matter volume were estimated at each intracerebral voxel after registration of the images in standard space. The relationship between clinical symptom scores and brain structure was also examined within the patient group. Spatial statistics and permutation tests were used for inference. RESULTS: Significant deficits of gray matter volume in the patient group were found at three main locations: 1) the left superior temporal gyrus and insular cortex, 2) the left medial temporal lobe (including the parahippocampal gyrus and hippocampus), and 3) the anterior cingulate and medial frontal gyri. The volume of these three regions combined was 14% lower in the patients relative to the comparison subjects. White matter deficits were found in similar locations in the left temporal lobe and extended into the left frontal lobe. The patient group showed a relative excess of gray matter volume in the basal ganglia. Within the patient group, basal ganglia gray matter volume was positively correlated with positive symptom scores. CONCLUSIONS: Anatomical abnormalities in these schizophrenic patients with marked negative symptoms were most evident in left hemispheric neocortical and limbic regions and related white matter tracts. These data are compatible with models that depict schizophrenia as a supraregional disorder of multiple, distributed brain regions and the axonal connections between them.

Adult↗
PubMed2001

Relationship of deep white matter hyperintensities and apolipoprotein E genotype to depressive symptoms in older adults without clinical depression.

OBJECTIVE: This study examined whether evidence of cerebrovascular disease in the form of magnetic resonance imaging (MRI) signal hyperintensities in white matter was associated with depressive symptoms in a high-functioning group of normal elderly volunteers. METHOD: Ninety-two community-dwelling elderly individuals participating in a study of white matter hyperintensities (WMHs) in normal aging whose apolipoprotein E (APOE) genotype had been determined completed the Geriatric Depression Scale and received an MRI scan. Univariate analyses of variance were used to examine the relationship between depressive symptoms and the location of WMHs (in deep white matter versus in periventricular white matter) and to determine whether WMHs were more likely to be associated with symptoms of impaired motivation and concentration or with mood symptoms. The effect on depressive symptoms of the interaction between severity of cerebrovascular disease as evidenced by WMHs and APOE genotype was also examined. RESULTS: Hyperintensities in the deep white matter, but not in the periventricular white matter, were associated with depressive symptoms, especially symptoms of impaired motivation, concentration, and decision making. The relationship between deep WMHs and depressive symptoms was especially strong in individuals carrying the APOE-4 allele. CONCLUSIONS: The pattern of depressive symptoms associated with WMHs in this study was similar to the pattern described in the literature as characterizing "vascular" depression in older persons with major depression. The results suggest that cerebrovascular disease may also underlie the depressive symptoms often found in older individuals who are not clinically depressed.

Aged↗
PubMed2001

White matter lesions and season of birth of patients with bipolar affective disorder.

OBJECTIVE: It is established that patients with bipolar disorder have an excess of births in winter or early spring. The authors investigated a link between season of birth and white matter lesions with magnetic resonance imaging (MRI). METHOD: T(2)-weighted and proton density MRI scans were examined for 79 patients with bipolar disorder (DSM-IV) for the presence of deep subcortical and periventricular white matter lesions. The birth seasons of patients with white matter lesions were compared with those of the general population. RESULTS: Thirteen subjects exhibited deep subcortical white matter lesions, of whom nine (69.2%) were born in the winter months (January to March). Seven of these patients remained symptomatic, despite adequate treatment for more than 2 years. CONCLUSIONS: Birth season, illness outcome, and deep subcortical white matter lesions appear to be closely linked. Deep subcortical white matter lesions may be a marker of a toxic or infective insult in utero.

Adult↗
PubMed2002

Frontal white matter biochemical abnormalities in late-life major depression detected with proton magnetic resonance spectroscopy.

OBJECTIVE: Neuroanatomical abnormalities have been identified in patients with late-life mood disorders by using magnetic resonance imaging. This study examined the biochemical correlates of late-life major depression in the frontal gray and white matter by using single-voxel proton spectroscopy. METHOD: Twenty elderly patients with major depression and 18 comparison subjects similar in age and gender to the patients were scanned on a 1.5-T magnetic resonance scanner with head coil. Voxels were placed in the left dorsolateral white matter and bilaterally in the anterior cingulate gray matter. Absolute levels of N-acetylaspartate, choline, myo-inositol, and creatine were estimated with the LC-Model algorithm. Ratios of metabolite to creatine levels were computed from the absolute values. RESULTS: myo-Inositol/creatine and choline/creatine ratios were significantly higher in the frontal white matter in the major depression group than in the comparison group. The groups had no significant differences in the metabolite ratios in the gray matter. CONCLUSIONS: Biochemical changes in the white matter may provide some of the neurobiological substrates to late-life major depression.

Aged↗
PubMed2003

MRI assessment of gray and white matter distribution in Brodmann's areas of the cortex in patients with schizophrenia with good and poor outcomes.

OBJECTIVE: High-resolution magnetic resonance imaging (MRI) was used to compare cortical gray and white matter and CSF volumes in schizophrenia patients with poor outcomes, schizophrenia patients with good outcomes, and healthy comparison subjects. METHOD: T(1)-weighted, 1.2-mm-thick MR images were acquired for 37 patients with schizophrenia and 37 healthy, age- and sex-matched comparison subjects. The patients were assigned to subgroups with poor outcomes (N=13) and good outcomes (N=24) on the basis of clinical characteristics. Poor-outcome patients were those who were continuously hospitalized or completely dependent on others for basic needs, were unemployed, and had severe negative symptoms and severe formal thought disorder. The MR images were reoriented to standard position parallel to the anterior commissure-posterior commissure line and segmented into CSF, gray matter, and white matter tissue types. The tissue types were assigned to Brodmann's areas by using the Perry postmortem histological atlas, and tissue-type volumes in the three subject groups were compared. RESULTS: Compared to the healthy subjects, the overall patient group had a significantly smaller mean cortical gray matter volume and significantly larger mean CSF volume, especially in the frontal lobe and left temporal lobe. The smaller frontal lobe volume in schizophrenia was confirmed for unadjusted volumes and for volumes with adjustment for whole brain volumes. Compared to patients with good outcomes, patients with poor outcomes (Kraepelinian schizophrenia) had significantly smaller gray matter volumes in the temporal and occipital lobes, but no difference between groups was found for total frontal lobe volume. Only 21% of the healthy subjects had volumes 0.5 standard deviations below the mean for healthy subjects in any area of the frontal or temporal lobes, compared with 62% of poor-outcome patients. CONCLUSIONS: Poor outcome in patients with schizophrenia may be associated with a more posterior distribution (posteriorization) of gray matter deficits across widely distributed cortical regions.

Activities of Daily Living↗