Cerebral magnetic resonance changes associated with fibromyalgia syndrome

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La creatinina está en negro ya que se utiliza como valor de referencia. a: RM corte coronal, indicando los valores de los metabolitos estudiados referidos a ambos hipocampos. Nótese que en el hipocampo izquierdo diferentes autores dan valores opuestos para la colina. b: RM corte horizontal, indicando los valores de los metabolitos estudiados referidos a la cabeza del caudado bilateralmente y a la ínsula (región anterior y posterior). c: RM corte sagital, indicando los valores de los metabolitos estudiados referidos a la corteza prefrontal ventrolateral, y a la corteza anterior y posterior de la circunvolución del cíngulo. Cho: colina; Cr: creatina; GABA: ácido gamma-aminobutírico; Gln: glutamina; Glu: glutamato; Glx: glutamato+glutamina; Lact: lactato; MI: mioinositol; NAA: N-acetilaspartato; NAAG: N-acetilaspartato glutamato." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Iñigo Murga, Virginia Guillen, José-Vicente Lafuente" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Iñigo" "apellidos" => "Murga" ] 1 => array:2 [ "nombre" => "Virginia" "apellidos" => "Guillen" ] 2 => array:2 [ "nombre" => "José-Vicente" "apellidos" => "Lafuente" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020617303571" "doi" => "10.1016/j.medcle.2017.05.011" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020617303571?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775317301902?idApp=UINPBA00004N" "url" => "/00257753/0000014800000011/v1_201705140041/S0025775317301902/v1_201705140041/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2387020617303339" "issn" => "23870206" "doi" => "10.1016/j.medcle.2017.05.003" "estado" => "S300" "fechaPublicacion" => "2017-06-07" "aid" => "3981" "copyright" => "Elsevier España, S.L.U." 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Creatinine is in bold as it is used as the reference value. (a) Coronal-slice MRI, indicating the values of the metabolites studied regarding both hippocampus. Note that in the left hippocampus, different authors give opposite values for choline. (b) Horizontal-slice MRI, indicating the values of the studied metabolites referred to the head of the caudate nucleus bilaterally and to the insula (anterior and posterior region). (c) Sagittal-slice MRI, indicating the values of the metabolites studied referred to the ventrolateral prefrontal cortex, and the anterior and posterior cortex of the cingulate gyrus. Cho: choline; Cr: creatine; GABA: gamma-aminobutyric acid; Gln: glutamine; Glu: glutamate; Glx: glutamate+glutamine; Lact: lactate; MI: myo-inositol; NAA: N-acetylaspartate; NAAG: N-acetylaspartate glutamate." ] ] ] "textoCompleto" => "IntroductionFibromyalgia syndrome (FMS) is characterized by widespread chronic musculoskeletal pain, of unknown etiology, with hyperalgesia and allodynia. It is accompanied by other symptoms, such as: fatigue, insomnia, paresthesias, swelling in the hands, neurovegetative changes, concentration problems, memory and mood disorders. Symptom intensity fluctuates throughout the natural course of FMS.Diagnostic criteria for this syndrome were provided by the American College of Rheumatology in 1990,<a class="elsevierStyleCrossRef" href="#bib0215">1</a> although in 2010 this same organization proposed new criteria that have not been validated yet.The World Health Organization<a class="elsevierStyleCrossRef" href="#bib0220">2</a> classifies FMS under the heading of diseases of the musculoskeletal system and connective tissue (code M79.7), and the International Association for the Study of Pain<a class="elsevierStyleCrossRef" href="#bib0225">3</a> has classified it under code X33.X8a.In a study conducted in 5 European countries (France, Germany, Italy, Portugal and Spain), prevalence was 4.7%, and the female/male ratio was 3 to one.<a class="elsevierStyleCrossRef" href="#bib0230">4</a> Its high prevalence, the disability it causes and the frequency of long-term sick-leaves of these patients, make the economic cost be high, making it an increasingly important social and health problem.The diagnosis is clinical. There is currently no specific analytical, imaging or anatomopathological test to verify this diagnosis. In the perception and experience of pain, various brain structures are included, such as the somatosensory cortex (primary and secondary), the cingulate gyrus (anterior region), the insula, thalamus, the posterior parietal cortex and the prefrontal cortex. All of them are involved in the so-called “pain network”, a set of areas, structures and nuclei dealing with the perception, transmission and processing of the various sensory and affective components that constitute the experience of pain.The quantitative study of anatomical and biochemical variables is an important strategy for the diagnosis, prognosis and follow-up of various diseases.<a class="elsevierStyleCrossRef" href="#bib0235">5</a> Many authors have shown, by using neuroimaging techniques, changes in volume, connectivity and metabolism of the brain areas involved in the “pain network” in FMS. The morphometric study of certain brain structures by using the voxel based morphometry technique, plus the identification of the variations in some metabolites by magnetic resonance spectroscopy (MRS), and the study of functional connectivity with the analysis of the blood-oxygenation-level dependent signal, are a very promising tool to elucidate the morphobiological component of various disorders, including FMS.This paper is a critical review of the neuroimaging contribution to FMS. The ultimate aim is to find clues or evidence on indicators that might help determine the diagnosis and/or evolution of this condition.DevelopmentThe diagnostic criteria followed in all the studies considered are those of the American College of Rheumatology.<a class="elsevierStyleCrossRef" href="#bib0215">1</a> However, so many and diverse inclusion-exclusion criteria between the different series makes it difficult to include them in a meta-analysis.Changes in the size of brain structuresVoxel-based morphometry analyzes the anatomical regions of the brain such as the thalamus, insula, amygdala, hippocampus or cingulate gyrus. In all of them the size decreases,<a class="elsevierStyleCrossRefs" href="#bib0240">6–9</a> only in one study the size increases in the basal nuclei, in the cerebellum and in the orbitofrontal cortex.<a class="elsevierStyleCrossRef" href="#bib0260">10</a>Another method of study is the diffusion tensor imaging, which allows to evaluate microstructural changes through the analysis of the diffusion direction of hydrogen protons (water) in the tissue (anisotropy). This method requires further computational processing time, but the results are very sensitive to differences in shape and volume in small brain structures.<a class="elsevierStyleCrossRef" href="#bib0265">11</a> The imaging studies obtained by means of diffusion tensor show in the gray matter of both thalamus an anisotropy drop, as well as in the white matter tracts connecting them with the cortex, corresponding to changes in the microstructure of these anatomical areas<a class="elsevierStyleCrossRef" href="#bib0270">12</a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The thalamus plays a central role in the sensory-discriminative component of pain. Therefore, a detailed volumetric analysis of the different thalamic nuclei would be interesting.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Distribution of metabolites in various brain areasMR spectroscopy allows in vivo determination of the level of various molecules in particular regions of the brain. We should consider the various normal metabolites depending on location, age and echo time used.<a class="elsevierStyleCrossRef" href="#bib0275">13</a>The most common metabolites determined are: creatine (Cr), the basic compound of the energy metabolism of the brain, is a very stable metabolite, therefore, used as a reference for calculating the rates of others; N-acetylaspartate (NAA), is used as a marker neuronal density marker, although dynamic changes in their rates may reflect neuronal dysfunction rather than loss; Choline (Cho), a marker of phospholipid metabolism, reflects cell proliferation and is higher in tumor processes; lactate is the end product of anaerobic glycolysis, present in brain tissue at very low levels, which under normal conditions are not detectable by spectroscopy. Their presence is indicative of ischemia or infiltration by highly glycolytic cells, such as macrophages; Myo-inositol (MI), used as a glia marker; Glutamine (Gln) and glutamate (Glu), the latter being the most abundant excitatory amino acid in the brain acting as a neurotransmitter.<a class="elsevierStyleCrossRef" href="#bib0280">14</a> The changes in the relative concentration of these metabolites, plus the occurrence of others, which in normal circumstances are not present, are a reflection of the pathological changes occurring in a particular area of the brain parenchyma.<a class="elsevierStyleCrossRef" href="#bib0285">15</a>This technique has important limitations, for example, the threshold of definition or discrimination of the equipment gathering the data, or the computer software used for its analysis. The resonance–metabolite correlation is not accurate, since different protons in the same compound can show resonances in different locations of the spectrum. Similarly, protons from various compounds can overlap in the same spectrum.<a class="elsevierStyleCrossRef" href="#bib0290">16</a>The analysis of the metabolites by spectroscopy in FMS yields heterogeneous and sometimes discordant data depending on the structure and the hemisphere studied. The studies consulted do not include information on hemispheric dominance in the subjects studied, which might be relevant to understand some of these data (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>If we consider the hippocampus, one of the most referenced structures in the medical literature, we find a reduction in the NAA/Cr index in the right hemisphere,<a class="elsevierStyleCrossRef" href="#bib0295">17</a> Cho and NAA+NAA glutamate index in the left hippocampus, as well as a reduction in MI and MI/Cr in both hippocampi.<a class="elsevierStyleCrossRef" href="#bib0300">18</a> Likewise, decreased values have also been reported in both hippocampi for Cho and only in the left hippocampus for Glu.<a class="elsevierStyleCrossRef" href="#bib0305">19</a> In contrast, other authors report low NAA levels on both sides, and Cho increases only on the right hippocampus<a class="elsevierStyleCrossRef" href="#bib0310">20</a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>In the right posterior insula, Glu and Glx -Glu+Gln-<a class="elsevierStyleCrossRef" href="#bib0315">21</a> increase, and the NAA/Cr index decreases.<a class="elsevierStyleCrossRef" href="#bib0305">19</a> This region is closely related to somatosensory connections, unlike the anterior region, which is more involved in limbic and vegetative processes. The distribution of these metabolites (higher Glu and lower NAA) explores the hypothesis of the existence of hyperexcitable and dysfunctional areas in the processing of nociceptive signals. In this regard, a reduction in the GABA levels in the right anterior insula has been reported, inducing metabolic imbalance for Glu/GABA<a class="elsevierStyleCrossRef" href="#bib0320">22</a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>b).Activation of the cingular cortex (limbic system) has been reported in several studies in response to pain as part of the emotional component of the cortex.<a class="elsevierStyleCrossRefs" href="#bib0325">23,24</a> In the posterior cingular cortex, Glx and Glx/Cr<a class="elsevierStyleCrossRef" href="#bib0300">18</a> index appear to be higher, and Cho has dropped.<a class="elsevierStyleCrossRef" href="#bib0305">19</a> In the anterior cingulate cortex, GABA has been reported higher<a class="elsevierStyleCrossRef" href="#bib0320">22</a>(<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>c). The right and left caudate nucleus (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>b) and the right ventrolateral prefrontal cortex present an increased Cho/Cr ratio.<a class="elsevierStyleCrossRef" href="#bib0335">25</a> Another author observed increased Glu/Cr and Glx/Cr ratios in the ventrolateral prefrontal cortex.<a class="elsevierStyleCrossRef" href="#bib0340">26</a> In FMS, there are no metabolite changes in the thalamus<a class="elsevierStyleCrossRefs" href="#bib0300">18,25,26</a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>c).Functional synchronization of brain areas and centersFunctional MRI (fMRI) allows mapping brain activation patterns. This technique helps understand their timing. When a brain area is activated, blood flow increases in that area, which can be detected, mapped and quantified by processing appropriate signals (e.g., blood oxygenation level dependent).Functional neuroimaging studies demonstrate that some patients with FMS present increased neuronal responses, both to painful stimuli and to innocuous stimuli,<a class="elsevierStyleCrossRef" href="#bib0345">27</a> which corroborates allodynia and hyperalgesia reported in the tests.<a class="elsevierStyleCrossRef" href="#bib0350">28</a> Both during painful stimulation and prior to pain there are clear differences in the activation of the anterior cingulate cortex, supplementary motor area and thalamus. These results show that mechanisms of pain in the medial system (affective/cognitive component), even during their anticipation, play an important role in the processing of these signals in subjects suffering from FMS.<a class="elsevierStyleCrossRef" href="#bib0250">8</a>It has also been observed that brain activation is significantly higher in both insulas in this group as a response to thumb pressure stimulation.<a class="elsevierStyleCrossRef" href="#bib0355">29</a> Recent studies show connectivity changes in the insula and in the somatosensory cortex S1, associated with the experience of chronic pain in patients with fibromyalgia.<a class="elsevierStyleCrossRefs" href="#bib0360">30,31</a>Chronicity and painNumerous neuroimaging studies reveal the involvement of the anterior cingular cortex in chronic pain patients. The cingulate gyrus is part of the limbic system and the activation of its anterior region is involved in the emotional and cognitive component of pain.<a class="elsevierStyleCrossRefs" href="#bib0330">24,32</a> This region, together with the prefrontal cortex, is, in part, responsible for pain modulation (inhibiting and facilitating). Structural changes in these systems might contribute to pain maintenance and chronification both in FMS and in other chronic pain syndromes.Apkarian et al. proposed a transition model from acute to chronic pain that entails a cortical reorganization of the sensory and affective pathways of pain. This would imply a contribution of the central nervous system independent of the peripheral nociceptive input.<a class="elsevierStyleCrossRef" href="#bib0375">33</a>In FMS the metabolite distribution is modified nonspecifically, but consistent with the morphometric studies. NAA reduction in the hippocampus contributes to the loss of volume observed in the molecular correlate in the morphometry studies,<a class="elsevierStyleCrossRefs" href="#bib0305">19,20</a> corroborating that in FMS we are faced with a chronic neuronal damage or an axonal metabolic dysfunction, or a combination of both. This issue might only be verified through a postmortem neuropathological study, in case of maintaining the same clinical status when decease occurred.Some data on the differential concentration of metabolites in the right and left hippocampus point to the need to consider lateralization if we want to progress in understanding these disorders. This data is not included in any of the publications reviewed.If we focus on the insula, a formation that might encode the subjective magnitude of pain stimulus regardless of the sensory modality,<a class="elsevierStyleCrossRef" href="#bib0380">34</a> we observe that a lower gray matter volume in the left insula<a class="elsevierStyleCrossRefs" href="#bib0240">6,9,10</a> is correlated with higher Glu<a class="elsevierStyleCrossRef" href="#bib0315">21</a> and lower GABA<a class="elsevierStyleCrossRef" href="#bib0320">22</a> in the right insula. These changes indicate a metabolic dysregulation in favor of hyperexcitability in the central nervous system, being probably responsible for the widespread increased sensitivity to nociceptive stimuli (hyperalgesia).Glu is a neurotransmitter involved in strengthening the pain-associated negative effects and related to chronic sensitization.<a class="elsevierStyleCrossRef" href="#bib0385">35</a> Decreased levels of both Glu and Glx in the posterior insula are associated with a clinical improvement in the perception of pain.<a class="elsevierStyleCrossRef" href="#bib0315">21</a> The Glu/Cr ratio is increased in the posterior cingulate gyrus, and is significantly correlated with pain measured objectively with a sphygmograph, and with the overall function assessed through the Fibromyalgia Impact Questionnaire.<a class="elsevierStyleCrossRef" href="#bib0390">36</a>Recent studies report that the translocator protein (TSPO), related to the glia activation and involved in the modulation of synaptic transmission, is overexpressed in chronic pain. Patients with the TSPO genotype (rs6971) and polymorphisms for the serotonin transporter (5-HTTLPR/rs25531) suffer from more severe pain and more severe FMS symptoms. The analysis of connectivity through MRf showed higher activation in the right frontoparietal network in these groups, as a response to pain.<a class="elsevierStyleCrossRef" href="#bib0395">37</a>Dysfunction of the endogenous opioid system contributes to chronic pain in FMS. In this sense, changes in the endogenous mechanisms of pain have been reported, evidencing functional modifications, such as an increased connectivity between the periaqueductal gray matter (PAGM) and the insula, the anterior cingulate cortex and the anterior prefrontal cortex. However, this does not occur between the PAGM and the spinal cord at a rostral level. The correlation between this connectivity and certain clinical variables such as severity of pain, duration of disease and depressive personality traits has been evidenced.<a class="elsevierStyleCrossRef" href="#bib0400">38</a> In addition, a reduction of the μ-opioid receptor (MOR) in the anterior cingular cortex and in the dorsolateral prefrontal cortex (antinociceptive regions) has been reported, where lower availability of MOR is associated with lower pain. This finding reinforces the relevant role of the endogenous opioid system in the brain processing of pain.<a class="elsevierStyleCrossRef" href="#bib0405">39</a>These results represent a significant progress in the understanding of the central pathophysiological mechanisms of pain chronification, providing targets and approachable pathways for the development of new therapeutic strategies.<a class="elsevierStyleCrossRef" href="#bib0410">40</a>LimitationsMany studies on this disorder omit relevant data for the assessment of the sample, such as: associated comorbidities, time of clinical exploration, hemispheric dominance or if the examinations have been performed during the menstrual period in the case of women.<a class="elsevierStyleCrossRef" href="#bib0415">41</a> The variability in the inclusion and exclusion criteria, the disparity of pain questionnaires used, and the low number of subjects in every series (below 30 patients) are added to the inevitable interindividual variations. Furthermore, it is important to keep in mind that the painful experience fluctuates depending on the circadian rhythms, the climatic season or the stressful situations.<a class="elsevierStyleCrossRef" href="#bib0420">42</a> In only 3 of the reviewed studies neuroimaging was used, including a painful stimulus to select the areas of study.<a class="elsevierStyleCrossRefs" href="#bib0255">9,21,22</a>ConclusionsMRI, through its various techniques, is helping significantly to understand the pathophysiological processes underlying various disorders. In this case, it has provided relevant evidence for the understanding of the neural circuits involved in the perception, transmission and modulation of nociceptive input.Pain is an unpleasant sensory and emotional experience difficult to objectify due to its varied expression. FMS is a widespread chronic pain syndrome, although its diagnosis is still controversial.The clinical use of MRI is not widespread for the diagnosis of fibromyalgia, but it seems clear that its findings on both volumetry and structural and functional connectivity and brain metabolism reveal changes in the “brain network” of pain. All of this contributes significantly to a better understanding of its pathophysiology. However, the modifications reported to date are poorly sensitive and non-specific, being reported in other chronic pain-associated processes.The lack of homogeneous protocols and the low number of published series does not allow us to draw conclusions that confirm or at least help in the diagnosis of this disease or its follow-up. However, the evidence summarized in this study justify a broad and deep study with an homogeneous clinical-radiological protocol.FundingThis study has been supported by GIC IT-901/16 (Basque Government) and UFI 11/32 (University of the Basque Country-Euskal Herriko Unibertsitatea).Conflict of interestThe authors report no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres856946" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec850990" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres856945" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec850991" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Development" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Changes in the size of brain structures" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Distribution of metabolites in various brain areas" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Functional synchronization of brain areas and centers" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Chronicity and pain" ] ] ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Limitations" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Conclusions" ] 8 => array:2 [ "identificador" => "sec0045" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflict of interest" ] 10 => array:2 [ "identificador" => "xack287341" "titulo" => "Acknowledgements" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-01-14" "fechaAceptado" => "2017-01-31" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec850990" "palabras" => array:5 [ 0 => "Fibromyalgia syndrome" 1 => "Brain magnetic resonance" 2 => "Morphometry" 3 => "Spectroscopy" 4 => "Connectivity" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec850991" "palabras" => array:5 [ 0 => "Síndrome de fibromialgia" 1 => "Resonancia magnética cerebral" 2 => "Morfometría" 3 => "Espectroscopia" 4 => "Conectividad" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Fibromyalgia syndrome is a chronic disease, of unknown origin, whose diagnostic criteria were established in 1990 by the American College of Rheumatology. New criteria were proposed in 2010 that have not yet been validated. It is characterized by a generalized chronic musculoskeletal pain, accompanied by hyperalgesia and allodynia, as well as other motor, vegetative, cognitive and affective symptoms and signs.We have reviewed a set of studies with cerebral magnetic resonance (morphometry, connectivity and spectroscopy) that refer to changes in areas involved in pain processing.Modifications in gray and white matter volume, as well as in levels of N-acetylaspartate, choline or glutamate, among other metabolites, have been observed in the hippocampus, insula, prefrontal and cingular cortex. Neuroradiological findings are nonspecific and similar to those found in other examples of chronic pain. An increase in the sample size and a standardized methodology would facilitate comparison, allowing the drawing of general conclusions." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El síndrome de fibromialgia es un trastorno crónico, de origen desconocido, cuyos criterios diagnósticos estableció en 1990 el Colegio Americano de Reumatología; en 2010 propuso unos criterios nuevos que aún no están validados. Se caracteriza por dolor musculoesquelético generalizado, crónico, acompañado de fenómenos de hiperalgesia y alodinia, así como otros síntomas y signos, motores, vegetativos, cognitivos y afectivos.Revisamos un conjunto de estudios con resonancia magnética cerebral (morfometría, conectividad y espectroscopia) que refieren alteraciones en áreas de procesamiento del dolor.Se observan cambios en el volumen de la sustancia gris y blanca, así como de los niveles de N-acetilaspartato, colina o glutamato, entre otros metabolitos, en hipocampo, ínsula, corteza prefrontal y cingular, principalmente. Los hallazgos neurorradiológicos son inespecíficos y superponibles a los de otros cuadros de dolor crónico, pero un aumento del tamaño muestral y una metodología estandarizada facilitaría la comparación entre series, permitiendo extraer conclusiones generalizables." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Murga I, Guillen V, Lafuente J-V. Cambios en la resonancia magnética cerebral asociados al síndrome de fibromialgia. Med Clin (Barc). 2017;148:511–516." ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3016 "Ancho" => 1736 "Tamanyo" => 370836 ] ] "descripcion" => array:1 [ "en" => "Magnetic resonance imaging (MRI) indicating whether the values for the referred metabolites are increased (in red) or decreased (in green). Creatinine is in bold as it is used as the reference value. (a) Coronal-slice MRI, indicating the values of the metabolites studied regarding both hippocampus. Note that in the left hippocampus, different authors give opposite values for choline. (b) Horizontal-slice MRI, indicating the values of the studied metabolites referred to the head of the caudate nucleus bilaterally and to the insula (anterior and posterior region). (c) Sagittal-slice MRI, indicating the values of the metabolites studied referred to the ventrolateral prefrontal cortex, and the anterior and posterior cortex of the cingulate gyrus. Cho: choline; Cr: creatine; GABA: gamma-aminobutyric acid; Gln: glutamine; Glu: glutamate; Glx: glutamate+glutamine; Lact: lactate; MI: myo-inositol; NAA: N-acetylaspartate; NAAG: N-acetylaspartate glutamate." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "FA: fractional anisotropy." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Related author \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Result \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Anatomical area \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kuchinad et al.<a class="elsevierStyleCrossRef" href="#bib0240">6</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↓ Gray matter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Posterior cingulate cortex (bilateral) Medial prefrontal cortex Insula (left) Parahippocampal gyrus (left) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Schmidt-Wilcke et al.<a class="elsevierStyleCrossRef" href="#bib0260">10</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↓ Gray matter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Upper temporal cortex (right) Insula (left) Thalamus (left post) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↑ Gray matter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Orbitofrontal cortex (left) Striated nucleus (bilateral) Cerebellum (left) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lutz et al.<a class="elsevierStyleCrossRef" href="#bib0270">12</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↓ Gray matter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hippocampus (bilateral) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↓ FA gray matter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Posterior thalamus (bilateral) Insula (bilateral) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↑ FA gray matter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Anterior cingulate cortex (bilateral) Superior frontal cortex (bilateral) Postcentral gyrus (bilateral) Amygdala (bilateral) Hippocampus (bilateral) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↑ FA white matter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Anterior cingulate cortex (bilateral) Superior frontal cortex (bilateral) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↓ FA white matter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Talamocortical pathway (bilateral) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Wood et al.<a class="elsevierStyleCrossRef" href="#bib0245">7</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↓ Gray matter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Anterior cingulate cortex (left) Posterior cingulate cortex (right) Parahippocampal gyrus (bilateral) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Burgmer et al.<a class="elsevierStyleCrossRef" href="#bib0250">8</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↓ Gray matter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Anterior cingulate cortex (right) Lateral prefrontal cortex Amygdala (left) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Robinson et al.<a class="elsevierStyleCrossRef" href="#bib0255">9</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↓ Gray matter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Anterior cingulate cortex (left) Medial insula (left) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1447603.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Analysis of brain morphometry and diffusion tensor by magnetic resonance imaging in fibromyalgia syndrome." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Ant: anterior; ACC: anterior cingulate cortex; PCC: posterior cingulate cortex; Cho: choline; VLPFC: ventrolateral prefrontal cortex; Cr: creatine; STC: superior temporal cortex; GABA: gamma-aminobutyric acid; Gln: glutamine; Glu: glutamate; Glx: glutamate+glutamine; HP: hippocampus; INS: insula; MI: myoinositol; NAA: N-acetylaspartate; NAAG: N-acetylaspartate glutamate; Post: posterior; TALM: thalamus.The data in bold highlight the results obtained. In the images the metabolite Cr (in bold letters) is the reference metabolite." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Related author \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Metabolites \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Striate nucleus Caudate nucleus Lenticular nucleus \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">INS \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">STC \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">ACC \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PCC \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">VLPFC \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">TALM \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">HP \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Petrou et al.<a class="elsevierStyleCrossRef" href="#bib0335">25</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NAA Cr Cho \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↑ Cho/Cr Caudate nucleus (bilateral) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No modifications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↑ Cho/Cr (right) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No modifications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Wood et al.<a class="elsevierStyleCrossRef" href="#bib0295">17</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NAA Cr Cho MI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↓ NAA/Cr (right) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Harris et al.<a class="elsevierStyleCrossRef" href="#bib0315">21</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NAA Cr Cho Glu Gln Glx MI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↑ Glu y ↑ Glx (post right) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fayed et al.<a class="elsevierStyleCrossRef" href="#bib0300">18</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NAA Cr Cho Glu Glx MI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No modifications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↑ Glx ↑ Glx/Cr \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No modifications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↓ NAA+NAAG (left) ↓ Cho (left) ↓ MI and MI/Cr (bilateral) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Feraco et al.<a class="elsevierStyleCrossRef" href="#bib0340">26</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NAA Cr Cho Glu Glx MI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↑ Glu/Cr ↑ Glx/Cr \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No modifications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Emad et al.<a class="elsevierStyleCrossRef" href="#bib0310">20</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NAA Cr Cho  \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↓ NAA (bilateral) ↑ Cho (right) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Foerster et al.<a class="elsevierStyleCrossRef" href="#bib0320">22</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NAA Glx GABA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↓ GABA (ant right)  \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↑ GABA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fayed et al.<a class="elsevierStyleCrossRef" href="#bib0305">19</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NAA Cr Cho Glu Glx MI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↓ NAA+NAAG/Cr (post) ↓ NAA/Cr (post) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↑ Glx ↓ Cho \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Does not analyze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">↓ NAA+NAAG (left) ↓ Cho (bilateral) ↓ MI and MI/Cr (left) ↓ Glu (left) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1447604.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Evaluation of brain metabolites. 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Cerebral magnetic resonance changes associated with fibromyalgia syndrome

Cambios en la resonancia magnética cerebral asociados al síndrome de fibromialgia

Iñigo Murgaa,

Corresponding author

imurga005@ikasle.ehu.eus

Corresponding author.

, Virginia Guillena, José-Vicente Lafuentea,b,c

a LaNCE, Departamento de Neurociencia, Universidad del País Vasco, Leioa, Bizkaia, Spain

b Grupo de Nanoneurocirugía, Instituto de Investigación Sanitaria BioCruces, Barakaldo, Bizkaia, Spain

c Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago de Chile, Chile

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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Magnetic resonance imaging &#40;MRI&#41; indicating whether the values for the referred metabolites are increased &#40;in red&#41; or decreased &#40;in green&#41;&#46; Creatinine is in bold as it is used as the reference value&#46; &#40;a&#41; Coronal-slice MRI&#44; indicating the values of the metabolites studied regarding both hippocampus&#46; Note that in the left hippocampus&#44; different authors give opposite values for choline&#46; &#40;b&#41; Horizontal-slice MRI&#44; indicating the values of the studied metabolites referred to the head of the caudate nucleus bilaterally and to the insula &#40;anterior and posterior region&#41;&#46; &#40;c&#41; Sagittal-slice MRI&#44; indicating the values of the metabolites studied referred to the ventrolateral prefrontal cortex&#44; and the anterior and posterior cortex of the cingulate gyrus&#46;</p> <p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Cho&#58; choline&#59; Cr&#58; creatine&#59; GABA&#58; gamma-aminobutyric acid&#59; Gln&#58; glutamine&#59; Glu&#58; glutamate&#59; Glx&#58; glutamate<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>glutamine&#59; Lact&#58; lactate&#59; MI&#58; myo-inositol&#59; NAA&#58; N-acetylaspartate&#59; NAAG&#58; N-acetylaspartate glutamate&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Fibromyalgia syndrome &#40;FMS&#41; is characterized by widespread chronic musculoskeletal pain&#44; of unknown etiology&#44; with hyperalgesia and allodynia&#46; It is accompanied by other symptoms&#44; such as&#58; fatigue&#44; insomnia&#44; paresthesias&#44; swelling in the hands&#44; neurovegetative changes&#44; concentration problems&#44; memory and mood disorders&#46; Symptom intensity fluctuates throughout the natural course of FMS&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Diagnostic criteria for this syndrome were provided by the American College of Rheumatology in 1990&#44;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">1</span></a> although in 2010 this same organization proposed new criteria that have not been validated yet&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The World Health Organization<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">2</span></a> classifies FMS under the heading of diseases of the musculoskeletal system and connective tissue &#40;code M79&#46;7&#41;&#44; and the International Association for the Study of Pain<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">3</span></a> has classified it under code X33&#46;X8a&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In a study conducted in 5 European countries &#40;France&#44; Germany&#44; Italy&#44; Portugal and Spain&#41;&#44; prevalence was 4&#46;7&#37;&#44; and the female&#47;male ratio was 3 to one&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">4</span></a> Its high prevalence&#44; the disability it causes and the frequency of long-term sick-leaves of these patients&#44; make the economic cost be high&#44; making it an increasingly important social and health problem&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The diagnosis is clinical&#46; There is currently no specific analytical&#44; imaging or anatomopathological test to verify this diagnosis&#46; In the perception and experience of pain&#44; various brain structures are included&#44; such as the somatosensory cortex &#40;primary and secondary&#41;&#44; the cingulate gyrus &#40;anterior region&#41;&#44; the insula&#44; thalamus&#44; the posterior parietal cortex and the prefrontal cortex&#46; All of them are involved in the so-called &#8220;pain network&#8221;&#44; a set of areas&#44; structures and nuclei dealing with the perception&#44; transmission and processing of the various sensory and affective components that constitute the experience of pain&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The quantitative study of anatomical and biochemical variables is an important strategy for the diagnosis&#44; prognosis and follow-up of various diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">5</span></a> Many authors have shown&#44; by using neuroimaging techniques&#44; changes in volume&#44; connectivity and metabolism of the brain areas involved in the &#8220;pain network&#8221; in FMS&#46; The morphometric study of certain brain structures by using the voxel based morphometry technique&#44; plus the identification of the variations in some metabolites by magnetic resonance spectroscopy &#40;MRS&#41;&#44; and the study of functional connectivity with the analysis of the blood-oxygenation-level dependent signal&#44; are a very promising tool to elucidate the morphobiological component of various disorders&#44; including FMS&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">This paper is a critical review of the neuroimaging contribution to FMS&#46; The ultimate aim is to find clues or evidence on indicators that might help determine the diagnosis and&#47;or evolution of this condition&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Development</span><p id="par0040" class="elsevierStylePara elsevierViewall">The diagnostic criteria followed in all the studies considered are those of the American College of Rheumatology&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">1</span></a> However&#44; so many and diverse inclusion-exclusion criteria between the different series makes it difficult to include them in a meta-analysis&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Changes in the size of brain structures</span><p id="par0045" class="elsevierStylePara elsevierViewall">Voxel-based morphometry analyzes the anatomical regions of the brain such as the thalamus&#44; insula&#44; amygdala&#44; hippocampus or cingulate gyrus&#46; In all of them the size decreases&#44;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">6&#8211;9</span></a> only in one study the size increases in the basal nuclei&#44; in the cerebellum and in the orbitofrontal cortex&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">10</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Another method of study is the diffusion tensor imaging&#44; which allows to evaluate microstructural changes through the analysis of the diffusion direction of hydrogen protons &#40;water&#41; in the tissue &#40;anisotropy&#41;&#46; This method requires further computational processing time&#44; but the results are very sensitive to differences in shape and volume in small brain structures&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">11</span></a> The imaging studies obtained by means of diffusion tensor show in the gray matter of both thalamus an anisotropy drop&#44; as well as in the white matter tracts connecting them with the cortex&#44; corresponding to changes in the microstructure of these anatomical areas<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">12</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The thalamus plays a central role in the sensory-discriminative component of pain&#46; Therefore&#44; a detailed volumetric analysis of the different thalamic nuclei would be interesting&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Distribution of metabolites in various brain areas</span><p id="par0055" class="elsevierStylePara elsevierViewall">MR spectroscopy allows <span class="elsevierStyleItalic">in vivo</span> determination of the level of various molecules in particular regions of the brain&#46; We should consider the various normal metabolites depending on location&#44; age and echo time used&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">13</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The most common metabolites determined are&#58; creatine &#40;Cr&#41;&#44; the basic compound of the energy metabolism of the brain&#44; is a very stable metabolite&#44; therefore&#44; used as a reference for calculating the rates of others&#59; N-acetylaspartate &#40;NAA&#41;&#44; is used as a marker neuronal density marker&#44; although dynamic changes in their rates may reflect neuronal dysfunction rather than loss&#59; Choline &#40;Cho&#41;&#44; a marker of phospholipid metabolism&#44; reflects cell proliferation and is higher in tumor processes&#59; lactate is the end product of anaerobic glycolysis&#44; present in brain tissue at very low levels&#44; which under normal conditions are not detectable by spectroscopy&#46; Their presence is indicative of ischemia or infiltration by highly glycolytic cells&#44; such as macrophages&#59; Myo-inositol &#40;MI&#41;&#44; used as a glia marker&#59; Glutamine &#40;Gln&#41; and glutamate &#40;Glu&#41;&#44; the latter being the most abundant excitatory amino acid in the brain acting as a neurotransmitter&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">14</span></a> The changes in the relative concentration of these metabolites&#44; plus the occurrence of others&#44; which in normal circumstances are not present&#44; are a reflection of the pathological changes occurring in a particular area of the brain parenchyma&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">15</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">This technique has important limitations&#44; for example&#44; the threshold of definition or discrimination of the equipment gathering the data&#44; or the computer software used for its analysis&#46; The resonance&#8211;metabolite correlation is not accurate&#44; since different protons in the same compound can show resonances in different locations of the spectrum&#46; Similarly&#44; protons from various compounds can overlap in the same spectrum&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">16</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">The analysis of the metabolites by spectroscopy in FMS yields heterogeneous and sometimes discordant data depending on the structure and the hemisphere studied&#46; The studies consulted do not include information on hemispheric dominance in the subjects studied&#44; which might be relevant to understand some of these data &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">If we consider the hippocampus&#44; one of the most referenced structures in the medical literature&#44; we find a reduction in the NAA&#47;Cr index in the right hemisphere&#44;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a> Cho and NAA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NAA glutamate index in the left hippocampus&#44; as well as a reduction in MI and MI&#47;Cr in both hippocampi&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> Likewise&#44; decreased values have also been reported in both hippocampi for Cho and only in the left hippocampus for Glu&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a> In contrast&#44; other authors report low NAA levels on both sides&#44; and Cho increases only on the right hippocampus<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">20</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">In the right posterior insula&#44; Glu and Glx -Glu<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Gln-<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">21</span></a> increase&#44; and the NAA&#47;Cr index decreases&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a> This region is closely related to somatosensory connections&#44; unlike the anterior region&#44; which is more involved in limbic and vegetative processes&#46; The distribution of these metabolites &#40;higher Glu and lower NAA&#41; explores the hypothesis of the existence of hyperexcitable and dysfunctional areas in the processing of nociceptive signals&#46; In this regard&#44; a reduction in the GABA levels in the right anterior insula has been reported&#44; inducing metabolic imbalance for Glu&#47;GABA<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">22</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>b&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Activation of the cingular cortex &#40;limbic system&#41; has been reported in several studies in response to pain as part of the emotional component of the cortex&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">23&#44;24</span></a> In the posterior cingular cortex&#44; Glx and Glx&#47;Cr<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> index appear to be higher&#44; and Cho has dropped&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a> In the anterior cingulate cortex&#44; GABA has been reported higher<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">22</span></a>&#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>c&#41;&#46; The right and left caudate nucleus &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>b&#41; and the right ventrolateral prefrontal cortex present an increased Cho&#47;Cr ratio&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">25</span></a> Another author observed increased Glu&#47;Cr and Glx&#47;Cr ratios in the ventrolateral prefrontal cortex&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">26</span></a> In FMS&#44; there are no metabolite changes in the thalamus<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">18&#44;25&#44;26</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>c&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Functional synchronization of brain areas and centers</span><p id="par0090" class="elsevierStylePara elsevierViewall">Functional MRI &#40;fMRI&#41; allows mapping brain activation patterns&#46; This technique helps understand their timing&#46; When a brain area is activated&#44; blood flow increases in that area&#44; which can be detected&#44; mapped and quantified by processing appropriate signals &#40;<span class="elsevierStyleItalic">e&#46;g&#46;</span>&#44; blood oxygenation level dependent&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Functional neuroimaging studies demonstrate that some patients with FMS present increased neuronal responses&#44; both to painful stimuli and to innocuous stimuli&#44;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">27</span></a> which corroborates allodynia and hyperalgesia reported in the tests&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">28</span></a> Both during painful stimulation and prior to pain there are clear differences in the activation of the anterior cingulate cortex&#44; supplementary motor area and thalamus&#46; These results show that mechanisms of pain in the medial system &#40;affective&#47;cognitive component&#41;&#44; even during their anticipation&#44; play an important role in the processing of these signals in subjects suffering from FMS&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">8</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">It has also been observed that brain activation is significantly higher in both insulas in this group as a response to thumb pressure stimulation&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">29</span></a> Recent studies show connectivity changes in the insula and in the somatosensory cortex S1&#44; associated with the experience of chronic pain in patients with fibromyalgia&#46;<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">30&#44;31</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Chronicity and pain</span><p id="par0105" class="elsevierStylePara elsevierViewall">Numerous neuroimaging studies reveal the involvement of the anterior cingular cortex in chronic pain patients&#46; The cingulate gyrus is part of the limbic system and the activation of its anterior region is involved in the emotional and cognitive component of pain&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">24&#44;32</span></a> This region&#44; together with the prefrontal cortex&#44; is&#44; in part&#44; responsible for pain modulation &#40;inhibiting and facilitating&#41;&#46; Structural changes in these systems might contribute to pain maintenance and chronification both in FMS and in other chronic pain syndromes&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Apkarian et al&#46; proposed a transition model from acute to chronic pain that entails a cortical reorganization of the sensory and affective pathways of pain&#46; This would imply a contribution of the central nervous system independent of the peripheral nociceptive input&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">33</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">In FMS the metabolite distribution is modified nonspecifically&#44; but consistent with the morphometric studies&#46; NAA reduction in the hippocampus contributes to the loss of volume observed in the molecular correlate in the morphometry studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">19&#44;20</span></a> corroborating that in FMS we are faced with a chronic neuronal damage or an axonal metabolic dysfunction&#44; or a combination of both&#46; This issue might only be verified through a postmortem neuropathological study&#44; in case of maintaining the same clinical status when decease occurred&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Some data on the differential concentration of metabolites in the right and left hippocampus point to the need to consider lateralization if we want to progress in understanding these disorders&#46; This data is not included in any of the publications reviewed&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">If we focus on the insula&#44; a formation that might encode the subjective magnitude of pain stimulus regardless of the sensory modality&#44;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">34</span></a> we observe that a lower gray matter volume in the left insula<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">6&#44;9&#44;10</span></a> is correlated with higher Glu<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">21</span></a> and lower GABA<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">22</span></a> in the right insula&#46; These changes indicate a metabolic dysregulation in favor of hyperexcitability in the central nervous system&#44; being probably responsible for the widespread increased sensitivity to nociceptive stimuli &#40;hyperalgesia&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Glu is a neurotransmitter involved in strengthening the pain-associated negative effects and related to chronic sensitization&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">35</span></a> Decreased levels of both Glu and Glx in the posterior insula are associated with a clinical improvement in the perception of pain&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">21</span></a> The Glu&#47;Cr ratio is increased in the posterior cingulate gyrus&#44; and is significantly correlated with pain measured objectively with a sphygmograph&#44; and with the overall function assessed through the Fibromyalgia Impact Questionnaire&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">36</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Recent studies report that the translocator protein &#40;TSPO&#41;&#44; related to the glia activation and involved in the modulation of synaptic transmission&#44; is overexpressed in chronic pain&#46; Patients with the TSPO genotype &#40;rs6971&#41; and polymorphisms for the serotonin transporter &#40;5-HTTLPR&#47;rs25531&#41; suffer from more severe pain and more severe FMS symptoms&#46; The analysis of connectivity through MRf showed higher activation in the right frontoparietal network in these groups&#44; as a response to pain&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">37</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Dysfunction of the endogenous opioid system contributes to chronic pain in FMS&#46; In this sense&#44; changes in the endogenous mechanisms of pain have been reported&#44; evidencing functional modifications&#44; such as an increased connectivity between the periaqueductal gray matter &#40;PAGM&#41; and the insula&#44; the anterior cingulate cortex and the anterior prefrontal cortex&#46; However&#44; this does not occur between the PAGM and the spinal cord at a rostral level&#46; The correlation between this connectivity and certain clinical variables such as severity of pain&#44; duration of disease and depressive personality traits has been evidenced&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">38</span></a> In addition&#44; a reduction of the <span class="elsevierStyleItalic">&#956;-opioid receptor</span> &#40;MOR&#41; in the anterior cingular cortex and in the dorsolateral prefrontal cortex &#40;antinociceptive regions&#41; has been reported&#44; where lower availability of MOR is associated with lower pain&#46; This finding reinforces the relevant role of the endogenous opioid system in the brain processing of pain&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">39</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">These results represent a significant progress in the understanding of the central pathophysiological mechanisms of pain chronification&#44; providing targets and approachable pathways for the development of new therapeutic strategies&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">40</span></a></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Limitations</span><p id="par0150" class="elsevierStylePara elsevierViewall">Many studies on this disorder omit relevant data for the assessment of the sample&#44; such as&#58; associated comorbidities&#44; time of clinical exploration&#44; hemispheric dominance or if the examinations have been performed during the menstrual period in the case of women&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">41</span></a> The variability in the inclusion and exclusion criteria&#44; the disparity of pain questionnaires used&#44; and the low number of subjects in every series &#40;below 30 patients&#41; are added to the inevitable interindividual variations&#46; Furthermore&#44; it is important to keep in mind that the painful experience fluctuates depending on the circadian rhythms&#44; the climatic season or the stressful situations&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">42</span></a> In only 3 of the reviewed studies neuroimaging was used&#44; including a painful stimulus to select the areas of study&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">9&#44;21&#44;22</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusions</span><p id="par0155" class="elsevierStylePara elsevierViewall">MRI&#44; through its various techniques&#44; is helping significantly to understand the pathophysiological processes underlying various disorders&#46; In this case&#44; it has provided relevant evidence for the understanding of the neural circuits involved in the perception&#44; transmission and modulation of nociceptive input&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Pain is an unpleasant sensory and emotional experience difficult to objectify due to its varied expression&#46; FMS is a widespread chronic pain syndrome&#44; although its diagnosis is still controversial&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">The clinical use of MRI is not widespread for the diagnosis of fibromyalgia&#44; but it seems clear that its findings on both volumetry and structural and functional connectivity and brain metabolism reveal changes in the &#8220;brain network&#8221; of pain&#46; All of this contributes significantly to a better understanding of its pathophysiology&#46; However&#44; the modifications reported to date are poorly sensitive and non-specific&#44; being reported in other chronic pain-associated processes&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">The lack of homogeneous protocols and the low number of published series does not allow us to draw conclusions that confirm or at least help in the diagnosis of this disease or its follow-up&#46; However&#44; the evidence summarized in this study justify a broad and deep study with an homogeneous clinical-radiological protocol&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Funding</span><p id="par0175" class="elsevierStylePara elsevierViewall">This study has been supported by GIC IT-901&#47;16 &#40;Basque Government&#41; and UFI 11&#47;32 &#40;University of the Basque Country-Euskal Herriko Unibertsitatea&#41;&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflict of interest</span><p id="par0180" class="elsevierStylePara elsevierViewall">The authors report no conflict of interest&#46;</p></span></span>"
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          "titulo" => "Abstract"
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            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec850990"
          "titulo" => "Keywords"
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        2 => array:3 [
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          "titulo" => "Resumen"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
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        3 => array:2 [
          "identificador" => "xpalclavsec850991"
          "titulo" => "Palabras clave"
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        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Development"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Changes in the size of brain structures"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Distribution of metabolites in various brain areas"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Functional synchronization of brain areas and centers"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Chronicity and pain"
            ]
          ]
        ]
        6 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Limitations"
        ]
        7 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Conclusions"
        ]
        8 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Funding"
        ]
        9 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Conflict of interest"
        ]
        10 => array:2 [
          "identificador" => "xack287341"
          "titulo" => "Acknowledgements"
        ]
        11 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2017-01-14"
    "fechaAceptado" => "2017-01-31"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec850990"
          "palabras" => array:5 [
            0 => "Fibromyalgia syndrome"
            1 => "Brain magnetic resonance"
            2 => "Morphometry"
            3 => "Spectroscopy"
            4 => "Connectivity"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec850991"
          "palabras" => array:5 [
            0 => "S&#237;ndrome de fibromialgia"
            1 => "Resonancia magn&#233;tica cerebral"
            2 => "Morfometr&#237;a"
            3 => "Espectroscopia"
            4 => "Conectividad"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Fibromyalgia syndrome is a chronic disease&#44; of unknown origin&#44; whose diagnostic criteria were established in 1990 by the American College of Rheumatology&#46; New criteria were proposed in 2010 that have not yet been validated&#46; It is characterized by a generalized chronic musculoskeletal pain&#44; accompanied by hyperalgesia and allodynia&#44; as well as other motor&#44; vegetative&#44; cognitive and affective symptoms and signs&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We have reviewed a set of studies with cerebral magnetic resonance &#40;morphometry&#44; connectivity and spectroscopy&#41; that refer to changes in areas involved in pain processing&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Modifications in gray and white matter volume&#44; as well as in levels of N-acetylaspartate&#44; choline or glutamate&#44; among other metabolites&#44; have been observed in the hippocampus&#44; insula&#44; prefrontal and cingular cortex&#46; Neuroradiological findings are nonspecific and similar to those found in other examples of chronic pain&#46; An increase in the sample size and a standardized methodology would facilitate comparison&#44; allowing the drawing of general conclusions&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El s&#237;ndrome de fibromialgia es un trastorno cr&#243;nico&#44; de origen desconocido&#44; cuyos criterios diagn&#243;sticos estableci&#243; en 1990 el Colegio Americano de Reumatolog&#237;a&#59; en 2010 propuso unos criterios nuevos que a&#250;n no est&#225;n validados&#46; Se caracteriza por dolor musculoesquel&#233;tico generalizado&#44; cr&#243;nico&#44; acompa&#241;ado de fen&#243;menos de hiperalgesia y alodinia&#44; as&#237; como otros s&#237;ntomas y signos&#44; motores&#44; vegetativos&#44; cognitivos y afectivos&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Revisamos un conjunto de estudios con resonancia magn&#233;tica cerebral &#40;morfometr&#237;a&#44; conectividad y espectroscopia&#41; que refieren alteraciones en &#225;reas de procesamiento del dolor&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se observan cambios en el volumen de la sustancia gris y blanca&#44; as&#237; como de los niveles de N-acetilaspartato&#44; colina o glutamato&#44; entre otros metabolitos&#44; en hipocampo&#44; &#237;nsula&#44; corteza prefrontal y cingular&#44; principalmente&#46; Los hallazgos neurorradiol&#243;gicos son inespec&#237;ficos y superponibles a los de otros cuadros de dolor cr&#243;nico&#44; pero un aumento del tama&#241;o muestral y una metodolog&#237;a estandarizada facilitar&#237;a la comparaci&#243;n entre series&#44; permitiendo extraer conclusiones generalizables&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Murga I&#44; Guillen V&#44; Lafuente J-V&#46; Cambios en la resonancia magn&#233;tica cerebral asociados al s&#237;ndrome de fibromialgia&#46; Med Clin &#40;Barc&#41;&#46; 2017&#59;148&#58;511&#8211;516&#46;</p>"
      ]
    ]
    "multimedia" => array:3 [
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        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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        "figura" => array:1 [
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Magnetic resonance imaging &#40;MRI&#41; indicating whether the values for the referred metabolites are increased &#40;in red&#41; or decreased &#40;in green&#41;&#46; Creatinine is in bold as it is used as the reference value&#46; &#40;a&#41; Coronal-slice MRI&#44; indicating the values of the metabolites studied regarding both hippocampus&#46; Note that in the left hippocampus&#44; different authors give opposite values for choline&#46; &#40;b&#41; Horizontal-slice MRI&#44; indicating the values of the studied metabolites referred to the head of the caudate nucleus bilaterally and to the insula &#40;anterior and posterior region&#41;&#46; &#40;c&#41; Sagittal-slice MRI&#44; indicating the values of the metabolites studied referred to the ventrolateral prefrontal cortex&#44; and the anterior and posterior cortex of the cingulate gyrus&#46;</p> <p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Cho&#58; choline&#59; Cr&#58; creatine&#59; GABA&#58; gamma-aminobutyric acid&#59; Gln&#58; glutamine&#59; Glu&#58; glutamate&#59; Glx&#58; glutamate<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>glutamine&#59; Lact&#58; lactate&#59; MI&#58; myo-inositol&#59; NAA&#58; N-acetylaspartate&#59; NAAG&#58; N-acetylaspartate glutamate&#46;</p>"
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">FA&#58; fractional anisotropy&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Related author&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Result&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Anatomical area&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kuchinad et al&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">6</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; Gray matter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Posterior cingulate cortex &#40;bilateral&#41;<br>Medial prefrontal cortex<br>Insula &#40;left&#41;<br>Parahippocampal gyrus &#40;left&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Schmidt-Wilcke et al&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">10</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; Gray matter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Upper temporal cortex &#40;right&#41;<br>Insula &#40;left&#41;<br>Thalamus &#40;left post&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8593; Gray matter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Orbitofrontal cortex &#40;left&#41;<br>Striated nucleus &#40;bilateral&#41;<br>Cerebellum &#40;left&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lutz et al&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">12</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; Gray matter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hippocampus &#40;bilateral&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; FA gray matter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Posterior thalamus &#40;bilateral&#41;<br>Insula &#40;bilateral&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8593; FA gray matter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Anterior cingulate cortex &#40;bilateral&#41;<br>Superior frontal cortex &#40;bilateral&#41;<br>Postcentral gyrus &#40;bilateral&#41;<br>Amygdala &#40;bilateral&#41;<br>Hippocampus &#40;bilateral&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8593; FA white matter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Anterior cingulate cortex &#40;bilateral&#41;<br>Superior frontal cortex &#40;bilateral&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; FA white matter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Talamocortical pathway &#40;bilateral&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Wood et al&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">7</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; Gray matter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Anterior cingulate cortex &#40;left&#41;<br>Posterior cingulate cortex &#40;right&#41;<br>Parahippocampal gyrus &#40;bilateral&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Burgmer et al&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">8</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; Gray matter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Anterior cingulate cortex &#40;right&#41;<br>Lateral prefrontal cortex<br>Amygdala &#40;left&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Robinson et al&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">9</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; Gray matter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Anterior cingulate cortex &#40;left&#41;<br>Medial insula &#40;left&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Analysis of brain morphometry and diffusion tensor by magnetic resonance imaging in fibromyalgia syndrome&#46;</p>"
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Ant&#58; anterior&#59; ACC&#58; anterior cingulate cortex&#59; PCC&#58; posterior cingulate cortex&#59; Cho&#58; choline&#59; VLPFC&#58; ventrolateral prefrontal cortex&#59; Cr&#58; creatine&#59; STC&#58; superior temporal cortex&#59; GABA&#58; gamma-aminobutyric acid&#59; Gln&#58; glutamine&#59; Glu&#58; glutamate&#59; Glx&#58; glutamate<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>glutamine&#59; HP&#58; hippocampus&#59; INS&#58; insula&#59; MI&#58; myoinositol&#59; NAA&#58; N-acetylaspartate&#59; NAAG&#58; N-acetylaspartate glutamate&#59; Post&#58; posterior&#59; TALM&#58; thalamus&#46;</p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">The data in bold highlight the results obtained&#46; In the images the metabolite Cr &#40;in bold letters&#41; is the reference metabolite&#46;</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Related author&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Metabolites&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">ACC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PCC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">VLPFC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">TALM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">HP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Petrou et al&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">25</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NAA<br>Cr<br>Cho&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">&#8593; Cho&#47;Cr</span><br><span class="elsevierStyleBold">Caudate nucleus &#40;bilateral&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No modifications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">&#8593; Cho&#47;Cr &#40;right&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">No modifications</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Wood et al&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NAA<br>Cr<br>Cho<br>MI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">&#8595; NAA&#47;Cr &#40;right&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Harris et al&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NAA<br>Cr<br>Cho<br>Glu<br>Gln<br>Glx<br>MI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">&#8593; Glu y &#8593; Glx &#40;post right&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fayed et al&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NAA<br>Cr<br>Cho<br>Glu<br>Glx<br>MI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No modifications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">&#8593; Glx</span><br><span class="elsevierStyleBold">&#8593; Glx&#47;Cr</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">No modifications</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">&#8595; NAA</span><span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">NAAG &#40;left&#41;</span><br><span class="elsevierStyleBold">&#8595; Cho &#40;left&#41;</span><br><span class="elsevierStyleBold">&#8595; MI and MI&#47;Cr &#40;bilateral&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Feraco et al&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">26</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NAA<br>Cr<br>Cho<br>Glu<br>Glx<br>MI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">&#8593; Glu&#47;Cr</span><br><span class="elsevierStyleBold">&#8593; Glx&#47;Cr</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">No modifications</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Emad et al&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">20</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NAA<br>Cr<br>Cho<br>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">&#8595; NAA &#40;bilateral&#41;</span><br><span class="elsevierStyleBold">&#8593; Cho &#40;right&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Foerster et al&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">22</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NAA<br>Glx<br>GABA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">&#8595; GABA &#40;ant right&#41;</span><br>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">&#8593; GABA</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fayed et al&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NAA<br>Cr<br>Cho<br>Glu<br>Glx<br>MI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">&#8595; NAA</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">&#43;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">NAAG&#47;Cr &#40;post&#41;</span><br><span class="elsevierStyleBold">&#8595; NAA&#47;Cr &#40;post&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">&#8593; Glx</span><br><span class="elsevierStyleBold">&#8595; Cho</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Does not analyze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">&#8595; NAA</span><span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">NAAG &#40;left&#41;</span><br><span class="elsevierStyleBold">&#8595; Cho &#40;bilateral&#41;</span><br><span class="elsevierStyleBold">&#8595; MI and MI&#47;Cr &#40;left&#41;</span><br><span class="elsevierStyleBold">&#8595; Glu &#40;left&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab1447604.png"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Evaluation of brain metabolites&#46; Magnetic resonance imaging &#40;spectroscopy&#41; in fibromyalgia syndrome&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:42 [
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            1 => array:3 [
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              "referencia" => array:1 [
                0 => array:2 [
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                      "titulo" => "World Health Organization&#46; International statistical classification of diseases and related health problems&#46; 10th revision"
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                  "host" => array:1 [
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                      "Libro" => array:3 [
                        "fecha" => "2010"
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            2 => array:3 [
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                        "titulo" => "Task Force on Taxonomy of the International Association for the Study of Pain&#46; Classification of chronic pain&#58; Descriptions of chronic pain syndromes and definitions of pain terms"
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                  "contribucion" => array:1 [
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                      "titulo" => "Prevalence of fibromyalgia&#58; a survey in five European countries"
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                          "etal" => true
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                            1 => "B&#46; Bannwarth"
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            4 => array:3 [
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                      "doi" => "10.1006/nimg.2000.0582"
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            5 => array:3 [
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                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Accelerated brain gray matter loss in fibromyalgia patients&#58; premature aging of the brain&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            0 => "A&#46; Kuchinad"
                            1 => "P&#46; Schweinhardt"
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                            3 => "P&#46;B&#46; Wood"
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                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1523/JNEUROSCI.0098-07.2007"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neuroscience"
                        "fecha" => "2007"
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                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17428976"
                            "web" => "Medline"
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            6 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Changes in gray matter density in fibromyalgia&#58; correlation with dopamine metabolism"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "P&#46;B&#46; Wood"
                            1 => "M&#46;F&#46; Glabus"
                            2 => "R&#46; Simpson"
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                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Pain"
                        "fecha" => "2009"
                        "volumen" => "10"
                        "paginaInicial" => "609"
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            7 => array:3 [
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                  "contribucion" => array:1 [
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                      "titulo" => "Decreased gray matter volumes in the cingulo-frontal cortex and the amygdala in patients with fibromyalgia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Burgmer"
                            1 => "M&#46; Gaubitz"
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                            3 => "M&#46; Wrenger"
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                  "host" => array:1 [
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            8 => array:3 [
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              "etiqueta" => "9"
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                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Gray matter volumes of pain related brain areas are decreased in fibromyalgia syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46;E&#46; Robinson"
                            1 => "J&#46;G&#46; Craggs"
                            2 => "D&#46;D&#46; Price"
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                            4 => "R&#46; Staud"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
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        "texto" => "<p id="par0185" class="elsevierStylePara elsevierViewall">The authors are particularly grateful to Dr&#46; Nicol&#225;s Fayed&#44; head of the Neurradiology Service at Cl&#237;nica Quir&#243;n in Zaragoza&#44; for his invaluable support in preparing the manuscript&#46;</p>"
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Article information

ISSN: 23870206
Original language: English

DOI:10.1016/j.medcle.2017.05.011

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