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1.
Int J Mol Sci ; 24(17)2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37686304

RESUMO

In many parts of the world, ethanol is a widely consumed substance that displays its effect in the brain, the target organ for desired, but also negative impact. In a previous study, the ethanol concentrations were analyzed in different regions of the brain by magnetic resonance spectroscopy (MRS). In this study, the same method is used to demonstrate the kinetics of the ethanol concentration in the human brain after oral ethanol uptake. A drinking study was performed with 10 healthy participants. After the uptake of ethanol in a calculated amount leading to a plasma ethanol concentration of 0.92 g/L (19.95 mM corresponding to a blood ethanol concentration of 0.7 g/kg), brain ethanol concentrations were continuously measured by means of MRS on a 3 Tesla human magnetic resonance imaging (MRI) system. For the data acquisition a single-voxel sLASER sequence was used, with the volume of interest located in the occipital cortex. Intermittently, blood samples were taken and plasma was analyzed for ethanol using headspace gas chromatography with flame ionization detection (HS-GC-FID). The obtained MRS brain ethanol curves showed distinct inter-individual differences; however, a good intra-individual correlation of plasma and brain ethanol concentrations was observed. The results suggest a rapid equilibration between blood and brain. The ethanol concentrations measured in the brain were substantially lower than the measured plasma ethanol results, suggesting an MRS visibility of about 63% for ethanol in brain tissue. The maximum individual ethanol concentrations in the brain (normalized to water content) ranged between 7.1 and 14.1 mM across the cohort, while the highest measured plasma concentrations were in the range between 0.35 g/L (9.41 mM) and 0.95 g/L (20.52 mM).


Assuntos
Encéfalo , Etanol , Humanos , Cinética , Encéfalo/diagnóstico por imagem , Concentração Alcoólica no Sangue , Espectroscopia de Ressonância Magnética
2.
Neuroimage ; 241: 118430, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34314848

RESUMO

PURPOSE: Heating of gradient coils and passive shim components is a common cause of instability in the B0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites. METHOD: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC). RESULTS: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p < 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI. DISCUSSION: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Análise de Dados , Bases de Dados Factuais/normas , Imageamento por Ressonância Magnética/normas , Espectroscopia de Ressonância Magnética/normas , Humanos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos
3.
Magn Reson Med ; 85(3): 1160-1174, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32975334

RESUMO

PURPOSE: A flexible MEGA editing scheme which decouples the editing efficiency from TE is proposed and the utility of asymmetric adiabatic pulses for this new technique is explored. It is demonstrated that the method enables robust T2 measurement of lactate in healthy human brain. METHODS: The proposed variation of the MEGA scheme applies editing pulses in both acquired spectra, ensuring that the difference in J-evolution of the target resonance leads to maximal signal yield in the difference spectrum for arbitrary TE. A MEGA-sLASER sequence is augmented with asymmetric adiabatic editing pulses for enhanced flexibility and immunity to B1+ miscalibration and inhomogeneities. The technique is validated and optimized for flexible lactate editing via a simple analytical model, numerical simulations and in vitro experiments. The T2 relaxation constant of lactate is determined in vivo via multiple-TE measurements with the proposed method and a dedicated postprocessing and quantification approach. RESULTS: Asymmetric adiabatic editing pulses improve robustness and facilitate efficient J-editing in sequences or protocols with strong timing constraints. Single voxel measurements using the proposed MEGA scheme in the occipital cortex of six healthy subjects yield a relaxation constant of T2=171±19  ms for the methyl resonance of lactate at a field strength of 3T. CONCLUSIONS: The proposed MEGA editing scheme allows for novel kinds of J-editing experiments and promises to be an asset to robust T2 measurement of lactate and potentially other J-coupled metabolites in vivo.


Assuntos
Ácido Láctico , Ácido gama-Aminobutírico , Encéfalo/diagnóstico por imagem , Voluntários Saudáveis , Humanos , Espectroscopia de Ressonância Magnética
4.
Magn Reson Med ; 86(3): 1284-1298, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33829538

RESUMO

PURPOSE: Prospective motion correction (PMC) and retrospective motion correction (RMC) have different advantages and limitations. The present work aims to combine the advantages of both for rigid body motion, aiming at correcting for faster motions than was previously achievable. Additionally, it provides insights into the effects of motion on pulse sequences and MR signals with a goal of further improving motion correction in the future. METHODS: The effective encoding trajectory and a global phase offset in a moving object are calculated based on complete gradient waveforms of an arbitrary sequence and a continuous motion model. These data are used to feed the forward signal model, which is then used in iterative image reconstruction to suppress the artifacts still present after the PMC. RESULTS: Verification experiments with a rotation phantom and in vivo were performed. Predictions of simulated motion artifacts for PMC based on sequence waveforms are very accurate. The performance at combined PMC+RMC is limited by Nyquist violations in the sampled k-space and can be compensated by oversampling. CONCLUSION: The combined correction results in better images than pure PMC in the presence of fast motion. The predictions of artifacts are very accurate, allowing for comparing sequences or protocols in simulations. The observed artifacts due to Nyquist violations are expected to be corrected by utilizing parallel imaging.


Assuntos
Artefatos , Imageamento por Ressonância Magnética , Algoritmos , Processamento de Imagem Assistida por Computador , Movimento (Física) , Imagens de Fantasmas , Estudos Prospectivos , Estudos Retrospectivos
5.
Radiology ; 295(1): 171-180, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32043950

RESUMO

Background The hardware and software differences between MR vendors and individual sites influence the quantification of MR spectroscopy data. An analysis of a large data set may help to better understand sources of the total variance in quantified metabolite levels. Purpose To compare multisite quantitative brain MR spectroscopy data acquired in healthy participants at 26 sites by using the vendor-supplied single-voxel point-resolved spectroscopy (PRESS) sequence. Materials and Methods An MR spectroscopy protocol to acquire short-echo-time PRESS data from the midparietal region of the brain was disseminated to 26 research sites operating 3.0-T MR scanners from three different vendors. In this prospective study, healthy participants were scanned between July 2016 and December 2017. Data were analyzed by using software with simulated basis sets customized for each vendor implementation. The proportion of total variance attributed to vendor-, site-, and participant-related effects was estimated by using a linear mixed-effects model. P values were derived through parametric bootstrapping of the linear mixed-effects models (denoted Pboot). Results In total, 296 participants (mean age, 26 years ± 4.6; 155 women and 141 men) were scanned. Good-quality data were recorded from all sites, as evidenced by a consistent linewidth of N-acetylaspartate (range, 4.4-5.0 Hz), signal-to-noise ratio (range, 174-289), and low Cramér-Rao lower bounds (≤5%) for all of the major metabolites. Among the major metabolites, no vendor effects were found for levels of myo-inositol (Pboot > .90), N-acetylaspartate and N-acetylaspartylglutamate (Pboot = .13), or glutamate and glutamine (Pboot = .11). Among the smaller resonances, no vendor effects were found for ascorbate (Pboot = .08), aspartate (Pboot > .90), glutathione (Pboot > .90), or lactate (Pboot = .28). Conclusion Multisite multivendor single-voxel MR spectroscopy studies performed at 3.0 T can yield results that are coherent across vendors, provided that vendor differences in pulse sequence implementation are accounted for in data analysis. However, the site-related effects on variability were more profound and suggest the need for further standardization of spectroscopic protocols. © RSNA, 2020 Online supplemental material is available for this article.


Assuntos
Encéfalo/metabolismo , Comércio , Espectroscopia de Ressonância Magnética/métodos , Adulto , Feminino , Humanos , Masculino , Estudos Prospectivos , Adulto Jovem
6.
Int J Legal Med ; 134(5): 1713-1718, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32524191

RESUMO

AIMS: Ethanol is a widespread substance that inherits desired effects, but also negative consequences with regard to DUI or battery. Where required, the ethanol concentration is usually determined in peripheral venous blood samples, while the brain is the target organ of the ethanol effects. The aim of this study with three participants was the determination of the ethanol concentration in functionally relevant regions of the brain and the comparison with serum ethanol concentrations. DESIGN: After the uptake of ethanol in a calculated amount, leading to a serum ethanol concentration of 0.99 g/L, the ethanol concentrations in the brain were directly analyzed by means of magnetic resonance spectroscopy on a 3 Tesla human MRI system and normalized to the water content. The measurement voxels were located in the occipital cortex, the cerebellum, the frontal cortex, and the putamen and successively examined. Intermittently blood samples were taken, and serum was analyzed for ethanol using HS-GC-FID. FINDINGS AND CONCLUSIONS: Ethanol concentrations in brain regions normalized to the water content were lower than the measured serum ethanol results and rather homogenous within the three participants and the various regions of the brain. The maximum ethanol concentration in the brain (normalized to water content) was 0.68 g/L. It was measured in the frontal cortex, in which the highest results were gained. The maximum serum concentration was 1.19 g/L. The course of the brain ethanol curve seems to be flatter than the one of the serum ethanol concentrations.


Assuntos
Concentração Alcoólica no Sangue , Encéfalo/diagnóstico por imagem , Cerebelo/química , Etanol/análise , Lobo Frontal/química , Lobo Occipital/química , Putamen/química , Química Encefálica , Humanos , Espectroscopia de Ressonância Magnética , Masculino
7.
Neuroimage ; 191: 537-548, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30840905

RESUMO

Accurate and reliable quantification of brain metabolites measured in vivo using 1H magnetic resonance spectroscopy (MRS) is a topic of continued interest. Aside from differences in the basic approach to quantification, the quantification of metabolite data acquired at different sites and on different platforms poses an additional methodological challenge. In this study, spectrally edited γ-aminobutyric acid (GABA) MRS data were analyzed and GABA levels were quantified relative to an internal tissue water reference. Data from 284 volunteers scanned across 25 research sites were collected using GABA+ (GABA + co-edited macromolecules (MM)) and MM-suppressed GABA editing. The unsuppressed water signal from the volume of interest was acquired for concentration referencing. Whole-brain T1-weighted structural images were acquired and segmented to determine gray matter, white matter and cerebrospinal fluid voxel tissue fractions. Water-referenced GABA measurements were fully corrected for tissue-dependent signal relaxation and water visibility effects. The cohort-wide coefficient of variation was 17% for the GABA + data and 29% for the MM-suppressed GABA data. The mean within-site coefficient of variation was 10% for the GABA + data and 19% for the MM-suppressed GABA data. Vendor differences contributed 53% to the total variance in the GABA + data, while the remaining variance was attributed to site- (11%) and participant-level (36%) effects. For the MM-suppressed data, 54% of the variance was attributed to site differences, while the remaining 46% was attributed to participant differences. Results from an exploratory analysis suggested that the vendor differences were related to the unsuppressed water signal acquisition. Discounting the observed vendor-specific effects, water-referenced GABA measurements exhibit similar levels of variance to creatine-referenced GABA measurements. It is concluded that quantification using internal tissue water referencing is a viable and reliable method for the quantification of in vivo GABA levels.


Assuntos
Encéfalo/metabolismo , Espectroscopia de Ressonância Magnética/normas , Ácido gama-Aminobutírico/análise , Adolescente , Adulto , Conjuntos de Dados como Assunto , Feminino , Humanos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Valores de Referência , Água , Adulto Jovem
8.
NMR Biomed ; 32(7): e4100, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31038254

RESUMO

Lactate and ß-hydroxybutyrate are important MRS-visible biomarkers for the energy metabolism of the human brain. A major obstacle for their unambiguous detection and quantification in vivo is their inherently low concentration and spectral overlap with resonances from lipids and macromolecules. In this work, we demonstrate the improved detectability of lactate and ß-hydroxybutyrate with MEGA-sLASER compared to MEGA-PRESS at the clinical field strength of 3 T. The method is validated by numerical simulations, in vitro measurements and in vivo experiments on healthy subjects. It is demonstrated that MEGA-sLASER offers an SNR increase of approximately 70% for lactate and ß-hydroxybutyrate detection compared to MEGA-PRESS in various brain regions. This increased SNR translates into reduced Cramér-Rao lower bounds for quantification and enables a more robust detection of subtle changes in the (brain) energy metabolism. The sensitivity of the method for detection of ß-hydroxybutyrate concentration changes is demonstrated through measurements before and during a ketogenic diet while the sensitivity for detection of lactate concentration changes is shown by measurements before and after an intensive anaerobic exercise.


Assuntos
Ácido 3-Hidroxibutírico/metabolismo , Ácido Láctico/metabolismo , Espectroscopia de Ressonância Magnética , Adulto , Encéfalo/metabolismo , Simulação por Computador , Humanos , Masculino , Imagens de Fantasmas
9.
Neuroimage ; 159: 32-45, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28716717

RESUMO

Magnetic resonance spectroscopy (MRS) is the only biomedical imaging method that can noninvasively detect endogenous signals from the neurotransmitter γ-aminobutyric acid (GABA) in the human brain. Its increasing popularity has been aided by improvements in scanner hardware and acquisition methodology, as well as by broader access to pulse sequences that can selectively detect GABA, in particular J-difference spectral editing sequences. Nevertheless, implementations of GABA-edited MRS remain diverse across research sites, making comparisons between studies challenging. This large-scale multi-vendor, multi-site study seeks to better understand the factors that impact measurement outcomes of GABA-edited MRS. An international consortium of 24 research sites was formed. Data from 272 healthy adults were acquired on scanners from the three major MRI vendors and analyzed using the Gannet processing pipeline. MRS data were acquired in the medial parietal lobe with standard GABA+ and macromolecule- (MM-) suppressed GABA editing. The coefficient of variation across the entire cohort was 12% for GABA+ measurements and 28% for MM-suppressed GABA measurements. A multilevel analysis revealed that most of the variance (72%) in the GABA+ data was accounted for by differences between participants within-site, while site-level differences accounted for comparatively more variance (20%) than vendor-level differences (8%). For MM-suppressed GABA data, the variance was distributed equally between site- (50%) and participant-level (50%) differences. The findings show that GABA+ measurements exhibit strong agreement when implemented with a standard protocol. There is, however, increased variability for MM-suppressed GABA measurements that is attributed in part to differences in site-to-site data acquisition. This study's protocol establishes a framework for future methodological standardization of GABA-edited MRS, while the results provide valuable benchmarks for the MRS community.


Assuntos
Encéfalo/metabolismo , Espectroscopia de Ressonância Magnética/normas , Ácido gama-Aminobutírico/análise , Adulto , Conjuntos de Dados como Assunto , Feminino , Humanos , Espectroscopia de Ressonância Magnética/instrumentação , Espectroscopia de Ressonância Magnética/métodos , Masculino , Adulto Jovem
10.
NMR Biomed ; 29(12): 1739-1747, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27779348

RESUMO

Valine and lactate have been recognized as important metabolic markers to diagnose brain abscess by means of MRS. However, in vivo unambiguous detection and quantification is hampered by macromolecular contamination. In this work, MEGA-PRESS difference editing of valine and lactate is proposed. The method is validated in vitro and applied for quantitative in vivo experiments in one healthy subject and two brain abscess patients. It is demonstrated that with this technique the overlapping lipid signal can be reduced by more than an order of magnitude and thus the robustness of valine and lactate detection in vivo can be enhanced. Quantification of the two abscess MEGA-PRESS spectra yielded valine/lactate concentration ratios of 0.10 and 0.27. These ratios agreed with the concentration ratios determined from concomitantly acquired short-TE PRESS data and were in line with literature values. The quantification accuracy of lactate (as measured with Cramér-Rao lower bounds in LCModel processing) was better for MEGA-PRESS than for short-TE PRESS in all acquired in vivo datasets. The Cramér-Rao lower bounds of valine were only better for MEGA-PRESS in one of the two abscess cases, while in the other case coediting of isoleucine confounded the quantification in the MEGA-PRESS analysis. MEGA-PRESS and short-TE PRESS should be combined for unambiguous quantification of amino acids in abscess measurements. Simultaneous valine/lactate MEGA-PRESS editing might benefit the distinction of brain abscesses from tumors, and further categorization of bacteria with reasonable sensitivity and specificity.


Assuntos
Abscesso Encefálico/metabolismo , Encéfalo/metabolismo , Ácido Láctico/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Imagem Molecular/métodos , Processamento de Sinais Assistido por Computador , Valina/metabolismo , Algoritmos , Biomarcadores/metabolismo , Encéfalo/patologia , Abscesso Encefálico/patologia , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
12.
Mol Autism ; 14(1): 44, 2023 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978557

RESUMO

INTRODUCTION: Autism spectrum disorder (ASD) encompasses a heterogeneous group with varied phenotypes and etiologies. Identifying pathogenic subgroups could facilitate targeted treatments. One promising avenue is investigating energy metabolism, as mitochondrial dysfunction has been implicated in a subgroup of ASD. Lactate, an indicator of energy metabolic anomalies, may serve as a potential biomarker for this subgroup. This study aimed to examine cerebral lactate (Lac+) levels in high-functioning adults with ASD, hypothesizing elevated mean Lac+ concentrations in contrast to neurotypical controls (NTCs). MATERIALS AND METHODS: Magnetic resonance spectroscopy (MRS) was used to study cerebral Lac+ in 71 adults with ASD and NTC, focusing on the posterior cingulate cortex (PCC). After quality control, 64 ASD and 58 NTC participants remained. Lac+ levels two standard deviations above the mean of the control group were considered elevated. RESULTS: Mean PCC Lac+ levels were significantly higher in the ASD group than in the NTC group (p = 0.028; Cohen's d = 0.404), and 9.4% of the ASD group had elevated levels as compared to 0% of the NTCs (p = 0.029). No significant correlation was found between blood serum lactate levels and MRS-derived Lac+ levels. LIMITATIONS: A cautious interpretation of our results is warranted due to a p value of 0.028. In addition, a higher than anticipated proportion of data sets had to be excluded due to poor spectral quality. CONCLUSION: This study confirms the presence of elevated cerebral Lac+ levels in a subgroup of adults with ASD, suggesting the potential of lactate as a biomarker for mitochondrial dysfunction in a subgroup of ASD. The lower-than-expected prevalence (20% was expected) and moderate increase require further investigation to elucidate the underlying mechanisms and relationships with mitochondrial function.


Assuntos
Transtorno do Espectro Autista , Humanos , Adulto , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Imageamento por Ressonância Magnética , Ácido Láctico/metabolismo , Biomarcadores
13.
Autism Res ; 15(7): 1222-1236, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35587691

RESUMO

The excitatory-inhibitory imbalance hypothesis postulates dysregulation of the gamma-aminobutyric acid (GABA) and glutamate (Glu) neurotransmitter systems as a common underlying deficit in individuals with autism spectrum disorders (ASD). Previous studies suggest an important role of these systems in the pathophysiology of ASD, including a study of our group reporting decreased glutamate concentrations in the pregenual anterior cingulate cortex (ACC) of adults with ASD. The aim of this study was to replicate our previous findings of impaired glutamate metabolism in ASD in a new sample and to additionally quantify GABA in the ACC and dorsolateral prefrontal cortex (dlPFC). Concentrations of GABA and glutamate-glutamine (Glx; combined glutamate and glutamine signal) were quantified in the ACC and dlPFC of 43 adults with ASD and 43 neurotypical controls (NTC) by magnetic resonance spectroscopy (MRS). The ASD group showed increased absolute GABA concentrations and elevated GABA/creatine ratios in the left dlPFC compared to NTC, while no group differences were detected in the pregenual and dorsal ACC. Previous findings of altered Glx concentration in the pregenual ACC of the ASD group could not be replicated. Regarding Glx concentrations and Glx/creatine ratios, there were no significant differences in the dlPFC and ACC either. The study supports the hypothesis of an altered GABA and glutamate equilibrium, indicating an imbalance between excitatory and inhibitory metabolism in ASD patients. However, inconsistent results across studies and brain regions suggest a complex underlying phenomenon. LAY SUMMARY: Adults of the autism spectrum exhibit elevated levels of the inhibitory neurotransmitter GABA in the left dorsolateral prefrontal cortex. This finding supports the hypothesis of an imbalance between excitatory and inhibitory equilibrium in patients with autism spectrum disorders.


Assuntos
Transtorno do Espectro Autista , Glutamina , Adulto , Transtorno do Espectro Autista/metabolismo , Creatina/metabolismo , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Humanos , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/metabolismo , Ácido gama-Aminobutírico/metabolismo
14.
J Clin Med ; 9(5)2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32365843

RESUMO

OBJECTIVE: An insular involvement in the pathogenesis of anorexia nervosa (AN) has been suggested in many structural and functional neuroimaging studies. This magnetic resonance spectroscopy (MRS) study is the first to investigate metabolic signals in the anterior insular cortex in patients with AN and recovered individuals (REC). METHOD: The MR spectra of 32 adult women with AN, 21 REC subjects and 33 healthy controls (HC) were quantified for absolute N-acetylaspartate (NAA), glutamate + glutamine (Glx), total choline, myo-inositol, creatine concentrations (mM/L). After adjusting the metabolite concentrations for age and partial gray/white matter volume, group differences were tested using one-way multivariate analyses of variance (MANOVA). Post-hoc analyses of variance were applied to identify those metabolites that showed significant group effects. Correlations were tested for associations with psychometric measures (eating disorder examination), duration of illness, and body mass index. RESULTS: The MANOVA exhibited a significant group effect. The NAA signal was reduced in the AN group compared to the HC group. The REC and the HC groups did not differ in metabolite concentrations. In the AN group, lower NAA and Glx signals were related to increased weight concern. DISCUSSION: We interpret the decreased NAA availability in the anterior insula as a signal of impaired neuronal integrity or density. The association of weight concern, which is a core feature of AN, with decreased NAA and Glx indicates that disturbances of glutamatergic neurotransmission might be related to core psychopathology in AN. The absence of significant metabolic differences between the REC and HC subjects suggests that metabolic alterations in AN represent a state rather than a trait phenomenon.

15.
Front Psychiatry ; 10: 270, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118906

RESUMO

Background: Schizophrenic disorders are common and debilitating due to their symptoms, which can include delusions, hallucinations, and other negative symptoms. Organic forms can result from various cerebral disorders. In this paper, we discuss a potential association between schizophrenia and hereditary polyneuropathies (PNPs). Case presentation: We present the case of a 55-year-old female patient with chronically paranoid-hallucinatory schizophrenia, severe cognitive deficits since the age of 30, and comorbid repeated focal pressure neuropathies beginning at age 20. At the age of 35, genetic testing revealed a deletion on chromosome 17p12 covering the peripheral myelin protein 22 gene (PMP22), which led to the diagnosis of hereditary neuropathy with liability to pressure palsy (HNPP). Cerebral magnetic resonance imaging showed internal atrophy, magnetic resonance spectroscopy found alteration of the glutamate and myo-inositol levels in the anterior cingulate cortex, neuropsychological testing showed deficits in working memory and psychomotor speed, and electrophysiological testing detected signs of sensorimotor demyelinating PNP (accentuated in the legs). Conclusion: There may be an association between schizophrenia and HNPP. In observational studies, the deletion of interest (chromosome 17p12) was nearly 10 times more common in schizophreniform patients than in controls. This potential association could be pathophysiologically explained by the role of PMP22, which is mainly expressed in the peripheral nervous system. However, PMP22 mRNA and protein can also be found in the brain. PMP22 seems to play an important role in regulating cell growth and myelination, functions that are disturbed in schizophrenia. Such a connection obviously cannot be clarified on the basis of one case. Future studies should analyze whether patients with HNPP exhibit increased rates of psychotic disorders, and patients with schizophrenia and repeated focal pressure neuropathies should be examined for the PMP22 mutation. Alternatively, the co-occurrence of schizophrenia and HNPP could be coincidental.

16.
Front Immunol ; 10: 412, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949164

RESUMO

Background: Mitochondrial diseases are caused by dysfunctions in mitochondrial metabolic pathways. MELAS syndrome is one of the most frequent mitochondrial disorders; it is characterized by encephalopathy, myopathy, lactic acidosis, and stroke-like episodes. Typically, it is associated with a point mutation with an adenine-to-guanine transition at position 3243 of the mitochondrial DNA (mtDNA; m.3243A>G) in the mitochondrially encoded tRNA leucine 1 (MT-TL1) gene. Other point mutations are possible and the association with polyglandular autoimmune syndrome type 2 has not yet been described. Case presentation: We present the case of a 25-year-old female patient with dysexecutive syndrome, muscular fatigue, and continuous headache. Half a year ago, she fought an infection-triggered Addison crisis. As the disease progressed, she had two epileptic seizures and stroke-like episodes with hemiparesis on the right side. Cerebral magnetic resonance imaging showed a substance defect of the parieto-occipital left side exceeding the vascular territories with a lactate peak. The lactate ischemia test was clearly positive, and a muscle biopsy showed single cytochrome c oxidase-negative muscle fibers. Genetic testing of blood mtDNA revealed a heteroplasmic base exchange mutation in the mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4 (MT-ND4) gene (m.12015T>C; p.Leu419Pro; heteroplasmy level in blood 12%, in muscle tissue: 15%). The patient suffered from comorbid autoimmune polyglandular syndrome type 2 with Hashimoto's thyroiditis, Addison's disease, and autoimmune gastritis. In addition, we found increased anti-glutamic acid decarboxylase 65, anti-partial cell, anti-intrinsic factor, and anti-nuclear antibodies. Conclusion: We present an atypical case of MELAS syndrome with predominant symptoms of a dysexecutive syndrome, two stroke-like episodes, and fast-onset fatigue. The symptoms were associated with a not yet described base and aminoacid exchange mutation in the MT-ND4 gene (m.12015T>C to p.Leu419Pro). The resulting changed protein complex in our patient is part of the respiratory chain multicomplex I and might be the reason for the mitochondriopathy. However, different simulations for pathogenetic relevance are contradictory and rather speak for a benign variant. To our knowledge this case report is the first reporting MELAS syndrome with comorbid polyglandular autoimmune syndrome type 2. Screening for autoimmune alterations in those patients is important to prevent damage to end organs.


Assuntos
Síndrome MELAS/complicações , Síndrome MELAS/genética , NADH Desidrogenase/genética , Mutação Puntual , Poliendocrinopatias Autoimunes/complicações , Doença de Addison/complicações , Adulto , Disfunção Cognitiva/complicações , DNA Mitocondrial/genética , Fadiga/complicações , Feminino , Gastrite/complicações , Doença de Hashimoto/complicações , Cefaleia/complicações , Humanos , Convulsões/complicações
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