Effects of abstinence from alcohol on the broad phospholipid signal in human brain: an in vivo 31P magnetic resonance spectroscopy study

BACKGROUND: In vivo phosphorus magnetic resonance spectroscopy (31P MRS) at a magnetic field strength of 1.5 T allows measurement of fairly mobile membrane phospholipids in the human brain. We previously showed that subjects who are heavy drinkers had a smaller signal and a shorter transverse relaxation time (T2) of white matter phospholipids than light drinkers, which suggested lower concentrations and molecular mobility of phospholipids in heavy drinkers. The purpose of the present study was to measure if such chronic alcohol-induced white matter tissue changes are persistent in long-term abstinent alcoholics. METHODS: Fourteen abstinent alcoholics (mean age 45 years, seven men and seven women) were studied by localized 31P MRS in the centrum semiovale and were compared with 13 male, alcohol-dependent, heavy drinkers and 23 nondependent light drinkers (17 men, 6 women) of similar age. Methods for measurements of the broad membrane phospholipid signal and its relaxation time were described previously. RESULTS: Phospholipid concentrations and relaxation times in alcoholics abstinent for an average of 31 months were not significantly different from those measured in light drinkers. The contribution of fast and slowly relaxing signal components to the broad phospholipid signal, however, was still different in abstinent alcoholics compared with light drinkers. No effects of sex or of family history of alcoholism were noted on any of our spectroscopic measures within the light-drinking or abstinent groups. CONCLUSIONS: Most of our results suggest at least partial recovery of chronic alcohol-induced white matter phospholipid damage with long-term abstinence. They offer myelination changes and/or dendritic rearborization as a possible mechanism for the commonly observed white matter volume gain with prolonged abstinence. But the results also suggest a persistent abnormality in the nature and/or physical properties of white matter phospholipids in long-term abstinent alcoholics.     

Evaluation of in vivo cerebral metabolism on proton magnetic resonance spectroscopy in patients with impaired glucose tolerance and type 2 diabetes mellitus

The aim of this study was to investigate possible metabolic alterations in cerebral tissues on magnetic resonance spectroscopy (MRS) in patients with impaired glucose tolerance (IGT) and with type 2 diabetes mellitus (T2-DM). Twenty-five patients with T2-DM, 13 patients with IGT, and 14 healthy volunteers were included. Single-voxel spectroscopy (TR: 2000 ms, TE: 31 ms) was performed in all subjects. Voxels were placed in the frontal cortex, thalamus, and parietal white matter. N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, and myo-inositol (MI)/Cr ratios were calculated. Frontal cortical Cho/Cr ratios were increased in patients with IGT compared to control subjects. Parietal white matter Cho/Cr ratios were significantly higher in patients with IGT when compared to patients with T2-DM. In the diabetic group, frontal cortical MI/Cr ratios were increased, and parietal white matter Cho/Cr ratios were decreased when compared to the control group. Frontal cortical NAA/Cr and Cho/Cr ratios and parietal white matter Cho/Cr ratios were decreased in diabetic patients with poor glycemic control (A1C>10%). A1C levels were inversely correlated with frontal cortical NAA/Cr and Cho/Cr ratios and with parietal white matter Cho/Cr ratios. T2-DM and IGT may cause subtle cerebral metabolic changes, and these changes may be shown with MRS. Increased Cho/Cr ratios may suggest dynamic change in membrane turnover in patients with IGT. Diabetic patients with poor glycemic control may be associated with neuronal dysfunction/damage in brain in accordance with A1C levels and, in some, extend with insulin resistance.     

Quantitative brain MRI in alcohol dependence: preliminary evidence for effects of concurrent chronic cigarette smoking on regional brain volumes

BACKGROUND: Recent in vivo research using magnetic resonance spectroscopy demonstrated that chronic cigarette smoking exacerbates regional chronic alcohol-induced brain injury. Other studies associated cigarette smoking with gray matter volume reductions in healthy adults, with greater brain atrophy in aging, and with poorer neurocognition. Although cigarette smoking is common among alcohol-dependent individuals, previous research did not account for the potential effects of chronic smoking on regional brain volumes in alcoholism. METHODS: High-resolution T1-weighted magnetic resonance images from one-week-abstinent, alcohol-dependent individuals and light drinkers were automatically segmented into gray matter, white matter, and cerebral spinal fluid of lobes and subcortical structures. A brief neuropsychological test battery was used to assess cognition in alcohol-dependent individuals. The alcoholic and nondrinking groups were retrospectively divided into chronic smokers and nonsmokers, and the volumetric data were analyzed as a function of alcohol and smoking status. RESULTS: Chronic alcohol dependence was associated with smaller volumes of frontal and parietal white matter, parietal and temporal gray matter, and thalami, accompanied by widespread sulcal but not ventricular enlargements. Chronic cigarette smoking was associated with less parietal and temporal gray matter and with more temporal white matter. Among alcoholics, better visuospatial learning and memory and greater visuomotor scanning speed were correlated with larger lobar white matter volumes in the nonsmoking alcohol-dependent group only. CONCLUSIONS: These data provide preliminary evidence that comorbid chronic cigarette smoking accounts for some of the variance associated with cortical gray matter loss and appears to alter relationships between brain structure and cognitive functions in alcohol-dependent individuals.     

The pathogenesis of the white matter abnormalities in phenylketonuria. A multimodal 3.0 tesla MRI and magnetic resonance spectroscopy (1H MRS) study

Objective: To gain insights into the nature and pathogenesis of white matter (WM) abnormalities in PKU. Methods: Thirty-two patients with phenylalanine hydroxylase deficiency (21 with early and 11 with late diagnosis and treatment) and 30 healthy controls underwent an integrated clinical, neuroimaging (3.0 T MRI, diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI)) and neurochemical (¹H MRS) investigation. Results: All patients had white matter abnormalities on T2-weighted (T2W) and fluid-attenuated inversion recovery (FLAIR) scans; parietal white was consistently affected, followed by occipital, frontal and temporal white matter. T1-weighted hypointense alterations were also found in 8 of 32 patients. DWI hyperintense areas overlapped with those detected on T2W/FLAIR. The apparent diffusion coefficient (ADC) was reduced and correlated inversely with severity of white matter involvement. Fractional anisotropy index, eigenvalues λ_min, λ_middle, λ_max obtained from DTI data, and the principal brain metabolites assessed by ¹H MRS (except brain phenylalanine (Phe)) were normal. Brain Phe peak was detected in all but two subjects. Brain and blood Phe were strictly associated. Blood Phe at the diagnosis, patient’s age, and concurrent brain Phe independently influence white matter alteration (as expressed by conventional MRI or ADC values). Conclusions: (a) MRI abnormalities in phenylketonuria are the result of a distinctive alteration of white matter suggesting the intracellular accumulation of a hydrophilic metabolite, which leaves unaffected white matter architecture and structure. (b) White matter abnormalities do not seem to reflect the mechanisms involved in the derangement of mental development in PKU. (c) Our data do not support the usefulness of conventional brain MRI examination in the clinical monitoring of phenylketonuria patients. Communicating editor: Georg Hoffmann Competing interests: None declared     

Evidence of Multiple Ethanol Pools in the Brain: An in Vivo Proton Magnetization Transfer Study

Studies of isolated cell membranes and animal brain extracts have shown that ethanol (EtOH) partitions into cell membranes. We tested the hypothesis that EtOH in the living brain after EtOH administration exists in two or more pools: a free, mobile pool of EtOH and one or more EtOH pools that are restricted in their molecular mobility, possibly because of association with membranes. In vivo brain proton magnetic resonance spectroscopy (¹H MRS) routinely detects the methyl protons of the mobile EtOH pool but does not detect motion-ally restricted EtOH. We used in vivo brain ¹H MRS in rat brain (n = 11) after intraperitoneal EtOH administration to measure the signal intensity of methyl EtOH protons in the presence and absence of off-resonance saturation. Off-resonance saturation resulted in a 33 ± 4% decrease of the EtOH methyl proton signal. We interpret this signal reduction as a magnetization transfer effect. It is consistent with the existence of an MRS-invisible EtOH pool with restricted molecular mobility, which is in exchange with the free EtOH pool. Off-resonance saturation at the water frequency resulted in an even larger decrease of the EtOH methyl signal, consistent with water molecules being in close proximity to EtOH molecules at the restricted motion site(s). These results provide support for the hypothesis that partial MRS-invisibility of brain EtOH is at least to some extent caused by the presence of a (MRS-invisible) pool of motionally restricted EtOH. They also strongly suggest that water suppression, routinely used in in vivo ¹H MRS, may reduce the observable EtOH methyl signal intensity through a magnetization transfer mechanism. These studies may provide both a mechanism of, and a means to investigate the alterations of EtOH MRS visibility observed in heavy drinkers.     

Effects of Abstinence on the Brain: Quantitative Magnetic Resonance Imaging and Magnetic Resonance Spectroscopic Imaging in Chronic Alcohol Abuse

Background: Structural brain damage, especially to white matter, is well documented in chronic alcohol abuse. There is also evidence for brain metabolic abnormalities in this condition. It is unknown, however, to what extent these structural and metabolic changes are present in treated alcohol abusers who achieve long-term abstinence versus treatment-naïve, heavily drinking individuals. Methods: This study compared 12 recovering alcoholics with 8 actively heavily drinking subjects. Participants underwent magnetic resonance (MR) imaging and proton MR spectroscopic imaging of the brain. Semiautomated image segmentation techniques yielded volumes for gray matter, white matter, white matter lesions, and cerebral spinal fluid in multiple brain regions defined by Talairach stereotaxic coordinates. Automated spectral processing methods yielded gray and white matter concentrations of the metabolites N-acetylaspartate, creatine, and choline for the same regions. Results: Recovering alcoholics had greater volumes of frontal white matter, but the opposite was true for white matter in a “remainder” region encompassing the basal frontal and temporal lobes, the cerebellum, and the brainstem. Recovering alcoholics also had smaller volumes of white matter lesions in whole brain, in occipital and mesial parietal regions, and in the remainder region. Recovering alcoholics had greater gray matter volumes in the orbital frontal pole and postcentral gyrus, but smaller gray matter volumes in the anterior cingulate. Whole-brain and regional metabolite concentrations did not differ significantly between the two groups. Conclusions: White and gray matter volumes in different regions of the brain were greater or smaller in recovering, treated alcoholics. The findings suggest region-specific structural recovery from chronic alcohol–induced brain injury, but also region-specific long-term structural damage in abstinent alcoholics. White matter lesions were widespread in active drinkers and may partly resolve during long-term abstinence. Proton MR spectroscopic measures, as applied in this cross-sectional study, were largely ineffective in revealing metabolic effects of abstinence on the alcohol-damaged brain.     

Progression of silent cerebral infarction in Japanese: a hospital-based study

Little is known about the risk factors for progression of silent cerebral infarction (SCI). We evaluated the 5-year change in high signal intensity on T2-weighted MR images of the brain in 50 asymptomatic patients with SCI. SCI progression was evaluated by the sum of the high intensity score (HIS) and the number of new lesions found on reexamination. Progression of SCI was seen in 19 patients (38%) on the 5-year follow-up examination. The baseline HIS in the whole brain was 8.02 +/- 6.93 and the follow-up HIS was 8.7 +/- 7.16 (p < 0.001). SCI progression was frequently seen in the corona radiata (p < 0.02 or < 0.05) or posterior periventricular white matter (p < 0.05). Patients with poor control of hypertension (> 160/95 mmHg) have a higher prevalence of SCI progression (9/12 (75%) vs. 10/38 (26.3%); OR = 8.4, p < 0.005) than the patients with effective control of BP (< or = 160/95 mmHg). The progression group showed a significantly higher baseline-HIS in the whole brain than the nonprogressing group (9.7 +/- 5.6 vs. 7 +/- 7.5; p < 0.05). Neither age percentages of alcohol drinkers, male sex, current smokers, hypertensives, hyperuricemia, hypercholesterolemia, diabetes, obesity, left ventricular hypertrophy, ischemic heart disease, nor differences in the controls of diabetes and hypercholesterolemia during the study were different between the progressing and the nonprogressing groups. Our data showed that poor control of high blood pressure and the degree of T2 high intensity in the baseline were strong predictors of SCI progression.     

Alcohol consumption and mortality in Alameda County

The association between level of alcohol consumption and 15-year mortality, focusing particularly on the possible protective effect of light drinking compared to abstention, was studied in a representative population sample of 6928 residents of Alameda County, California. Because abstainers differ from light, moderate and heavy drinkers on a number of demographic, physical, and psychosocial characteristics, the role of these as confounders of the alcohol/mortality association was examined. Using multiple logistic models, the mortality experience of abstainers, moderate drinkers, heavy drinkers and very heavy drinkers was compared with that of light drinkers. Among men only, very heavy drinkers were at significantly greater risk of death from all causes than were light drinkers (OR = 2.5, p less than 0.01). Neither abstainers nor other drinkers were at significantly higher risk of death from ischemic heart disease than were light drinkers. This pattern of results persisted with adjustment for 11 covariates of alcohol consumption in addition to age.     

Effects of heavy drinking, binge drinking, and family history of alcoholism on regional brain metabolites

BACKGROUND: The main goals are to investigate the effects of chronic active heavy drinking on N-acetylaspartate (NAA) and other metabolites throughout the brain and to determine whether they are affected by family history (FH) of alcoholism and long-term drinking pattern. METHODS: Forty-six chronic heavy drinkers (HD) and 52 light drinkers (LD) were recruited from the community and compared on measures of regional brain structure using magnetic resonance imaging and measures of common brain metabolites in gray matter (GM) and white matter (WM) of the major lobes, subcortical nuclei, brainstem, and cerebellum using short-echo time magnetic resonance spectroscopic imaging. Regional atrophy-corrected levels of NAA, myoinositol (mI), creatine, and choline-containing metabolites were compared as a function of group, FH of alcoholism, and bingeing. RESULTS: Frontal WM NAA was lower in FH-negative HD than FH-positive HD and tended to be lower in women than men. Creatine-containing metabolites in parietal GM were higher in HD than LD. FH-negative compared with FH-positive HD also had more mI in the brainstem and tended to have lower NAA and more mI in frontal GM. Although parietal GM NAA was not significantly lower in HD than LD, it was lower in non-binge drinkers than bingers. Frontal WM NAA was lower in HD than LD, with the difference driven by a small number of women, FH-negative HD, and older age. Lower frontal WM NAA in HD was associated with lower executive and working memory functions and with lower P3b amplitudes at frontal electrodes. CONCLUSIONS: Community-dwelling HD who are not in alcoholism treatment have brain metabolite changes that are associated with lower brain function and are likely of behavioral significance. Age, FH, and binge drinking modulate brain metabolite abnormalities. Metabolite changes in active HD are less pronounced and present with a different spatial and metabolite pattern than reported in abstinent alcoholics.     

Advanced magnetic resonance imaging of the brain in patients treated with TNF-alpha blocking agents

OBJECTIVE: Neurological symptoms have been reported in patients treated with anti-TNF-alpha. In a pilot study we evaluated the effect of anti-TNF-alpha on cerebral parenchyma using advanced Magnetic Resonance (MR) techniques. METHODS: Seven patients with a systemic inflammatory disease (5 rheumatoid arthritis, 2 psoriatic arthritis) had Magnetization Transfer Imaging, Diffusion Weighted Imaging (DWI) and Magnetic Resonance Spectroscopy (MRS) of the brain before and after administration of anti-TNF-alpha. Four patients were neuropsychologically evaluated. RESULTS: After treatment with TNF-alpha blocking agents the Magnetization Transfer Ratio histogram Peak-heights (MTR-Pht) of the white and gray matter decreased (p < 0.01 and p < 0.05 respectively). The Apparent Diffusion Coefficient for the white and gray matter and the metabolite ratios in the centrum semiovale did not significantly change after therapy. Neuropsychological assessment showed no difference before and after anti-TNF-alpha. CONCLUSION: The decrease of the MTR-Pht after anti-TNF-alpha therapy suggests loss of parenchyma integrity; however, these changes could not be attributed to inflammation or demyelination based on our complementary DWI and MRS data. The decrease of the MTR-Pht did not result in decreased cognitive function.     

Effects of chronic alcohol consumption in a visual attention task and an auditory oddball task: an event-related potential study

BACKGROUND: In alcohol-dependent individuals changes in brain functioning, as measured with Event Related Potentials (ERP) have been reported. METHODS: In the present study a visual attention and an auditory oddball task were used to investigate possible differences between light, moderate, and heavy social drinkers and excessive drinkers. It was hypothesized that with increasing alcohol intake an increasing number of ERP components elicited in the visual attention task and the auditory oddball task would show diminished amplitudes. RESULTS: No differences were found between light, moderate, and heavy social drinkers. A trend for a smaller P3 amplitude in the visual attention task was found when comparing the alcohol-dependent participants with the light social drinkers. It is argued that this difference might be an effect of alcohol dependence and/or a reflection of possible unknown or undetected family history of alcohol-related disturbances. CONCLUSIONS: In the current study, even at rather large amounts of regular alcohol intake, no evidence was found for any toxic effect of social alcohol use neither in a visual attention task nor in an auditory oddball task.     

Proton spin-lattice relaxation of retinal rod outer segment membranes and liposomes of extracted phospholipids.

A large fraction of the phospholipid protons of bovine retinal rod outer segment (ROS) disc membrane vesicles yield well-resolved nuclear magnetic resonance lines near physiological temperature. The spin-lattice (T1) relaxation rates of the resolved sharp resonance of ROS disc membranes appear biphasic above 10 degrees C. The rate of the more rapidly relaxing component of each resonance matches closely the relaxation rate of the corresponding resonances of liposomes of purified ROS phospholipids. The slowly relaxing component of each disc membrane resonance is most likely due to phospholipids whose motion is affected by rhodopsin. The primary difference in the relaxation behavior of phospholipids in the ROS membrane vesicles and ROS liposomes appears to be in T1, rather than T2, since the corresponding sharp resonances of both preparations have similar linewidths. These observations suggest that the interaction of rhodopsin with the more fluid membrane phospholipids predominantly affects relatively high frequency segmental motions, which determine T1, while having minimal effects on the lower frequency segmental motions, which influence T2. This conclusion can be rationalized by assuming that a substantial fraction of the interacting phospholipids are relatively fluid with respect to less frequent, larger amplitude segmental motions, but that the more frequent segmental motions (such as beta-coupled trans-gauche isomerizations) are significantly restricted by interaction with protein.     

1H-MRS对碘异常引起脑损伤的诊断价值

目的 探讨氢质子磁共振波谱分析（^1H-MRS）在碘异常引起脑损伤病变中的应用价值。方法 收集临床诊断碘异常引起脑损伤的病例28例，其中低碘组16例，高碘组12例。使用西门子1．5TMPd，多体素相位矩阵扫描。检测低碘组和高碘组病人海马区与正常参照区域的代谢物浓度，利用SPSS12．0分析各种代谢物的变化。结果 ^1H-MRS示低碘组胆碱降低、γ-氨基丁酸、N-乙酰天门冬氨酸减少；高碘组胆碱增加、谷氨酸升高，γ-氨基丁酸、N-乙酰天门冬氨酸减少。结论 ^1H-MRS在碘异常引起脑损伤病变定性诊断中有重要的临床价值。     

Biphasic alcohol response differs in heavy versus light drinkers

BACKGROUND: Most studies of risk factors for alcohol-related problems have focused on biological family history as a primary risk factor. However, other factors, such as early-age heavy drinking, are also risk factors for sustained or progressive heavy consumption. Little is currently known about the mechanisms underlying binge or heavy drinking. METHODS: This study examined the acute subjective and objective effects of ethanol in heavy drinkers versus light drinkers. Thirty-four subjects participated in this within-subjects study consisting of three early-evening testing sessions in which subjects consumed a beverage containing either 0.8 or 0.4 g/kg ethanol or placebo. RESULTS: Compared with lighter drinkers, heavy drinkers were more sensitive to the positive stimulant-like effects of ethanol (p < 0.05), especially during the increasing limb of the blood alcohol curve. Heavy drinkers also showed less sedation and cortisol response after alcohol than the light drinkers (p < 0.05). CONCLUSIONS: The results indicate that young adult binge drinkers show a biphasic alcohol response, with heightened sensitivity to stimulant-like alcohol effects and greater tolerance to sedative alcohol effects compared with their light-drinking counterparts.     

Associations between alcohol intake and brain volumes in male and female moderate drinkers

BACKGROUND: Alcohol-dependent individuals have brain volume loss. Possibly, moderate drinkers who are not alcohol dependent have similar but less prominent brain damage. The authors investigated whether current or lifetime alcohol intake is related to volumes of total brain, cerebellum, ventricles, peripheral cerebrospinal fluid, and cerebral gray and white matter in moderate drinkers. METHODS: The relation between current or lifetime alcohol intake and brain volumes of 47 male moderate drinkers (current alcohol intake 20 drinks per week, lifetime alcohol intake 240 kg) and 44 female moderate drinkers (current alcohol intake 15 drinks per week, lifetime alcohol intake 170 kg), all without a personal or family history of alcohol dependence, was determined using high-resolution magnetic resonance images, corrected for intracranial volume, age, and sex. RESULTS: In males, mean lifetime alcohol intake was positively associated with cerebral white matter volume, particularly in the frontal region. In females, mean lifetime alcohol intake was not associated with brain volumes. Current alcohol intake was unrelated to brain volumes in either males or females. CONCLUSIONS: Neither current nor lifetime alcohol intake is associated with decreases in brain volumes in male or female moderate drinkers. Because all participants had a negative personal and family history of alcohol dependence, the current results relatively purely concern the effects of moderate alcohol intake on brain volumes.     

T-cell lymphoma showing a non-enhancing diffuse white matter lesion with marked brain atrophy.

We report an autopsy case of T-cell lymphoma with diffuse white matter infiltration. Cranial magnetic resonance (MR) images showed atrophy of the brain with a diffuse, non-enhancing, T2-high signal intensity lesion in the cerebral white matter. Intra-axial infiltration of T-cell lymphoma should be considered a differential diagnosis in patients with these MRI findings.     

Association between alcohol intake and metabolic syndrome in patients with hypertension

The aim of this study was to determine how alcohol consumption influences metabolic syndrome in patients with hypertension. The subjects were 3938 male workers being treated with anti-hypertensive drugs and they were divided into four groups by average ethanol intake [non-, light (<22 g/day), moderate (≥22 and <44 g/day), and heavy (≥44 g/day) drinkers]. The relationships of alcohol intake with atherosclerotic risk factors and metabolic syndrome were investigated. Waist circumference and hemoglobin A1c were significantly smaller and lower, respectively, in light, moderate, and heavy drinkers than in nondrinkers. Systolic blood pressure and log-converted triglyceride were significantly higher in heavy drinkers than in nondrinkers. HDL cholesterol was significantly higher in all of the drinker groups than in nondrinkers and tended to be higher as alcohol intake increased. Prevalence of metabolic syndrome was significantly lower in light, moderate, and heavy drinkers than in nondrinkers. Age- and smoking history-adjusted odds ratios (ORs) vs. nondrinkers for metabolic syndrome were significantly low in light drinkers (OR = 0.71, 95% confidence interval [CI]: 0.56-0.89), moderate drinkers (OR = 0.64, 95% CI: 0.54-0.75) and heavy drinkers (OR = 0.68, 95% CI: 0.57-0.82). The results suggest that alcohol drinking is associated with a lower risk of metabolic syndrome in patients with hypertension.     

White matter hyperintensities on brain magnetic resonance in systemic sclerosis

OBJECTIVE: To evaluate the brain status of patients with systemic sclerosis (SSc). METHODS: Fourteen female patients with SSc aged 24-74, with a disease duration of 1-12 years and without other relevant systemic diseases, were enrolled. All patients and an age matched female control group (CG) of 14 clinically normal subjects, underwent brain magnetic resonance examination at 1.5 T; spin echo proton density weighted images were evaluated. Mann-Whitney U and Spearman rank correlation tests were used for statistical analysis. RESULTS: 170 white matter hyperintensities >/=2 mm in diameter were counted in the patient group (range 0-75, mean 12.1, median 4.5), only 13 in the CG (0-2, 0.9, 1, respectively), with a significant difference (p = 0.011). Moreover, 208 white matter hyperintensities <2 mm were found in the patient group (0-38, 14.9, 8, respectively), only 31 in the CG (0-7, 2.0, 1, respectively), with a significant difference (p = 0.006). No statistically significant correlation between the number of hyperintensities and either patient's age or disease duration was observed. CONCLUSION: White matter hyperintensities are more common in patients with SSc than in a CG. These findings might be related to obliterative microvascular processes due to the disease. Early brain involvement in patients with SSc may occur.     

Sensitivity of quantitative (1)H magnetic resonance spectroscopy of the brain in detecting early neuronal damage in systemic lupus erythematosus

OBJECTIVE: To quantify N-acetylaspartate (NAA), total creatines (tCr), total cholines (tCho), and myo-inositol (mI) levels in normal and abnormal appearing white matter of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) in order to determine the specific changes in metabolite concentrations. METHODS: Axial proton density and T(2) weighted magnetic resonance images, and short echo time (TE 30 ms) (1)H spectra were acquired with a GE SIGNA 1.5 T magnetic resonance system. Concentrations of NAA, tCr, tCho, and mI were determined, using brain tissue water as a reference, from nine patients (seven female, mean age 40.3 years, range 16-65) with NPSLE and eight healthy women (mean age 43 years, range 31-65). RESULTS: A significant rise of tCho (12.4%, p<0.05) and mI (31.4%, p<0.005) and a significant reduction in NAA (-12%, p<0.05) was found in normal appearing white matter compared with controls. Analysis according to severity of the clinical NPSLE features (subgrouped as major or minor) showed that SLE major had reduced NAA compared with SLE minor (-18.4%, p<0.05) and controls (-20%, p<0.005). The SLE major group showed a significant rise of mI (32%, p<0.01) and the SLE minor group a significant increase in tCho (18.6%, p<0.05) compared with controls. Longitudinal analysis of brain metabolites in normal appearing white matter showed consistent abnormalities in NAA, tCho, and mI in a patient with stable clinical features and a constant rise of tCho, but transient rise of mI was seen during a flare of disease in another patient. CONCLUSION: Quantitative (1)H magnetic resonance spectroscopy (MRS) suggests a particular course of neurometabolite changes that precedes irreversible reductions in NAA and permanent neuronal loss. Initially, in patients with SLE minor, there is a significant rise in tCho and a trend (reversible) for mI also to be raised. In patients with SLE major the NAA is significantly and permanently reduced and mI is significantly raised, whereas the tCho levels are near normal. Further investigations are needed to determine how specific MRS is as a clinical marker for brain disturbance in SLE.     

Cerebral bioenergetics in stable chronic obstructive pulmonary disease

Cerebral intracellular energy production (cerebral bioenergetics) via oxidative phosphorylation and the production of adenosine triphosphate (ATP) is critical to cerebral function. To test the hypothesis that patients with chronic stable hypoxia also generate neuronal ATP via an anaerobic metabolism, we studied the changes in cerebral (31)P magnetic resonance spectra ((31)P MRS) in patients with stable chronic obstructive pulmonary disease (COPD), and compared the results with MR spectra from similar areas of the brain in control subjects. Ten patients with stable COPD (age: 65 +/- 9 yr [mean +/- SD]; Pa(O(2)): 8.8 +/- 1.2 kPa; Pa(CO(2)): 6.1 +/- 0.8 kPa; pH 7.42 +/- 0.03, and FEV(1): 41 +/- 20% predicted) and five healthy volunteers underwent cerebral (31)P MRS (TR-5,000 ms) at 1.5 T. When COPD patients were compared with controls, the percentage MR signal with respect to total MR-detectable phosphorus-containing metabolites was increased from inorganic phosphate (Pi) (7.1 +/- 1. 3% versus 3.9 +/- 0.7%, p = 0.0001) and phosphomonoesters (PMEs) (9. 4 +/- 1.2% versus 6.9 +/- 0.3%, p = 0.0001), whereas the signal from phosphodiesters was reduced (34.8 +/- 3.2 versus 40.4 +/- 3.3%, p = 0.015). The ratios of Pi to betaATP (0.8 +/- 0.2 versus 0.4 +/- 0.1, p = 0.001) and of PME to betaATP (1.0 +/- 0.2 versus 0.7 +/- 0.1, p = 0.015) were increased, but the phosphocreatine-to-Pi ratio (2.1 +/- 0.6 versus 3.2 +/- 0.6, p = 0.01) was reduced in patients as compared with controls. This alteration in phosphorus-containing metabolites within cerebral cells provides evidence of extensive use of anaerobic metabolism in hypoxic COPD patients.