Difference in Regional Brain Volume between Fibromyalgia Patients and Long-Term Meditators.

BACKGROUND: The practice of meditation has been shown to improve pain-related quality of life and also to alter brain activity. To assess brain volumetry in fibromyalgia (FM) patients, healthy meditators and healthy non-meditator control groups, and to elucidate the possible association between brain changes in meditators and years of meditation practice. METHODS: Twelve patients diagnosed with FM, eleven long-term Zen meditators and ten healthy control subjects closely matched for sex and age were recruited. A high resolution T1-3D sequence was acquired and a high-dimensional DARTEL normalization strategy was applied. Questionnaires on anxiety, depression and cognitive impairment were administered. RESULTS: There was a statistically significant increase in grey matter volume in the Brodmann area 20 (right and left inferior temporal gyri) in patients with fibromyalgia and a significant decrease in the meditator group as compared to controls. On the other hand, there was a significant increase in grey matter volume in fibromyalgia patients as compared to controls and meditators, to the right temporal gyrus (p=0.03, t=6.85) and left temporal gyrus (p=0.04, t=6.31). The number of months of meditation did not correlate with significant grey matter volume changes in the meditator group. CONCLUSIONS: FM and meditation appears to be reliably associated with altered anatomical structure in the Brodmann area 20 (in both inferior temporal gyri), and these changes are associated with anxiety and depression levels. In addition, exploratory morphometric analyses for fibromyalgia patients and meditators may reveal relevant brain regions showing structural diminution in meditation practitioners. Morphologic changes might predispose toward vulnerability to develop a chronic pain state. Such structural diminutions could potentially indicate functional benefits.

Cost-utility and biological underpinnings of Mindfulness-Based Stress Reduction (MBSR) versus a psychoeducational programme (FibroQoL) for fibromyalgia: a 12-month randomised controlled trial (EUDAIMON study).

BACKGROUND: The EUDAIMON study focuses on fibromyalgia syndrome (FMS), a prevalent chronic condition characterized by pain, fatigue, cognitive problems and distress. According to recent reviews and meta-analyses, Mindfulness-Based Stress Reduction (MBSR) is a promising therapeutic approach for patients with FMS. The measurement of biomarkers as part of the analysis of MBSR effects would help to identify the neurobiological underpinnings of MBSR and increase our knowledge of FMS pathophysiology. The main objectives of this 12-month RCT are: firstly, to examine the effectiveness and cost-utility for FMS patients of MBSR as an add-on to treatment as usual (TAU) versus TAU + the psychoeducational programme FibroQoL, and versus TAU only; secondly, to examine pre-post differences in brain structure and function, as well as levels of specific inflammatory markers in the three study arms and; thirdly, to analyse the role of some psychological variables as mediators of 12-month clinical outcomes. METHODS: Effectiveness, cost-utility, and neurobiological analyses performed alongside a 12-month RCT. The participants will be 180 adult patients with FMS recruited at the Sant Joan de Déu hospital (St. Boi de Llobregat, Spain), randomly allocated to one of the three study arms: TAU + MBSR vs. TAU + FibroQol vs. TAU. A comprehensive assessment to collect functional, quality of life, distress, costs, and psychological variables will be conducted pre-, post-intervention, and at 12-month post-intervention. Fifty per cent of study participants will be evaluated at pre- and post-treatment using Voxel-Based Morphometry, Diffusion Tensor Imaging, pseudo-continuous Arterial Spin Labeling, and resting state fMRI. A cytokine multiplex kit of high-sensitivity will be applied (cytokines IL-6, IL-8, IL-10 + high-sensitivity CRP test). DISCUSSION: The findings obtained from this RCT will indicate whether MBSR is potentially cost-effective for FMS and contribute to knowledge of any brain and inflammatory changes associated with MBSR in FMS patients. Specifically, we will determine whether there are morphometric and functional changes associated with participation in MBSR in brain regions related to meta-awareness, body awareness, memory consolidation-reconsolidation, emotion regulation and in networks postulated to underpin the sensory-discriminative, cognitive-evaluative and affective-motivational aspects of the pain experience. TRIAL REGISTRATION: NCT02561416 . Registered 23 September 2015.

Different Brain Phenotypes in Magnetic Resonance Imaging of Healthy Children after Prenatal Insults.

In this study, we used magnetic resonance imaging (MRI) to identify the different brain phenotypes within apparently healthy children and to evaluate whether these phenotypes had different prenatal characteristics. We included 65 healthy children (mean age, 10 years old) with normal neurological examinations and without structural abnormalities. We performed cluster analyses to identify the different brain phenotypes in the brain MRI images. We performed descriptive analyses, including demographic and perinatal characteristics, to assess the differences between the clusters. We identified two clusters: Cluster 1, or the "small brain phenotype" (n = 44), which was characterized by a global reduction in the brain volumes, with smaller total intracranial volumes (1044.53 ± 68.37 vs. 1200.87 ± 65.92 cm3 (p < 0.001)), total grey-matter volumes (644.65 ± 38.85 vs. 746.79 ± 39.37 cm3 (p < 0.001)), and total white-matter volumes (383.68 ± 40.17 vs. 443.55 ± 36.27 cm3 (p < 0.001)), compared with Cluster 2, or the "normal brain phenotype" (n = 21). Moreover, almost all the brain areas had decreased volumes, except for the ventricles, caudate nuclei, and pallidum areas. The risk of belonging to "the small phenotype" was 82% if the child was preterm, 76% if he/she was born small for his/her gestational age and up to 80% if the mother smoked during the pregnancy. However, preterm birth appears to be the only substantially significant risk factor associated with decreased brain volumes.

The Bed Nucleus of the Stria Terminalis as a Brain Correlate of Psychological Inflexibility in Fibromyalgia.

This study explored the brain structural correlates of psychological flexibility (PF) as measured with the Psychological Inflexibility in Pain Scale (PIPS) in patients with fibromyalgia (FM). Structural magnetic resonance imaging data from 47 FM patients were used to identify Gray Matter Volume (GMV) alterations related to PIPS scores. Brain GMV clusters related to PIPS were then correlated with clinical and cognitive variables to further explore how emerged brain clusters were intertwined with FM symptomatology. Longitudinal changes in PIPS-related brain clusters values were assessed by studying pre-post data from 30 patients (15 allocated to a mindfulness-based stress reduction (MBSR) program and 15 to treatment-as-usual). Changes in PIPS-related brain clusters were also explored in participants showing greater/lower longitudinal changes in PIPS scores. PIPS scores were positively associated with GMV in a bilateral cluster in the ventral part of the bed nucleus of the stria terminalis (BNST). Significant associations between BNST cluster with functional impairment, depressive symptomatology, perceived stress and the nonjudging mindfulness facet were observed. Participants reporting greater pre-post increases in PIPS scores showed greater increases in BNST cluster values. These findings contribute to the understanding on the neurobiological bases of PF in FM and encourage further explorations of the role of the BNST in chronic pain.

Comparative test-retest reliability of metabolite values assessed with magnetic resonance spectroscopy of the brain. The LCModel versus the manufacturer software.

OBJECTIVE: Reproducibility is an essential strength of any diagnostic technique for cross-sectional and longitudinal works. To determine in vivo short-term comparatively, the test-retest reliability of magnetic resonance spectroscopy (MRS) of the brain was compared using the manufacturer's software package and the widely used linear combination of model (LCModel) technique. METHODS: Single-voxel H-MRS was performed in a series of patients with different pathologies on a 1.5 T clinical scanner. Four areas of the brain were explored with the point resolved spectroscopy technique acquisition mode; the echo time was 35 milliseconds and the repetition time was 2000 milliseconds. We enrolled 15 patients for every area, and the intra-individual variations of metabolites were studied in two consecutive scans without removing the patient from the scanner. Curve fitting and analysis of metabolites were made with the software of GE and the LCModel. Spectra non-fulfilling the minimum criteria of quality in relation to linewidths and signal/noise ratio were rejected. RESULTS: The intraclass correlation coefficients for the N-acetylaspartate/creatine (NAA/Cr) ratios were 0.93, 0.89, 0.9 and 0.8 for the posterior cingulate gyrus, occipital, prefrontal and temporal regions, respectively, with the GE software. For the LCModel, the coefficients were 0.9, 0.89, 0.87 and 0.84, respectively. For the absolute value of NAA, the GE software was also slightly more reproducible than LCModel. However, for the choline/Cr and myo-inositol/Cr ratios, the LCModel was more reliable than the GE software. The variability we have seen hovers around the percentages observed in previous reports (around 10% for the NAA/Cr ratios). CONCLUSION: We did not find that the LCModel software is superior to the software of the manufacturer. Reproducibility of metabolite values relies more on the observance of the quality parameters than on the software used.

Changes in metabolites in the brain of patients with fibromyalgia after treatment with an NMDA receptor antagonist.

The aims of this work were to evaluate whether the treatment of patients with fibromyalgia with memantine is associated with significant changes in metabolite concentrations in the brain, and to explore any changes in clinical outcome measures. Magnetic resonance spectroscopy was performed of the right anterior and posterior insula, both hippocampi and the posterior cingulate cortex. Questionnaires on pain, anxiety, depression, global function, quality of life and cognitive impairment were used. Ten patients were studied at baseline and after three months of treatment with memantine. Significant increases were observed in the following areas: N-acetylaspartate (4.47 at baseline vs. 4.71 at three months, p = 0.02) and N-acetylaspartate+N-acetylaspartate glutamate in the left hippocampus (5.89 vs. 5.98; p = 0.007); N-acetylaspartate+N-acetylaspartate glutamate in the right hippocampus (5.31 vs 5.79; p = 0.01) and the anterior insula (7.56 vs. 7.70; p = 0.033); glutamate+glutamine/creatine ratio in the anterior insula (2.03 vs. 2.17; p = 0.022) and the posterior insula (1.77 vs. 2.00; p = 0.004); choline/creatine ratio in the posterior cingulate (0.18 vs. 0.19; p = 0.023); and creatine in the right hippocampus (3.60 vs. 3.85; p = 0.007). At the three-month follow-up, memantine improved cognitive function assessed by the Cognition Mini-Exam (31.50, SD = 2.95 vs. 34.40, SD = 0.6; p = 0.005), depression measured by the Hamilton Depression Scale (7.70, SD = 0.81 vs. 7.56, SD = 0.68; p = 0.042) and severity of illness measured by the Clinical Global Impression severity scale (5.79, SD = 0.96 vs. 5.31, SD = 1.12; p = 0.007). Depression, clinical global impression and cognitive function showed improvement with memantine. Magnetic resonance spectroscopy could be useful in monitoring response to the pharmacological treatment of fibromyalgia.

Utility of different MR modalities in mild cognitive impairment and its use as a predictor of conversion to probable dementia.

RATIONALE AND OBJECTIVES: Mild cognitive impairment has been regarded as a pre-Alzheimer condition, but some patients do not develop dementia. The authors' objective was to determine whether findings from a combined use of H1 magnetic resonance spectroscopy (MRS), perfusion imaging (PI), and diffusion-weighted imaging (DWI) would predict conversion from amnesic mild cognitive impairment to dementia and to compare the diagnostic accuracy in discriminating patients with probable Alzheimer disease (AD), mixed dementia (MD), Lewy body dementia (LBD), pre-Alzheimer disease mild cognitive impairment (MCI), vascular MCI (VaMCI), and anxious or depression patients with cognitive impairment (DeMCI). MATERIALS AND METHODS: A longitudinal cohort of 119 consecutive and incident subjects (73 women, 46 men; age 70+/-9.5 years) who fulfilled the criteria of amnesic MCI was followed for a mean period of 29 months. At baseline, a neuropsychological examination and standard blood test were performed, and different areas were examined by proton MRS, PI, and DWI. Among the group of patients considered to have AD, we also included patients with MD because these patients have a neurodegenerative component. RESULTS: After the follow-up period, 54 patients were considered as converted to dementia (49 with AD; 5 with LBD), 28 patients as MCI, 22 patients as DeMCI, and 15 patients as VaMCI. We found that N-acetylaspartate (NAA)/creatine (Cr) ratios in posterior cingulated gyri (PCG) predict the conversion to probable AD with a sensitivity of 82% and specificity of 72%, and NAA/Cr ratios in the left occipital cortex (LOC) had a sensitivity of 78% and specificity of 69%. When we used spectroscopy in the PCG and LOC to differentiate the types of MCI and dementias, we found significance differences in NAA/Cr, NAA/myoinositol (mI), NAA/choline (Cho), mI/NAA, and Cho/Cr ratios. The apparent diffusion coefficient (ADC) values in the right hippocampus showed differences in patients with LBD and DeMCI (P=.003), LBD with MCI (P=0.48), and LBD and VaMCI (P=.009). CONCLUSIONS: NAA/Cr ratios in PCG and LOC can predict the conversion from MCI to dementia with high sensitivity and specificity. MRS can differentiate AD from MCI, but cannot differentiate the types of MCI. DWI in the right hippocampus presents higher values of ADC in LBD and allows differentiating it from MCI.

Malignancy assessment of brain tumours with magnetic resonance spectroscopy and dynamic susceptibility contrast MRI.

Magnetic resonance imaging (MRI) is the most common and well-established imaging modality for evaluation of intracerebral neoplasms, but there are still some incompletely solved challenges, such as reliable distinction between high- and low-grade tumours, exact delineation of tumour extension, and discrimination between recurrent tumour and radiation necrosis. The aim of this study was to evaluate the contribution of two MRI techniques to non-invasively estimate brain tumour grade. Twenty-four patients referred to MRI examination were analyzed and diagnosed with single intra-axial brain tumour. Lastly, histopathological analysis was performed to verify tumour type. Ten patients presented low-grade gliomas, while the remaining patients showed high-grade tumours, including glioblastomas in eight cases, isolated metastases in four patients and two cases with anaplastic gliomas. MRI examinations were performed on a 1.5-T scanner (Signa, General Electric). The acquisition protocol included the following sequences: saggital T1-weighted localizer, axial T1- and T2-weighted MRI, single-voxel magnetic resonance spectroscopy (MRS), dynamic susceptibility contrast (DSC) MRI and contrast-enhanced T1-weighted MRI. MRS data was analyzed with standard software provided by the scanner manufacturer. The metabolite ratio with the largest significant difference between tumour grades was the choline/creatine (Ch/Cr) ratio with elevated values in high-grade gliomas and metastases. A Ch/Cr ratio equal or larger than 1.55 predicted malignancy grade with 92% sensitivity and 80% specificity. The area under the ROC curve was 0.92 (CI: 95%; 0.81-1). Regarding to perfusion parameters, relative cerebral blood volume (rCBV) maps were estimated from the MR signal intensity time series during bolus passage with two commercial software packages. Two different regions of interest (ROI) were used to evaluate rCBV: lesion centre and perilesional region. All rCBV values were normalized to CBV in a contrallateral normal appearing white matter region. Statistical differences were not found between different tumour types. However, the presence of blood-brain barrier (BBB) damage was illustrated from concentration-time curves calculated in DSC-MRI. A cluster analysis of the time series was used to identify regions with contrast agent extravasation where T1-effects are superimposed to T2-effects. The presence of BBB damage from concentration-time curves was highly correlated with enhancement of post-contrast T1-weighted images and predicted tumour malignancy with a 92% sensitivity and 90% specificity. A large spatial heterogeneity in concentration-time curves was observed from the cluster analysis, supporting the assumption that ROI selection to compute hemodynamic parameters must be done carefully in order to extract robust parameters.

Evidence of brain dysfunction in attention deficit-hyperactivity disorder: a controlled study with proton magnetic resonance spectroscopy.

RATIONALE AND OBJECTIVES: Attention deficit-hyperactivity disorder (ADHD) is a socially disabling condition whose pathophysiology is mostly unknown. Previous magnetic resonance imaging (MRI)-based reports have shown structural abnormalities in the prefrontal region and the striatum, but with inconsistencies across the studies with regard to right/left specificity of changes. Our study is aimed at finding evidence of dysfunction with more refined MRI techniques such as diffusion-weighted MRI and spectroscopy. MATERIALS AND METHODS: We enrolled 22 ADHD children (mean age 9; SD 2.91) and 8 healthy children (mean age 7.5; SD 3). All of them underwent diffusion-weighted MRI in several areas of the brain bilaterally: prefrontal, lentiform nucleus, posterior cingulate, and centrum semiovale; and single-voxel proton magnetic resonance spectroscopy in the left centrum semiovale and right prefrontal region. RESULTS: We did not see either apparent structural abnormalities of the brain in conventional MRI or differences in the apparent-diffusion coefficients in any of the areas studied. However, we observed significant differences in the N-acetyl-aspartate/creatine ratios in relation to controls in the right prefrontal corticosubcortical region: 1.58 (SD 0.09) versus 1.47 (0.08), P = .01); and in the left centrum semiovale: 2.02 (0.13) versus 1.79 (0.13), P = .0003. This finding is consistent with a published report on eight ADHD children in whom N-acetyl-aspartate/creatine ratios were also elevated. CONCLUSIONS: Given these results, we hypothesize that a biochemical dysfunction might underlie in the brain of ADHD children. The N-acetyl-aspartate/creatine ratio may be regarded as a potential marker of the disease.

Magnetic resonance spectroscopy and brain volumetry in mild cognitive impairment. A prospective study.

OBJECTIVE: To assess the accuracy of magnetic resonance spectroscopy (1H-MRS) and brain volumetry in mild cognitive impairment (MCI) to predict conversion to probable Alzheimer's disease (AD). METHODS: Forty-eight patients fulfilling the criteria of amnestic MCI who underwent a conventional magnetic resonance imaging (MRI) followed by MRS, and T1-3D on 1.5 Tesla MR unit. At baseline the patients underwent neuropsychological examination. 1H-MRS of the brain was carried out by exploring the left medial occipital lobe and ventral posterior cingulated cortex (vPCC) using the LCModel software. A high resolution T1-3D sequence was acquired to carry out the volumetric measurement. A cortical and subcortical parcellation strategy was used to obtain the volumes of each area within the brain. The patients were followed up to detect conversion to probable AD. RESULTS: After a 3-year follow-up, 15 (31.2%) patients converted to AD. The myo-inositol in the occipital cortex and glutamate+glutamine (Glx) in the posterior cingulate cortex predicted conversion to probable AD at 46.1% sensitivity and 90.6% specificity. The positive predictive value was 66.7%, and the negative predictive value was 80.6%, with an overall cross-validated classification accuracy of 77.8%. The volume of the third ventricle, the total white matter and entorhinal cortex predict conversion to probable AD at 46.7% sensitivity and 90.9% specificity. The positive predictive value was 70%, and the negative predictive value was 78.9%, with an overall cross-validated classification accuracy of 77.1%. Combining volumetric measures in addition to the MRS measures the prediction to probable AD has a 38.5% sensitivity and 87.5% specificity, with a positive predictive value of 55.6%, a negative predictive value of 77.8% and an overall accuracy of 73.3%. CONCLUSION: Either MRS or brain volumetric measures are markers separately of cognitive decline and may serve as a noninvasive tool to monitor cognitive changes and progression to dementia in patients with amnestic MCI, but the results do not support the routine use in the clinical settings.

Retinal structure assessed by OCT as a biomarker of brain development in children born small for gestational age.

PURPOSE: To identify differences in neuronal tissue from retinal and brain structures in children born small for gestational age (SGA) with no abnormality in neonatal brain ultrasonography and no previous neurological impairment, and to evaluate the relationship between retinal structure and brain changes in school-age children born SGA. METHODS: Two cohorts of children were recruited: 25 children born SGA and 25 children born with an appropriate birth weight according to gestational age. All the children underwent an ophthalmic examination, which included retinal imaging using spectral-domain optical coherence tomography, and a brain MRI. MRI images were automatically segmented and global and regional brain volumes were obtained. RESULTS: Although visual function did not differ between both groups, the complex ganglion cell and inner plexiform layers (GCL-IPL) was thinner in SGA children. Total intracranial volume, and global grey and white matter volumes in brain and cerebellum were correlated with birthweight centile, as were certain regional volumes (temporal and parietal lobes, hippocampus and putamen). Abnormal GCL-IPL measurements accurately identified SGA children with the most severe grey and white matter changes in the brain. CONCLUSIONS: SGA children, both preterm and term born, showed evidence of structural abnormalities in the retina, which may be an accurate and non-invasive biomarker of neuronal damage in brain tissue.

Changes in metabolite ratios after treatment with rivastigmine in Alzheimer's disease: a nonrandomised controlled trial with magnetic resonance spectroscopy.

BACKGROUND: Alzheimer's disease is associated with abnormalities in the levels of some brain metabolites, including decreases in N-acetyl-aspartate (NAA) and increases in myo-inositol and choline levels. Cholinesterase inhibitors have proven modest effects on cognition in patients with mild or moderate Alzheimer's disease; however, there is little information on the effects of these drugs on metabolic parameters in the brain. Magnetic resonance spectroscopy (MRS) provides a method of determining changes in such parameters. OBJECTIVE: To assess the effect of rivastigmine on metabolite levels in different areas of the brain, and whether changes in metabolite levels correlate with clinical outcome, in patients with Alzheimer's disease compared with untreated patients with Alzheimer's disease. METHODS: Twenty-four consecutive patients with mild or moderate Alzheimer's disease were enrolled in the study and were treated with rivastigmine at a target dosage of 12 mg/day for 4 months. A comparison group of ten consecutive untreated patients with Alzheimer's disease with similar cognitive impairment to the treatment group were also enrolled. Each patient underwent assessment using the Mini-Mental State Examination (Spanish version), the Blessed Dementia Rating Scale, the Clinical Dementia Rating scale, the Interview for Deterioration in Daily living activities in Dementia, the Alzheimer's Disease Assessment Scale cognitive and noncognitive subscales, and single-voxel MRS of the frontal, parietal and occipital cortices of the brain to assess levels of brain metabolites (NAA, creatine, choline and myo-inositol) and their ratios to creatine. All assessments were performed at baseline and after 4 months of treatment with rivastigmine, and at baseline and 1 month later in the comparison group. RESULTS: Globally, although there was some mean improvement, no significant changes in the cognitive and noncognitive scale scores between baseline and post-treatment assessments were seen in patients who received rivastigmine. A significant increase in the NAA/creatine ratio in the frontal cortex (1.23 at baseline vs 1.3 after treatment; p = 0.026) and in the myo-inositol/creatine ratio in the occipital cortex (0.61 vs 0.65; p = 0.009) was seen in rivastigmine-treated patients. No other significant changes in the metabolite levels or their ratios to creatine were seen in these patients. After correction for multiple comparisons, the significant effects disappeared. Only in the frontal cortex did the changes in metabolite ratios correlate with changes on the clinical scales. In the comparison group, no significant differences between the metabolite levels or ratios to creatine seen with the two scans were detected. CONCLUSION: Treatment with rivastigmine showed modest neuronal functional recovery in the frontal cortex only (being able to reverse disease-related decreases in NAA/creatine ratio in this area but unable to affect the disease-related increase in myo-inositol/creatine ratio in any cortex). Since the modest clinical changes correlated with the small changes in the metabolite rates, MRS could be useful in monitoring response to current or future treatments for Alzheimer's disease.

Contrast/Noise ratio on conventional MRI and choline/creatine ratio on proton MRI spectroscopy accurately discriminate low-grade from high-grade cerebral gliomas.

RATIONALE AND OBJECTIVES: Histopathology is the gold standard to establish the grade of brain tumors but biopsy and/or surgery are not always possible. The aim of this study is to determine whether histological grade of tumors may be predicted by means of conventional gadolinium-enhanced MRI and proton magnetic resonance spectroscopy (MRS). MATERIALS AND METHODS: In this study, we included 35 consecutive patients with single brain tumors and final histopathological verification: 12 had low-grade glioma, 16 had high-grade glioma, and 7 had single metastasis. Initially, we carried out T1 and T2 MRI paying attention to the following features: border definition, mass effect, heterogeneity of signal, perilesional edeme, hemorrhage, necrosis, and corpus callosum invasion. Gadolinium-enhancement was evaluated with the contrast-to-noise ratio (CNR). Next, single-voxel proton MRS was carried out to measure the absolute values of metabolites (N-acetyl-aspartate, creatine, choline, and myo-inositol) and their ratios in the area of maximum contrast enhancement. RESULTS: We found that gadolinium-enhancement measured with the CNR (CNR > 35.86) predicted malignancy at 82.6% sensitivity and 91.7% specificity (area under the curve, 0.88; 95% confidence interval [CI], 0.73-0.97). With regard to MRS a choline/creatine ratio higher than 1.56 predicted malignancy at 88.9% sensitivity and 91.7% specificity (area under the curve, 0.94; 95% CI, 0.78-0.99). When we combined the CNR value, the choline/creatine ratio, and the presence of lactates in a model of discriminant analysis the predictive power improved significantly with an area under the curve of 0.99% (95% CI, 0.87-1). However, the used techniques were unable to distinguish metastases from high-grade gliomas accurately. CONCLUSIONS: The intensity of contrast enhancement measured with the CNR, the choline/creatine ratio, and the presence of lactate were the most powerful variables to predict malignancy in brain tumors. The CNR is a simple, objective, and useful tool in the initial assessment of gliomas and metastases.

White matter proton MR spectroscopy in children with isolated developmental delay: does it mean delayed myelination?

RATIONALE AND OBJECTIVES: Isolated developmental delay (IDD) is a common disorder in preschool and school-age children. Conventional magnetic resonance imaging (MRI) usually does not disclose abnormalities, but a myelination delay is suspected as causative or associated factor. N-acetyl-aspartate is a surrogate marker of neuronal integrity but also of axonal integrity. The goal of our study is to determine whether magnetic resonance spectroscopy (MRS) is able to detect alterations in the white matter supporting the hypothesis of delayed myelination in children with IDD and normal MRI. MATERIALS AND METHODS: In this cross-sectional study, we enrolled 12 consecutive children meeting the criteria if IDD and aged between 3 and 12 years (mean 7.25 years) and 11 healthy children as control group (mean age 7.18, range 3-12 years) on whom we performed conventional MRI and MRS. We did not include children with abnormal MRI. Single voxel (8 cm(3)) was placed in the white matter of the left centrum semiovale. The mode of acquisition was probe-p (PRESS technique) with a TR of 2500 milliseconds and a TE of 30 milliseconds. We measured the metabolite concentration of n-acetyl-aspartate (NAA), choline (Ch), creatine (Cr) y myo-inositol (mI), and ratios of NAA, Ch, and mI to creatine. RESULTS: In children with IDD, we found a significant decrease of the following ratios: NAA/Cr (P < .016), NAA/Ch (P < .026), and NAA/mI (P < .023) in relation to controls. The mean NAA/Cr ratio in IDD children was 1.92 (SD 0.14), and in controls it was 2.09 (SD 0.14); t = 2.62, fd (freedom degrees) = 21, P < .016. No differences were seen in the remaining ratios. CONCLUSIONS: The lower NAA/Cr ratio in children with IDD in relation to controls may be a promising marker of this disorder and supports the hypothesis of delayed myelination. MRS can provide important information in children with neurodevelopmental disorders.

Conversion from mild cognitive impairment to probable Alzheimer's disease predicted by brain magnetic resonance spectroscopy.

OBJECTIVE: Mild cognitive impairment has been regarded as a pre-Alzheimer condition, but some patients do not develop dementia. Given the available therapies for Alzheimer's disease, early diagnosis is of paramount importance. The authors' objective was to determine whether findings from magnetic resonance spectroscopy (MRS) of the hippocampus and other cortical areas would predict conversion from amnestic mild cognitive impairment to probable Alzheimer's disease. METHOD: A longitudinal inception cohort of 53 consecutive and incident subjects fulfilling the criteria of amnestic mild cognitive impairment was followed for a mean period of 3 years. At baseline, a neuropsychological examination (Mini-Mental State Examination, Blessed Dementia Rating Scale, Clinical Dementia Rating, verbal fluency test, and memory tests) and standard blood tests were performed, and three cortical areas were examined by proton MRS: left hippocampus, right parietal cortex, and left occipital cortex. The patients were evaluated periodically to detect conversion to probable Alzheimer's disease. The statistical analysis of predictions was based on receiver operating characteristic curves. RESULTS: By the follow-up assessment that occurred on average after 3 years, 29 patients (55%) had developed probable Alzheimer's disease. An occipital cortex N-acetylaspartate/creatine ratio < or =1.61 predicted dementia at 100% sensitivity and 75% specificity (area under the curve=0.91, 95% CI=0.80-0.97). The positive predictive value was 83%, and the negative predictive value was 100%, with an overall cross-validated classification accuracy of 88.7%. None of the values in the hippocampus and parietal cortex had significant predictive value. CONCLUSIONS: MRS of the brain performed on patients with mild cognitive impairment is a valuable tool in predicting conversion to probable Alzheimer's disease. Occipital values were more reliable than hippocampal values in this prediction.

Comparative study of cerebral white matter in autism and attention-deficit/hyperactivity disorder by means of magnetic resonance spectroscopy.

RATIONALE AND OBJECTIVES: Autism and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental disorders whose pathophysiology is mostly unknown. As far as the symptoms are different and, in some aspects, opposed, we hypothesize that there must be biochemical differences in the brain of the afflicted children. The aim of the study is to analyze comparatively the metabolite concentration of the cerebral white matter in autism, in ADHD, and in a control group of healthy children to test the hypothesis that N-acetyl aspartate (NAA) is decreased in autism and increased in ADHD. PATIENTS AND METHODS: We included 21 autistic children according to DSM-IV criteria, 8 children with ADHD meeting the respective criteria of DSM-IV, and 12 healthy controls of similar age. Single-voxel proton magnetic resonance spectroscopy was performed on all of them with an echo time of 30 milliseconds and a repetition time of 2500 milliseconds. The voxel was placed in the left centrum semiovale. Metabolite ratios relative to creatine were reported for NAA, choline, and myoinositol. RESULTS: Although we did not observe differences between autistic children and controls, we found a mean higher concentration of NAA in the left centrum semiovale of ADHD children (2.2; SD, 0.21) than that found in autistic children (1.88; SD, 0.18) and controls (1.91; SD, 0.01), which was significant (P = .01 in parametric and in nonparametric test). CONCLUSION: We conclude that white matter of autistic children does not present alterations on MRS. We hypothesize that the higher concentration of NAA in the white matter of ADHD points to mitochondrial hypermetabolism. This may constitute a new substrate in the pathophysiology and merits further research.

MR spectroscopy of intracranial tuberculomas: A singlet peak at 3.8 ppm as potential marker to differentiate them from malignant tumors.

PURPOSE: The diagnosis of intracranial tuberculomas is often challenging. Our purpose is to describe the most common metabolic patterns of tuberculomas by MR spectroscopy (MRS) with emphasis on potential specific markers. METHODS: Single-voxel MRS short echo time was performed in 13 cases of tuberculomas proven by histology and/or response to anti-mycobacterial therapy. For comparison MRS was also performed in 19 biopsy-proven malignant tumors (13 high-grade gliomas and six metastasis). Presence of metabolic peaks was assessed visually and categorical variables between groups were compared using chi-square. Metabolite ratios were compared using Mann-Whitney test and diagnostic accuracy of the metabolite ratios was compared using receiver-operating characteristic (ROC) curves analysis. RESULTS: Spectroscopic peaks representing lipids and glutamate/glutamine (Glx) as well as a peak at ∼3.8 ppm were well defined in 77% (10/13), 77% (10/13) and 69% (nine of 13) of tuberculomas, respectively. Lipid and Glx peaks were also present in most of the malignant lesions, 79% (15/19) and 74% (14/19) respectively. However, a peak at ∼3.8 ppm was present in only 10% (two of 19) of the tumor cases (p < 0.001). Higher Cho/Cr and mI/Cr ratios helped discriminate malignant lesions with an area under the ROC curve of 0.86 (SE: 0.078, p < 0.002, CI: 0.7-1) and 0.8 (SE: 0.1, p < 0.009, CI: 0.6-1), respectively. Threshold values between 1.7-1.9 for Cho/Cr and 0.8-0.9 for mI/Cr provided high specificity (91% for both metabolites) and adequate sensitivity (75% and 80%, respectively) for discrimination of malignant lesions. CONCLUSION: A singlet peak at ∼3.8 ppm is present in the majority of tuberculomas and absent in most malignant tumors, potentially a marker to differentiate these lesions. The assignment of the peak is difficult from our analysis; however, guanidinoacetate (Gua) is a possibility. Higher Cho/Cr and mI/Cr ratios should favor malignant lesions over tuberculomas. The presence of lipids and Glx is non-specific.

Higher glutamate+glutamine and reduction of N-acetylaspartate in posterior cingulate according to age range in patients with cognitive impairment and/or pain.

RATIONALE AND OBJECTIVES: The aim of the study was to analyze 1) whether the metabolite levels in the posterior cingulate cortex (PCC) are different in healthy individuals compared to a group of patients with cognitive impairment and/or pain and 2) whether there exists a correlation between brain metabolites and the age of a patient. MATERIALS AND METHODS: Two hundred seven patients with cognitive impairment and/or pain (66 mild cognitive impairment, 54 fibromyalgia, 36 Alzheimer disease, 33 interictal migraine, 10 somatization disorder, and 8 after trigeminal neuralgia, and 193 healthy participants adjusted for gender and age. Proton magnetic resonance spectroscopy (MRS) of the brain was performed with the voxel placed in the ventral PCC and postprocessed with LCModel (Stephen Provencher, Oakville, Ontario, Canada). RESULTS: Using linear regression and adjusting for gender and age, mean brain metabolite values for the pathological group, when compared to healthy controls, were significantly lower in N-acetylaspartate (P=.003) and N-acetylaspartate/creatine (P=.015) and significantly greater in glutamate+glutamine (P<.001) and glutamate+glutamine/creatine (P<.000). All metabolites were significantly correlated with age: glutamate, glutamate+glutamine, N-acetylaspartate, and their creatine ratios exhibited a negative correlation, whereas myoinositol and choline exhibited a positive correlation. CONCLUSIONS: Although the number of patients is relatively small with heterogeneous state of disease, MRS in PCC may serve as a useful noninvasive tool for diagnostic of patients with cognitive impairment and pain.

Changes in metabolites after treatment with memantine in fibromyalgia. A double-blind randomized controlled trial with magnetic resonance spectroscopy with a 6-month follow-up.

AIM: To evaluate the efficacy of memantine on metabolite levels in different areas of the brain and to determine whether changes in metabolite levels correlate with clinical variables in Fibromyalgia (FM) patients. METHODS: Doubled-blind parallel randomized controlled trial. Twenty-five patients diagnosed with FM were enrolled in the study. Patients were administered questionnaires on pain, anxiety, depression, quality of life, and cognitive impairment, and single-voxel MRS of the brain was performed. All assessments were performed at baseline and after 6 months of treatment with memantine or placebo. RESULTS: Patients treated with memantine exhibited a significant increase in the glutamate (P = 0.010), glutamate/creatine ratio (P = 0.013), combined glutamate + glutamine (P = 0.016) and total N-acetyl-aspartate (NAA+NAAG) (P = 0.034) in the posterior cingulate cortex compared with those on placebo. Furthermore, the memantine group exhibited increases in creatine (P = 0.013) and choline (Cho) (P = 0.025) in the right posterior insula and also a correlation between choline and the Fibromyalgia Impact Questionnaire (FIQ) in the posterior insula (P = 0.050) was observed. CONCLUSION: Memantine treatment resulted in an increase in cerebral metabolism in FM patients, suggesting its utility for the treatment of the illness.

Efficacy of memantine in the treatment of fibromyalgia: A double-blind, randomised, controlled trial with 6-month follow-up.

Fibromyalgia (FM) is a prevalent and disabling chronic disease. Recent studies have found elevated levels of glutamate in several brain regions, leading to hypotheses about the usefulness of glutamate-blocking drugs such as memantine in the treatment of FM. The aim of this study was to evaluate the efficacy of memantine in the treatment of pain and other clinical variables (global function, clinical impression, depression, anxiety, quality of life) in FM patients. A double-blind, parallel randomised controlled trial was developed. A total of 63 patients diagnosed with FM were recruited from primary health care centres in Zaragoza, Spain. Memantine was administered at doses of 20mg/d after 1 month of titration. Assessments were carried out at baseline, posttreatment, and 3- and 6-month follow-up. Compared with a placebo group, memantine significantly decreased ratings on a pain visual analogue scale (Cohen's d=1.43 at 6 months) and pain measured with a sphygmomanometer (d=1.05). All other secondary outcomes except anxiety also improved, with moderate-to-large effect sizes at 6 months. Compared with placebo, the absolute risk reduction obtained with memantine was 16.13% (95% confidence interval=2.0% to 32.6%), and the number needed to treat was 6.2 (95% confidence interval=3 to 47). Tolerance was good, with dizziness (8 patients) and headache (4 patients) being the most frequent side effects of memantine. Although additional studies with larger sample sizes and longer follow-up times are needed, this study provides preliminary evidence of the utility of memantine for the treatment of FM.