In-vivo proton MR-spectroscopy of the human brain: assessment of N-acetylaspartate (NAA) reduction as a marker for neurodegeneration

Summary.  Proton magnetic resonance spectroscopy (¹H-MRS) is a non-invasive method to investigate changes in brain metabolite composition in different cerebral diseases. We performed proton spectroscopy in patients with dementia of the Alzheimer's type (AD) and in patients with motor neuron disease (MND) with the aim to detect the specific metabolic pattern for these neurodegenerative disorders. In the MND group we found a significant reduction of NAA/tCr metabolite ratios in the motor cortex, which correlates with the disease severity and the clinical lateralization of neurological symptoms and further decreases in the time course of the disease. In AD patients a reduction of NAA/tCr was observed in the medial temporal lobe. Since NAA is exclusively expressed in neurons as shown by immunohistochemical studies, reduced NAA levels suggest neuronal loss or dysfunction in the observed regions. The observed regional metabolic alterations reflect the neuronal basis of the characteristic neurological symptoms in AD (dementia) and MND (muscular palsy) and mirrors the disease progress over time. Received June 29, 2001 Accepted August 6, 2001 Published online August 9, 2002     

重度OSAS患者前额叶皮质及岛叶1H-MR波谱研究

目的:利用氢质子MRS(1H-MRS)探讨重度阻塞性呼吸睡眠暂停综合症(Severe obstructive sleep apnea syndrome,S-OSAS)患者前额叶皮质及岛叶脑代谢产物特征。方法:选择18例S-OSAS患者(S-OSAS组)和15名健康志愿者(HC组)行左侧前额叶皮质及岛叶1H-MRS检查,测量两组左侧前额叶皮质区及岛叶N-乙酰天冬氨酸/肌酸(NAA/Cr)、胆碱/肌酸(Cho/Cr)值。对患S-OSAS累计时间与前额叶皮质及岛叶NAA/Cr作直线相关分析。结果:与正常对照组相比,S-OSAS患者左侧前额叶皮质、岛叶NAA/Cr比值降低,分别为1.43±0.47、1.34±0.06,对照组分别为1.51±0.65、1.45±0.07;S-OSAS组患者左侧前额叶皮质、岛叶Cho/Cr分别为0.90±0.08、1.19±0.13,对照组分别为0.87±0.07、1.09±0.02,两组差异有统计学意义。前额叶皮质及岛叶代谢物NAA/Cr与患S-OSAS累计时间成负相关性(r值分别为-0.965、-0.955,P<0.01)。结论:1H-MRS显示S-OSAS患者前额叶皮质及岛叶病理生理变化,从该区代谢物的改变反应出S-OSAS患者执行及情感功能的异常,其NAA/Cr改变程度与患S-OSAS累计时间相关。     

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

Proton magnetic resonance spectroscopy (1H-MRS) offers a unique non-invasive approach to measurement of N-acetylaspartate (NAA) and choline (Cho), putative markers of neuronal and glial integrity. Previous studies revealed that these neurochemicals predict cognitive impairment in diseased subjects, although little is known about their relationship to cognitive functioning in healthy people. We measured the concentrations of NAA and Cho in the left occipitoparietal white matter of 26 healthy adults and compared them with intellectual performance assessed by the Wechsler Adult Intelligence Scale-3. We found that NAA (b = 0.6, p < 0.01) and Cho (b = -0.42, p < 0.01) were independently associated with the Full-Scale Intelligence Quotient. Together, these metabolites accounted for a large proportion of the variance in intelligence (r2 = 0.45). Possible mechanisms underlying these correlations, such as mitochondrial function and myelin turnover, are discussed. 1H-MRS is a sensitive new tool to assess the neuronal underpinnings of cognitive function non-invasively.     

重度OSAS患者前额叶皮质及岛叶1H—MR波谱研究

目的：利用氢质子MRS（IH-MRS）探讨重度阻塞性呼吸睡眠暂停综合症（Severeobstructivesleepapneasyndrome,S-OSAS）患者前额叶皮质及岛叶脑代谢产物特征。方法：选择18例S-OSAS患者（S-OSAS组）和15名健康志愿者（HC组）行左侧前额叶皮质及岛叶1H-MRS检查,测量两组左侧前额叶皮质区及岛叶N-乙酰天冬氨酸／肌酸（NAA／Cr）、胆碱／肌酸（Cho／Cr）值。对患S-OSAS累计时间与前额叶皮质及岛叶NAA／Cr作直线相关分析。结果：与正常对照组相比,S-OSAS患者左侧前额叶皮质、岛叶NAA／Cr比值降低,分别为1．43±0．47、1．34±0．06,对照组分别为1．51±0．65、1．45±0．07;S-OSAS组患者左侧前额叶皮质、岛叶Cho／Cr分别为0．90±0．08、1．195：0．13,对照组分别为0．87±0．07、1．09±0．02,两组差异有统计学意义。前额叶皮质及岛叶代谢物NAA／Cr与患S-OSAS累计时间成负相关性（r值分别为-0．965、-0．955,P〈0．01）。结论：1H-MRS显示S-OSAS患者前额叶皮质及岛叶病理生理变化,从该区代谢物的改变反应出S-OSAS患者执行及情感功能的异常,其NAA/Cr改变程度与患S-OSAS累计时间相关。     

Transient alterations of creatine, creatine phosphate, N-acetylaspartate and high-energy phosphates after mild traumatic brain injury in the rat

In this study, the concentrations of creatine (Cr), creatine phosphate (CrP), N-acetylaspartate (NAA), ATP, ADP and phosphatidylcholine (PC) were measured at different time intervals after mild traumatic brain injury (mTBI) in whole brain homogenates of rats. Anaesthetized animals underwent to the closed-head impact acceleration “weight-drop” model (450 g delivered from 1 m height = mild traumatic brain injury) and were killed at 2, 6, 24, 48 and 120 h after the insult (n = 6 for each time point). Sham-operated rats (n = 6) were used as controls. Compounds of interest were synchronously measured by HPLC in organic solvent deproteinized whole brain homogenates. A reversible decrease of all metabolites but PC was observed, with minimal values recorded at 24 h post-injury (minimum of CrP = 48 h after impact). In particular, Cr and NAA showed a decrease of 44.5 and 29.5%, respectively, at this time point. When measuring NAA in relation to other metabolites, as it is commonly carried out in “in vivo” ¹H-magnetic resonance spectroscopy (¹H-MRS), an increase in the NAA/Cr ratio and a decrease in the NAA/PC ratio was observed. Besides confirming a transient alteration of NAA homeostasis and ATP imbalance, our results clearly show significant changes in the cerebral concentration of Cr and CrP after mTBI. This suggests a careful use of the NAA/Cr ratio to measure NAA by ¹H-MRS in conditions of altered cerebral energy metabolism. Viceversa, the NAA/PC ratio appears to be a better indicator of actual NAA levels during energy metabolism impairment. Furthermore, our data suggest that, under pathological conditions affecting the brain energetic, the Cr–CrP system is not a suitable tool to buffer possible ATP depletion in the brain, thus supporting the growing indications for alternative roles of cerebral Cr.     

The effect of stimulation therapy and donepezil on cognitive function in Alzheimer¿s disease. A community based RCT with a two-by-two factorial design

ABSTRACT: BACKGROUND: Progressive neurodegeneration in Alzheimer's disease (AD) induces cognitive deterioration, and there is controversy regarding the optimal treatment strategy in early AD. Stimulation therapy, including physical exercise and cholinesterase inhibitors are both reported to postpone cognitive deterioration in separate studies. We aimed to study the effect of stimulation therapy and the additional effect of donepezil on cognitive function in early AD. METHOD: DESIGN: A two-by-two factorial trial comprising stimulation therapy for one year compared to standard care to which a randomized double-blinded placebo controlled trial with donepezil was added. SETTING: Nine rural municipalities in Northern Norway. PARTICIPANTS: 187 participants [greater than or equal to]65 years with a recent diagnosis of mild or moderate AD were included in the study of which 146 completed a one-year follow-up. INTERVENTIONS: In five municipalities the participants received stimulation therapy whereas participants in four received standard care. All participants were randomised double-blinded to donepezil or placebo and tested with three different cognitive tests four times during the one-year study period. MAIN OUTCOME: Changes in MMSE sum score. SECONDARY OUTCOME: Changes in ADAS-Cog and Clock Drawing Test. RESULTS: MMSE scores remained unchanged amongst AD participants receiving stimulation therapy and those receiving standard care. The results were consistent for ADAS-Cog and Clock Drawing Test. No time trend differences were found during one-year follow-up between groups receiving stimulation therapy versus standard care or between donepezil versus placebo. CONCLUSION: In rural AD patients non-pharmacological and pharmacological therapy did not improve outcome compared with standard care but all groups retained cognitive function during one year follow-up. Other studies are needed to confirm these results. ClinicalTrials.gov (Identifier: NCT00443014). EudraCT database (no 2004-002613-37). KEYWORDS: Alzheimer's disease. Symptomatic treatment. Postponement of cognitive deterioration.     

磁共振波谱成像结合扩散加权成像在脑胶质瘤及脑转移瘤鉴别诊断中的意义

目的:评估磁共振波谱成像(Proton Magnetic Resonance Spectroscopy,1H-MRS)联合磁共振扩散加权成像(Diffusion Weighted Imaging,DWI)在鉴别脑胶质瘤及孤立的脑转移瘤中的作用。方法:应用3.0T磁共振扫描仪,对临床手术确诊及组织病理学诊断证实的49例脑肿瘤患者(35例多形性胶质母细胞瘤,14例脑转移瘤)进行常规磁共振成像、磁共振波谱成像及磁共振扩散加权成像,并并对获得的数据进一步测量瘤内及瘤周区的代谢比、N-乙酰天门冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr)值以及表观弥散系数(ADC值),分析两肿瘤组之间不同参数的统计学差异。此外,我们研究了感兴趣区域(ROI)的大小对肿瘤区域的病变扩散性能潜在影响。结果:胶质母细胞瘤瘤周N-乙酰天门冬氨酸(NAA)、肌酸(Cr),胆碱(Cho)/Cr,Cho/NAA和r CBV显著高于颅内转移瘤(P0.05);ADC值在两肿瘤组之间无显著差异(P0.05)。结论:在瘤周区1H-MRS有助于鉴别胶质母细胞瘤与单发的脑转移瘤。在瘤内扩散性的定量特性依赖ROI大小的设置。     

Changes in brain metabolites measured with magnetic resonance spectroscopy in antidepressant responders with comorbid major depression and posttraumatic stress disorder

In a present pilot study, performed on 11 subjects, we studied proton magnetic resonance spectroscopy (1H-MRS) changes in early to intermediate (3-6 weeks) responders to antidepressant treatment with selective serotonin reuptake inhibitors (SSRIs). All subjects had diagnosis of major recurrent depression comorbid to posttraumatic stress disorder (PTSD). Magnetic spectroscopy was done in the region of dorsolateral prefrontal cortex on a 3T MRI-unit. Participants were selected out of the larger sample due to an early response to antidepressant treatment within 3-6 weeks, measured with Beck Depression Inventory (BDI). We measured levels of neuronal marker N-acetyl-aspartate (NAA), choline (CHO) and creatine (Cr). There was no difference in NAA/Cr ratios between the first and the second spectroscopic scans (p= 0.751). However, CHO/Cr ratios showed increasing trend with mean value at the first scan of 1.09 (SD =0.22) while mean value at second scan was 1.25 (SD=0.24), displaying statistically significant difference (p=0.015). In conclusion, significant increase in choline to creatine ratio from the first to the second spectroscopic scan during the antidepressant treatment, compared to almost identical values of NAA to creatine ratio, suggests increased turnover of cell membranes as a mechanism of the early response to the antidepressant drug therapy.     

In vitro study of astrocytic tumour metabolism by proton magnetic resonance spectroscopy

In vivo magnetic resonance spectroscopy (MRS) studies of glial brain tumours reported that higher grade of astrocytoma is associated with increased level of choline-containing compounds (Cho) and decreased levels of N-acetylaspartate (NAA) and creatine and phosphocreatine (Cr). In this work, we studied the metabolism of glioma tumours by in vitro proton magnetic resonance spectroscopy (1H-MRS). 1H-MR spectra were recorded in vitro from perchloric acid extracts of astrocytoma (WHO II) and glioblastoma multiforme (WHO IV) samples. We observed differences between astrocytoma and glioblastoma multiforme in the levels of Cho, alanine, lactate, NAA, and glutamate/glutamine. In astrocytoma samples, we found higher MR signal of NAA and lower signal of Cho and alanine. MR spectra of glioblastoma samples reported significantly higher levels of lactate and glutamate/glutamine. In contrast, levels of Cr were the same in both tumour types. We also determined NAA/Cr and Cho/Cr ratios in the tumour samples. The NAA/Cr ratio was higher in astrocytomas than in glioblastomas multiforme. Conversely, the Cho/Cr ratio was higher in glioblastoma multiforme. The results indicate that MRS is a promising method for distinguishing pathologies in human brain and for pre-surgical grading of brain tumours.     

Changes in cognitive domains during three years in patients with Alzheimer's disease treated with donepezil

Background  

The objective was to identify separate cognitive domains in the standard assessment tools (MMSE, ADAS-Cog) and analyze the process of decline within domains during three years in Alzheimer's disease (AD) patients with donepezil treatment.     

Metabolic Changes in the Visual Cortex of Binocular Blindness Macaque Monkeys: A Proton Magnetic Resonance Spectroscopy Study

Purpose

To evaluate proton magnetic resonance spectroscopy (¹H-MRS) in a study of cross-modal plasticity in the visual cortex of binocular blindness macaque monkeys.

Materials and Methods

Four healthy neonatal macaque monkeys were randomly divided into 2 groups, with 2 in each group. Optic nerve transection was performed in both monkeys in the experimental group (group B) to obtain binocular blindness. Two healthy macaque monkeys served as a control group (group A). After sixteen months post-procedure, ¹H-MRS was performed in the visual cortex of all monkeys. We compared the peak areas of NAA, Cr, Cho, Glx and Ins and the ratios of NAA/Cr, Cho/Cr, Glx/Cr and Ins/Cr of each monkey in group B with group A.

Results

The peak area of NAA and the NAA/Cr ratio in the visual cortex of monkey 4 in group B were found to be dramatically decreased, the peak area of NAA slightly decreased and the NAA/Cr ratio clearly decreased in visual cortex of monkey 3 in group B than those in group A. The peak area of Ins and the Ins/Cr ratio in the visual cortex of monkey 4 in group B slightly increased. The peak area of Cho and the Cho/Cr ratio in the visual cortex of all monkeys in group B dramatically increased compared with group A. The peak area of Glx in the visual cortex of all monkeys in group B slightly increased compared with group A.

Conclusions

¹H-MRS could detect biochemical and metabolic changes in the visual cortex and therefore this technique can be used to provide valuable information for investigating the mechanisms of cross-modal plasticity of binocular blindness in a macaque monkey model.     

Analysis of brain metabolism by proton magnetic resonance spectroscopy (1H-MRS) in attention-deficit/hyperactivity disorder suggests a generalized differential ontogenic pattern from controls

Attention-deficit/hyperactivity disorder (ADHD) is the most common behavioral disorder of childhood. Preliminary studies with proton magnetic resonance spectroscopy (¹H-MRS) of the brain have reported differences in brain metabolite concentration-to-Cr ratios between individuals with ADHD and unaffected controls in several frontal brain regions including anterior cingulate cortex. Using multivoxel ¹H-MRS, we compared 14 individuals affected with ADHD to 20 individuals without ADHD from the same genetic isolate. After controlling by sex, age, and multiple testing, we found significant differences at the right posterior cingulate of the Glx/Cr ratio density distribution function between ADHD cases and controls (P?<?0.05). Furthermore, we found several interactions of metabolite concentration-to-Cr ratio, age, and ADHD status: Ins/Cr and Glx/Cr ratios at the left posterior cingulate, and NAA/Cr at the splenius, right posterior cingulate, and at the left posterior cingulate. We also found a differential metabolite ratio interaction between ADHD cases and controls for Ins/Cr and NAA/Cr at the right striatum. These results show that: (1) NAA/Cr, Glx/Cr, and Ins/Cr ratios, as reported in other studies, exhibit significant differences between ADHD cases and controls; (2) differences of these metabolite ratios between ADHD cases and controls evolve in specific and recognizable patterns throughout age, a finding that replicates previous results obtained by structural MRI, where is demonstrated that brain ontogeny follows a different program in ADHD cases and controls; (3) Ins/Cr and NAA/Cr ratios, at the right striatum, interact in a differential way between ADHD cases and controls. As a whole, these results replicate previous 1H-MRS findings and add new intriguing differential metabolic and ontogeny patterns between ADHD cases and controls that warrant further pursue.     

Proton Magnetic Resonance Spectroscopy (1H-MRS) Reveals Geniculocalcarine and Striate Area Degeneration in Primary Glaucoma

Background

Glaucoma is a collection of neurodegenerative diseases that affect both the retina and the central visual pathway. We investigated whether metabolites'' concentrations changed in the geniculocalcarine (GCT) and the striate area of occipital lobe by proton magnetic resonance spectroscopy (¹H-MRS), suggesting neurodegeneration of the central visual pathway in primary glaucoma.

Methodology/Principal Findings

20 patients with glaucoma in both eyes were paired with 20 healthy volunteers in same gender and an age difference less than 3 years. All the participants were examined by MR imaging including T₁ Flair, T₂ FSE and ¹H-MRS. The T₁ intensity and T₂ intensity of their GCTs and striate areas were measured. The ratio of N-acetylaspartate (NAA)/Creatine (Cr), Choline (Cho)/Cr, glutamine and glutamate (Glx)/Cr were derived by multi-voxels ¹H-MRS in the GCT and the striate area of each brain hemisphere. The T₁ intensity and T₂ intensity had no difference between the groups. Significant decreases in NAA/Cr and Cho/Cr but no difference in Glx/Cr was found between the groups in both the GCT and the striate area.

Conclusions/Significance

Primary glaucoma affects metabolites'' concentrations in the GCT and the striate area suggesting there is ongoing neurodegenerative process.     

Cerebrospinal fluid acetylcholinesterase changes after treatment with donepezil in patients with Alzheimer's disease

We analyzed whether donepezil differently influences acetylcholinesterase (AChE) variants from cerebrospinal fluid (CSF) in patients with Alzheimer's disease (AD) after long-term treatment. Overall CSF-AChE activity in AD patients before treatment was not different from controls, but the ratio between the major tetrameric form, G(4), and the smaller G(1) and G(2) species was significantly lower. AChE levels at study outset were found to correlate positively with beta-amyloid (1-42) (Abeta42). When patients were re-examined after 12 months treatment with donepezil, there was a remarkable increase in both the G(4) and the lighter species of CSF AChE. As compared with placebo, donepezil caused decreases in the percentage of AChE that failed to bind to the lectin concanavalin A and the antibody AE1. These non-binding species comprised primarily a small subset of G(1) and G(2) forms. In treated patients, these light variants were the only subset of CSF AChE that correlated with CSF-Abeta42 levels. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that a 77-kDa band, attributed in part to inactive AChE, was lower in AD patients than in controls. Unlike enzyme activity, the intensity of this band did not increase after donepezil treatment. The varying responses of different AChE species to ChE-I treatment suggest different modes of regulation, which may have therapeutic implications.     

当归注射液对脑缺血/再灌注神经元代谢物的影响

目的：研究当归注射液对脑缺血／再灌注时神经元代谢物及血流速度的作用,阐明当归对脑缺血损伤神经修复过程的影响。方法：雄性SD大鼠69只,体重150～170g,随机分成假手术组(n=4)、缺血损伤组(n=30)和当归治疗组(n=35)。制作右大脑中动脉血供阻断(MCA0)模型。缺血2h后,当归治疗组立即腹腔注射当归注射液(5g／kgbw)。在再灌注后3～4h和5～6h,以磁共振成像(MRI)技术研究大脑T2加权成像(T2WI)和局域质子谱(^1H MRS)的变化,观察当归对成像和神经元代谢物N-乙酰天门冬氨酸(NAA)、肌酸／磷酸肌酸(Cr／PCr)和胆碱(Cho)的影响。激光多普勒血流仪观察当归注射液对血流速度的影响,测定脑表面血管密度。结果：与缺血损伤组比较,当归治疗组的高信号强度区信号减弱、体积小,NAA值大,Cr/NAA和Cho/NAA比值小,再灌注时的血流速度显著加快,单位面积内的血管长度增加。结论：当归注射液加快缺血脑组织的血液循环,改善神经元的代谢。     

Medial-frontal cortex hypometabolism in chronic phencyclidine exposed rats assessed by high resolution magic angle spin 11.7 T proton magnetic resonance spectroscopy

BackgroundProton magnetic resonance spectroscopy (¹H-MRS) clinical studies of patients with schizophrenia document prefrontal N-acetylaspartate (NAA) reductions, suggesting an effect of the disease or of antipsychotic medications. We studied in the rat the effect of prolonged exposure to a low-dose of the NMDA glutamate receptor antagonist phencyclidine (PCP) on levels of NAA, glutamate and glutamine in several brain regions where metabolite reductions have been reported in chronically medicated patients with schizophrenia.MethodsTwo groups of ten rats each were treated with PCP (2.58 mg/kg/day) or vehicle and were sacrificed after 1 month treatment. Concentrations of neurochemicals were determined with high resolution magic angle (HR-MAS) ¹H-MRS at 11.7 T in ex vivo punch biopsies from the medial frontal and cingulate cortex, striatum, nucleus accumbens, amygdala and ventral hippocampus.ResultsPCP treatment reduced NAA, glutamate, glycine, aspartate, creatine, lactate and GABA in medial frontal cortex. In the nucleus accumbens, PCP reduced levels of NAA, aspartate and glycine; similarly aspartate and glycine were reduced in the striatum. Finally the amygdala and hippocampus had elevations in glutamine and choline, respectively.ConclusionsLow-dose PCP in rats models prefrontal NAA and glutamate reductions documented in chronically-ill schizophrenia patients. Chronic glutamate NMDA receptor blockade in rats replicates an endophenotype in schizophrenia and may contribute to the prefrontal hypometabolic state in schizophrenia.     

3.0T 1H-MRS对脑胶质瘤及脑转移瘤的鉴别诊断

目的：利用3.0T氢质子磁共振波谱对胶质瘤和转移瘤的肿瘤组织区、瘤周水肿区进行细胞代谢物水平的检测,试图找出胶质瘤和脑转移瘤的鉴别诊断的依据,以及胶质瘤高、低级别组间的差别。方法：对经病理证实的20例高级别胶质瘤组、16例低级别胶质瘤组和19例脑转移瘤组患者,先行MRI平扫及增强扫描,波谱均在增强扫描的基础上获得,使用MR点分辨波谱序列,检测肿瘤组织区、瘤周水肿组织区NAA/Cr、Cho/Cr、NAA/Cho、NAA、Cho、Cr、Lip/Lac等值,进行比较。结果：（1）高级别胶质瘤与转移瘤在肿瘤组织区NAA/Cr代谢物浓度的比值有统计学意义。（2）高、低级别胶质瘤肿瘤组织内Cho/Cr比值有统计学意义。（3）转移瘤与高、低级别胶质瘤在瘤周水肿区NAA/Cr,以及低级别胶质瘤与转移瘤Cho/Cr代谢物浓度的比值有统计学意义;高级别胶质瘤与转移瘤瘤周区NAA代谢物浓度有明显差异。（4）胶质瘤高、低级别组间在肿瘤周围区NAA峰、Cho峰及NAA/Cho Cho/Cr代谢物浓度比值有统计学意义。（5）高级别胶质瘤和转移瘤分别与低级别胶质瘤在肿瘤组织区及瘤周水肿区Lip/Lac有显著性差异（P〈0.01）。结论：利用氢质子波谱可对胶质瘤和转移瘤进行鉴别诊断;Cho/Cr及NAA/Cho比值可对胶质瘤进行分级;Lip/Lac峰的出现与肿瘤的恶性度呈正相关,但不特异。     

Proton magnetic resonance spectroscopy in diagnostics of epilepsy

Present paper presents proton MRS investigation results. The investigation was carried out with Magnetom Vision device. Twenty-five patients in the age of 20-44 years suffering with generalization epileptic fits validated by EEG (no visible changes on MRT) were examined. In all cases independently on the localization of the changes, decreasing of NAA and increasing of Cho were recorded. At one side temporal lobe injury recorded by EEG at the damaged part decreasing of NAA/Cr and NAA/Cho + Cr ratios were registered. Patients with bilateral changes registered by EEG showed non-equal changes of metabolite concentration on both sides. Examination of patients suffering with distinct symptoms of temple epileptics has shown ipsilaterality decrease of NAA and Cr concentration. But on the injured side NAA/Cr ratio decrease was more distinct. In general, the laterality was recorded in 14 patients out of 22 with pathological changes registered by proton MRS and in 10 patients out of 14 the above mentioned changes corresponds to the side of the fit initiation. In the patients with bilaterality changes NAA/Cr ratio asymmetry was recorded in all cases, but the most distinctly in the medium part of the temple lobe. Comparison of data recorded in 8 patients suffering with one side fit complex has shown significant asymmetry of metabolites which was observed in ipsilaterality and contra laterality NAA ratio obtained in hippocampal areas. Difference in NAA ratio obtained between left and right sides are 19-25%. Left-right ratio of other metabolites corresponded to that ratio in the control group and was symmetrical.     

Association between acetylcholinesterase and beta-amyloid peptide in Alzheimer's cerebrospinal fluid

The altered expression of acetylcholinesterase (AChE) in the brains of patients with Alzheimer's disease (AD) has raised much interest of late. Despite an overall decrease in the AD brain, the activity of AChE increases around beta-amyloid plaques and indeed, the beta-amyloid peptide (Abeta) can influence AChE levels. Such evidence stimulated our interest in the possibility that the levels of AChE and amyloid might vary together in AD. We previously found that the different AChE forms present in both the brain and in the cerebrospinal fluid (CSF) of AD patients varied in conjunction with abnormal glycosylation. Thus, the alterations in glycosylation are correlated with the accumulation of a minor subspecies of AChE monomers. We also recently analysed whether long-term exposure to the cholinesterase inhibitor (ChE-I) donepezil influences the AChE species found in AD CSF. The marked increase in CSF-AChE activity in AD patients following long-term treatment with donepezil was not paralleled by a rise in this subset of light variants. Hence, the correlation with the levels of CSF-Abeta is unique to these AChE species in patients receiving such treatment. The aim of this report is to review the links between AChE and beta-amyloid, and to discuss the significance of the responses of the distinct AChE species to ChE-I during the treatment of AD.     

Reduced NAA-Levels in the NAWM of Patients with MS Is a Feature of Progression. A Study with Quantitative Magnetic Resonance Spectroscopy at 3 Tesla

Background

Reduced N-acetyl-aspartate (NAA) levels in magnetic resonance spectroscopy (MRS) may visualize axonal damage even in the normal appearing white matter (NAWM). Demyelination and axonal degeneration are a hallmark in multiple sclerosis (MS).

Objective

To define the extent of axonal degeneration in the NAWM in the remote from focal lesions in patients with relapsing-remitting (RRMS) and secondary progressive MS (SPMS).

Material and Methods

37 patients with clinical definite MS (27 with RRMS, 10 with SPMS) and 8 controls were included. We used 2D ¹H-MR-chemical shift imaging (TR = 1500ms, TE = 135ms, nominal resolution 1ccm) operating at 3Tesla to assess the metabolic pattern in the fronto–parietal NAWM. Ratios of NAA to creatine (Cr) and choline (Cho) and absolute concentrations of the metabolites in the NAWM were measured in each voxel matching exclusively white matter on the anatomical T2 weighted MR images.

Results

No significant difference of absolute concentrations for NAA, Cr and Cho or metabolite ratios were found between RRMS and controls. In SPMS, the NAA/Cr ratio and absolute concentrations for NAA and Cr were significantly reduced compared to RRMS and to controls.

Conclusions

In our study SPMS patients, but not RRMS patients were characterized by low NAA levels. Reduced NAA-levels in the NAWM of patients with MS is a feature of progression.