Maria C. G. Otaduy

Reduced phospholipid breakdown in Alzheimer's brains: a 31P spectroscopy study.

BackgroundAbnormalities of membrane phospholipid metabolism have been described in Alzheimer’s disease (AD). We investigated, with the aid of 31P magnetic resonance spectroscopy, the in vivo intracerebral availability of phosphomonoesters (PME) and phosphodiesters (PDE) in patients with AD.MethodsEighteen outpatients with mild or moderate probable AD and 16 nondemented elderly volunteers were assessed with the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) and its cognitive subscale of the CAMDEX schedule (CAMCOG). Scans were performed on a 1.5xa0T magnetic resonance imager addressing a 40-cm3 voxel in the left prefrontal cortex. Main outcome measures were mean relative peak areas of PME and PDE, which provide an estimate of membrane phospholipid metabolism.ResultsPME resonance and the PME/PDE ratio were increased in AD patients as compared to controls (p<0.05). PME was negatively correlated with global cognitive performance as shown by the Mini-Mental State Examination (rs=−0.36, p=0.05) and CAMCOG scores (rs=−0.49, p=0.007), as well as with discrete neuropsychological functions, namely, memory (rs=−0.53, p=0.004), visual perception (rs=−0.54, p=0.003), orientation (rs=−0.36, p=0.05), and abstract thinking (rs=−0.48, p=0.01).ConclusionsWe provide evidence of reduced membrane phospholipid breakdown in the prefrontal cortex of mild and moderately demented AD patients. These abnormalities correlate with neuropsychological deficits that are characteristic of AD.

Creatine supplementation in fibromyalgia: a randomized, double-blind, placebo-controlled trial.

To investigate the efficacy and safety of creatine supplementation in fibromyalgia patients.

Proton magnetic resonance spectroscopy: normal findings in the cerebellar hemisphere in childhood.

AbstractnBackground. The cerebellar hemispheres (CER) are different from the supratentorial white and gray matter embryologically, in cytoarchitecture, and probably in metabolic activity. Proton magnetic resonance spectroscopy (1H MRS) can provide a noninvasive biochemical analysis of this region.nObjective. To study, with 1H MRS, metabolite concentrations in CER as a function of age and compare these metabolic data with those of parietoccipital white matter (PO WM) in healthy children.nMaterials and methods. Using single-voxel 1H MRS, we studied 37 volunteers (3–18xa0years) with normal MRI scans of the brain. 1H MRS was performed using the PRESS technique in CER and PO WM. The NAA/Cr, Cho/Cr, NAA/H2O, Cr/H2O, and Cho/H2O ratios were analyzed as a function of age. Metabolic data from these regions were compared.nResults. The NAA/Cr ratio tended to increase with age in CER. Mean NAA/Cr and Cho/Cr ratios were found to be lower in CER than in PO WM. Mean NAA/H2O, Cr/H2O, and Cho/H2O ratios in CER were higher than in the PO WM.nConclusion. Our data confirm the regional variations between CER and PO WM metabolite ratios, and demonstrate a tendency of age-dependent change of the NAA/Cr ratio in CER. The creatine concentration was significantly higher in the cerebellum than in the PO WM.

Diffusion abnormalities of the corpus callosum in patients with malformations of cortical development and epilepsy

PURPOSEnDiffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that can characterize white matter (WM) architecture and microstructure. DTI has demonstrated extensive WM changes in patients with several epileptic syndromes, but few studies have focused on patients with malformations of cortical development (MCD). Our aim was to investigate the quantitative diffusion properties of the corpus callosum (CC), a major commissural bundle critical in inter-hemispheric connectivity, in a large group of patients with MCD.nnnMETHODSnThirty-two MCD patients and 32 age and sex-matched control subjects were evaluated with DTI at 3.0 T. We analyzed the three major subdivisions of the CC (genu, body, and splenium) with deterministic tractography to yield fractional anisotropy (FA), mean diffusivity (MD), parallel diffusivity (λ||) and perpendicular diffusivity (λ⊥). We further assessed the CC with region of interest (ROI)-based analyses and evaluated different subgroups of MCD (polymicrogyria/schizencephaly, heterotopia, and cortical dysplasia). Partial correlations between diffusion changes and clinical parameters (epilepsy duration and age at disease onset) were also queried.nnnRESULTSnThere were significant reductions of FA, accompanied by increases in MD and λ⊥ in all segments of the CC in the patients group with both analytical methods. The absolute differences in FA were greater on ROI-analyses. There were no significant differences between the MCD subgroups, and no correlations between clinical parameters of epilepsy and FA.nnnCONCLUSIONSnOur study indicates DTI abnormalities consistent with microstructural changes in the corpus callosum of MCD patients. The findings support the idea that patients with epilepsy secondary to cortical malformations present widespread WM changes that extend beyond the macroscopic MRI-visible lesions.

A Longitudinal (6-week) 3T (1)H-MRS Study on the Effects of Lithium Treatment on Anterior Cingulate Cortex Metabolites in Bipolar Depression.

The anterior cingulate cortex (ACC) is a key area in mood regulation. To date, no longitudinal study has specifically evaluated lithium׳s effects on ACC metabolites using (1)H-MRS, as well as its association with clinical improvement in bipolar depression. This (1)H-MRS (TE=35ms) study evaluated 24 drug-free BD patients during depressive episodes and after lithium treatment at therapeutic levels. Brain metabolite levels (N-acetyl aspartate (NAA), creatine (tCr), choline, myo-inositol, and glutamate levels) were measured in the ACC at baseline (week 0) and after lithium monotherapy (week 6). The present investigation showed that ACC glutamate (Glu/tCr) and glutamate+glutamine (Glx/tCr) significantly increased after six weeks of lithium therapy. Regarding the association with clinical improvement, remitters showed an increase in myoinositol levels (mI/tCr) after lithium treatment compared to non-remitters. The present findings reinforce a role for ACC glutamate-glutamine cycling and myoinositol pathway as key targets for lithium׳s therapeutic effects in BD.

Assessment of irradiated brain metastases using dynamic contrast-enhanced magnetic resonance imaging

IntroductionThe purpose of this study was to evaluate the effect of stereotactic radiosurgery (SRS) on cerebral metastases using the transfer constant (Ktrans) assessed by dynamic contrast-enhanced (DCE) MRI. Furthermore, we aimed to evaluate the ability of Ktrans measurements to predict midterm tumor outcomes after SRS.MethodsThe study received institutional review board approval, and informed consent was obtained from all subjects. Twenty-six adult patients with a total of 34 cerebral metastases underwent T1-weighted DCE MRI in a 1.5-T magnet at baseline (prior to SRS) and 4–8xa0weeks after treatment. Quantitative analysis of DCE MRI was performed by generating Ktrans parametric maps, and region-of-interest-based measurements were acquired for each metastasis. Conventional MRI was performed at least 16xa0weeks after SRS to assess midterm tumor outcome using volume variation.ResultsThe mean (±SD) Ktrans value was 0.13u2009±u20090.11xa0min−1 at baseline and 0.08u2009±u20090.07xa0min−1 after 4–8xa0weeks post-treatment (pu2009<u20090.001). The mean (±SD) total follow-up time was 7.9u2009±u20094.7xa0months. Seventeen patients (22 lesions) underwent midterm MRI. Of those, nine (41xa0%) lesions had progressed at the midterm follow-up. An increase in Ktrans after SRS was predictive of tumor progression (hazard ratiou2009=u20091.50; 95xa0% CIu2009=u20091.16–1.70, pu2009<u20090.001). An increase of 15xa0% in Ktrans showed a sensitivity of 78xa0% and a specificity of 85xa0% for the prediction of progression at midterm follow-up.ConclusionSRS was associated with a reduction of Ktrans values of the cerebral metastases in the early post-treatment period. Furthermore, Ktrans variation as assessed using DCE MRI may be helpful to predict midterm outcomes after SRS.

Phosphorus magnetic resonance spectroscopy in malformations of cortical development.

Purpose:u2002 The aim of this study was to evaluate phospholipid metabolism in patients with malformations of cortical development (MCDs).

Further diffusion tensor imaging contribution in horizontal gaze palsy and progressive scoliosis

In two siblings with clinical diagnosis of horizontal gaze palsy associated with progressive scoliosis (HGPPS) we could demonstrate by diffusion tensor imaging: (1) An anterior displacement of the transverse pontine fibers; (2) Posterior clumping of the corticospinal, medial lemniscus and central tegmental tracts and of the medial and dorsal longitudinal fasciculi complex; (3) Absent decussation of superior cerebellar peduncle. Those findings can contribute as surrogate markers for the diagnosis.

Effects of Beta-Alanine Supplementation on Brain Homocarnosine/Carnosine Signal and Cognitive Function: An Exploratory Study

Objectives Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d-1 on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). Methods In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. Results In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P<0.05), although there was no effect (P>0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. Conclusion 28 d of beta-alanine supplementation at 6.4g d-1 appeared not to influence brain homocarnosine/carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists.

Increased Brain Lactate During Depressive Episodes and Reversal Effects by Lithium Monotherapy in Drug-Naive Bipolar Disorder A 3-T H-1-MRS Study

Objective Mitochondrial dysfunction and energy metabolism impairment are key components in the pathophysiology of bipolar disorder (BD) and may involve a shift from aerobic to anaerobic metabolism. Measurement of brain lactate in vivo using proton magnetic resonance spectroscopy (1H-MRS) represents an important tool to evaluate mitochondrial and metabolic dysfunction during mood episodes, as well as to monitor treatment response. To date, very few studies have quantified brain lactate in BD. In addition, no study has longitudinally evaluated lactate using 1H-MRS during depressive episodes or its association with mood stabilizer therapy. This study aimed to evaluate cingulate cortex (CC) lactate using 3-T 1H-MRS during acute depressive episodes in BD and the possible effects induced by lithium monotherapy. Methods Twenty medication-free outpatients with short length of BD (80% drug-naive) in a current major depressive episode were matched with control subjects. Patients were treated for 6 weeks with lithium monotherapy at therapeutic doses in an open-label trial (blood level, 0.48 ± 0.19 mmol/L). Cingulate cortex lactate was measured before (week 0) and after lithium therapy (week 6) using 1H-MRS. Antidepressant efficacy was assessed with the 21-item Hamilton Depression Rating Scale as the primary outcome. Results Subjects with BD depression showed a significantly higher CC lactate in comparison to control subjects. Furthermore, a significant decrease in CC lactate was observed after 6 weeks of lithium treatment compared with baseline (P = 0.002). CC Lactate levels was associated with family history of mood disorders and plasma lithium levels. Conclusions This is the first report of increased CC lactate in patients with bipolar depression and lower levels after lithium monotherapy for 6 weeks. These findings indicate a shift to anaerobic metabolism and a role for lactate as a state marker during mood episodes. Energy and redox dysfunction may represent key targets for lithium’s therapeutic actions.