Distinct clinical and metabolic deficits in PCA and AD are not related to amyloid distribution.

BACKGROUND/OBJECTIVE: Patients with posterior cortical atrophy (PCA) often have Alzheimer disease (AD) at autopsy, yet are cognitively and anatomically distinct from patients with clinical AD. We sought to compare the distribution of ß-amyloid and glucose metabolism in PCA and AD in vivo using Pittsburgh compound B (PiB) and FDG-PET. METHODS: Patients with PCA (n = 12, age 57.5 ± 7.4, Mini-Mental State Examination [MMSE] 22.2 ± 5.1), AD (n = 14, age 58.8 ± 9.6, MMSE 23.8 ± 6.7), and cognitively normal controls (NC, n = 30, age 73.6 ± 6.4) underwent PiB and FDG-PET. Group differences in PiB distribution volume ratios (DVR, cerebellar reference) and FDG uptake (pons-averaged) were assessed on a voxel-wise basis and by comparing binding in regions of interest (ROIs). RESULTS: Compared to NC, both patients with AD and patients with PCA showed diffuse PiB uptake throughout frontal, temporoparietal, and occipital cortex (p < 0.0001). There were no regional differences in PiB binding between PCA and AD even after correcting for atrophy. FDG patterns in PCA and AD were distinct: while both groups showed hypometabolism compared to NC in temporoparietal cortex and precuneus/posterior cingulate, patients with PCA further showed hypometabolism in inferior occipitotemporal cortex compared to both NC and patients with AD (p < 0.05). Patients with AD did not show areas of relative hypometabolism compared to PCA. CONCLUSIONS: Fibrillar amyloid deposition in PCA is diffuse and similar to AD, while glucose hypometabolism extends more posteriorly into occipital cortex. Further studies are needed to determine the mechanisms of selective network degeneration in focal variants of AD.

CT angiography and diffusion-perfusion MR imaging in a patient with ipsilateral reversible cerebral vasoconstriction after carotid endarterectomy.

Reversible cerebral vasoconstriction syndromes (RCVS) typically affect the bilateral medium-sized intracerebral arteries and their branches. We describe a woman with RCVS restricted to the ipsilateral hemisphere after carotid endarterectomy. Serial CT angiography proved useful in documenting vasoconstriction. Perfusion MR imaging showed hypoperfusion in the deep watershed regions of the ipsilateral cerebral arteries but relatively normal perfusion in superficial cortical regions. Diffusion MR imaging showed progressive borderzone infarcts. These novel imaging findings provide insights into the pathophysiology of stroke in RCVS.

Sex differences in corpus callosum size: relationship to age and intracranial size.

This quantitative MRI study reports measurement of corpus callosum area taken from midsagittal brain images in 51 healthy men and 41 healthy women, spanning the adult age range (22 to 71 years). Men had larger brains and corpora callosa than women, but callosal size did not correlate with age in either sex. Intracranial (i.c.) volume (ICV) and midsagittal i.c. area (ICA) of brain were used in covariate, regression, and ratio analyses to determine whether sex differences in the corpus callosum endured with statistical adjustment for sex differences in maximally attained brain size. With the exception of one ratio measure, the different statistical adjustments for the contribution of sex differences in brain size to corpus callosum size all indicated that men had larger corpora callosa than women for their brain size. A subsample of men and women selected to be matched on i.c. volume and age confirmed this statistical observation. Sexual dimorphism in the corpus callosum is not a simple artifact of sex differences in brain size and may reflect differences in connectivity necessitated by differences in brain size.

Sex differences in the effects of alcohol on brain structure.

OBJECTIVE: This study investigated whether alcoholic women manifest deficits in cortical gray and white matter volumes and ventricular enlargement similar to those seen in alcoholic men. METHOD: Volumetric measures of intracranium, cortical gray matter, white matter and sulci, and lateral and third ventricles were obtained from magnetic resonance images of 42 women and 44 men with DSM-III-R alcoholism and age-matched healthy comparison groups (37 women and 48 men). Groups of alcoholic men and women were matched on age and length of sobriety, but men had a 2.5 times higher lifetime alcohol consumption than women. RESULTS: Women, regardless of diagnosis, had less cortical gray and white matter and smaller third ventricles than men, consistent with sex-related differences in intracranial volume. Alcoholics had larger volumes of cortical sulci and lateral and third ventricles than comparison subjects. Diagnosis-by-sex interactions for cortical white matter and sulcal volumes were due to abnormalities in alcoholic men but not alcoholic women, relative to same-sex comparison subjects. This interaction persisted for cortical sulci after covarying for lifetime alcohol consumption. Slopes relating cortical gray matter and sulcal volumes to age were steeper in alcoholic than in comparison men. Slopes relating lateral ventricle volume to age were steeper in alcoholic than in comparison women. In alcoholic women, longer sobriety was associated with larger white matter volumes. CONCLUSIONS: Alcoholic men and women show different brain morphological deficits, relative to same-sex comparison subjects. However, age and alcoholism interact in both sexes, which puts all older alcoholics at particular risk for the negative sequelae of alcoholism.

Contribution of alcohol abuse to cerebellar volume deficits in men with schizophrenia.

BACKGROUND: It is controversial whether cerebellar tissue volume deficits occur in schizophrenia and, if so, what regions and tissue types are affected. Complicating such investigations is the high incidence of alcoholism comorbidity in patients with schizophrenia that itself can contribute to cerebellar abnormalities. METHOD: We studied 61 healthy men (control subjects), 25 men with alcoholism, 27 men with schizophrenia, and 19 men comorbid for schizophrenia and alcoholism with the use of magnetic resonance imaging. Cerebellar structures were outlined manually, tissue classification was determined statistically, and regional volumes were corrected for normal variation in head size and age. RESULTS: Patients with schizophrenia alone had enlarged fourth ventricles (1.5 SD relative to controls) but showed no cerebellar tissue volume deficits. The alcoholic group had gray and white matter vermian deficits (-0.5 SD), most prominent in anterior superior lobules, and gray matter hemisphere deficits (-0.8 SD), but not fourth ventricle enlargement. The comorbid group had cerebellar hemisphere (-1.3 SD) and vermian gray matter volume deficits (-0.7 SD) and fourth ventricular enlargement (1.6 SD); these abnormalities were greater than in either single-diagnosis group, despite significantly lower levels of alcohol consumption compared with the alcoholic group. Gray matter volume in the anterior superior vermis correlated with lifetime alcohol consumption in the schizophrenic and comorbid groups when combined. CONCLUSIONS: Cerebellar tissue volume deficits were detected in schizophrenia only when accompanied by alcoholism. By contrast, fourth ventricular enlargement occurred in schizophrenia even without alcoholism, although it was exacerbated by alcoholism. These findings support a model of cerebellar supersensitivity to alcohol-related tissue volume deficits in schizophrenia.

Pattern of motor and cognitive deficits in detoxified alcoholic men.

BACKGROUND: Chronic excessive consumption of alcohol produces marked deficits in cognitive and motor abilities, although not all functions are affected to the same extent. Furthermore, although the occurrence of neuropsychological deficits in recently detoxified alcoholics is firmly established, the relative severity of these deficits, the specific neural systems that underlie the deficits, and their relationship to age and alcohol consumption variables either are less established or have proven elusive altogether. METHODS: We administered an extensive battery of neuropsychological tests, chosen for their known sensitivity to brain lesions in specific locations, to 71 recently (1 month) detoxified alcoholic men and 74 healthy controls who spanned the adult age range. Test scores were standardized to the controls for age and grouped a priori into composites that reflected performance in six functional domains: executive functions, short-term memory, upper limb motor ability, declarative memory, visuospatial abilities, and gait and balance. Analogous verbal and nonverbal materials and left- and right-hand upper limb motor tasks were used to test whether alcohol-related deficits were greater for left or right hemisphere. RESULTS: Compared with controls, the alcoholics were impaired on executive functions, visuospatial abilities, and gait and balance even after we accounted for group differences in estimated premorbid IQ and education. Within the alcoholic group, the most salient deficits were in gait and balance and visuospatial abilities. No consistent lateralized deficit was observed across the four domains tested. Unlike the cognitive composites, the upper limb motor ability and gait and balance composites both showed increasing vulnerability to age, with an independent contribution to the gait and balance dysfunction from the amount of alcohol consumed over a lifetime. CONCLUSIONS: The pattern of functional deficits implicates at least two principal neural systems: the cerebellar-frontal system and the corticocortical system between the prefrontal and parietal cortices. In addition, age and amount of alcohol consumption were better predictors of motor than cognitive impairments.

Longitudinal changes in cognition, gait, and balance in abstinent and relapsed alcoholic men: relationships to changes in brain structure.

Chronic alcoholism is associated with cognitive and motor deficits, and there is evidence for reversibility with sobriety. Alcoholic men were examined after 1 month of sobriety and 2 to 12 months later with cognitive and motor tests and magnetic resonance imaging. In this naturalistic study, 20 alcoholic participants had abstained and 22 had resumed drinking at retesting. Abstainers sustained greater improvement than relapsers on tests of delayed recall of drawings, visuospatial function, attention, gait, and balance. Shrinkage in 3rd ventricle volume across all participants significantly correlated with improvement in nonverbal short-term memory. Additional brain structure-function relationships, most involving short-term memory, were observed when analyses were restricted to alcoholic men who had maintained complete abstinence, were light relapsers for at least 3 months, or had consumed no more than 10 drinks prior to follow-up testing. Thus, alcoholic men who maintain abstinence can show substantial functional improvement that is related to improvement in brain structure condition.

P300 reduction and prolongation with illness duration in schizophrenia.

BACKGROUND: The P300 component of the auditory event-related potential (ERP) is both reduced in amplitude and delayed in schizophrenia. P300 is prolonged and, less consistently, reduced with normal aging. Additional latency delays are observed in neurodegenerative disorders. We asked whether P300 is reduced and delayed with longer illness duration in schizophrenia, consistent with a neurodegenerative process. METHODS: P300 amplitude and latency were recorded to infrequent auditory target stimuli from 35 men with schizophrenia (DSM-III-R) and 26 control men. Effects of current age, age of onset, and duration of illness on P300 were assessed using regression analysis. RESULTS: P300 amplitude showed no age-related decrease in either group; however, among schizophrenic participants, P300 amplitude correlated positively with onset age and negatively with illness duration. P300 latency correlated positively with age in schizophrenic participants and also tended to increase with age in controls. Slopes of the latency-age relationships were significantly greater in schizophrenic participants than in control participants. Latency also correlated positively with illness duration but showed no relationship to onset age. CONCLUSIONS: P300 amplitude and latency are reduced and delayed with longer illness duration in schizophrenia, consistent with a progressive pathophysiological process. Reduced P300 amplitude may also be a marker of an early onset variant of schizophrenia.

In vivo mammillary body volume deficits in amnesic and nonamnesic alcoholics.

BACKGROUND: Neuropathological studies use the presence of mammillary body (MB) pathology as a cardinal, diagnostic feature of Wernicke's encephalopathy (WE) in neuropsychiatric diseases, most notably alcoholism. Although Korsakoffs Syndrome (KS), which is marked behaviorally by dense global amnesia, is a typical sequela of WE, it remains controversial whether these two conditions necessarily co-occur and whether MB pathology is therefore a diagnostic requisite for KS. METHODS: We investigated these issues by examining, in vivo, 24 nonamnesic alcoholics (ALC), 5 amnesic alcoholics (KS), and 51 normal controls with three-dimensional MRI and memory testing. MB volume was determined from successive, 1 mm thick slices. RESULTS: The ALC group had significantly smaller MB volumes bilaterally (mean = 54.5 +/- 22.0 mm3) than controls (mean = 66.3 +/- 17.1 mm3), and the KS group had even smaller MB volumes than the ALC group (mean = 20.7 +/- 14.8 mm3). Only 2 ALC patients met historical clinical criteria for past WE, and their MB volumes were well within range of the remaining 22 ALC patients. Although all five KS patients met historical clinical criteria for WE, three KS did not have accompanying dementia and had the same degree of MB volume loss as the ALC; the remaining two KS had accompanying dementia and MB volumes half the volume of the ALC group and of KS patients without dementia. CONCLUSIONS: These findings provide volumetric in vivo evidence that: (1) MB volume deficits do occur in alcoholics without amnesia, although these deficits are not present in ail such alcoholics; (2) greater MB volume deficits are present in alcoholics with clinically detectable amnesia or dementia; (3) MB shrinkage is related to severity of cognitive and memory dysfunction, which suggests a continuum of MB pathology in chronic alcoholism to KS; and (4) the presence of WE in all of the KS patients and in the two ALC patients with the greatest long-term declarative memory deficit supports the possibility of an additional and unique pathology distinguishing nonamnesic and amnesic alcoholism.

Does sufentanil concentration influence isoflurane requirements during coronary artery bypass grafting?

OBJECTIVE: To search for concentration-related suppression of hemodynamic responsiveness by sufentanil. DESIGN: Prospective, randomized, double-blind study. SETTING: University hospital. PARTICIPANTS: Patients undergoing elective coronary artery bypass grafting (CABG). INTERVENTION: Patients were assigned to target effect-site sufentanil concentrations of 1.5 ng/mL (group L; n = 14), 3.0 ng/mL (group M; n = 13), or 4.5 ng/mL (group H; n = 12). Sufentanil was administered by computer-assisted continuous infusion. Isoflurane was used to maintain intraoperative hemodynamics near preoperative values. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, the electroencephalographic spectral edge (SE95), and end-tidal isoflurane concentration (ET-ISO) were measured every 10 to 30 seconds during the prebypass period. Serum sufentanil concentration was measured at intervals. Prebypass serum sufentanil concentrations were stable, averaging 3.0 +/- 0.7, 5.1 +/- 1.1, and 7.1 +/- 1.3 ng/mL in groups L, M, and H, respectively. The groups did not differ with respect to the speed of induction, intraoperative hemodynamics, incidence of isoflurane use, or isoflurane concentrations required. ET-ISO and serum sufentanil levels were not correlated. Among seven group L patients who did not require isoflurane, the average prebypass serum sufentanil concentration ranged from 1.7 to 3.3 ng/mL. CONCLUSION: Sufentanil does not induce concentration-related suppression of hemodynamic responsiveness over the range studied. A stable serum sufentanil concentration of 3.0 +/- 0.7 ng/mL induces the maximal opioid effect and need not be exceeded in patients undergoing CABG. A sufentanil concentration of 1.7 ng/mL provides clinically adequate anesthesia without supplementation in some premedicated patients undergoing CABG.

A two-center study evaluating the hemodynamic and pharmacodynamic effects of cisatracurium and vecuronium in patients undergoing coronary artery bypass surgery.

OBJECTIVE: To determine the hemodynamic and pharmacodynamic effects of rapid bolus administration of cisatracurium compared with vecuronium. DESIGN: A randomized, prospective, double-blind study. SETTING: Tertiary-care university hospitals. PARTICIPANTS: Seventy-nine adult patients with diagnosed coronary artery disease (CAD). INTERVENTION: Elective coronary artery bypass graft surgery (CABG). MEASUREMENTS AND MAIN RESULTS: Patients were randomly divided into four groups. Patients received a rapid bolus of two or four times the 95% peak depression of twitch (ED95) of either cisatracurium (groups 1 and 2) or vecuronium (groups 3 and 4). Three minutes after a midazolam induction, all patients received a rapid bolus administration of either study drug. Maintenance of anesthesia was with a standardized propofol-sufentanil-oxygen anesthetic. Patients were monitored with radial and pulmonary artery catheters and electromyography. End points of the study were hemodynamic stability at induction, after bolus administration of study drugs, and after intubation; the quality of intubating conditions; drug interventions to correct hemodynamic instability; the onset, duration, and recovery of neuromuscular function; and drug cost. Mean arterial pressure (MAP) and heart rate (HR) decreased in a similar proportion in all four groups after induction while, following study drug administration, MAP and HR did not change significantly. Both cisatracurium groups required more boluses to maintain neuromuscular block, but spontaneous recovery rates were faster. Both agents, but cisatracurium to a lesser degree, showed increased duration with repeated maintenance doses. Both agents afforded good to excellent intubating conditions, but the cost of cisatracurium was significantly less. CONCLUSION: The authors conclude there is no evidence of a hemodynamic difference between the two neuromuscular blocking drugs (NMBDs). There are some clinical and cost advantages in favor of cisatracurium.

Cortical gray matter deficit in patients with bipolar disorder.

BACKGROUND: cortical gray matter volume deficit and ventricular enlargement are well documented in schizophrenia, but their presence in bipolar disorder is less well established. METHODS: global cortical gray matter, white matter and sulcal CSF, as well as lateral and third ventricular volume measures, were derived from axial MRI brain images obtained on age-matched bipolar (n=9), schizophrenic (n=9), and control (n=16) subjects. All subjects were free of history of alcohol or other substance dependence. RESULTS: relative to controls, bipolar patients had widespread volume deficits of cortical gray matter but not of cortical white matter. Schizophrenic patients had an even more severe cortical gray matter deficit and greater sulcal and lateral ventricular enlargement than the bipolar patients. CONCLUSIONS: this group of patients with bipolar disorder had a widespread deficit of cortical gray matter similar to, but less pronounced than, that observed in patients with schizophrenia.

Hemodynamics and left ventricular mass regression following implantation of the Toronto SPV stentless porcine valve.

Stentless tissue valves may provide more favorable hemodynamics than conventional stented valves. Hemodynamic findings from a large multicenter trial have not been previously reported. The present report describes the hemodynamic findings from a multinational, multicenter study after implantation of the Toronto SPV valve. A total of 577 patients underwent aortic valve replacement with the Toronto SPV valve at 12 sites in 3 countries. Echocardiograms were recorded in the early postoperative period, 3 to 6 months after surgery, 1 year after surgery, and yearly thereafter, with follow-up to 3 years. Gradients decreased and effective orifice area increased in the months after surgery. One year after surgery, mean gradient for valve sizes 20 to 22, 23, 25, 27, and 29 mm was 7.3 +/- 4.4, 7.4 +/- 4.5, 6.1 +/- 3.3, 4.9 +/- 2.4, and 4.0 +/- 2.1 mm Hg, respectively; effective orifice area was 1.3 +/- 0.7, 1.5 +/- 0.5, 1.7 +/- 0.4, 2.0 +/- 0.4, and 2.4 +/- 0.6 cm2, respectively. There was a very low prevalence of significant aortic regurgitation at all time periods. There was significant left ventricular (LV) mass regression between the early and 3- to 6-month periods and between the 3- to 6-month and 1-year postoperative periods. The Toronto SPV valve has an excellent hemodynamic profile supported by significant regression of LV hypertrophy in the year after implantation. Data through 3 years demonstrates maintenance of low gradients and freedom from significant aortic regurgitation.

A controlled study of cortical gray matter and ventricular changes in alcoholic men over a 5-year interval.

BACKGROUND: We report on structural brain changes during a 5-year period in healthy control and alcoholic men. METHODS: Alcoholic patients (n = 16), from an initial group of 58 who underwent brain magnetic resonance imaging scanning while in treatment, were rescanned with the same acquisition sequence approximately 5 years later. Control subjects (n = 28) spanning the same age range also were scanned twice at a comparable interval. Changes in brain volume were corrected for error due to differences in head placement between scans and expressed as slopes (cubic centimeters per year), percentage of change over baseline for the control subjects, and standardized change for the alcoholic patients. The alcoholic patients varied considerably in the percentage of time that symptoms of alcohol dependence were present and in the amount of alcohol consumed during follow-up. RESULTS: The cortical gray matter diminished in volume over time in the control subjects, most prominently in the prefrontal cortex, while the lateral and third ventricles enlarged. The alcoholic patients showed similar age-related changes with a greater rate of gray matter volume loss than the control subjects in the anterior superior temporal lobe. The amount of alcohol consumed during follow-up predicted the rate of cortical gray matter volume loss, as well as sulcal expansion. The rate of ventricular enlargement in alcoholic patients who maintained virtual sobriety was comparable to that in the control subjects. CONCLUSIONS: During a 5-year period, brain volume shrinkage is exaggerated in the prefrontal cortex in normal aging with additional loss in the anterior superior temporal cortex in alcoholism. The association of cortical gray matter volume reduction with alcohol consumption over time suggests that continued alcohol abuse results in progressive brain tissue volume shrinkage.

Association between regional brain volumes and clozapine response in schizophrenia.

BACKGROUND: Clozapine has shown considerable therapeutic promise in the treatment of schizophrenia; however, the clinical risks and initial high treatment costs associated with its administration motivate the search to identify patients who will best respond. Neuroimaging studies have suggested that prefrontal sulcal prominence may be a predictor of nonresponsiveness. METHODS: We used magnetic resonance imaging (MRI) to test whether volumes in any cortical regions of the brain were associated with symptom improvement with clozapine treatment. The 21 schizophrenic men studied were clinically evaluated during treatment with typical neuroleptics (baseline) and after a mean of 6.2 months treatment with clozapine (final dose 300-900, median = 562 mg/day). At least a 20% improvement on total Brief Psychiatric Rating Scale (BPRS) was seen in 47.6% of the schizophrenics. Clinical improvement was regressed on baseline differences in clinical severity, and the residual scores were related to MRI values. RESULTS: Patients with larger anterior superior temporal lobe cerebrospinal fluid volumes (primarily sylvian fissure) showed greater improvement on total BPRS and withdrawal/retardation symptoms. CONCLUSIONS: Even schizophrenics with significant brain dysmorphology can have a positive clinical response to clozapine.

Proton magnetic resonance spectroscopic imaging of cortical gray and white matter in schizophrenia.

OBJECTIVE: To apply in vivo proton magnetic resonance spectroscopy imaging estimates of N-acetylaspartate (NAA), a neuronal marker, to clarify the relative contribution of neuronal and glial changes to the widespread volume deficit of cortical gray matter seen in patients with schizophrenia with magnetic resonance images. METHODS: Ten male veterans meeting criteria of the DSM-IV, for schizophrenia and 9 healthy age-matched men for comparison were scanned using spectroscopic, anatomical, and field-map sequences. Instrument and collection variables were standardized to allow an estimation of comparable values for NAA, choline, and creatine for all subjects. Metabolite values from each voxel on 3 upper cortical slices were regressed against the gray tissue proportion of that voxel to derive estimates of gray and white matter NAA, creatine, and choline concentrations. RESULTS: The volume of cortical gray matter was reduced in patients with schizophrenia, but NAA signal intensity from a comparable region was normal. In contrast, the volume of cortical white matter was normal in patients with schizophrenia, but NAA signal intensity from a comparable region was reduced. CONCLUSIONS: The lack of reduction in gray matter NAA signal intensity suggests that the cortical gray matter deficit in these patients involved both neuronal and glial compartments rather than a neurodegenerative process in which there is a decrease in the neuronal relative to the glial compartment. Reduced white matter NAA signal intensity without a white matter volume deficit may reflect abnormal axonal connections.