Pulse pressure variability is associated with unfavorable outcomes in acute ischaemic stroke patients treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: Blood pressure (BP) variability has been associated with worse neurological outcomes in acute ischaemic stroke (AIS) patients receiving treatment with intravenous thrombolysis (IVT). However, no study to date has investigated whether pulse pressure (PP) variability may be a superior indicator of the total cardiovascular risk, as measured by clinical outcomes. METHODS: Pulse pressure variability was calculated from 24-h PP measurements following tissue plasminogen activator bolus in AIS patients enrolled in the Combined Lysis of Thrombus using Ultrasound and Systemic Tissue Plasminogen Activator for Emergent Revascularization (CLOTBUST-ER) trial. The outcomes of interest were the pre-specified efficacy and safety end-points of CLOTBUST-ER. All associations were adjusted for potential confounders in multivariable regression models. RESULTS: Data from 674 participants was analyzed. PP variability was identified as the BP parameter with the most parsimonious fit in multivariable models of all outcomes, and was independently associated (P < 0.001) with lower likelihood of both 24-h neurological improvement and 90-day independent functional outcome. PP variability was also independently related to increased odds of any intracranial bleeding (P = 0.011) and 90-day mortality (P < 0.001). Every 5-mmHg increase in the 24-h PP variability was independently associated with a 36% decrease in the likelihood of 90-day independent functional outcome (adjusted odds ratio 0.64, 95% confidence interval 0.52-0.80) and a 60% increase in the odds of 90-day mortality (adjusted odds ratio 1.60, 95% confidence interval 1.23-2.07). PP variability was not associated with symptomatic intracranial bleeding at either 24 or 36 h after IVT administration. CONCLUSIONS: Increased PP variability appears to be independently associated with adverse short-term and long-term functional outcomes of AIS patients treated with IVT.

Outcome in hyperglycemic stroke with ultrasound-augmented thrombolytic therapy.

Hyperglycemia independently predicts poor outcome after acute ischemic stroke. CLOTBUST (Combined Lysis Of Thrombus in Brain ischemia using transcranial Ultrasound and Systemic tPA) demonstrated that ultrasound-augmented thrombolysis improves recanalization and 24-hour outcome in patients with acute ischemic stroke. We hypothesized that ultrasound would preferentially benefit hyperglycemic patients, and reviewed CLOTBUST with respect to admission glucose and good outcome. We found that ultrasound's benefit on 90-day outcome was primarily apparent at higher glucose levels, suggesting that ultrasound therapy may improve outcome following hyperglycemic stroke.

Heterogeneity affecting outcome from acute stroke therapy: making reperfusion worse.

BACKGROUND: Stroke patients are heterogeneous not only with respect to etiology but also in terms of preexisting clinical conditions. Approximately one fifth of patients with acute stroke are hyperglycemic and/or have had a recent infectious or inflammatory condition. Summary of Review-- Experimental research indicates that these factors can alter and accelerate the evolution of stroke and reperfusion injury, although these effects are complex and some may have a favorable impact. Both conditions involve activation of inflammatory and reactive oxygen mechanisms. In addition, hyperglycemia has concomitant deleterious vascular and metabolic effects that worsen infarct size and encourage hemorrhagic transformation in reperfusion models. Clinical data are less extensive but in general support an adverse impact on outcome. CONCLUSIONS: After examining these data in detail, we concluded that the presence of these clinical conditions could assist in identification of those at increased risk for complications of reperfusion therapy. Furthermore, consideration of these factors may provide a rational basis for combination therapy and improve the clinical relevance of experimental stroke models.

Differential NF-kappa B regulation of bcl-x gene expression in hippocampus and basal forebrain in response to hypoxia.

Cell death often occurs after hypoxic/ischemic injury to the central nervous system. Changes in levels of the anti-apoptotic Bcl-X(L) protein may be a determining factor in hypoxia-induced neuronal apoptosis. The transcription factor NF-kappa B regulates bcl-x gene expression. In this study, we examined the role of NF-kappa B in the regulation of bcl-x in hypoxia-induced cell death. Rat hippocampus and basal forebrain tissues were collected at different time points after hypoxia (7%O(2), 93% N(2) for 10 or 20 min). We found that 1) hypoxia induced apoptosis in the hippocampus and basal forebrain; 2) the NF-kappa B dimers c-Rel/p50 and p50/p50 bound to the bcl-x promoter NF-kappa B sequence (CS4) in the hippocampus, but only p50/p50 bound to the CS4 sequence in the basal forebrain and hypoxia-induced differential binding patterns of c-Rel/p50 and p50/p50 correlated with the bcl-x expression pattern in the hippocampus; 3) the hypoxia-induced patterns of binding of c-Rel/p50 to the bcl-x promoter CS4 sequence were different from those to the IgG-kappa B enhancer sequence, whereas those of p50/p50 were similar to both sequences; 4) nuclear protein levels of c-Rel, but not p50, correlated with the c-Rel/p50 DNA binding patterns to the bcl-x CS4 site; and 5) there were differential responses to hypoxia among the different NF-kappa B protein subunits. These results suggest that there is a tissue-specific regulation of bcl-x gene expression by NF-kappa B in hypoxia-induced cell death in the hippocampus. The absence of these regulating features in the basal forebrain may account for the early appearance of apoptosis in response to hypoxia as compared with that in hippocampus.

Electrochemical monitoring of superoxide anion production and cerebral blood flow: effect of interleukin-1 beta pretreatment in a model of focal ischemia and reperfusion.

Conditions associated with systemic infection, such as endotoxinemia, are known to increase the levels of pro-inflammatory cytokines such as interleukin (IL)-1 in the central nervous system. Systemic infection has been shown to be a common preexisting condition in patients with stroke. To examine a possible consequence of systemic infection, we used a novel electrochemical technique, which combines measurement of cerebral blood flow with measurement of superoxide anion concentrations, to examine the effect of pretreatment of pial vasculature with a proinflammatory cytokine, IL-1 beta, on cerebral blood flow and superoxide anion concentration in a rat model of middle cerebral artery occlusion and reperfusion. In addition, neutrophil recruitment was measured using an immunohistochemical technique. Our results indicate that exposure of pial and cerebral vasculature to IL-1 beta significantly accelerates recruitment of neutrophils, reduces cerebral blood flow, and increases superoxide anion concentration at the pial surface during reperfusion. These results support the idea that prior exposure of brain vasculature to IL-1 beta results in acceleration of cerebrovascular injury by accelerating recruitment of neutrophils, which secrete superoxide anion, during reperfusion. This finding has possible implications for the treatment of stroke with reperfusion agents in patients with preexisting infections.

A fuzzy logic approach to identifying brain structures in MRI using expert anatomic knowledge.

We report a novel computer method for automatic labeling of structures in 3D MRI data sets using expert anatomical knowledge that is coded in fuzzy sets and fuzzy rules. The method first identifies major structures and then uses spatial relationships to these landmarks to recognize other structures. This labeling process simulates the iterative process that we ourselves use to locate structures in images. We demonstrate its application in three data sets, labeling brain MRI by locating the longitudinal and lateral fissures and the central sulci and then determining boundaries for the frontal lobes. Our method is adaptable to the identification of other anatomical structures.

Impulsive and premeditated aggression: a factor analysis of self-reported acts.

Although aggression research in general has been hampered by a lack of objective measurements of aggressive acts, two types of aggressive acts, impulsive vs. premeditated, have been studied extensively in recent years. These two types of aggression have been primarily measured by structured or semi-structured interviews. The current study was designed to assess the construct validity of these two types of aggression using a self-report questionnaire which included items gleaned from the content of interviews used in past studies. For this study, 216 college students assessed their own aggressive acts rather than answering general questions about aggression. The students were not significantly different from normative sample groups on self-report measures of impulsiveness, aggression, and anger/hostility. A PCA factor analysis with a promax rotation of the items on the self-report questionnaire identified four factors: impulsive aggression; mood on the day the act occurred; premeditated aggression; and agitation. Thus, impulsive and premeditated aggression are independent constructs which exist in varying degrees among these 'normal' persons in a non-clinical sample. Impulsive aggression was characterized in part by feelings of remorse following the acts and by thought confusion. Premeditated aggression was related to social gain and dominance.

Effect of NGF treatment on outcome measures in a rat model of middle cerebral artery occlusion.

Ischemic insults to the brain result in a time-dependent increase in neuronal death that is responsible for some of the functional deficits associated with stroke. Our working hypothesis is that ischemia results in a prompt depletion of high energy phosphate species resulting in decreased pH and glutathione levels in brain in a temporal and spatial pattern that disrupts nerve growth factor homeostasis and increases neuronal apoptosis. Here we show hemispheric depletion of active phosphate species after ischemia. Also, we observed that the striatum is an early target for oxidative stress that is followed by energy metabolic impairment and altered neurotrophin levels that were detected by noninvasive magnetic resonance imaging (MRI) measurements of cytotoxicity and conventional biochemical determinations of apoptosis, glutathione, and nerve growth factor (NGF) protein levels in a pattern distinct from that observed in the hippocampus. Furthermore, early assessment of intracellular pH by 31P-magnetic resonance spectroscopy (31P-MRS) was a predictor of later infarct development as determined by MRI. We also show that pretreatment with pharmacological doses of NGF did not have overall significant beneficial consequences on irreversible ischemia in an intraluminal unilateral irreversible model of stroke in rat brain.

New genetic hypothesis of schizophrenia.

Lack of complete concordance for schizophrenia in monozygotic twins has been interpreted as indicative of non-genetic cofactors in transmission of the illness. We present an alternative hypothesis that can parsimoniously explain, using known genetic mechanisms, the heredity pattern, the phenotypic spectrum and the biological abnormalities found in schizophrenia. The inheritance of a single recessive mutated allele of a gene crucial in brain development if followed by a somatic mutation in the normal allele during critical periods of brain development could result in developmental abnormalities that are expressed behaviorally as schizophrenic illness. Acquisition of this somatic mutation is likely enhanced during periods of intense cell division; therefore, the window of opportunity would be restricted to key periods in neurodevelopment. The somatic mutation may not always occur, thus explaining the variability of expression seen in the clinical population. Because the single allele mutation is still transmissible, the equal incidence of schizophrenia in the offspring of monozygotic twins discordant for the disease could also be explained. This possibility has implications for the development of genetic models and the source of genetic material for studies isolating the gene(s) of schizophrenia.

Superoxide anion production during reperfusion is reduced by an antineutrophil antibody after prolonged cerebral ischemia.

Neutrophils may be involved in the pathophysiology of reperfusion injury following cerebral ischemia. One potential mechanism of reperfusion injury by neutrophils is through production of the superoxide anion. We hypothesized that, due to progressive endothelial damage during ischemia, neutrophil activation would be more prominent after longer periods of ischemia prior to reperfusion. Thus, neutrophils would contribute more to pathological processes such as superoxide anion formation after longer than after shorter periods of ischemia. A reversible middle cerebral artery occlusion model in rats was employed and superoxide anion concentration was measured with a cytochrome c coated electrode placed on the cortical penumbral region. Occlusion times were varied from 60 min to 2 h, and neutrophils were inhibited with an antiCD18 antibody administered prior to occlusion. Neutrophil accumulation and reduction with antibody treatment was confirmed immunohistochemically. Superoxide anion (O2*-) concentration was detected during the hours following 60 min of occlusion, and increased further with 2 h of occlusion. Treatment with the antiCD18 antibody had no effect on O2*- concentration during reperfusion in the 60-90 min occlusion groups, but O2*- concentration was significantly lower in the antiCD18 antibody treated group than in the control group during reperfusion after 120 min of ischemia. The antibody also reduced cortical neutrophil accumulation in the 120 min ischemia group. These results indicate for the first time that superoxide production by neutrophils becomes more important with longer periods of ischemia, and other quantitatively less important sources of superoxide predominate with shorter periods of ischemia. This phenomenon may explain some of the variation seen between different models of ischemia with different durations of ischemia when targeting reactive oxygen species, and supports an approach to combination therapy to extend the therapeutic window and reduce the deleterious effects of reperfusion.

Enhanced neocortical neural sprouting, synaptogenesis, and behavioral recovery with D-amphetamine therapy after neocortical infarction in rats.

BACKGROUND AND PURPOSE: D-Amphetamine administration increases behavioral recovery after various cortical lesions including cortical ablations, contusions, and focal ischemia in animals and after stroke in humans. The purpose of the present study was to test the enhanced behavioral recovery and increased expression of proteins involved in neurite growth and synaptogenesis in D-amphetamine-treated rats compared with vehicle-treated controls after a focal neocortical infarct. METHODS: Unilateral neocortical ischemia was induced in male spontaneously hypertensive Wistar rats (n=8 per time point per group) by permanently occluding the distal middle cerebral artery and ipsilateral common carotid artery in 2 groups of rats: D-amphetamine treated (2 mg/kg IP injections) and vehicle treated (saline IP injections). To determine the spatial and temporal distribution of neurite growth and/or synaptogenesis, growth-associated protein (GAP-43), a protein expressed on axonal growth cones, and synaptophysin, a calcium-binding protein found on synaptic vesicles, were examined by immunohistochemical techniques, and both density and distribution of reaction product were measured. Since the resulting infarction included a portion of the forelimb neocortex, behavioral assessments of forelimb function using the foot-fault test of Hernandez and Schallert were performed on the same rats used for immunohistochemical studies during the period of drug action and 24 hours later. A Morris water maze and other indices of behavioral assays were also measured similarly. Recovery times were 3, 7, 14, 30, and 60 days postoperatively. RESULTS: Both GAP-43 and synaptophysin proteins demonstrated statistically significant increases in density and distribution of immunoreaction product as determined by optical density measurements in the neocortex of the infarcted group treated with D-amphetamines compared with vehicle-treated infarcted controls. The GAP-43 was elevated to statistically significant levels in forelimb, hindlimb, and parietal neocortical regions ipsilateral to the infarction only at days 3, 7, and 14. By contrast, the synaptophysin demonstrated no statistically significant changes in expression at 3 or 7 days but demonstrated statistically significant increases at 14, 30, and 60 days in the forelimb, hindlimb, and parietal neocortical regions ipsilateral to the infarction as well as increased distribution in the contralateral parietal neocortex. Behavioral assessment of forelimb function indicated that improved recovery of forelimb placement on the side contralateral to the infarction was statistically significant in the D-amphetamine-treated group compared with the vehicle-treated group (P<0.025). Spatial memory, as measured with the Morris water maze, worsened in the vehicle-treated group compared with the D-amphetamine-treated group at 60 days (P<0.025). CONCLUSIONS: These data support the occurrence of neurite growth followed by synaptogenesis in the neocortex in a pattern that corresponds both spatially and temporally with behavioral recovery that is accelerated by D-amphetamine treatment. While the specific mechanisms responsible for D-amphetamine-promoted expression of proteins involved in neurite growth and synaptogenesis and of enhanced behavioral recovery are not known, it is suggested that protein upregulation occurs as a result of functional activation of pathways able to remodel in response to active behavioral performance.

The 21-aminosteroid U-74389G reduces cerebral superoxide anion concentration following fluid percussion injury of the brain.

We examined the effects of the 21-aminosteroid antioxidant U-74389G (16-desmethyl-tirilazad) on the concentration of extracellular superoxide anion following fluid percussion traumatic brain injury (TBI) measured by a cytochrome c-coated electrode and on local cerebral perfusion (CBFld) measured by laser Doppler flowmetry (LDF). U-74389G in a dose of 3 mg/kg reduced superoxide anion concentrations 60 min after TBI significantly but had no significant effect on CBFld. These results indicate that reduction of CBF after TBI can be dissociated from superoxide anion production. Persistent ischemia may limit neuroprotection efficacy and may contribute to divergent outcome results in clinical and animal trials using agents to modify reactive oxygen species.

APE/Ref-1 responses to ischemia in rat brain.

Cerebral ischemia and the aftermath of reperfusion form a hypoxic/hyperoxic sequence of events that can trigger oxidative stress response cascades in neurons of the central nervous system. After transient ischemia there is an increase in intracellular Ca2+ release, extracellular glutamate, reactive oxygen species (ROS) and nitric oxide, genotoxic events that stimulate DNA repair. Increased oxidative stress and interrupted blood flow in ischemia, like DNA repair, also deplete cellular ATP and commit neurons to apoptosis. We report that levels of the DNA repair enzyme apurinic/apyrimidinic endonuclease (APE/Ref-1) decreased significantly in the hippocampus but not other brain areas after 6 h of reperfusion following an induced ischemic insult. This specific inhibition of APE/Ref-1 expression may affect the extent of apoptosis after ischemia.

The effects of phenytoin on impulsive and premeditated aggression: a controlled study.

Studies of the effects of phenytoin on aggression have produced equivocal results primarily because of a lack of (1) common objective criterion measures of aggressive acts across studies; (2) rigorous inclusion and exclusion criteria for selecting subjects; and (3) a nosologic basis for classifying different types of aggression. The current study was designed to remedy these deficiencies. Aggression was defined using a nosology that defines three types of aggression: (1) medically related; (2) premeditated; and (3) impulsive. The purpose of this study was to test the hypothesis that phenytoin will decrease impulsive aggressive acts but not have a significant influence on premeditated aggressive acts. Sixty inmates were divided into two groups on the basis of committing primarily impulsive aggressive acts or premeditated aggressive acts while in prison. Medical aggression was ruled-out by subject selection. The study used a double-blind, placebo-controlled, crossover design. As hypothesized, phenytoin (200 mg a.m. and 100 mg p.m.) significantly reduced impulsive aggressive acts but not premeditated aggressive acts. Event-related potentials (ERPs) measured information processing in the cortex during drug/placebo conditions. The amplitudes of P300 ERP waveforms among impulsive aggressive subjects were increased significantly during the phenytoin condition but not during the placebo condition. There were no significant changes in P300 ERP waveforms between drug/placebo conditions among nonimpulsive aggressive subjects.

Moclobemide in social phobia: a controlled dose-response trial.

Although the monoamine oxidase inhibitor phenelzine has proven efficacious in social phobia, the risk of hypertensive crises has reduced its acceptability. The reversible monoamine oxidase inhibitor moclobemide has less potential for such reactions, but its efficacy in this disorder remains unproven. A double-blind, placebo-controlled study was undertaken to assess the efficacy and safety of fixed doses of moclobemide. After a 1-week placebo run-in, subjects with social phobia were randomly assigned to placebo or one of five doses (75 mg, 150 mg, 300 mg, 600 mg, or 900 mg daily) of moclobemide for 12 weeks. Although a trend toward greater efficacy of higher doses of moclobemide was observed at 8 weeks, no differences in response to various doses of the drug and placebo were observed at 12 weeks. At 12 weeks, 35% of subjects on 900 mg of moclobemide and 33% of those on placebo were at least much improved. Moclobemide was well tolerated, insomnia being the only dose-related adverse event observed with the drug. In this dose-response trial, moclobemide did not demonstrate efficacy at 12 weeks. Some other controlled studies have found moclobemide and brofaromine, another reversible monoamine oxidase inhibitor, efficacious in social phobia. Possible reasons for inconsistent findings are discussed.

NG-nitro-L-arginine methyl ester modifies the input function measured by dynamic susceptibility contrast magnetic resonance imaging.

In rat brain dynamic susceptibility contrast magnetic resonance (MR) images, vessels visible on the same scan plane as the brain tissue were used to measure the characteristics of the input function of the MR contrast agent gadopentetate dimeglumine. MR images were acquired 30 and 60 minutes after intravenous injections of 3 mg/kg and 15 mg/kg NG-Nitro-L-arginine methyl ester (L-NAME) (n = 9). The time of arrival (TOA) and the mean transit time corrected for TOA of the input function were increased by 3 mg/kg or 15 mg/kg L-NAME. The area of the input function was increased by 15 mg/kg L-NAME. In two animals, similar modifications of the input function induced by 20 mg/kg L-NAME were reversed by infusion of sodium nitroprusside. In two other animals, MABP was increased by phenylephrine to a similar extent as in L-NAME experiments, but did not induce the same modifications of the input function, showing that the action of L-NAME on the input function was not simply caused by an effect on MABP. These results show that the input function can be significantly altered by manipulations widely used in cerebrovascular studies. These input function changes have important implications for calculation of cerebral blood flow.

Perfusion deficit parallels exacerbation of cerebral ischemia/reperfusion injury in hyperglycemic rats.

Magnetic resonance imaging (MRI) techniques were used to determine the effect of preexisting hyperglycemia on the extent of cerebral ischemia/reperfusion injury and the level of cerebral perfusion. Middle cerebral artery occlusion (MCAO) was induced by a suture insertion technique. Forty one rats were divided into hyperglycemic and normoglycemic groups with either 4 hours of continuous MCAO or 2 hours of MCAO followed by 2 hours of reperfusion. Diffusion-weighted imaging (DWI) was performed at 4 hours after MCAO to quantify the degree of injury in 6 brain regions. Relative cerebral blood flow (CBF) and cerebral blood volume (CBV) were estimated using gradient echo (GE) bolus tracking and steady-state spin echo (SE) imaging techniques, respectively. Brain injury correlated with the perfusion level measured in both SE CBV and dynamic GE CBF images. In the temporary MCAO model, mean lesion size in DWI was 118% larger and hemispheric CBV was reduced by 37% in hyperglycemic compared with normoglycemic rats. Hyperglycemia did not significantly exacerbate brain injury or CBV deficit in permanent MCAO models. We conclude that preexisting hyperglycemia increases acute postischemic MRI-measurable brain cellular injury in proportion to an associated increased microvascular ischemia.

Neuropsychological and cognitive psychophysiological substrates of impulsive aggression.

The purpose of this study was to test whether subjects who commit impulsive vs non-impulsive aggression differ on measurements of personality, neuropsychology, and cognitive psychophysiology, and whether these differences can yield information regarding the etiology of impulsive aggression. Subjects were two groups of prison inmates, distinguished by their committal of impulsive or nonimpulsive aggression, and matched noninmate controls. All inmates met DSM III-R criteria for an antisocial personality disorder but for no other disorder. Impulsiveness, anger, and peak P300 latencies did not differ between the inmate groups, but verbal symbol decoding and peak P300 amplitudes did. Impulsiveness and verbal skills were inversely correlated. Impulsiveness was inversely correlated with, and verbal skills positively correlated with P300 amplitudes. The results indicate that aggression is not homogenous, even among antisocial persons, and that impulsive aggression is related to neuropsychological and cognitive psychophysiological measures of information processing beyond those factors related to criminality alone.

DNA binding and transcriptional enhancement by purified TCDD.Ah receptor complex.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcriptional enhancer which mediates the biochemical and toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and structurally related chemicals and which may have a role in the normal development of some tissues. We have previously reported the purification of the transformed TCDD.receptor complex from rat liver cytosol based on binding to its dioxin-responsive enhancer sequence (DRE) and that it comprises the AhR ligand-binding monomer and its dimerization partner, ARNT. The present studies were designed to compare the DRE-binding characteristics of the purified receptor with the cruder preparations that are commonly used and ultimately to determine whether the purified receptor complex itself (in the absence of additional cytosolic or nuclear factors) is capable of enhancing transcription in an in vitro system. The purified AhR retained in vitro DRE binding activity in the presence of carrier protein and dithiothreitol, and its affinity for the DRE oligonucleotide was equivalent to that of the other receptor preparations (crude and partially purified cytosolic and crude nuclear). When the ligand.receptor complex was bound to a DRE oligonucleotide containing BrdU and then UV-irradiated, two proteins in each of the receptor preparations were found to crosslink to BrdU-DRE, and we concluded that they are the AhR monomer and ARNT protein. All receptor preparations also gave a similar footprint of interaction with G-residues within the DRE consensus sequence, as assessed by methylation interference. Furthermore, purified and partially purified receptors were able to stimulate transcription from a DRE-containing template in a cell-free system in the presence of HeLa cell nuclear extract. Transcriptional enhancement was receptor dose-dependent, TCDD-dependent, and specific for the DRE sequence upstream of the promotor in our template construct. These data document for the first time that a purified TCDD.Ah receptor complex retains both specific DNA binding and transcriptional activities. This observation constitutes an important step toward understanding the mechanism of gene regulation by TCDD since it implies that the transformed receptor.ligand complex itself is competent as a transcriptional enhancer without a requirement for other factors.

Expansion of the cerebral ventricles and correlation with acquired immunodeficiency syndrome neuropathology in 232 patients.

BACKGROUND: Expansion of the cerebral ventricles is highly prevalent in patients with the acquired immunodeficiency syndrome (AIDS). The mechanism remains unclear. The purpose of this study was to correlate the volume of the cerebral ventricles with histopathologic abnormalities in the brain. METHODS: At autopsy, the volume of the cerebral ventricles in brain slices was estimated planimetrically in 232 patients with AIDS and 77 age-appropriate controls. Estimated volumes were compared with the neuropathologic results using multiple regression analysis. RESULTS: Multiple regression analysis demonstrated a significant relationship between ventricular volume and cerebral cytomegalovirus infection (P < .0004). When human immunodeficiency virus (HIV) encephalitis with multinucleated cells was present, median volume did not differ significantly from other subjects with AIDS. In 11 patients who had HIV-1 proviral DNA detected using the polymerase chain reaction, average volume was not different from 22 patients who tested negatively using polymerase chain reaction. Ventricular expansion did not have a clear-cut neuropathologic substrate in many instances. CONCLUSIONS: In some subjects with AIDS, cytomegalovirus encephalitis was the underlying neuropathologic lesion associated with ventricular expansion. Key indicators of brain HIV-1 infection were related either weakly or not at all, and the role of HIV-1 remains uncertain in most cases.